|Year : 2012 | Volume
| Issue : 5 | Page : 21-22
Design, development and optimization of selfmicroemulsifying drug delivery system of an anti-obesity drug
Jagruti Desai1, Nirav Khatri1, Sachin Chauhan2, Avinash Seth2
1 Department of Pharmacy, Faculty of Technology and Engineering, The Maharaja Sayajorao University of Baroda, Kalabhavan, Vadodara, Gujarat, India
2 Department of Pharmacy, Sumandeep Vidyapeeth, Piparia, Vadodara, Gujarat, India
|Date of Web Publication||21-Mar-2012|
Department of Pharmacy, Faculty of Technology and Engineering, The Maharaja Sayajorao University of Baroda, Kalabhavan, Vadodara, Gujarat
Source of Support: None, Conflict of Interest: None
| Abstract|| |
The aim of the present work was to formulate a self-microemulsifying drug delivery system (SMEDDS) containing orlistat. The oil, surfactant and co-surfactant were decided based on the solubility studies. Pseudoternary phase diagrams were plotted, microemulsification area was determined and different formulations were prepared. Particle size, zeta potential, dispersibility test and thermodynamic stability studies were measured. In-vitro dissolution test of thermodynamically stable formulations OS-B and OS-C were carried and results were compared with those of plain drug and suspension formulation. Stability studies performed indicated that formulation OS-C remained stable over 12 months period. Thus this investigation concluded that hydrophobic drugs like orlistat can be delivered effectively through the formulation of SMEDDS.
Keywords: Dissolution, Orlistat, phase diagram, thermodynamic stability
|How to cite this article:|
Desai J, Khatri N, Chauhan S, Seth A. Design, development and optimization of selfmicroemulsifying drug delivery system of an anti-obesity drug. J Pharm Bioall Sci 2012;4, Suppl S1:21-2
|How to cite this URL:|
Desai J, Khatri N, Chauhan S, Seth A. Design, development and optimization of selfmicroemulsifying drug delivery system of an anti-obesity drug. J Pharm Bioall Sci [serial online] 2012 [cited 2022 Jul 6];4, Suppl S1:21-2. Available from: https://www.jpbsonline.org/text.asp?2012/4/5/21/94124
Orlistat is a drug, used to treat Obesity by inhibiting pancreatic lipase enzyme. It is highly lipophilic having bioavailability of less than 1%. Self-microemulsifying drug delivery system (SMEDDS), being lipid based formulation can its increase the bioavailability. Hence, Orlistat SMEDDS were formulated having increased solubility, dissolution rate and therapeutic efficacy.
| Materials and Methods|| |
Orlistat was procured from Centurion Laboratories, Vadodara. Propylene glycol monocaprylate, Propylene glycol laurate and Caprylic triglyceride were obtained from Gattefosse. Cremophor Rh 40, Poly ethylene glycol (PEG) 400, Propylene glycol and Polysorbate 80 were obtained from Sigma-Aldrich, Mumbai. Propylene glycol caprylocaprate, Glyceryl tricaprylate, Glyceryl monocaprylate and Decaglycerol Decaolate were obtained from Abitec Corporation. Propylene glycol was obtained from shivam industries, Mumbai. All other chemicals and solvents were of analytical grade.
The equilibrium solubility of Orlistat in various oils, surfactants and co-surfactants was determined by adding excess orlistat to various vials in vehicle.
Construction of pseudoternary phase diagram
Different Pseudo-ternary phase diagram of oil (Propylene glycol monocaprylate), surfactant (Propylene glycol laurate), co-surfactant (Polysorbate 80) and water were developed using titration method at 25±2°C.
Preparation of Orlistat SMEDDS
Orlistat containing oil solution was added in the surfactant system solution with continuous stirring and vortex mixing until homogenous mixture is formed.
Particle size distribution (PSD) and ζ-potential analysis
It was studied by Malvern Metasizer.
Orlistat SMEDDS were diluted with an aqueous medium and centrifuged at 3500 rpm for 30 min and formulations were observed visually for phase separation. Formulations were subjected to freeze thaw cycles (-20°C for 2 days followed by +40°C for 2 days).
It was assessed in standard USP XXII dissolution apparatus 2 by dispersing the formulation in 900 ml of deinonized water and 0.1 N HCl at 37±0.5°C, 50 RPM.
In vitro drug release
It was carried out in 900 ml of 3% SLS in 0.5% NaCl, pH 6.0. Liquid SMEDDS were filled in hard gelatin capsule and commercial form and plain drug were taken.
C 18 column (250×4.6 mm) with 5 μm particle size was taken. The mobile phase consisted of orthophosphoric acid 0.1%-acetonitrile (10:90 v/v).
Formulations which were found to be thermodynamically stable were subjected to stability studies in empty hard gelatin capsule size "O" at 25°C±2°C/60±5% RH, 35°C±2°C/65±5% RH and 40°C±2°C/75±5% RH.
| Results and Discussion|| |
Propylene glycol laurate and Propylene glycol monocaprylate followed by Polysorbate 80 showed the highest solubilization capacity for orlistat so they were selected as oil, surfactant and co-surfactant respectively. The region of microemulsion existence for Propylene glycol monocaprylate - Propylene glycol laurate+polysorbate 80-water was determined by pseudoternary plot. The microemulsion area increased as the S/Cos ratio increased upto 2:1 so this ratio was selected for formulation study. Four different formulations OS-A, B, C and D based on this study was selected. The formulation OS-C had lowest particle size of 15.47nm with an average Zeta potential of -8.95 mV. During thermodynamic stability studies, the centrifugation test was cleared by all formulations but, OS-D did not pass freeze thaw cycle study. Hence, OS-D was dropped for further studies. Further, OS-A and OS-D did not pass the dispersibility test. Improved in-vitro drug release of Orlistat was observed in SMEDDS formulation as compared to marketed formulation and free drug. During stability studies, physical parameters like homogeneity and clarity were examined during which OS-B formulation was found to be unstable while OS-C formulation was found physically stable. Hence, Chemical stability was examined for formulation OS-C. There was no decrease in drug content found at the end of stability studies indicating that the formulation OS-C remained chemically stable. Furthermore, there were no sign of capsule shell deformations or capsule leaks indicating that formulation was compatible with the hard gelatin capsule shells.
| Conclusion|| |
An optimized orlistat loaded SMEDDS formulation consisting orlistat (7.9% w/w), Propylene glycol monocaprylate (18.42% w/w), Propylene glycol laurate (49.21% w/w) and Polysorbate 80 (24.47% w/w) was successfully developed. It offers increased solubility, increased dissolution rate resulting in increased bioavailability of orlistat in comparision with the conventional oral formulation of orlistat. Results further conclude that SMEDDS formulation of lipophilic drug like orlistat has potential for increased bioavailability and can be explored as good alternative to conventional formulations. ,
| References|| |
|1.||Dolenc A, Govedarica B, Dreu R, Kocbek P, Srcic S, Kristl J. Nanosized particles of orlistat with enhanced in vitro dissolution rate and lipase inhibition. Int J Pharm 2010;396:149-55. |
|2.||Franks I. Obesiy: Orlistat 60 mg reduces levels of visceral adipose tissue in obese individuals. Nat Rev Gastroenterol Hepatol 2011;8:476. |