FORMULATION DEVELOPMENT AND IN-VITRO EVALUATION OF SOLID AND LIQUID SELF EMULSIFYING DRUG DELIVERY SYSTEM OF POORLY WATER SOLUBLE DRUG KETOPROFEN

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1 Page6565 Indo American Journal of Pharmaceutical Research, 2016 ISSN NO: FORMULATION DEVELOPMENT AND IN-VITRO EVALUATION OF SOLID AND LIQUID SELF EMULSIFYING DRUG DELIVERY SYSTEM OF POORLY WATER SOLUBLE DRUG KETOPROFEN Annanya Gangopadhyay *, Shubhrajit Mantry, C.Soundrapandian Department of Pharmaceutics, Himalayan Pharmacy Institute, Majhitar, Rangpo, East Sikkim , India. ARTICLE INFO Article history Received 13/09/2016 Available online 15/10/2016 Keywords S-Sedds, Ketoprofen, Aerosil 200, Solubility Study, Pseudo Ternary Phase Diagram, In-Vitro Drug Release Study. Corresponding author Annanya Gangopadhyay Department of Pharmaceutics, Himalayan Pharmacy Institute, Majhitar, Rangpo, East Sikkim , India. ABSTRACT The purpose of the present study was to formulate the solid self-emulsifying drug delivery system by using Cinnamon oil, Cremephore RH 40, PEG 600, Ethanol as oil phase, surfactant, co-surfactant, and co-solvent of poorly water soluble (BCS Class II type) drug ketoprofen. Aerosil 200 was used as an adsorbing agent and convert liquid form to solid form and develop S-SEDDS by adsorption to solid carrier technique. The main objective of study was to prepared S-SEDDS of ketoprofen on the basis of preformulation study like solubility study, pseudo ternary phase diagram, standard curve preparation and FTIR study in order to achieve a better dissolution rate which would further help in enhancing absorption and oral bioavailability. The solubility of Ketoprofen was determined in several oils, surfactants and co-surfactants using an UV method. For stable SEDDS, micro-emulsion region was identified by constructing pseudo ternary phase diagram containing different portion of surfactant: cosurfactant (1:1, 2:1, 3:1), oil and water. Four Solid and Liquid SEDDS were prepared by selecting different proportions from self-micro emulsifying region and evaluated for their self-dispersibility, thermodynamic stability of emulsion, micromeritic property, drug content, in-vitro drug release study. The formulation was found to show a significant improvement in the drug release from powered drug ketoprofen. Drug release from S-SEDDS (F3) is % in 6 hrs. and the conventional release self-emulsifying formulations followed first order release kinetics model. Please cite this article in press as Annanya Gangopadhyay et al. Formulation Development and in-vitro Evaluation of Solid and Liquid Self Emulsifying Drug Delivery System of Poorly Water Soluble Drug Ketoprofen. Indo American Journal of Pharmaceutical Research.2016:6(10). Copy right 2016 This is an Open Access article distributed under the terms of the Indo American journal of Pharmaceutical Research, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

