Essay: Oral administration of drugs

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  • Oral administration of drugs
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1.0 INTRODUCTION
Today various routs available for the administration of drugs but the oral route is the simplest and most preferable route for the administration of dosage forms. Different dosage forms are available for the administration orally.
1. Tablets
2. Capsules
3. Emulsion suspensions
4. Solutions etc
But the problems is there in the recently invented drugs having problem with there bioavability approx. 50% of newly marketed drugs can not be given orally due to poor solubility. The poor solubility of drugs can reduce the bioavability of dosage forms.
Recent approaches have included the administration of drug components with lipid vehicles such as oils, liposomes and self-emulsifying formulations [1, 2]. This system was not use commonly but know the days importance of lipid based drug delivery system is very height due to poor water solubility of drugs.
For the improving bioavability we formulate a new drug delivery system called self emulsifying drug delivery system By example, the bioavailability of Tipranavir (TPV), a nonpeptidic protease inhibitor anti-HIV drug, was doubled when dosed to rats in a SEDDS formulation versus delivered as solid powder in a hard filled capsule [3]. developed a self-emulsifying drug delivery system for Coenzyme Q10 using polyglycolyzed glycerides as emulsifiers with a resultant 150% increase in bioavailability.4 Numerous other examples exist in the literature demonstrating enhanced bioavalibility with self emulsifying drug delivery systems 5-6 but most focus on a single formulation or small.[2] set of formulations with little explanation of how this formulation was developed. Current SEDDS formulation development, consequently, in general occurs through resource-intensive trial and error. Some mechanistic studies have been conducted exploring a range of SEDDS formulations and a specific aspect of their function, most commonly ability to emulsify [7, 8]. . Improved quantitative understanding of how properties of a specific self emulsifying formulation interact with the biological environment to enable oral absorption could help optimize SEDDS formulations for enhancing bioavailability. Although a significant amount of literature exists from other fields concerning the function of emulsions [9-10], pharmaceutical formulations have not been broadly studied with respect to fundamental aspects of emulsion function, with few studies statistically developing predictive models that relate emulsion properties with formulation parameters [11]. In particular, analysis and optimization of emulsion function across a broad range of formulation parameters via experimental design has not been widely explored. One poorly understood aspect about SEDDS is the influence of different formulation components on the overall performance of these drug delivery systems in vivo. Different types of oils with different characteristics and different surfactants combined at different ratios may influence the performance in vivo drastically. There is no guidance currently available for formulating a drug with specific properties with self
emulsifying drug delivery formulations.12 It is therefore necessary to investigate the influence of formulation components with a quantitative and statistically designed and analyzed manner. 3 Another knowledge in which there is a lack of understanding is the mechanism of how self emulsifying drug delivery systems work to enhance the overall bioavailability of a hydrophobic drug orally. Suggested mechanisms responsible of functioning of SEDDS in the GI tract environment includes the increased drug solubilization in the aqueous lumen phase due to alterations in the composition and character of colloidal environment in the GI tract fluid and increased drug absorption due to enhanced permeability permeability (e.g. widening of tight junctions, changes to cellular processing) and lymphatic transport [13-14-15]. Important mechanisms that would influence drug solubilization in the lumen is the rate and extent of digestion of lipidic formulation components. Another one is the rate at which the drug is released from oil droplets especially during the process of ‘degradation’ of the emulsified drug carriers by the digestive enzymes in vivo. It is essential to investigate the rate of digestion of self emulsifying formulation lipids, rate of drug release, as well as the rate and extent of drug transport across intestinal monolayer incorporated with SEDDS in order to understand and predict formulation functioning in GI tract. Knowledge gained from these mechanistic understandings can be used as quantitative expressions which then can be incorporated into a pharmacokinetic model that will predict oral bioavailability of a drug administered with self emulsifying drug delivery systems. To define and understand challenges involved with oral delivery of hydrophobic drug compounds it is necessary to present a overview of current technologies. 16
Oral intake has been the most sought-after route of drug delivery by the patients as well as the manufacturers for the treatment of most pathological states. Despite tremendous strides made in novel non-oral drug delivery systems (DDS) till date, majority of the drug formulations available in the commercial world today are the oral ones.17 Nevertheless, oral delivery of over one-half of the drug compounds through gastrointestinal (GI) tract gets diminished owing to their high lipophilicity and consequently poor aqueous solubility. Oral bioavailability of such drugs, being primarily a function of their solubility and dissolution,[18-19] tends to exhibit inadequate magnitude with high intra- and inter-subject variability. Besides, oral bioavailability also depends upon a multitude of other drug factors such as stability in GI fluidsintestinal permeability, resistance to metabolism by cytochrome P450 family of enzymes present in gut enterocytes and liver hepatocytes, and interaction with efflux transporter systems like P-glycoprotein (P-gp).[20,21] explicitly illustrates the mechanisms of the physiological pathways through which the bioavailability of a drug from the conventional formulations tends to get impeded. Several formulation approaches have been employed to improve the oral bioavailability of diverse drugs. Amongst these, oral lipid-based DDS have proved their immense potential in improving the poor and inconsistent drug absorption of many poorly water-soluble drugs, especially following their administration after meals.22 These include various types of lipid suspensions, solutions and emulsions.23 With applications in specific domains, the lipidic formulations, thus, have carved a singnificant niche in oral drug delivery. Self-emulsifying drug delivery systems (SEDDS) are relatively newer lipid-based technological innovations with immense promise in oral bioavailability enhancement of drugs. These formulations have shown to reduce the slow and incomplete dissolution of a drug, facilitate the formation of its solubilized phase, increase the extent of its transportation via intestinal lymphatic system, and bypass the P-gp efflux, thereby augmenting drug absorption from the GI tract.24
Self emulsion having grate capacity yo increase the bioavability of poorly water soluble drugs. It’s a isotropic mixture of oil ,surfactant, co-surfactant.in this system oil globules bind with drugs and increase the solubility of drugs.
SEDDS is also known as microemulsion system. It will increase bioavability of drugs 50-100% .25-26
Type of SEDDS :-
1. Solid self emulsifying drug delivery system (SSEDDS)
2. Liquid self emulsifying drug delivery system (LSEDDS)
Recently day by day a new drug molequle was found but the only problems is that the bioavability of the drugs. Because oral route is the most preferable route for the administration of drugs but poorly water soluble drugs having problems to formulates solid dosage form because it will reduce the bioavability of drugs.26
In the solid dosage forms numbers of excipients are use for the increasing drug solubility. They can be help in enhancing the solubility of drugs.
In the SEDDS we number of excipients are use.
1. Oils
2. Surfactant
3. Co- surfactants
4. Solidifying agent
They all the excipients help in the inhancing the bioavability of drugs.26
SEDDS is the isotropic mixture of oil, surfactant and co-surfactant. Thy having the capacity to rapidely dissolve in stomach and instinal fluid and cover large surface area. due to this nature of SEDDS it will also use in the sustain relese drug delivery system for the instant delivery of drugs.
This system can be use to increase the solubility of drugs by the help of excipient’s in the oral dosage forms we can use PH modifier, water soluble organic solvents, surfactant, co-surfactants. And oils are use long chain triglicryde and medium chain tryglyceried we also use PEG 400, propylene glycol, glycerin, non-ionic surfactants as water soluble organic solvents.36,37
1.1 Composition of SEDDSs:-
‘ The nature of the oil’surfactant pair.
‘ The surfactant concentration.
‘ The temperature at which self-emulsification occurs.
1.1.1 Oils:- Oils can solubilize the lipophilic drug in a specific amount. It is the most important excipient because it can facilitate self-emulsification and increase the fraction of lipophilic drug transported via the intestinal lymphatic system, thereby increasing absorption from the GI tract . Long-chain triglyceride and medium-chain triglyceride oils with different degrees of saturation have been used in the design of SEDDSs. Modified or hydrolyzed vegetable oils have contributed widely to the success of SEDDSs owing to their formulation and physiological advantages. Novel semisynthetic medium-chain triglyceride oils have surfactant properties and are widely replacing the regular medium- chain triglyceride.
1.1.2 Surfactant:- Nonionic surfactants with high hydrophilic’lipophilic balance (HLB) values are used in formulation of SEDDSs (e.g., Tween, Labrasol, Labrafac CM 10, Cremophore, etc.). The usual surfactant strength ranges between 30’60% w/w of the formulation in order to form a stable SEDDS. Surfactants have a high HLB and hydrophilicity, which assists the immediate formation of o/w droplets and/or rapid spreading of the formulation in the aqueous media. Surfactants are amphiphilic in nature and they can dissolve or solubilize relatively high amounts of hydrophobic drug compounds. This can prevent precipitation of the drug within the GI lumen and for prolonged existence of drug molecules.
1.1.3 Cosolvents:- Cosolvents like diehylene glycol monoethyle ether (transcutol), propylene glycol, polyethylene glycol, polyoxyethylene, propylene carbonate, tetrahydrofurfuryl alcohol polyethylene glycol ether (Glycofurol), etc., may help to dissolve large amounts of hydrophilic surfactants or the hydrophobic drug in the lipid base. These solvents sometimes play the role of the cosurfactant in the microemulsion systems.27
1.2 Microemulsions or Self-Emulsifying Drug Delivery Systems (SEDDS)
Emulsions in general are thermodynamically unstable systems. The droplets of the dispersed phase are large. Microemulsions on the other hand are emulsion systems that have a droplet size of a few to hundreds of nanometers and are typical complex fluids that consist of three essential components: two immiscible fluids and a surfactant. Typically these are water-in-oil or oil-in-water microemulsions where the rheological properties of these two liquids and microstructure of the surfactant strongly affect the resulting microemulsion . Microemulsions and micellar solutions are distinguished from emulsions by the fact that the average drop size does not grow with time, which is a manifestation of thermodynamic unstability. Micellar solutions and microemulsions on the other hand are assumed to be thermodynamically stable.
Reasons why there is tremendous attention on SEDDS include industrial trend towards the discovery and development on hydrophobic drugs and the resolution of technology transfer, stability and regulatory issues by SEDDS and the fact that they have proven pharmaceutical benefit with commercially available compounds of up to 5 fold increase in bioavailability (cyclosporine, lipid soluble vitamins, HIV protease inhibitors etc.)
Self-emulsifying drug delivery systems by definition are mixtures of an oil, one or more surfactants and optionally a co-solvent or co-surfactant which when introduced into an aqueous media, under gentle agitation, forms fine oil-in-water emulsions. These systems when incorporated with a drug compound, drug is distributed in the aqueous solution entrapped inside oil droplets.
