In Vitro
Bioequivalence
for complex
generics

GVK BIO offers rapid and cost-effective establishment of Bioequivalence of complex generics:

For locally acting compounds in gastrointestinal tract such as bile acid and phosphate binders by USFDA approved In vitro methods – In vitro binding studies.



In vitro binding studies:

Locally acting drugs such as phosphate binders for chronic renal failure and bile acid binders for hypercholesterolemia gets released in the gastrointestinal environment which are not absorbed into the systemic circulation, binds with phosphate and bile acids to form insoluble complexes in the intestine and excreted through the faeces.

Sucralfate suspension/tablet, an anti-ulcer drug adsorbs bile acids, adsorbs and inhibits pepsin, and seals of the wound by binding to exudate proteins.

Conventional clinical BA/BE studies do not allow to characterize the bioequivalence of locally acting drugs. Hence, FDA has developed a set of In vitro BE guidelines for bile acid and phosphate binding drugs, and sucralfate to compare the rate and extent of binding between Test and Reference formulations for bioequivalence establishment.

Kinetic binding study:

This study is conducted to characterize the maximum (saturation) binding of bile acids or phosphate to the test and innovator formulation with respect to time. This study is a support to the pivotal equilibrium binding study.

Equilibrium binding study:

The equilibrium binding study characterize Langmuir’s binding constants such as affinity constant (K1) and capacity constant (K2) for Test and Reference formulations. Bioequivalence is established between Test and Reference formulation based on K2 with an appropriate confidence interval.

Sequential steps involved in design and conduct of in vitro binding studies

  • Method development and validation of bile acids/phosphate/Human Serum Albumin (HSA) or Bovine Serum Albumin (BSA) using HPLC/IC/ICP-MS as per USFDA published bioanalytical guidelines
  • Kinetic binding study is conducted for Test and Reference formulations with bile acids/phosphate/HSA or BSA concentrations and pH variation resembling the gastrointestinal pH. Free bile acids/phosphate/HSA or BSA concentration is determined and bound concentration is computed. Saturation binding with respect to time and binding similarity between test and reference formulation is characterized
  • Equilibrium binding study for test and reference formulations with appropriate bile acids/phosphate/HSA or BSA ranging across 8 different concentrations and pH variations resembling the gastrointestinal pH. Free bile acids/phosphate/HSA or BSA concentration is determined and bound concentration is computed to calculate Langmuir adsorption constants: K1 and K2
  • Bioequivalence between test and reference formulation is determined based on the capacity constant (K2)

Brochure

BCS-based In vitro Biowaiver

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Whitepaper

Developability Assessment of Small Molecules

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