2 Page6566 INTRODUCTION Self-emulsifying drug delivery system is an isotropic mixture of oil, surfactant, co-surfactant that has able to self-emulsify rapidly and form oil in water emulsion in the presence of GI fluid with the help of gentle agitation and improve solubility and dissolution profile of poorly water soluble drug [1].Lipophilic drug exhibit dissolution rate limited absorption [2]. But here prepared a formulation in which first pre dissolving the drug compound for this overcome the initial rate limiting step dissolution in aqueous environment. 40% of new chemical compound (drug) are poorly water soluble or lipophilic in nature. For this reason, which leads to poor oral bioavailability, high intra and inter subject variability and lack of dose proportionality. Has some way to overcome this problem such as micronization, salt formation, solid dispersions, inclusion complexes with cyclodextrin and lipid based drug delivery system like self-emulsifying drug delivery systems. But every process has some difficulties. In salt formation salt may convert back to their original acid or base form and lead to aggregation in GI tract. Particle size reduction may not be desirable in situations where handling difficulties and poor wettability are experienced for very fine powders [3].Lipid based formulation are important, because of their some advantages like SEDDS has unique property that they are able to self-emulsify rapidly and form o/w emulsion and results in small droplets of oil dispersed in GI fluid that provide a large interfacial area and enhancing the activity, improved drug dissolution, increased intestinal epithelial permeability, increased tight junction permeability [4]. If liquid SEDDS are enclosed in hard or soft gelatin capsule to facilitate oral administration, but it produces some disadvantages such as stability, incompatibility, drug leakage, precipitation and capsule ageing for this reason liquid form convert to solid form and overcome this problem. For converting L- SEDDS to S-SEDDS has some way such as spray drying, adsorption into solid carriers, melt granulation, melt extrusion. Adsorption by solid carrier is simple method for converting the solid form. Solid carrier such as aerosil 200 mixed with required amount of liquid self-emulsifying drug delivery system by a blender and convert it to solid form [5]. Ketoprofen [(RS) 2-(3-benzoylphenyl)-propionic acid] is one of the propionic acid derivatives of non-steroidal antiinflammatory drugs (NSAID) with analgesic and antipyretic effects. It is used to relieve pain from various conditions [6]. It also reduces pail, swelling and joint stiffness from arthritis. It works by blocking our body s production of certain natural substances that cause inflammation. Ketoprofen is classified as BCS class II drug, having high permeability and poor water solubility [2]. Ketoprofen [C 16 H 14 O 3 ] has a short biological half-life of 2 to 2.5 hrs [6]. It is lipophilic in nature with log P value of 0.97 in the n-octanol/water system and λ max 256 nm in ethanol [7]. The main objective of the study was to formulate, develop and evaluate a solid selfemulsifying drug delivery system containing ketoprofen and comparison with normal powered ketoprofen drug. It was chosen as the drug of choice in the present investigation for the development of self-emulsifying drug delivery systems. Figure 1: Picture of the Liquid and Solid Self Emulsifying formulation. MATERIALS & METHODS Materials This substances were used for the preparation of solid and liquid Self emulsifying drug delivery system. Ketoprofen was a gift sample from Yarrow Chem. Products, Mumbai. Cinnamon Oil was purchased from Yucca enterprises Mumbai. Cremephore RH 40 were of analytical grade, obtained from Ozone international, Mumbai. PEG 600 & Ethanol were purchased from S.D. Fine-Chem. Limited, Mumbai. Aerosil 200 were gifted by Lupin Pharmaceuticals, Aurangabad. Distilled water was prepared in our laboratory. Methods PREFORMULATION STUDY Determination of saturation solubility of Ketoprofen in different oils, surfactant, and co-surfactant [8] The most important criterion for the screening of components for self-emulsifying drug delivery system is the solubility of poorly soluble drug in oils, surfactants and co surfactants. The solubility of ketoprofen in various oils was determined by adding an excess amount of drug.

3 Page ml of selected oils (Cinnamon oil, Clove oil, Arachis oil, Sesame oil, Coconut oil, Cod-liver oil, Olive oil, Oleic acid) and surfactants (tween-20, tween-80, Cremephore RH 40) and co-surfactant (Span 20, Span80, PEG 200, PEG 600, PEG 400, PEG 4000) and co-solvent (Ethanol, Propylene glycol, glycerol) was taken in 50ml beaker An excess amount of drug was individually mixed with selected every oils, surfactant, co-surfactant, cosolvents in the presence of heat Dissolve properly 2 ml was withdrawn and put in 5 ml capacity stopper vials and properly sealed the vials After sealing the mixture was heated at 40 degree centigrade in a water bath to facilitate the solubilisation using a vortex mixer Mixtures were shaken for 48hrs After reaching equilibrium, each vial was centrifuged at 3000 rpm for 15 min Excess insoluble ketoprofen was discarded by filtration using a membrane filter The concentration of ketoprofen was determined using UV- spectrophotometer at 256 nm Pseudo ternary phase diagram for identification of micro-emulsion region [3,8] The purpose of this study for selecting the ratio of surfactant and co-surfactant. Phase diagram study suggests that how much which ratio or combination of surfactant/co-surfactant shows good micro emulsion region. Phase diagram study was done by using water titration method. The physical state of the nano/micro emulsion was marked on a pseudo-three-component phase diagram with one axis representing aqueous phase, the other representing oil and the third representing a mixture of surfactant and co-surfactant at fixed weight ratios (Smix ratio). The selection of these excipients was based on the solubility study of ketoprofen.