SEDDS enable distribution of hydrophobic drug component in the aqueous media and creates a drug solubilization in the gastrointestinal environment. Distribution of drug inside oil droplets prevents drug from being an undisolved substance, precipitating and being excreted from body. However their mechanisms of action in the body are not limited to solubilization enhancement and also include other processes such as intestinal permeability and lymphatic transport enhancement.
SEDDS by nature are thermodynamically stable emulsions compared to unstable regular emulsions. Their stability is thought to be dependent on their relatively small dispersed oil droplet size and narrow range of droplet distribution. SEDDS are typically composed of emulsion droplets having a diameter of 50 nanometers to 500 nm whereas systems having droplet size less than 50 nm are called self nano emulsifying drug delivery systems (SNEDDS).
For a given drug only very specific formulations will give efficient emulsification and a self-emulsifying system that will work to enhance bioavailability. Efficiency of SEDDS therefore, as explained in detail by Gursoy et al., is governed by surfactant concentration, oil/surfactant ratio, polarity of the emulsion, droplet size and charge of the droplets. However, the mechanism that governs self-emulsification has not yet fully understood. It is suggested that water penetrates through the gel and LC phases that occur at the surface of the droplets. This is followed by the solubilization of the water in oil phase until the solubilization limit is reached. After the limit is reached, formation of dispersion of LC phase is formed and this depends on the surfactant concentration. Wit this formation, SEDDS become resistant to coalescence. Emulsion stability is governed by a variety of factors such as physical nature of the interfacial film, presence of electrostatic or steric barriers on the droplet, viscosity of the continuous phase, droplet size distribution, oil to water ratio, temperature and the amount of surfactant that is absorbed on the surface of the oil droplet. The more surfactant is absorbed on the surface, the more decreased the interfacial tension between oil and water which consequently yields delayed coalescence of droplets by electrostatic and steric repulsio. Although with the addition of high amounts of drug, which is common case for potential oral dosage forms, it is harder to have stabilized emulsions. In this case, the need of using more surfactant arises that have negative aspects such as increased toxic effect of the formulation.
1.3 ADVANTAGES OF SEDDS :-
‘ More consistent drug absorption,
‘ Control of delivery profile
‘ Reduced variability including food effects
‘ Enhanced oral bioavailability enabling reduction in dose
‘ High drug loading efficiency.
‘ For both liquid and solid dosage forms.
‘ These dosage forms reduce the gastric irritation produced by drugs.25-26
1.4 APLLICATION OF SEDDS :
Main application of this SEDDS to increase the bioavability by increasing the solubility of drugs.
In this system we use oils for the increasing the solubility of drugs . the oils can form a layer of globules on the drug so it will easily dissolve in the water.27
1.5 Solubility and Process of Solubilization
In bioavailability of drug, solubility plays a key role because it is vital determinant of drug release and absorption. Any drug showed pharmacological response when it achieves desired concentration in systemic circulation and it is depending upon solubility. Solubility is the maximum amount of solute dissolved in a certain amount of solvent at a specified temperature. (Shinde A. J., 2007)
1.5.1 Process of solubilization
Factors affecting solubility
1. Particle size
2. Temperature
3. Pressure
4. Other: Nature of the solute solvent, Molecular size, Polarity, Polymorphs
1.5.2 Bioavailability
1.5.2.1 Absolute bioavailability and Relative bioavailability
Absolute bioavailability Intravenous dose is selected as a standard because the drug is administered directly into the systemic circulation (100% bioavailability) and avoids absorption step. Intramuscular dose can also be taken as a standard if the drug is poorly water soluble. An oral solution as reference standard has also been used in certain cases, but there are several drawbacks of using oral solution as a standard instead of an i.v. dose.
Relative or comparative bioavailability
It is also termed as comparative bioavailability. It is denoted by Fr. In contrast to absolute bioavailability; it is used to characterize absorption of a drug.
1.5.2.2 Methods for enhancement of bioavailability
As per definition of bioavailability, poor permeability through the biomembrane owing to inadequate partition coefficient or lipophilicity or large molecular size such as that of protein or peptide drugs are poor bioavailable drugs. Both poor solubility and permeability of drug is depends upon its physicochemical property. Biopharmaceutical Classification System (BCS) Based on intestinal permeability and solubility of drugs, Amidon et al., developed Biopharmaceutical Classification System (BCS) which classify drugs into one of the four groups.
Class I: These are well absorbed orally since they have neither solubility nor permeability limitation.
Class II: Shows variable absorption owing to solubility limitation.
Class III: also shows variable absorption owing to permeability limitation.
Class IV: are poorly absorbed orally owing to both solubility and permeability limitation. There are three approaches in overcoming bioavailability problems are:
Pharmaceutical approach:
It includes alteration of formulation, manufacturing process or physicochemical properties of drug devoid of changing chemical structure.
Pharmacokinetic approach:
It includes modification of pharmacokinetic of drug by changing its chemical structure by developing new chemical entity with desirable feature or prodrug design.
1.5.2.3 By enhancing drug solubility or dissolution rate:
1. Micronization
2. Nanonization
3. Supercritical fluid recrystallization
4. Spray freezing into liquid
5. Evaporative precipitation into aqueous solution
6. Use of surfactants
7. Use of salt forms
8. Use of precipitation inhibitors
9. Alteration of pH of drug microenvironment
10. Use of amorphous, anhydrates, solvates and metastable polymorphs
11. Solvent deposition
12. Precipitation
13. Selective adsorption on insoluble carriers
14. Solid solution
15. Eutectic mixture
16. Solid dispersion
17. Molecular encapsulation with cyclodextrin
1.5.2.4 By enhancing drug permeability across biomembrane
1. Lipid technology
2. Ion pairing
3. Penetration enhancers
1.5.2.5 By enhancing drug stability
1. Enteric coating
2. Complexation
3. Use of metabolism inhibitors
1.5.3 Problems and Breakthroughs of Bioavailability Enhancement Techniques
When poor wetting properties and difficulties in processing of powders are problems reduction in particle size can not applicable in such conditions. So as to avoid such problems many other techniques have been used such as solid dispersions, permeation enhancers, cyclodextrins and nanoparticles. In fact, in some special cases, such approaches have been doing well.In the technique of reducing the size of particles, there is affinity for agglomeration of particles due to high surface charges on small discrete particles.
1.5.4 Lipid based drug delivery
Ideal properties of Lipid based formulations.
1. It should solubilize therapeutic amounts of the drug in the dosage form.
2. It should maintain adequate drug solubility over the entire shelf-life of the drug product (generally 2 years) under all anticipated storage conditions.
3. It should provide adequate chemical and physical stability for the drug and formulation components.
4. It must be composed of approved excipients in safe amounts.
5. It should adapt to the digestive processes of the GI tract such that digestion either enhances or maintains drug solubilization.
6. It should present the drug to the intestinal mucosal cells such that absorption into the cells and into the systemic circulation is optimized.
NEES FOR STUDY
&
OBJECTIVE
2.0 NEED FOR STUDY & OBJECTIVE
Oral route is the most convenient and preferable route for the administration of drugs but the problems is occurs due to the low solubility of drugs. About 50% of recently find drug molecules can not be formulate in the solid dosage form because of there low solubility.
The need of this study was to increase the solubility of poorly soluble compound. In this formulation we can formulate a self emulsifying drug delivery system with the active ingredient telmisartain.
Telmisartain practically water insoluble drugs. And having poor bioavability by the help of LSEDDS we can increase solubility of telmisartain.
