Pharmacodynamic testing and new validated HPLC method to assess the interchangeability between multi-source orlistat
Abdel Naser Zaid1, Nihal Zohud1, Bushra E'layan1
1Department of Pharmacy.
Drug Design, Development and Therapy
|December 5, 2017
Summary
This study developed a new HPLC method and used lipase inhibition assays to demonstrate the interchangeability of orlistat capsules. Pharmacodynamic testing offers a viable alternative to bioequivalence studies for orlistat formulations.
Area of Science:
- Pharmacology
- Analytical Chemistry
- Pharmaceutical Sciences
Background:
- Orlistat is an irreversible lipase inhibitor used for weight control by reducing calorie absorption.
- Its mechanism of action does not require systemic absorption, making in vivo bioavailability studies less relevant.
- In vitro pharmacodynamic studies offer an alternative for assessing drug efficacy.
Purpose of the Study:
- To develop and validate a high-performance liquid chromatography (HPLC) method for orlistat analysis.
- To evaluate the potency and equivalence of three orlistat formulations.
- To utilize pharmacodynamic lipase inhibition as a surrogate for pharmaceutical interchangeability.
Main Methods:
- A novel HPLC method was established for orlistat analysis and dissolution studies.
- Lipase inhibition assays were performed on three orlistat capsule formulations (Orlislim®, Slimcare®, Xenical®).
- Porcine pancreatic lipase inhibition was measured using p-nitrophenyl butyrate (PNPB) substrate at 37°C, determining the IC50 values.
Main Results:
- The developed HPLC method proved suitable for orlistat quantification.
- The IC50 values for Orlislim®, Xenical®, and Slimcare® were determined to be 6.14 μg/mL, 7.80 μg/mL, and 8.43 μg/mL, respectively.
- These results indicate comparable lipase inhibition across the tested formulations.
Conclusions:
- In vitro pharmacodynamic lipase inhibition studies can support dissolution data to demonstrate orlistat capsule interchangeability.
- This approach provides a potential alternative to traditional bioequivalence studies for oral orlistat products.
- The findings support the use of in vitro methods for assessing pharmaceutical equivalence of orlistat generics.
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