4 Page6568 Based on the observations of solubility studies, components of emulsion oil phases, surfactants and co surfactants indicating highest solubility of ketoprofen were selected The surfactants and co-surfactants were blended together in 1:1, 2:1, 3:1 proportions respectively These blends of surfactants: co surfactants (Smix) were mixed with oily phase by adding small amounts with constant stirring The proportions of oil: Smix were varied as 9:1, 8:2, 7:1, 6:4, 5:5, 4:6, 3:7, 2:8 and 1:9 The resultant blends were titrated with distilled water with proper stirring Systems were allowed to reach equilibrium and the samples were checked visually for Clarity The point indicating the clear and isotropic mixtures were considered to be within the micro-emulsion region FTIR study FTIR spectra are mainly used to determine if there is any interaction between the drug and any of the excipient used. The presence of interaction is detected by the disappearance of important functional group of the drug [9]. Standard Curve preparation A 1 mg/ml pure drug containing stock solution was prepared by dissolving ketoprofen with few amount of ethanol and volume was make up with phosphate buffer ph-7.4. This stock solution was further diluted with phosphate buffer 7.4 and prepared 100μg/ml concentrating solution. From this solution 5 μg/ml, 10 μg/ml, 15 μg/ml, 20 μg/ml, concentrating solution was prepared with the help of ph7.4 phosphate buffer [10]. PREPARATION OF LIQUID & SOLID SELF EMULSIFYING DRUG DELIVERY SYSTEM OF KETOPROFEN [5] The appropriate quantities of oil phase, surfactant and co-surfactant were selected based on the result of solubility study and Pseudo ternary phase diagram. Required quantity of ketoprofen dispersed in appropriate required quantity of co-surfactant in a beaker in the presence of heat Accurately weighed quantity of oil and surfactant blends ware taken in small portion in a beaker which was placed on a magnetic stirrer The blends were mixed thoroughly This (drug + co-surfactant) mixture was added with (oil+surfactant) mixture+ At last, total (drug+co-surfactant+surfactant+oil phase) ware mixed properly with the help of magnetic stirrer Prepared Liquid self-emulsifying drug delivery system.

5 Page6569 The L-SEDDS of ketoprofen was adsorbed onto Aerosil200 carrier by physical mixing in a small mortar and pestle. The resulting solid SEDDS was uniformly homogenized to ensure that the mixture was uniformly distributed. The damp mass was passed through sieve No.120 and was dried at ambient temperature. Formulation Table 1: Selected combination of components of SEDDS. Drug (ketoprofen) (mg) Oil phase (Cinnamon Oil) (ml) Preparation of Liquid & Solid Self-Emulsifying Drug Delivery System. Surfactant (Chremephore RH 40) (ml) Co-Surfactant (PEG-600) (ml) F F F F Ketoprofen added in Co-surfactant Accurately weighed quantity Cinnamon oil was taken in a beaker Accurately weighed quantity of Cremephore RH 40 was mixed with Cinnamon oil L-SEDDS was taken in a Mortar Pestle Picture of Liquid SEDDS (drug + co-surfactant) mixture was added with oil+surfactant Adsorbent Arosil 200 mixed with L-SEDDS S-SEDDS before Sieving and proper drying Figure 2: Images of preparation of Liquid & Solid Self-Emulsifying Drug Delivery System. S-SEDDS after Sieving and proper drying