LITERATURE REVIEW
3. LITRATURE SURVEY
1. . Saritha,D. et al. (2014) Prapration a stable formulation for self emulsifying drug delivery systems (SEDDS) in order to enhance the solubility, release rate, and oral absorption of the poorly soluble drug, indomethacin. Based on the solubility of indomethacin in oil, surfactant and cosurfactant, pseudo-ternary phase diagrams were developed in 1:1, 1:2, 2:1, 1:3, 3:1, 4:1 ratio for SEDDS composed of labrafil, cremophor EL and transcutol P. Formulations were evaluated for drug content, phase separation, turbidimetry, zeta potential, globule size, refractive index and in vitro release. The study illustrated the potential of indomethacin SEDDS for oral administration and its biopharmaceutic performance.33
2. Damineni,S et al (2014) developed self emulsifying drug delivery system of ibuprofen to enhance solubility, dissolution rate which may improve therapeutic performance and drug loading capacity so as to develop alternative to traditional oral formulations to improve bioavailability. In this study Labrafac, Tween 80 and PEG 200 were selected as oil, surfactant and co-surfactant respectively. Formulation development and screening was done based on results obtained from phase diagrams and characteristics of resultant microemulsions. The developed SEDDS were evaluated for droplet size analysis, zeta potential, polydispersibility index, viscosity, refractive index, % transmittance, drug content and in vitro diffusion profiles.34
3. Kumar,S. et al (2014) in this article we have study upper surface of SEDDS. The main advanced topic in this article is solidification process of LSEDDS and the development of solid SE dosage forms.at the last find he prolems of the system and solve it.35
4. Reddy,M. et al (2014) In this article we have conclude, today huge numbers of formulation avalables for the increasing poor water solubility of drugs , dissolution rate and bioavailability of insoluble drugs. One of the promising techniques is Self’Micro Emulsifying Drug Delivery Systems (SMEDDS). Liquid SEDDS were prepared using LLWL 1349, Labrafac PG as oils and cremophor EL, cremophor RH40 as surfactants and labrasol, transcutol HP as co-surfactants. Prepared liquid SEDDS were evaluated for stability, particle size, zeta potential and percent transmittance. Selected liquid formulations were converted to solid SEDDS by adsorbing onto a solid carrier Neusilin. Prepared solid SEDDS were evaluated for flow properties and in-vitro drug release studies. Results proved that prepared solid SEDDS have good flow properties and improved drug solubility and dissolution profiles (99.95%) when compared to pure efavirenz.36
5. Amrutkar,C. et al (2014) The aim of the present study is to improve solubility and hence bioavailability of Rosuvastatin calcium using self nanoemulsifying drug delivery system (SNEDDS). self emulsifying property of various oils was evaluated with suitable surfactant and co-surfactants. Ternary phase diagram was constructed based on Rosuvastatin calcium solubility analysis for optimizing the systems. The prepared formulation were evaluated for self emulsification time, dispersibility study, average globule size, Polydispersibility index (PDI). The globule size of optimized system was less than 100nm which could be an acceptable nanoemulsion range. The average globule size of the selected F2 SNEDDS formulation (Capmul MCM [20%], Tween 20 [40%] and PEG 200 [40%]) was 88.01nm. In vitro drug release studies showed remarkable increase in dissolution of F2 SNEDDS compared to marketed formulation.37
6. . Choudhary,S.B. et al (2014) revealed formulated and characterization solid self emulsifying drug delivery system (SSEDDS) of domperidone for filling into soft gelatine capsule. Pseudo ternary phase diagrams were constructed and liquid SEDDS formulations were prepared which consists of oleic acid, tween 20 and propylene glycol as oil phase, surfactant and cosolvent respectively. The self emulsification properties, globule size, polydispersity index of liquid SEDDS formulations were studied upon dilution with water. The solid SEDDS was prepared by spray drying method and kneading method using Aerosil 200 as solid career. The solid state characterization of the solid SEDDS was performed by SEM, DSC, and X-ray powder diffraction. The results from this study demonstrate the potential use of SEDDS as a means of improving solubility, dissolution, and concomitantly the bioavailability.38
7. .Gikwad,S. et al. (2012) A reaserch on self-emulsifying drug delivery system (SEDDS) to enhance the solubility of the poorly water-soluble drug Orlistat. These drugs can be successfully formulated for oral administration, but care needs to be taken with formulation design to ensure consistent bioavailability. Solubility of Orlistat was evaluated in various nonaqueous carriers that included oils, surfactants, and cosurfactants. Pseudoternary phase diagrams were constructed to identify the self-microemulsification region. The self microemulsification properties, droplet size and thermodynamic stability of these formulations were studied upon dilution with water.38
8. . Sachan,R. et al. (2010) To develop a formulation For the improvement of bioavailability of drugs with such properties presents one of the greatest challenges in drug formulations dissolution rate which may improve therapeutic performance and drug loading capacity so as to develop alternative to traditional oral formulations to improve bioavailability. In this study Labrafac, Tween 80 and PEG 200 were selected as oil, surfactant and co-surfactant respectively. Formulation development and screening was done based on results obtained from phase diagrams and characteristics of resultant microemulsions.39
9. Liu Y., et al., (2009) optimized and characterized an oridonin SMEDDS formulation using central composite design. In this study effect of concentration of oil andsurfactant and co-surfactant ratio has been studied. Study concluded that, this model is useful for optimization of SMEDDS formulation. In-vitro drug release showed that, there was increase in drug release as compared to powder formulation.40
10. Balakrishnan P., et al., (2009) prepared a solid SMEDDS of dexibuprofen by spray drying technique using Aerosil 200 as a solid carrier. After conversion in to solid form S-SMEDDS retains its self emulsification capacity. In-vitro drug release showed that, there was increase in drug release as compared to powder formulation. In-vivo study showed that increase in bioavailability. Study concluded that, in the form of Solid SMEDDS it retains all characteristics of liquid and it can become helpful solid dosage form.41
11. Singh A. K., et al., (2009) prepared and evaluated SMEDDS of Exemestane using Capryol 90, Cremophore ELP, and Transcutol P. They compared drug release with marketed formulation in different pH. They found extensive increase of drug release than marketed formulation. They also compared absorption of drug with that of drug suspension. They found enhanced drug absorption from SMEDDS. Study concluded that, SMEDDS have potential of enhancing solubility, absorption and hence bioavailability of poorly water soluble drug.42
12. Shaji J., et al., (2008) formulated and evaluated SMEDDS of Celecoxib. They optimized formulation using 33 factorial design. Particle size was taken as response variable. Study showed that, concentration of different components showed prominent effect on particle size and appearance of dispersion. They found enhanced drug absorption from SMEDDS. Study concluded that, SMEDDS have potential of enhancing solubility, absorption and hence bioavailability of poorly water soluble drug.43
13. Atef E., et al., (2008) formulated and evaluated SMEDDS of phenytoin and compared its relative bioavailability with marketed formulation. Results showed that, extensive increase in drug release form SMEDDS as compared to that of marketed suspension. Also in-vivo study showed improvement in bioavailability. Study concluded that, SMEDDS is promising formulation to increase drug release as well as bioavailability of poorly water soluble compounds In-vitro drug release showed that, there was increase in drug release as compared to powder formulation.44
14. Fatouros D. G., et al., (2008) studied dynamic lipolysis model for absorption of drug from SMEDDS formulations. They also studied IVIVC with the help of neuro-fuzzy networks. Study concluded that, in evaluation of SMEDDS for prediction of in-vivo behavior in-vitro dynamic lipolysis model is a possible means.45
15. Shikov A., et al., (2008) Prepared and characterized SMEDDS of flavonoids. Prepared SMEDDS formulation was evaluated for self emulsification capacity, droplet size and for bioavailability. Results showed that, They found enhanced drug absorption from SMEDDS. Study concluded that, SMEDDS have potential of enhancing solubility, absorption and hence bioavailability of poorly water soluble drug. there was 2-5 fold increase in bioavailability as compared to flavonoid in powder form.46
16. Woo J. S., et al., (2008) developed SMEDDS of Itraconazole and studied and compared in-vivo study in human volunteers with marketed formulation having double dose. Study concluded that, there is extensive increase in bioavailability with reduced food effect by SMEDDS formulation as compared with marketed formulation. They found enhanced drug absorption from SMEDDS. Study concluded that, SMEDDS have potential of enhancing solubility, absorption and hence bioavailability of poorly water soluble drug.47
17. Mandawgade S. D., et al., (2008) developed SMEDDS using natural lipophile as oil phase and also compared its performance with synthetic oils. For this study beta-Artemether was used as drug. Oil was previously evaluated for toxicity studies. Prepared SMEDDS was evaluated for globule size, in-vitro and in-vivo study. Study concluded that, performance of natural lipophiles is better than that of commercially available synthetic oils hence can be used in SMEDDS as it is safe.48
18. Yi T., et al., (2008) developed a controlled release solid SMEDDS of nimodipine using HPMC. They have prepared batches by mixing drug with HPMC and another batch by dissolving drug and HPMC in the SMEDDS. Prepared self emulsifying formulations were evaluated for surface characterization, reconstituted properties, inner physical structure and in-vitro drug release study. Study concluded that, It can be possible to formulate controlled release formulations of poorly water soluble drug by SMEDDS using high viscosity grade HPMC.49
19. Yi T., et al., (2008) developed a S-SMEDDS of nimodipine. Prepared S-SMEDDS was evaluated for in-vitro and in-vivo absorption study. They have studied effect of dilution media and enzymatic digestion on solubilization of drug .Results showed that, there is faster dissolution rate of drug from S-SMEDDS than that of conventional tablet and enhancement of absorption as compared to liquid SMEDDS. . Prepared SMEDDS was evaluated for globule size, in-vitro and in-vivo study. Study concluded that, performance of natural lipophiles is better than that of commercially available synthetic oils hence can be used in SMEDDS as it is safe. Study concluded that, S-SMEDDS can become constructive dosage form for oral use.50
20. Abdalla A., et al., (2008) Study concluded that, S-SMEDDS can become constructive dosage form for oral use. developed self emulsifying formulation in the form of pellets by extrusion and spheronization technique. In. this study they found that, droplet size decreases after dilution. Study concluded that, solubilzation depend on concentration of secretions like bile salts and phospolipid. SMEDDS can besuccessfully transformed into pellets form and can become another method to encapsulate material into hard gelatin capsule.51
21. Lu J. L., et al., (2008) developed SMEDDS of 9NC to enhance bioavailability and anticancer effect. They prepared microemulsion of 9NC and characterized for citotoxicity and bioavailability study. Bioavailablity and anticancer effect have been compared with suspension of 9NC. Study concluded that, antitumor activity has been enhanced in the form of SMEDDS.52
22. Patel D., et al., (2007) developed SMEDDS of Acyclovir. Prepared formulations were evaluated for different parameters. Absorption of drug from SMEDDS was compared with plain drug solution. Results showed that, there was 3.5 fold increases in bioavailability by SMEDDS. Study concluded that, bioavailability of drug can be enhanced using SMEDDS approach. . Results showed that there were 5 fold reductions in plasma cholesterol and 4 fold reductions in plasma triglycerides when compared with reference formulation of drug suspension. Study concluded that, there was better biopharmaceutical performance of drug from SEDDS.53
23. Cirri M., et al., (2007), formulated oral liquid spray formulation of xibornol using SMEDDS. Prepared formulations were evaluated for rheological, stability, SAXS and in-vivo study. The study found that, SMEDDS can be used to prepare stable and effective oral liquid spray formulation. Absorption of drug from SMEDDS was compared with plain drug solution. Results showed that, there was 3.5 fold increases in bioavailability by SMEDDS. Study concluded that, bioavailability of drug can be enhanced using SMEDDS approach.54
