Interchangeability between Multi-sources Orlistat Capsules: Could Pharmacodynamic study support similarity and dissimilarity factors?

Supervisor: 

Dr. Abdel Naser Zaid

Abstract :

Background: Orlistat is an irreversible inhibitor of lipase enzyme. As undigested triglycerides are not hydrolyzed and absorbed, the resulting caloric deficit may have a positive effect on weight control. Systemic absorption of the drug is therefore not needed for the activity. Accordingly, an alternative in vitro study (Pharmacodynamic) has been introduced for this drug as in vivobioavailability studies are irrelevant to the achievement of the product's intended purposes.

Objective: To develop a new validated HPLC method for the analysis of Orlistat and to assess the potency and equivalence of three Orlistat formulations using the pharmacodynamic method as a surrogate indicator of pharmaceutical interchangeability.

Method: A new HPLC method was developed for the analysis and dissolution studies of Orlistat in capsules. Similarity and dissimilarity factors (f₂ and f₁) were calculated. Measurement of pancreatic lipase activity conducted on three different capsule products Orlislim^®, Slimcare^®and Xenical^®, G1, G2, and the brand respectively. Porcine pancreatic lipase and p-nitrophenyl butyrate (PNPB) in pH 7.4 reaction buffer at 37ºC, substrate hydrolysis was monitored by absorbance changes at 410 nm. The test was repeated on six capsules of each product. The inhibition was expressed by the concentration of product which inhibits 50% of the activity of the pancreatic lipase (IC₅₀).

Results: The new analytical method was suitable for Orlistat analysis. The release of Orlistat was higher than 85% within 15 minutes. The values of IC₅₀ from the regression lines and equations were 6.14, 8.43, 7.80µg/ml for Orlislim^®_, Xenical^® and Slimcare^® respectively.

Conclusion: Pharmacodynamic studies through lipase inhibition could be used to support the in vitro dissolution to demonstrate interchangeability between generic and brand Orlistat capsules. In addition, it could be suggested as an alternative tool to BE study for Orlistat oral products.