6 Page6570 CHARACTERIZATION OF LIQUID SELF EMULSIFYING DRUG DELIVERY SYSTEM Dispersibility Test The efficiency of self-emulsification of oral nano or micro emulsion is assessed by standard USP II dissolution apparatus. One ml of each formulation was dissolved in 500 ml of water at 37 ± 1 C. A standard stainless steel dissolution paddle is used with rotating speed of 50 rpm to provide gentle agitation. The in vitro performance of the formulations is visually assessed by following grading system. Grade A: Rapidly forming (within 1 min) nano emulsion, having a clear or bluish appearance. Grade B: Rapidly forming, slightly less clear emulsion, having a bluish white appearance. Grade C: Fine milky emulsion that formed within 2 min. Grade D: Dull, greyish white emulsion having slightly oily appearance that is slow to emulsify (longer than 2min). Grade E: Formulation, exhibiting either poor or minimal emulsification with large oil globules present on the surface. Grade A and Grade B formulation will remain as nano emulsion when dispersed in GIT [8]. Thermodynamic stability of emulsion The physical stability of lipid based formulation is also crucial to it performance, which can be adversely affected by precipitation the drug in the excipients matrix. In addition poor formulation physical stability can lead phase separation of the excipients affecting not only formulation performance but visual performance as well. Centrifugation study The formulations were centrifuged using laboratory centrifuge at 5000 rpm for 30 min. The resultant formulations were then checked for any instability problem, such as phase separation, creaming or cracking. Formulation which is stable selected for further studies. Heating and cooling cycle Three heating/cooling cycles between 4 C and 40 C with storage at each temperature for not less than 24 h. The resultant formulations were assessed for their physical instability like phase separation and precipitation. Formulation which passes this test subjected for further test. Freeze thaw cycle Freeze thawing was employed to evaluate the stability of ketoprofen SEDDS. Formulations were subjected to 3 freeze-thaw cycles, which included freezing at 4 C for 24 h followed by thawing at 40 C for 24 h. Centrifugation was performed at 3000 rpm for 5 min. The formulations were then observed for phase separation. Formulation which passes all these three test & those having least Smix concentration were optimized formulation [8]. Self-Emulsification Time The efficiency of self-emulsification is assessed using dissolution apparatus. 1ml SEDDS was dissolved in 250ml of water at 37±0.5 C. Gentle agitation was provided by paddle rotating at 60RPM. SEDDS was assessed visually according the rate of emulsification and the final appearance of the emulsion. Also any precipitation was observed visually [8]. CHARACTERIZATION OF SOLID SELF EMULSIFYING DRUG DELIVERY SYSTEM Micromeritic properties Flow properties of solid powder mixture in tablet and capsule manufacture depends on particle size, size distribution and surface area of the powder particle. The particle size of the drug affect the release from the dosage form administered orally, parenterally, rectally and topically. Dissolution rate is faster from smaller particle size due to its high specific surface area. This flow properties of powder mixture of drug and excipients are evaluated by bulk density, tapped density, Carr s index, hausner s ratio and angle of repose [11]. Bulk Density: The bulk density depend on the both the density of powder particle and the spatial arrangement of the particle in the powder bed. It can be expressed in gm/ cm3. Bulk Density (ρb) = Mass of Powder (w) Bulk volume of the blend before tapping (Vb) [12]

7 Page6571 Tapped Density: The tapped density is obtained by mechanically tapping a graduated measuring cylinder or vessel containing the powder blend. After observing the initial powder volume or mass, the measuring cylinder or vessel is mechanically tapped, and volume or mass readings are taken until little further volume or mass change is observed. Tapped Density (ρt) = Mass of Powder (w) Final volume of the blend after tapping (Vt) [13] Hausner s Ratio: The hausner s ratio is calculated by this following formula. Hausner s Ratio (H) = Tapped Density (ρt) Bulk density (ρb) [14] A hausner s ratio greater than 1.25 is considered to be an indication of poor flowability and less than 1.25 indicates better flowability. Carr s Index: A Carr index greater than 25 is considered to be an indication of poor flowability and below 15 indicates good flowability. Carr s Index was determined by following equation, Carr s Index (C) = Tapped Density - Bulk Density Tapped Density 100 [15] Angle of Repose: Angle of repose determined by Fixed Funnel method. The material is poured through a funnel to form a cone. The tip of the funnel should be held close to the growing cone and slowly raised as the pile grows, to minimize the impact of falling particles. Stop pouring the material when the pile reaches a predetermined height or the base a predetermined width. Rather than attempt to measure the angle of the resulting cone directly, divide the height by half the width of the base of the cone. The inverse tangent of the ratio is the angle of repose. The angle of repose can range from 0-90.Angle of repose was determined by following equation, tan ϴ = h/r, or, ϴ = tan-1 (h/r), ϴ= Angle of Repose, h=height of pile of powder blend, r= Radius of heap [16]. Table 2: Grading of powders for their flow properties according to Carr s index in Self Emulsifying Drug Delivery System. %Carr s Index Flow Properties 5-15 Excellent Good Fait to passable Poor Very poor >40 Very very poor Table 3: Grading of powders for their flow properties according to Angle of repose in Self Emulsifying Drug Delivery System. Angle of Repose(ϴ) Flow Properties <25 Excellent Good Passable >40 Very Poor Drug content determination Ketoprofen loaded S-SEDDS (100 mg) was dissolved in 10 ml of methanol in 10 ml volumetric flask.0.1 ml of stock solution measured accurately and transferred to 10 ml volumetric flask to which 10 ml methanol was added and filtered through whatman filter paper. The above solutions were analyzed by UV Spectrophotometer at λmax. 256nm. The amount of ketoprofen present in the formulation was determined using the prepared standard calibration curves of ketoprofen in methanol [8].