24. Patil P., et al., (2007) formulated a SEDDS for simvastatin. Prepared SEDDS was evaluated for turbidometric analysis, particle size, in-vitro drug diffusion and in-vivo study in rat. Results showed that there were 5 fold reductions in plasma cholesterol and 4 fold reductions in plasma triglycerides when compared with reference formulation of drug suspension. Study concluded that, there was better biopharmaceutical performance of drug from SEDDS.55
25. Patel A. R., et al., (2007) formulated and evaluated SMEDDS of fenofibrate. From solubility study of drug in different components oil, surfactant and co-surfactant were selected and pseudo ternary phase diagram were constructed. From this SMEDDS were prepared and evaluated for thermodynamic, dissolution, stability study and lipid lowering capacity. Study concluded that, SMEDDS can improve dissolution rate and hence bioavailability of drug which become substitute for oral drug delivery system. Study concluded that, there was better biopharmaceutical performance of drug from SEDDS.56
26. Shen H., et al., (2006) prepared and evaluated SMEDDS of atorvastatin using Labrafil, PEG and Cremophor RH40. From solubility study of drug in different components oil, surfactant and co-surfactant were selected and pseudo ternary phase diagram were constructed. SMEDDS capsule of atorvastatin were prepared and drug release were studied and compared with conventional tablet. Results showed that release of drug was much higher from SMEDDS capsule than that of tablet. Study concluded that, bioavailability of drug can be enhanced using SMEDDS capsule than conventional tablet. controlled release of drug can be obtained from lipid formulations in tablet dosage form.57
27. Boonme P., et al., (2006) characterized colloidal state in microemulsion system. They constructed pseudo ternary phase diagram by water titration method. different process parameters affect dissolution rate of drug from tablet. Study concluded that, controlled release of drug can be obtained from lipid formulations in tablet dosage form. Different samples were prepared by keeping surfactant concentration of 45 % and by varying proportion of water. Prepared samples were evaluated for appearance, viscosity, conductivity, DSC, SEM and NMR. Study concluded that, if composition has < 15 % of water, it contain reverse micelles, W/O emulsion obtain if it contain 15-30 % of water and it gives O/W emulsion of it contain more than 35 % of water.58 28. Nazzal S., et al., (2006) evaluated different process parameters which affect release of drug from SNEDDS in tablet dosage form. Solid preparation was prepared to study absorption of drug in rat and dog. Prepared tablets were evaluated for dissolution and stability studies. Results showed that, different process parameters affect dissolution rate of drug from tablet. Study concluded that, controlled release of drug can be obtained from lipid formulations in tablet dosage form.59 29. Wu W., et al., (2006) prepared SMEDDS of silymarin. From solubility study of drug Tween 80, ethyl alcohol and ethyl linoleate were selected as formulation components Solid preparation was prepared to study absorption of drug in rat and dog. Results showedthat Florite RE gives more absorption of drug both in rat and dog. Results showed that, there is increase in particle size as increase in drug loading in formulation. Drug release was much higher than that of crude drug powder. Study concluded that by using SMEDDS bioavailability of silymarin can be enhanced.60 30. Ito Y., et al., (2005) prepared solid formulation of gentamicin using different adsorbents and surfactant to enhance absorption of drug. Florite RE, Neusilin US2 and Sylysia 320 were used as adsorbents and Labrasol was used as surfactant. Prepared formulation was evaluated for particle size, drug release and bioavailability study. Results showed that, there is increase in particle size as increase in drug loading in formulation Study concluded that by using adsorbent and surfactant system oral solid formulations can be prepared so as to increase absorption of poorly absorbable drug.61 31. Sha X., et al., (2005) studied effect of charge and dilution on TEER and permeability of mannitol by formulating SMEDDS using Labrasol and also studied effect of dilution of surfactant on ZO-1 and F-actin. Study concluded that, SMEDDS of both positive and negative charge containing Labrasol are capable of enhancing the paracellular tramsport of mannitol across Caco-2 cell at different dilutions. , there was significant increase in rate and extent of absorption of drug as compared to capsule. It was also found that, there was 1.5 fold increases in bioavailability than tablet. Study concluded that, SMEDDS can be beneficial for oral delivery of poorly water soluble drug such as simvastatin.62 32. . Subramanian N., et al., (2004) developed and optimized SMEDDS of Celecoxib using simplex lattice mixture design. Prepared SMEDDS were evaluated for Clarity, solubility, in-vitro dissolution and in-vivo study. Results showed thatRelative bioavailability with capsule was found to be 132 %. Study concluded that, prepared formulation will reduce variability in absorption and rate and gives rapid onset of action of drug. It was also found that, there was 1.5 fold increases in bioavailability than tablet. Study concluded that, SMEDDS can be beneficial for oral delivery of poorly water soluble drug such as simvastatin.63 33. Kang B. K., et al., (2004) prepared SMEDDS of simvastatin using Carpryol 90, Cremophor EL and Carbitol. Prepared formulations were evaluated for Sustained drug release was achieved by using Silicon dioxide as gelling agent which retarded release of drug, in-vitro dissolution study and bioavailability study. Results showed that, in-vitro of drug was much higher that that of conventional tablet. It was also found that, there was 1.5 fold increases in bioavailability than tablet. Study concluded that, SMEDDS can be beneficial for oral delivery of poorly water soluble drug such as simvastatin.64 34. Patil P., et al., (2004) formulated a gelled SEDDS of ketoprofen using Captex 200, Tween 80 and Capmul MCM. Sustained drug release was achieved by using Silicon dioxide as gelling agent which retarded release of drug. Study concluded that, as concentration of gelling agent increases it increase droplet size of emulsion formed which helps in slowing drug diffusion. It was also found that, as concentration of co-surfactant increase drug release from dosage form also increases.65 35. Holm R., et al., (2003) importance of this examined oral absorption and lymphatic transport of halofantrine in SMEDDS containing triglycerides, Sustained drug release was achieved by using Silicon dioxide as gelling agent which retarded release of drug. Maisine-35-1 and Cremophor EL. Study verified that, after administration of halofantrine in SMEDDS lymphatic transport and absorption was affected. Study concluded that, by using differentstructure of triglycerides it is achievable to enhance lymphatic transport of compound without affecting its availability.66 36. Itoh K., et al., (2002) the aim of this present researched topic improved solubility of N-4472 by formulating self-micro emulsifying system using Gelucire�� 44/14, HCO and SDS. Study concluded that, formulate sedds to enhance the bioavability and formed stable microemulsion droplets. SDS showed vital role in stability of microemulsion droplets.67 37. Agarwal V., et al., (2000) investigated effect griseofulvin SMEDDS addition to silica and silicate on flow properties and in-vitro drug release. Results showed that, increase in surface area increases dissolution of drug. Study concluded that, nature and amount of adsorbent affect flow properties and dissolution of drug in SMEDDS. In-vitro drug release showed that, there was increase in drug release as compared to powder formulation.68 38. Kim H. J., et al., (2000) developed SMEDDS of idebenone using Labrafil 2609, Labrasol. Transcutol and Plurol oleique WL1173 so as to enhance bioavailability by the increasing the solubility of the poorly water solublr drug. Results showed that, in-vitro dissolution rate of drug were increased 2 folds than that of tablet. Study concluded that, SMEDDS can be used as substitute for traditional oral formulations to enhance bioavailability of idebenone.69 39. Chen G. L., et al., (1996) the importance of this present researched study was validated bioanalytical method for determination of Verapamil from plasma by HPLC for pharmacokinetic study of Verapamil. They also studied sensitivity, specificity, linearity, accuracy, precision and sample stability of method. For the purpose of sedds evaluation.70 40. Shah N. H., et al., (1994) the aim of this study was investigated emulsification efficiency of polyglycolyzed glycerides (PGG) and polyethylene glycol (PEG). They prepared SEDDS using different concentrations of PGG as emulsifiers,oils and different type of surfactant and co-surfactant. Neobee M5 and Peanut Oil were selected as oil. Drug having good solubility in oil was selected for this study. Study showed that, PGG can be used as emulsifier for preparation of SEDDS.71 MATERIAL & METHOD 4. MATERIAL AND METHOD 4.1 MATERIALS Table 4.1: List of materials with sources S. No. Materials Source 1. Telmisartan Skymap Pharmaceuticals, Roorie 2. Tween 80 Loba chemic laboratory regents Mumbai 3. PEG 400 Nasco laboratory 4. Methanol Loba chemic laboratory regents Mumbai 5. Hydrochloric acid Loba chemic laboratory regents Mumbai 6. Orange oil Burgone laboratory Mumbai Table 4.2: List of equipments with make S. No. Equipment Make 1. Analytical balance Fuji electronic balance 2. Melting point apparatus Jyoti digital auto melting apparatus 3. UV – Spectrophotometer Jasco japan-v630 4. Dissolution apparatus Jyoti standard dissolution apparatus 5. FTIR Jasco-jap
an FT/IR/4100 7. mixing Jyoti lab gwl. INDIA 8. Hot air oven Jyoti lab gwl. INDIA 9. Water bath Jyoti lab gwl.INDIA 4.1.1 Drug profile: Telmisartan72 Telmisartan is 4’-[[4-Methyl-6-(1-methyl-1H-benzimidazol-2-yl)-2-propyl-1H-benzimidazol-1- yl]methyl]biphenyl-2-carboxylic acid. Structural formula ‘ Figure 3.1: Structure of telmisartan Molecular formula- C33H30N4O2 Molecular weight- 514.6 Definition 4’-[[4-Methyl-6-(1-methyl-1H-benzimidazol-2-yl)-2-propyl-1H-benzimidazol-1- yl]methyl]biphenyl-2-carboxylic acid. Content: 99.0 per cent to 101.0 per cent (dried substance). Category: Antihypertensive. Dose: 20 to 80 mg. Half life: 24 hrs. Appearance: White or slightly yellowish, crystalline powder. Solubility: Practically insoluble in water, slightly soluble in methanol, sparingly soluble in methylene chloride. It dissolves in 1 M sodium hydroxide. It exhibits polymorphism. Melting point: 261 ‘ 263oC. Storage: it should be stored at room temperature (15 – 30 ��C), away from moisture and light. Mechanism of action: It is an angiotensin II receptor antagonist. Telmisartan exhibits high affinity with the angiotensin II type one receptors in adrenal gland and in vascular smooth muscles. It works by binding to the angiotensin II receptor. It inhibits the action of angiotensin which is a vasoconstrictor. Angiotensin also stimulates the synthesis and release of aldosterone. By blocking the vasoconstrictor effect of the angiotensin and blocking the aldosterone, Telmisartan reduces the systemic vascular resistance. Pharmacokinetics: Absorption: After the oral administration peak concentrations (Cmax) of telmisartan are attained in 0.5 to 1 hour. Ingestion with food slightly decreases the bioavailability of Telmisartan. Absolute bioavailability is dose dependent. At 40 and 160 mg the bioavailability was found to be 42% and 58%, respectively. Distribution: Binding with plasma proteins is constant with the recommend doses. It is highly binding with the plasma proteins (more than 99.5 %). It has a volume of distribution of around 500 L. Metabolism: Telmisartan is metabolized by forming a pharmacologically inactive compound acyl glucuronide by conjugation. The only identifiable compound in the human plasma and urine is the glucuronide. Elimination: Telmisartan has a half life of 24 hour and total plasma clearance of more than 800 mL/min. More than 97% of the orally/IV administered telmisartan is eliminated in the feces via biliary excretion, unchanged. Uses: It is used to treat high blood pressure (hypertension). Adverse effects: The common reported adverse effects of telmisartan are upper respiratory tract infection (URTI) (7%), Back pain (3%), Diarrhea (3%), Myalgia (3%), and Sinusitis (3%). Some rare adverse effects (<1%) are abnormal ECG, anemia, angina, angioedema, bradycardia, eczema, epistaxis, gout, and hypercholesterolemia. Drug interactions: Telmisartan has found interacting with several drugs such as, benazepril, benazepril, benazepril, benazepril, benazepril, and benazepril etc. Caution is advised when combination will be used. Dosage forms: It is commonly used in the form of tablets of 20, 40, and 80 mg. 4.1.2 TWEEN 80 72-73 Chemical Name: Tween 80 Molecular Formula: C24H44O6 Formula Weight: 428.600006103516 Tween 80 Property Boiling point- >100��C
Dencity – 1.08 g/mL at 20 ��C
Vapour pressure- 230 ��F
storage temp. : Store at RT.
