Reverse engineering and development of generic Orlistat formulation
DOI:
https://doi.org/10.56511/JIPBS.2016.v3.i04.pp17-25Abstract
Orlistat a weight loss drug is off patented in US in 2009, it has the annual sales of around $100 million of the innovator’s product and has a high commercial potential in generic market. The marketed capsule formulation was decoded by differential solubility technique using methanol, methylene chloride and water as solvents and anti solvents. The quantity of API and excipients such as Polyvinyl pyrrolidone, microcrystalline cellulose, Sodium lauryl sulphate, sodium starch glycollate and talc obtained after decoding is 118.60, 7.85, 84.95, 6.80 , 10.85 and 3.00 mg respectively. DSC thermogram of separated Orlistat gave a sharp endothermic peak at 46.5ºC. PXRD values of the separated API obtained at 2θ are 11.2, 12.2, 14.0, 15.4, 16.9, 18.3, 19.2, 22.5, 25.0. Based on the quantities of the API and excipients obtained after decoding, generic form of the Orlistat capsule was prepared, which consists of pellets in capsules. The prepared generic form was characterized for weight variation of ± 3%, angle of repose 28.5˚ and drug content of 95.35%. Generic dosage form had similar dissolution profile with that of marketed products and showed first order drug release mechanism with R2 of 0.9591. Greater similarity factor for dissolution was established with a value of 70.13.
Keywords:
Orlistat, anti-obesity, weight loss, generic, differential solubility, reverse engineeringDownloads
References
Somnath P: Shifts in the Generic-Drug Market: Trends and Causes. US Pharm 2013; 38(6):6-10.
DiMasi JA: The Price of Innovation: New Estimates of Drug Development Cost. Journal of Health Economics 2003; 22:151-185.
Koradia V, Chawla G, and Bansal AK: Comprehensive Characterization of the Innovator Product: Targeting Bioequivalence Generics. J Generic Med 2005; 2:335-346.
http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinfor mation/guidances/ucm377465.pdf. Retrieved on 01 October 2014.
York P: Solid-State Properties of Powders in the Formulation and Processing of Solid Dosage Forms. Int. J. Pharm 1983; 14(1):1 – 28.
Kocbek P, Baumgartner S, Kristi J: Preparation and evaluation of nanosuspensions for enhancing dissolution of poorly soluble drugs. Int J Pharm 2006; 312:179 – 86.
Skorda D. Kontoyannis C.G: Identification and quantitative determination of atorvastatin calcium polymorph in tablets using FT-Raman spectroscopy. Talanta 2008; 74:1066 – 70.
The British Pharmacopoeia. British Pharmacopoeia Commission. London: HMSO; 2007 (electronic version).
Mohammadi A, Haririan I, Rezanour N, Ghiasi L, Walker R B: A stability-indicating high performance liquid chromatographic assay for the determination of orlistat in capsules. J Chromatogr A 2006; 1116(12):153-7.
http://www.accessdata.fda.gov/scripts/cder/dissolution/dsp. Retrieved on
Higuchi T: Mechanism of sustained-action medication: theoretical analysis of rate of release of solid drug dispersed in solid matrices. J Pharm Sci 1963; 52:1145 – 1149.
Hixson AW, Crowell JH: Dependence of reaction velocity upon surface and agitation I-theoretical consideration. Ind Eng Chem 1931; 23:923 – 931.
Korsmeyer RW, Gurny R, Doelker E, Buri, P, Peppas NA: Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 1983; 15:25 – 35.
Ozturk SS, Palsson BO, Donohoe B, Dressman: Kinetics of release form enteric-coated tablets. J Pharm Res 1988; 5:550-565.
Moore JW, Flanner HH: Mathematical comparison of dissolution profiles. Pharma Tech. 1996; 20:64 – 74.
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Copyright (c) 2016 Zahid Zaheer, Furquan Nazimuddin Khan, Sarfaraz Khan, Moizul Hasan, Obaid Shaikh, Raheel Khan, Zeeshan Khan
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