8 Page6572 In vitro drug release study Drug release studies from solid SEDDS were performed using USP type II dissolution apparatus with 900 ml of phosphate buffer ph 7.4 separately as a medium at 37 ± 0.5 C. The speed of the paddle was adjusted to 50 rpm. Ketoprofen loaded solid SEDDS (equivalent to 50 mg of ketoprofen) were placed in a dissolution tester (Electro lab, Ahmadabad). At predetermined time intervals 15, 30,45and 60 min, an aliquot (5 ml) of the sample was collected, filtered and analyzed spectrophotometrically at 256 nm. And fresh 5 ml ph 7.4 buffer solution was added in the dissolution medium. The drug release of optimized S-SEDDS formulation was compared to the plain drug as well as marketed formulation of the drug in phosphate buffer ph 7.4 [5]. RESULT & DISCUSSION Solubility Study Different oils, surfactant, co-surfactant, co-solvent were screened for the solubility of ketoprofen. Maximum solubility was determined in cinnamon oil from all types of oil phase, Cremephore RH 40 from all types of surfactant, PEG 600 from all types of cosurfactant, ethanol from all types of co-solvents and all four reagent were selected for self-emulsifying formulation Cinnamon Oil Solubility In Oil Phase Solubility Cod Liver Oil Clove Oil Olive Oil Sesame Oil Coconut Oil Arachis Oil Oleic Acid Figure 3: Solubility profile of ketoprofen in different oil phase Solubility In Surfactant Solubility-mg/ml Creamephore RH 40 Tween 80 Tween 20 Figure 4: Solubility profile of ketoprofen in different surfactants.

9 Page Solubility In Co-Surfactant Solubility-mg/ml PEG-200 PEG-400 PEG-600 SPAN-20 SPAN-80 Figure 5: Solubility profile of ketoprofen in different co-surfactants Solubility In Co-Solvent Solubility-mg/ml Ethanol Propylene Glycol Glycerol Figure 6: Solubility profile of ketoprofen in different co-solvent. Pseudo Ternary Phase Diagram Pseudo-ternary phase diagram were constructed by using a series of SEDDS, to identify the self-emulsifying region and to optimize the concentration of oil, surfactant and co-surfactant in the SEDDS formulation. The phase diagram of the system containing Cinnamon Oil, Cremephore RH 40 and PEG 600 as oil, surfactant and co-surfactant respectively, with different ratios of surfactant and co-surfactant. It was observed that the mixture of surfactant and co-surfactant (Smix) ratio 1:1 showed the greater self-emulsifying (micro-emulsifying) region than the other ratios such as, 2:1, 3:1. The phase diagram was plotted using chemix ternary plot software. Figure 7: Ternary diagram for cinnamon oil /Cremephore RH 40: PEG600 (1:1): water system.

10 Page6574 Figure 8: Ternary diagram for cinnamon oil /Cremephore RH 40: PEG600 (2:1): water system. Figure 9: Ternary diagram for cinnamon oil /Cremephore RH 40: PEG600 (2:1): water system. Standard Curve of Ketoprofen A standard curve for ketoprofen was successfully obtained by measuring the absorbance of series of concentrations of ketoprofen at the λ max of 256nm.A corresponding standard curve generated by linear regression analysis with linear regression coefficient is Table 4: Standard Calibration Curve of Ketoprofen for ph 7.4. Concentration(µg/ml) Absorbance Equation R 2 value y=0.035x

11 Page6575 Figure 10: Standard Curve of ketoprofen. FTIR study Figure 11: FTIR study of drug ketoprofen. Figure 12: FTIR study of S-SEDDS (formulation 3). Figure 13: FTIR study of L-SEDDS (formulation 3).