From- viscous liquid
Water Solubility : 5-10 g/100 mL at 23 ��C
Merck : 14,7582
EPA Substance Registry System: Sorbitan, mono-(9Z)-9-octadecenoate, poly(oxy-1,2-ethanediyl) derivs.(9005-65-6)
Tween 80 Chemical Properties,Usage,Production
Chemical Properties
Yellow to amber liquid
General Description
Amber-colored viscous liquid. pH (5% aqueous solution) 5-7. Faint odor and bitter taste.
Air & Water Reactions
Water soluble.
Reactivity Profile
Tween 80 is incompatible with strong alkalis and oxidizers.
Fire Hazard
Tween 80 is probably combustible.
4.1.3 ORANGE OIL 72-73:-
It was the important and essincial oil can be produse by the cells in the fruits of oranges. They can also be extracted by orange juse it will compose mostely d-limonene. That will be extract to the oil by distillation.
Oil properties
Tast ‘ sweet
Odour- fresh and tangy smell,
Coloue- yellow to orange in color
Viscocity- watery .
Self life- approximately 6 months.
Origin of Sweet orange oil
This evergreen tree has dark green leaves and white flowers and bright orange round fruit with roughish skin. The trees are native to China, but are now cultivated extensively in America.
USE
1. It can be used many Curacao type liqueurs.
2. for the flavoring of food.
3. drink and confectionery.
4. when added to furniture polish.
5. helps to protect against damage from insects.
Extraction
The orange oil are extracted by cold-pressing and yields 0.3 -0.5 %.
Therapeutic properties
It can also use for the medicinal perpose that will gives several therapeutic actions are antiseptic, anti-depressant, antispasmodic, anti-inflammatory, carminative, diuretic, cholagogue, sedative and tonic.
Chemical composition
The main chemical components of orange oil are a-pinene, sabinene, myrcene, limonene, linalool, citronellal, neral and geranial.
Precautions
1. It is a safe non-toxic, non-irritant and non-sensitizing oil,
2. yet care must be taken with it since it can have a phototoxic effect.
3. It should therefore preferably not be applied before going out into sunlight for prolonged periods.
4.1.4 PEG 40072-73: –
Iupac name – polyethylene glycol
Chemical formula
-C2nh4n+2On+1,
Molar mass
-380-420 g/mol
Density
-1.128 g/cm3
Melting point
4 to 8 ��C
Viscosity
– 90.0 cst at 25 ��C, 7.3 cst at 99 ��C
PEG 400 properties
1. (polyethylene glycol 400) is a low-molecular-weight grade of polyethylene glycol.
2. It is a clear,
3. colorless,
4. viscous liquid.
5. Due in part to its low toxicity, PEG 400 is widely used in a variety of pharmaceutical formulations.
Chemical properties
1. PEG 400 is soluble in water, acetone, alcohols, benzene, glycerin, glycols, and aromatic hydrocarbons, and is slightly soluble in aliphatic hydrocarbons.
2. PEG 400 is strongly hydrophilic.
3. The partition coefficient of PEG 400 between hexane and water is 0.000015 (log ), indicating that when PEG 400 is mixed with water and hexane,
4. there are only 15 parts of PEG 400 in the hexane layer per 1 million parts of PEG 400 in the water layer.[1]
PEG 400 is soluble in water, acetone, alcohols, benzene, glycerin, glycols, and aromatic hydrocarbons, and is slightly soluble in aliphatic hydrocarbons.
4.2 Preformulation studies 72,73,74,75
To develop a safe, stable and therapeutically effective dosage form, preformulation studies are necessary to perform. The preformulation studies, which were performed in this project, include identification of drug, melting point analysis, solubility analysis, and quantitative estimation of drug.
4.2.1 Identification tests
Telmisartan 74
‘ Physical appearance: The drug was white, odorless crystalline powder.
‘ Melting point analysis: Melting point of telmisartan was determined by capillary method using melting point apparatus (Rolex- Digital melting point apparatus).
‘ FTIR study: Drug sample was vacuum dried for 12 h before IR studies. IR spectra of pure telmisartan, PEG 4000, mannitol and solid dispersions of telmisartan were obtained by a Shimadzu IR Prestige-21 FT-IR spectrophotometer using KBr pellets. The scanning range used was 4000 to 400cm-1. The observed peaks were reported for functional groups.
4.2.2 Loss on drying73-74
It was determined on 1 g drug by drying it in a hot air oven at 105oC. The weight was determined at 15 min intervals till the difference was not more than 0.5 mg. The total difference in weight should not be more than 0.5%.
4.2.3 Determination of ‘max 73
Accurately weighed sample of 10 mg of telmisartan was dissolved in 50 mL of methanol in a 100 mL volumetric flask and then the volume was made up to 100 mL with methanol. Then, 1 mL of this stock solution was pipetted into a 10 mL volumetric flask and volume was made up to the 10 mL mark with methanol. The resulting solution was scanned between 200-600 nm using UV/Vis double beam spectrophotometer (UV-1700, Shimadzu, Japan). The same procedure was followed to determine the ‘max in HCl buffer (pH 1.2). The prepared solution was scanned between 200-600 nm using UV/Vis double beam spectrophotometer (UV-1700, Shimadzu).
To determine ‘max in water, accurately weighed 10 mg sample of telmisartan was dissolved in 50 mL of methanol in a 100 mL volumetric flask and volume was made up to 100 mL with methanol. Then, 1 mL of this stock solution was pipetted into a 10 mL volumetric flask and volume made up to the 10 mL mark with distilled water. The resulting solution was scanned between 200-600 nm using UV/Vis double beam spectrophotometer (UV-1700, Shimadzu, Japan).
4.2.4 Quantitative estimation of drug73-74
Drug was estimated in the range of 3-15 mcg/mL for telmisartan in water (pH 7.0), HCl buffer (pH 1.2) and methanol.
Preparation of HCl buffer (pH 1.2): 50 mL of 0.2 M KCl was added in a 200 mL volumetric flask then 85 mL of HCl solution (0.2 M) was added in the flask and volume was adjusted to 200 mL with distilled water32.
4.2.5 Construction of calibration curve of telmisarta73
4.2.5.1. Preparation of calibration curve in methanol: The 25mg of accurately weighed telmisartan was dissolved in 25 mL of methanol to give standard solution (1000 ��g/mL). From this standard solution, 3 mL was pipetted out and volume was made up to 100 mL with methanol referred as stock solution of concentration 30��g/ mL. Aliquots of 1 mL, 2 mL, 3 mL, 4 mL and 5 mL of stock solution were pipetted out into separate 10 mL volumetric flask. The volume was made up to the mark with methanol. This results in samples of 3, 6, 9, 12 and 15 ‘g/mL concentration, respectively. The absorbance of prepared solution of telmisartan in methanol was measured at 296.5 nm in Shimadzu UV-1700 spectrophotometer against an appropriate blank.
4.2.5.2. Preparation of calibration curve in HCl buffer (pH 1.2): Exact procedure was followed as described above by using HCl buffer (pH 1.2) instead of methanol. The absorbance was recorded at 296 nm.
4.2.6. solublity of telmisartain in different medium.
Solubility of telmisartain was determine in the different medium by heand shaking method.
3.3 Formulation 76
4.3.1 identification of microemulsion region :
Determine solubility of telmisartain in different -2 medium then select three medium orange oil as oil, PEG 400 as surfactant and tween 80 as co-surfactant. Micro-emulsion region was identify by constructing pseudo ternary phase diagram with the help of different proportion of surfactant and co-surfactant (1:1, 2:1, 3:1). They are mix with oils at different proportion (1:9, 2:8, 3:7, 4:6, 5:5, 6:4, 7:3, 8:2, 9:1) and the complete mixture was titrate with water and noted the equbliurem point. At which point the mixture will show clear.
4.3.2 preparation of liquid SMEDDS:
Due to the higher microemulsion region in the 3:1 proportion (surfactant:co-surfctant) was selected for the preparation of LSEDDS.
1. Required amount of PEG 400 and tween 80 was take and mix with the help of stirrer until they compatibly mix.
2. Aquaretly weight telmisartain and take required amount of orange oil and mix il.
3. Drug mixture place on water bath until drug completely dissolve in oil.
4. Both the mixture are mix togather on the magnatic stirrer untill they are compleately mix and form a isotropic mixture.
5. Store in the glass bottle.
Table 4.3 chemical requirements.
Material Quantity
Orange oil 50 ml
Tween 80 12.5 ml
PEG 400 37.5 ml
Telmisartain 2000 mg
4.4 CHARACTERIZATION :76-77
4.4.1 stability study :76
4.4.1.1 heating cooling cycle:
for the stability study of LSEDDS pass six cycle between hot and cool temperature (40c-450c) with storing not less then 48hrs at each temp. not seen any type of phase sapration.
4.4.1.2 centrifugation test:
After passing heating cooling cycle it would be pass with centrifugation test. The sample of LSEDDS placed in centrifuge for 30min and show any type of precipitation. If not seen it would be go to the next stability test.
4.4.1.3 freeze thaw cycle:
This test is again at cool and hot temperature (-210C to +250C) 48 hrs at each temp.
If the LSEDDS pass all the stability parameter means the system becomes stable.
4.4.2 cloud point measurement : 76-77
Liquid SMEDDS was diluted with distilled water at 250 times LSEDDS : distill water(1:250), placed in a water bath and its temperature was increased slowely-2. Cloud point was measured as the temperature at which there was a sudden appearance of cloudiness visually.
4.4.3 solubility test .77-78
Solubility of LSEDDS was determine at buffer solution at 1.2ph, 7.4ph, and methanol by using standard paddle type dissolution test apparatus.
4.4.3.1 Preparation of HCl buffer (pH 1.2): 50 mL of 0.2 M KCl was added in a 200 mL volumetric flask then 85 mL of HCl solution (0.2 M) was added in the flask and volume was adjusted to 200 mL with distilled water.
4.4.3.2 Buffer pH 7.4: Mix 50 mI of solution containing 1.944 per cent w/v ofsodium acetate and 2.946 per cent w/v of barbitone sodium with 50.5 mI of 0.1 M hydrochloric acid, add 20 mI of an 8.5 per cent w/v solution of sodium chloride and dilute with water to 250 mI.
4.4.4 efficiency of self emulsification :76-77
Using USP- type-II dissolution test apparatus (Veego VDA-8DR). 1 mL of Liquid SMEDDS was added drop wise to 200 ml of 0.1 N HCl at 37��C. agitate using by using standard stainless at rotating paddle at 60 rpm. SMEDDS assessed visually according to the rate of emulsification and final appearance of the emulsion.
4.4.5 Robustness to dilution :76
it can be studied by by diluting LSEDDS at different concentration with distill wate.
1. Prepare HCL buffer solution PH 7.4, PH 1.2.
2. Prepare dilution with both the solution at following concentration
50,100,500,1000 times.
3. Store for 12 hrs.
4. Observe any type of phase saperation or pracipation.
4.4.6 % transmittance :76
For the determination of % transmittance take
1. 1ml of LSEDDS and diluted till 100ml with distilled water.
2. Scan this sample in the uv spectroscopy.
3. observe any type of turbidity and % transmittance.
4.4.7 Dye solubility test : 76
This test can be perform for the conformation of oil in water nature of LSEDDS by observing sopntenious dispersion.
1. Take water soluble dye and sufficient quantity of LSEDDS.
2. Rapidly incorporate dye into the system.
4.4.8. in vitro drug release:76-77
In vitro dissolution study of LSEDDS using type -2 dissolution test apparatus in buffer solution ph 1.2, ph 7.4 at 370 c.
4.4.8.1 Drug release in buffer solution at 1.2 PH :-
1. Prepare buffer solution 1.2 PH by the help of indian pharmacopeia.
2. Fill in the type-2 dissolution test apparatus upto 900ml .
3. Palce 2ml sapmle of LSEDDS in the apparatus. Start the assumbaly.
4. Take sample after regular interwal.
5 min, 10 min,15 min,30 min,45 min,60 min,90 min,120 min.
5. The all sample was filtered with whatmant filter paper. And dilute upto 10ml.
6. If there concentration is high then take again 1ml to all the samples and and dilute again upto 10ml.
7. The sample was scan into the uv spectroscopy at 296nm.
4.4.8.2 Drug release in buffer solution at 7.4 PH :-
1. Prepare buffer solution 7.4 PH by the help of indian pharmacopeia.
2. Fill in the type-2 dissolution test apparatus upto 900ml .
3. Palce 2ml sapmle of LSEDDS in the apparatus. Start the assumbaly.
4. Take sample after regular interwal.
5 min, 10 min,15 min,30 min,45 min,60 min,90 min,120 min.
5. The all sample was filtered with whatmant filter paper. And dilute upto 10ml.
6. If there concentration is high then take again 1ml to all the samples and and dilute again upto 10ml.
7. The sample was scan into the uv spectroscopy at 296nm.
4.4.9 drug contant:76-77-78-79
drug content of LSEDDS should be determine by diluting 1 ml sample of LSEDDS with distill water. Take there absorbance in uv-spectroscopy at296nm.
1. Take 1ml sample of LSEDDS and dilute with distill water upto 100ml.
2. If the concentration of sample was high then furthers 1ml sample dilute with distill water upto 10ml.
3. Scan this sample in uv-spactroscopy.
4. Calculate there percentage by the help of leaner line equation.
RESULT AND DISCUSSION
5. RESULTS
Table 5.1: Melting point of telmisartan
S. No. Melting point Result
Onset Complete
1. 261.2��C 263.5��C
261.4-263.3��C
2. 262.1��C 263.3��C
3. 260.9��C 263.1��C
5.1 LOSS ON DRYING:
The results were within the acceptable limit which is 0.5%.
Table 5.2: Loss on drying
S.No. Time (min) Weight (mg) Difference in weight (mg)
1 0 1000 –
2 15 999.12 0.88
3 30 998.36 0.76
4 45 997.62 0.74
5 60 997.22 0.44
6 75 997.1 0.12
Total difference 2.9
5.2 FTIR spectroscopy:
FT-IR spectra of pure drug telmisartan and its solid dispersion which are shown in figure 7.1 and 7.4. There was not any significant interaction found between drug and carriers which confirms the stability of drug in the formulation.
Table 5.3: Major peaks observed in FTIR spectrum of telmisartan
S. No. Standard peak Observed peak Comments
1. 3059.1cm-1 3080 cm-1 C-H stretching (aromatic)
2. 2958.8-2868.15 cm-1 2870-2738.92 cm-1 C-H stretching (aliphatic)
3. 1697.36 cm-1 1687.71 cm-1 C=O stretching
5. 1521.84-1458.18 cm-1 1462.04 C=C stretching ring
Figure 5.1: FT-IR spectra of pure telmisartan.
5.4 LEMDA MAX OF TELMISARTAIN IN DIFFERENT SOLVENT SYSTEM :
Table 5.4: Solvent systems, their parameters and values
S.No. Solvent system Parameters Values
1. Methanol ��max 296.5 nm
Beer’s law range 3 – 15 mcg/mL
Regression line equation y = 0.050x + 0.007
Regression coefficient (R2) 0.999
2. Buffer 7.4 ��max 298 nm
Beer’s law range 3 – 15 mcg/mL
Regression line equation y = 0.043x + 0.004
Regression coefficient (R2) 0.999
3. HCl buffer (pH 1.2) ��max 296 nm
Beer’s law range 3 – 15 mcg/mL
Regression line equation y = 0.046x + 0.007
Regression coefficient (R2) 0.999
5.5 CALIBRATION CURVE OF TELMISARTAN IN DIFFERENT SOLVENT SYSTEM
Table 5.5: Calibration curve of telmisartan in HCl buffer pH 7.4 and HCl buffer pH 1.2 at ‘max 298 nm and 296 respectively
S.No. Concentration (��g/mL) HCl buffer pH 7.4 HCl buffer pH 1.2
Absorbance Regressed Absorbance Absorbance Regressed Absorbance
1. 0 0 0 0 0
2. 3 0.139 0.133 0.153 0.145
3. 6 0.270 0.262 0.294 0.283
4. 9 0.401 0.391 0.423 0.421
5. 12 0.537 0.520 0.567 0.559
6. 15 0.657 0.649 0.706 0.697
S.No. Concentration (��g/mL) Methanol
Absorbance Regressed Absorbance
1. 0 0 0
2. 3 0.169 0.157
3. 6 0.312 0.307
4. 9 0.463 0.457
5. 12 0.620 0.607
6. 15 0.766 0.757
Table 5.6: Calibration curve of telmisartan in methanol at ‘max 296.5 nm
Figure 5.2: Calibration curve of telmisartan in buffer 7.4 ph at 298 nm
Figure 5.3: Calibration curve of telmisartan in HCl buffer pH 1.2 at 296 nm
Figure 5.4: Calibration curve of telmisartan in methanol at 296.5 nm
5.6 SOLUBILITY OF TELMISARTAIN :
Table 5.7: solubility of telmisartain in different medium.
S.NO. MEDIUM SOLUBILITY
1. Water Insoluble
2. Hcl Springly soluble
3. Methanol soluble
4. Oils Soluble
5. PEG400 Soluble
6. Tween 80 Springly soluble
7. Tween 20 Springly soluble
8. Span 80 Springly soluble
5.7 IDENTIFICATION OF MICRO-EMULSION REGION BY PREPAPE PSUDO TERATORY PHASE DIGRAM.
5.7.1 formula 1:
In this formulation preportion of surfactant and co surfactant is 1:1
Table 5.8: identification of micro-emulsion region
SMIX : OIL END POINT
1:9 2.0 ml
2:8 2.0 ml
3:7 2.0 ml
4:6 1.9 ml
5:5 1.8 ml
6:4 1.8 ml
7:3 Not seen
8:2 Not seen
9:1 Not seen
5.7.2 formula 2:
In this formulation preportion of surfactant and co surfactant is 2:1
Table 5.9: identification of micro-emulsion region.
SMIX : OIL END POINT
1:9 2.0 ml
2:8 2.0 ml
3:7 1.9 ml
4:6 1.9 ml
5:5 1.7 ml
6:4 Not seen
7:3 Not seen
8:2 Not seen
9:1 Not seen
5.7.3 formula 3:
In this formulation preportion of surfactant and co surfactant is 3:1
Table 5.10: identification of micro-emulsion region.
Smix : OIL END POINT
1:9 1.8 ml
2:8 1.8 ml
3:7 1.6 ml
4:6 1.6 ml
5:5 1.5 ml
6:4 Not seen
7:3 Not seen
8:2 Not seen
9:1 Not seen
Result- Best micromulsion was found to be In formulation 3 at 5:5 proportion of oil and mixture of surfactant and co-surfactant denoted as smi.
5.8 FORMULATION OF LIQUID-SELF EMULSIFYING DRUG DELIVERY SYSTEM (LSEDDS).
5.8.1 chemical requirement:
Table 5.11: chemicals requirements .
MATERIAL QUNTITY
Orange oil 50 ml
Tween 80 12.5 ml
PEG-400 37.5 ml
Telmisartain 2000 mg/2gm
5.9 EVALUATION OF LSEDDS.
5.9.1 stability study
Physical stability was important parameter in the emulsion system it can be affected the performance of the system, it can be occurs due to the precipitation of drug. Due to the poor stability of system bioavability of drug also affected.
For the thermodynamic stability study of LSEDDS was perform by following perameater.
1. Heating cooling cycle.
2. Centrifugation test
3. Freeze thaw cycle
When system can not show any type of phase separation during heating cooling cycle then syatem can be tested in the centrifugation for the drug pricipation then apply freeze thaw cycle for the stress test.
5.9.1.1 heating cooling cycle :
Temperature Stability
40c No separation
450c No separation
40c No separation
450c No separation
40c No separation
450c No separation
40c No separation
450c No separation
40c No separation
450c No separation
40c No separation
450c No separation
Table 5.12: six cycle of heating cooling temp
Result ‘ not seen any type of phase saperation.
5.9.1.2 Centrifugation test:
Result- LSEDDS was centrifuge for 30 min there was not seen any type of precipitation and phase saperation.
5.9.1.3 freeze thaw cycle
Table 5.13: three cycle of -210c to +250c.
Temperature Stability
Cool temp. No change
Hot temp. No change
Cool temp. No change
Hot temp. No change
Cool temp. No change
Hot temp. No change
5.9.2 cloud point measurement.
Table 5.14: Cloud point
Sample Cloud point
Sample 1 87.50c
Sample 2 86.70c
Sample 3 86.30c
Result- cloud point of this emulsion system was found to be more then 860c. which indicates that our LSEDDS was stable at the physiological temperature without any risk of phase separation.