12 Page6576 Thermodynamic Stability, Emulsification Time, Dispersibility Test for liquid self-emulsifying drug delivery system The thermodynamic stability study was performed three studies like heating cooling cycle, freeze thaw cycle, centrifugation. On the basis of the mentioned three studies formulations were selected. On the basis of the thermodynamic stability studies it was found that F1, F2, F3, and F4 all four formulations were passed and selected for further characterization. All the formulations showed good self-dispersibility, as soon as they added to dissolution medium and dispersions were found to be clear. The increased order of self-dispersibility time was found to be F3 < F4 < F1 < F 2. The emulsification time of SEDDS was determined as per procedure and maximum emulsification time was found in F2 formulation and minimum emulsification time was found in F3 formulation. Table 5: Results of thermodynamic stability of emulsion, emulsification time, and dispersibility test for liquid self-emulsifying drug delivery system. Formulatio Thermodynamic Stability of Emulsion Emulsification Dispersibili n No Centrifugation Study Heating and Cooling cycle Freeze Thaw Cycle Time (Second) ty Test (Grade) F1 Yes Yes Yes 0.62 B F2 Yes Yes Yes 0.65 B F3 Yes Yes Yes 0.50 A F4 Yes Yes Yes 0.57 A Micromeritic properties and drug content for Solid self-emulsifying drug delivery system All formulations hausner s ratio value less than 1.25, angle of repose value <25, Carr s index below 15 in formulation 1, indicates good flowability. From the data obtained, the optimized F1 batch shows good Micromeritic properties. Table 6: Results of micromeritic properties and drug content for Solid self-emulsifying drug delivery system. Formulation Bulk Density(ρb) Tapped Density(ρt) Carr s Hausner s Angle of Drug (gm/cm3) (gm/cm3) Index(C) Ratio(H) Repose (ϴ) Content F F F F In-vitro drug release of S-SEDDS and Plain ketoprofen in ph 7.4 Drug release from the all SEDDS formulation was found to be significantly higher as compared with plain powdered ketoprofen drug. Ketoprofen loaded S-SEDDS formulation (F3) has greater drug released, above 98% within 6hr. It could be suggested that the SEDDS formulation resulted in spontaneous formation of a micro-emulsion, which permitted a faster rate of drug release into the aqueous phase, much faster than that of plain Ketoprofen and adsorbing of SEDDS in the presence of Aerosil 200 may not affect the progress of emulsification as well as the release of drug. Almost all the formulations followed first order release kinetics model due to its highest regression coefficient value. Table 7: In-vitro drug release value of S-SEDDSs and Plain ketoprofen after 6 hr in ph 7.4. Time (hr) Cumulative % drug release Normal ketoprofen powder F1 F2 F3 F

13 Page6577 Table 8: Release kinetic parameter of different models for all formulation. Formulation Zero Order First Order Higuchi model K 0 R 2 K 1 R 2 K H R 2 F F F F Pure Drug Ketoprofen

14 Page6578 Figure 14: Different release kinetics model for the the basis of In-vitro drug release. CONCLUSION Ketoprofen is one of the propionic acid derivatives of non-steroidal anti-inflammatory drugs (NSAID) with analgesic and antipyretic effects. A self-emulsifying drug delivery system was prepared which enhance the solubility of poorly water soluble drug ketoprofen. S-SEDDS formulations of a poorly water-soluble drug ketoprofen were formulated for direct filling into hard gelatin capsules for oral administration. From pseudo-ternary phase diagram study, observed that the mixture of surfactant and co-surfactant (Smix) ratio 1:1 showed the greater self-emulsifying (micro-emulsifying) region than the other ratios such as, 2:1, 3:1. As per pseudo-ternary phase ratio the formulation of SEDDS was prepared. S-SEDDS of Ketoprofen prepared using Aerosil 200 by adsorption process. The conclusion was confirmed from the value of angle of repose less than 25, Hausner s ratio less than 1.25 and drug content in F3 was 97.58%. The formulations after reconstitution formed good emulsion with drug solubilisation. Drug release from S-SEDDS (F2, F3, F4) was found to be significantly higher as compared with that of plain powdered ketoprofen. Ketoprofen loaded S-SEDDS formulation (F3) has greater drug released, above 98% within 6hr. Almost all the formulations followed first order release kinetics model due to its highest regression coefficient value. Thus the solubility and the dissolution rate of BCS Class II type drug ketoprofen was enhanced which would prove a promising result of increased absorption and increased oral bioavailability of conventional release Ketoprofen formulation.

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