5.9.3 solubility study:
Table 5.15: solubility of LSEDDS
Medium Solubility time
Buffer solution PH 1.2 Less than 5min
Buffer solution PH Less than 5min
0.1 N HCL Less than 5min
Result ‘ solubility of this system was found to be less than 5min which indicates that the formulation also use in the sustain release drug delivery system with maximum bioavability.
5.9.4 Efficiency of self-emulsification
Table 5.16:
Sample Efficiency of LSEDDS
1 Less than 1min
2 Less than 1min
3 Less than 1min
Result ‘ this system rapidly form micro emulsion with in 1min it was clear and appearance was slightly blush
5.9.5 Robustness to dilution :
Table 5.15: dilution with different solvents
Concentration Water Buffer solution
PH 1.2 Buffer solution
PH 7.4
50 times No change No change No change
100 times No change No change No change
500 times No change No change No change
1000 times No change No change No change
Result ‘ in the robustness dilution not seen any type of phase separation and pracipation.
5.9.6 %transmittance
Result- % trasmittance of this system was found to be 93.5.
5.9.7. dye solubility test
Result- type of emulsion was conform by using dye solubility test in which a water soluble colourfull dye rapid incorporate in the LSEDDS and observe. Which indicates that the continuous phase in this system is water.
so it was conform that the LSEDDS was o/w micro emulsion.
5.9.8 in-vitro drug release profile.
5.9.8.1 drug release in buffer solution PH1.2
Table 5.16 in-vitro drug release of SEDDS
Time
% cumulative drug release
Plain drug LSEDDS
5 min 5.69 25.12
10 min 7.35 42.43
15 min 11.63 61.36
30 min 1.83 75.45
45 min 18.64 83.33
60 min 23.31 89.02
90 min 27.15 95.26
120 min 29.48 95.56
Figure 7.4 commulative % drug release of SEDDS and plain telmisartain in PH 1.2
5.9.8.2 drug release in buffer solution PH 7.4
Table 5.17 in-vitro drug release of SEDDS
Time
% cumulative drug release
Plain drug LSEDDS
5min 8.47 32.63
10 min 11.38 47.39
15 min 14.92 54.43
30 min 19.61 73.13
45 min 24.48 81.68
60 min 28.29 90.83
90 min 32.62 96.54
120 min 33.46 98.12
Figure 7.6 % commulative drug release of LSEDDS and plan telmisartain in PH 7.4
5.9.9 drug content estimation
Table 5.18 drug content:
Sample
Drug contant
PH 1.2 PH 7.4
1 94..63% 93.61%
2 95.21% 96.39%
CONCLUSION
6.0 CONCLUSION
The oral route is the most preferred method of administration of drugs. Unfortunately, this route is not possible for 50% of currently marketed drug compounds due to their low solubility in water and low oral bioavailability.
We study that self-emulsifying drug delivery system (SEDDS) can be used for the improvement of bioavailability of the drug. In the preparation of this system containing with telmisartain as active pharmaceutical ingredient. To increase bioavailability & solubility of this drug.
Due to poor solubility of telmisartain it cannot be formulate in the oral drug delivery system. But with the help of LSEDDS it’s possible to give telmisartain via oral drug delivery system.
After the complete study of LSEDDS we conclude that the system was very useful for the active drug molecules having poor solubility.
REFERENCE
7.0 REFERENCE
1. Yamamoto, J. and H. Tanaka, prepare neomatic phase in the liquid micro-emulsion. Nature (London), 2001. 409(6818): p. 321-325.
2. Porter, C.J.H., N.L. Trevaskis, and W.N. Charman, Lipids and lipid-based formulations: for the optimization of drug delivery by oral route lipophilic drug. Nature Reviews Drug Discovery, 2007. 6(3): p. 231-248.
3. Humberstone, A.J. and W.N. Charman, the oral drug delivery of poorly water soluble drugs. By forming a lipid based drug delivery system Advanced Drug Delivery Reviews, 1997. 25(1): p. 103-128.
4. Kommuru, T.R., et al., Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10: formulation development and bioavailability assessment By forming a lipid based drug delivery system Advanced Drug Delivery. Int J Pharm, 2001. 212(2): p. 233-46.
5. Neslihan Gursoy, R. and S. Benita, Self-emulsifying drug delivery systems (SEDDS) for improved bioavability of poorly water soluble drug. Biomedicine & Pharmacotherapy, 2004. 58(3): p. 173-182.
6. Hauss, D.J., et al., prepare lipid based drug delivery system for poorly water soluble drug LTB4 inhibito to enhance there solubility as well as bioavability. Journal of Pharmaceutical Sciences, 1998. 87(2): p. 164-169.
7. Gao, P., et al., Development of a super saturable SEDDS (S-SEDDS) formulation of paclitaxel with improved there solubility that can enhance the bioavability of poorlt water soluble drug. Journal of Pharmaceutical Sciences, 2003. 92(12): p. 2386-2398.
8. Patil Pradeep, R., et al., Bioavailability assessment of ketoprofen incorporated in gelled self-emulsifying formulation to improve the bioavability by using lipid based drug delivery systemAAPS PharmSciTech, 2005. 6(1): p. E9-13.
9. Kang, B.K., et al., Development of self-microemulsifying drug delivery system(SMEDDS) for improve the bioavability by using lipid based drug delivery. International Journal of Pharmaceutics, 2004. 274(1-2): p. 65-73.
10. Palamakula, A. and M.A. Khan, Self-Emulsifying Drug Delivery Systems (SEDDS) for improving bioavability of cytotoxicity of oils used in coenzyme Q10. International Journal of Pharmaceutics, 2004. 273(1-2): p. 63-73.
11. Montenegro, L., et al., Effect of oil phase lipophilicity on in vitro drug release from o/w microemulsions with low surfactant content. Drug Development and Industrial Pharmacy, 2006. 32(5): p. 539-548.
12. Attama, A.A. and M.O. Nkemnele, formulation and evaluation SEDDS using a biodegradable homolipid from Capra hircus. International Journal of Pharmaceutics, 2005. 304(1-2): p. 4-10.
13. Djordjevic, L., M. Primorac, and M. Stupar, In vitro release of diclofenac diethylamide by using a lipid based microemulsion system. International Journal of Pharmaceutics, 2005. 296(1-2): p. 73-79.
14. Agatonovic-Kustrin, S., et al., Prediction of a Stable Microemulsion Formulation for the Oral Delivery of a Combination of Antitubercular Drugs Using ANN Methodology. Pharmaceutical Research, 2003. 20(11): p. 1760-1765.
15. Taha, E.I. Response surface methodology for the development and evaluation of self nanoemulsified drug delivery system (SNEDDS) of all-trans-retinol acetate. Pharmaceutical Development and Technology, 2005. 10(3): p. 363-370.
16. Liu, Y., et al., Optimization and in situ intestinal absorption of self-microemulsifying drug delivery system of oridonin for improving bioavability of oridonin. Int. J. Pharm., 2009. 365: p. 136-142.
17. Holm, R., I.H.M. Jensen, and J. Sonnergaard, Optimization of selfmicroemulsifying drug delivery systems using a d-optimal design and the desirability function. Drug. Dev. Ind. Pharm., 2006. 32: p. 1025-1032.
18. Porter, C.J.H., N.L. Trevaskis, and W.N. Charman, Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat. Rev. Drug Discov., 2007. 6: p. 231-248.
19.Gupta H, Bhandari D and Sharma A. Recent trends in oral drug delivery: a review. Recent Pat Drug Deliv Formul. 2009; 3(2): 162-73.
20. de Smidt PC, Campanero MA and Troconiz IF. Intestinal absorption of penclomedine from lipid vehicles in the conscious rat: contribution of emulsification versus digestibility. Int J Pharm. 2004; 270(1-2): 109-18.
21. O’Driscoll CM and Griffin BT. Biopharmaceutical challenges associated with drugs with low aqueous solubility–the potential impact of lipid-based formulations. Adv Drug Deliv Rev. 2008; 60(6): 617-24.
22. Koga K, Kusawake Y, Ito Y, Sugioka N, Shibata N and Takada K. Enhancing mechanism of Labrasol on intestinal membrane permeability of the hydrophilic drug gentamicin sulfate. Eur J Pharm Biopharm. 2006; 64(1): 82-91.
23. Sha X, Yan G, Wu Y, Li J and Fang X. Effect of self-microemulsifying drug delivery systems containing Labrasol on tight junctions in Caco-2 cells. Eur J Pharm Sci. 2005; 24(5): 477-86.
24. Sha XY and Fang XL. Effect of self-microemulsifying system on cell tight junctions. Yao Xue Xue Bao. 2006; 41(1): 30-5.
25. Yang S, Gursoy RN, Lambert G and Benita S. Enhanced oral absorption of paclitaxel in a novel self-microemulsifying drug delivery system with or without concomitant use of P-glycoprotein inhibitors. Pharm Res. 2004; 21(2): 261-70.
26. Constantinides PP and Wasan KM. Lipid formulation strategies for enhancing intestinal transport and absorption of P-glycoprotein (P-gp) substrate drugs: in vitro/in vivo case studies. J Pharm Sci. 2007; 96(2): 235-48.
27. Charman WN, Rogge MC, Boddy AW and Berger BM. Effect of food and a monoglyceride emulsion formulation on danazol bioavailability. J. Clin. Pharmacol. 1993; 33: 381’6.
28. Welling PG. Effects of food on drug absorption. Ann. Rev. Nutr. 1996; 16 383’415.
29. Araya H, Tomita M and Hayashi M. The novel formulation design of O/W microemulsion for improving the gastrointestinal absorption of poorly water soluble compounds. Int J Pharm. 2005; 305(1-2): 61-74.
30. Shafiq S, Shakeel F, Talegaonkar S, Ahmad FJ, Khar RK and Ali M. Development and bioavailability assessment of ramipril nanoemulsion formulation. Eur J Pharm Biopharm. 2007; 66(2): 227-43.
31. Palin KJ, Phillips AJ and Ning A. The oral absorption of cefoxitin from oil and emulsion vehicles in rats. Int J Pharm. 1986; 33: 99-104.
32. Aungst BJ, Nguyen N, Rogers NJ, Rowe S, Hussain M, Shum L and White. Improved oral bioavailability of an HIV protease inhibitor using Gelucire 44/14 and Labrasol vehicles. SBT Gattefosse 1994; 87: 49’54.
33. Saritha D, Penjuri SCB, Nagaraju R. Formulation and evaluation of self emulsifying drug delivery system (SEDDS) of Indomethacin, International Journal of Research in Pharmacy and Science 2014; 4(2): 17-23.
34. Damineni S Penjuri S C B, and Nagaraju R. formulation and evaluation of self emulsifying drug delivery system (SEDDS) of ibuprofen, International Journal of Pharmaceutical science and research 2014; 5(8): 3511-3519.
35. . Kumar S, Kumar S G, Kumar P, Sharma R. self-Emulsifying Drug Delivery Systems (SEDDS) for Oral Delivery of Lipid Based Formulations, African Journal of Basic & Applied Sciences 2012; 4 (1): 07-11.
36. Reddy M S, Reddy N S, Reddy SM. solubility Enhancement of Poorly Water Soluble Drug Efavirenz by Solid Self Emulsifying Drug Delivery Systems, International Journal of Pharma Research & Review, 2014; 3(4): 20-28.
37. Amrutkar C, Salunkhe K, Chaudhari S. study on self nano emulsifying drug delivery system of poorly water soluble drug rosuvastatin calcium, World Journal of Pharmaceutical Research 2014; 3(4): 2137-2151.
38. Choudhari S.B., Mahajan N, Bhalerao A V, self Microemulsifying Drug Delivery System for Treatment of Emesis, Asian Journal of Pharmaceutical Technology &Innovation 2014; 02(06): 01-10.
38.Gaikwad G, Godbole M, potnos V, Daud A. Formulation and evaluation of self emulcifying drug delivery system of orlistat, Americal Journal Of Pharmtech Research 2012; 2 (6): 297-31
39. Sachan R, Khatri K, Kasture S. B. Self-Eumlsifying Drug Delivery System A Novel Approach for enhancement of Bioavalibility, International Journal of pharmtech Research 2010; 2(3): 1738-1745.
40. Liu Y., Zhang P., Feng N., Zhang X., Wu S., Zhao J. (2009): Optimization and in situ intestinal absorption of self-microemulsifying drug delivery system of oridonin, International Journal of Pharmaceutics, 365: 136-142.
41. Balakrishnan P., Lee B. J., Oh D. H., Kim J. O., Hong M. J., Jee J. P., Kim J. A., Yoo B. K., Woo J. S., Yong C. S., Choi H. G. (2009), Enhanced oral bioavailability of dexibuprofen by a novel solid Self-emulsifying drug delivery system (SEDDS), European Journal of Pharmaceutics and Biopharmaceutics, 72: 539-545.
42. Singh A. K., Chaurasiya A., Awasthi A., Mishra G., Asati D., Khar R. K., Mukherjee R. (2009), Oral Bioavailability Enhancement of Exemestane from Self-Microemulsifying Drug Delivery System (SMEDDS), AAPS PharmSciTech, 10(3): 906-916.
43. .Shaji J., Lodha S. (2008), Response surface methodology for the optimization of celecoxib self-
emulsifying drug delivery system, Indian Journal of Pharmaceutical Sciences, 70(5): 585-590.
44. Atef E., Belmonte A. A. (2008), Formulation and in vitro and in vivo characterization of a phenytoin self-emulsifying drug delivery system (SEDDS), European Journal of Pharmaceutical Sciences, 35: 257-263.
45. Fatouros D. G., Nielsen F. S., Douroumis D., Hadjileontiadis L. J., Mullertz A. (2008), In vitro’in vivo correlations of self-emulsifying drug delivery systems combining the dynamic lipolysis model and neuro-fuzzy networks, European Journal of Pharmaceutics and Biopharmaceutics, 69: 887-898.
46. Shikov A., Pozharitskaya O., Karlina M., Makarov V. (2008), Self-microemulsifying drug delivery system as nanosystems for bioavailability enhancement of flavonoids in vitro, European Journal of Pharmaceutical Sciences, 34 S: S25’S29.
47. Woo J. S., Songb Y. K., Hong J. Y., Lim S. J., Kim C. K. (2008), Reduced food-effect and enhanced bioavailability of a self-microemulsifying formulation of itraconazole in healthy volunteers, European Journal of Pharmaceutical Sciences, 33: 159-165.
48. Mandawgade S. D., Sharma S., Pathak S., Patravale V. B. (2008), Development of SMEDDS using natural lipophile: Application to ��-Artemether delivery, International Journal of Pharmaceutics, 362: 179-183.
49. Yi T., Wan J., Xu H., Yang X. (2008), Controlled poorly soluble drug release from solid self-microemulsifying formulations with high viscosity hydroxypropylmethylcellulose, European Journal of Pharmaceutical Sciences, 34: 274-280.
50. . Yi T., Wan J., Xu H. Yang X. (2008), A new solid self-microemulsifying formulation prepared by spray-drying to improve the oral bioavailability of poorly water soluble drugs, European Journal of Pharmaceutics and Biopharmaceutics, 70: 439-444.
51. Abdalla A., Klein S., M��der K. (2008), A new self-emulsifying drug delivery system (SEDDS) for poorly soluble drugs: Characterization, dissolution, in vitro digestion and incorporation into solid pellets, European Journal of Pharmaceutical Sciences, 35: 457-464.
52. Lu J. L., Wang J. C., Zhao S. X., Liu X. Y., Zhao H., Zhang X., Zhou S. F., Zhang Q. (2008), Self-microemulsifying drug delivery system (SMEDDS) improves anticancer effect of oral 9-nitrocamptothecin on human cancer xenografts in nude mice, European Journal of Pharmaceutics and Biopharmaceutics, 69: 899-907.
53. Thakkar H., Nangesh J., Parmar M., Patel D. (2011), Formulation and characterization of lipid based drug delivery system of raloxifene microemulsion and self microemulsifying drug delivery system, Journal of Pharmacy and Bioallied Sciences, 3(3): 442-448.
54. Cirri M., Muraa P., Mora P. C. (2007), Liquid spray formulations of xibornol by using self-microemulsifying drug delivery systems, International Journal of Pharmaceutics, 340: 84-91.
55. Patil P., Joshi P., Paradkar A. (2004), Effect of Formulation Variables on Preparation and Evaluation of Gelled Self-emulsifying Drug Delivery System (SEDDS) of Ketoprofen, AAPS PharmSciTech, 5(3) Article 42: 1-8.
56. Patel A. R., Vavia P. R. (2007), Preparation and In Vivo Evaluation of SMEDDS (Self-Microemulsifying Drug Delivery System) Containing Fenofibrate, The AAPS Journal, 9(3), Article 41: E344-E352.
57. Shen H., Zhong M. (2006), Preparation and evaluation of self-microemulsifying drug delivery systems (SMEDDS) containing atorvastatin, J Pharm Pharmacol., 58(9): 1183-1191.
58. Boonme P., Krauel K., Graf A., Rades T., Junyaprasert V. B. (2006), Characterization of Microemulsion Structures in the Pseudoternary Phase Diagram of Isopropyl Palmitate/Water/Brij 97:1-Butanol, AAPS PharmSciTech, 7(2) Article 45: E1-E6.
59. Agarwal V., Siddiqui A., Ali H., Nazzal S. (2006), Dissolution and powder flow characterization of solid self-emulsified drug delivery system (SEDDS), International Journal of Pharmaceutics, 366: 44-52.
60. Wu W., Wang Y., Que L. (2006), Enhanced bioavailability of silymarin by self-microemulsifying drug delivery system, European Journal of Pharmaceutics and Biopharmaceutics, 63: 288-294.
61. Itoa Y., Kusawake T., Ishida M., Tawa R., Shibata N., Takada K. (2005), Oral solid gentamicin preparation using emulsifier and adsorbent, Journal of Controlled Release, 105: 23-31.
62. Sha X., Yan G., Wu Y., Li J., Fang X. (2005), Effect of self-microemulsifying drug delivery systems containing Labrasol on tight junctions in Caco-2 cells, European Journal of Pharmaceutical Sciences, 24: 477-486.
63. Subramanian N., Ray S., Ghosal S. K., Bhadra R., Moulik S. P. (2004), Formulation Design of Self-Microemulsifying Drug Delivery Systems for Improved Oral Bioavailability of Celecoxib, Biol. Pharm. Bull., 27(12): 1993-1999.
64. Kang B. K., Lee J. S., Chon S. K., Jeong S. Y., Yuk S. H., Khang G, Lee H. B., Cho S. H. (2004), Development of self-microemulsifying drug delivery systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs, International Journal of Pharmaceutics, 274: 65-73.
65. Patil P., Joshi P., Paradkar A. (2004), Effect of Formulation Variables on Preparation and Evaluation of Gelled Self-emulsifying Drug Delivery System (SEDDS) of Ketoprofen, AAPS PharmSciTech, 5(3) Article 42: 1-8.
66. Holm R., Christopher J. H. P., Glenn A. E., Anette M., Henning G. K. , Charman W. N. (2003), Examination of oral absorption and lymphatic transport of halofantrine in a triple-cannulated canine model after administration in self-microemulsifying drug delivery systems (SMEDDS) containing structured triglycerides, European Journal of Pharmaceutical Sciences, 20: 91-97.
67. Itoh K., Tozuka Y., Oguchi T., Yamamoto K. (2002), Improvement of physicochemical properties of N-4472 part I formulation design by using self-microemulsifying system, International Journal of Pharmaceutics, 238: 153-160.
68. Agarwal V., Siddiqui A., Ali H., Nazzal S. (2000), Dissolution and powder flow characterization of solid self-emulsified drug delivery system (SEDDS), International Journal of Pharmaceutics, 366: 44-52.
69. Kim H. J., Yoon K. A., Hahn M., Park E. S., Chi S. C., (2000), Preparation and in vitro evaluation of self-microemulsifying drug delivery systems containing idebenone, Drug Dev Ind Pharm., 26(5): 523-529.
70. Chen G. L., Lee F. Y. (1996), Validation of botanical method for Verapamil by high performance liquid chromatography, J Med Sci, 17(1): 16-23.
71. Shah N.H., Carvajal M.T., Patel C.I., Infeld M.H., Malick A.W. (1994), Self-emulsifying drug delivery systems (SEDDS) with polyglycolyzed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs, International Journal of Pharmaceutics, 106: 15-23.
72. http://www.drugs.com
73. http://www.wikipedia.com
74. Indian pharmacopeia
75. British pharmacopeia
76. Bhagwat durgachara, D. souza I. development of self micro emulsifying drug delivery system.to inhance dissolution rate of telmisartain, IJDDR 2012,02(04);398-407.
77. Gaikwad G, Godbole M, potnos V, Daud A. Formulation and evaluation of self emulcifying drug delivery system of orlistat, Americal Journal Of Pharmtech Research 2012; 2 (6): 297-31

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