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Exploring a Bioequivalence Failure for Silodosin Products Due to Disintegrant Excipients
Isabel González-Álvarez1, Bárbara Sánchez-Dengra1, Raquel Rodriguez-Galvez1
1Engineering: Pharmacokinetics and Pharmaceutical Technology Area, Miguel Hernandez University, 03550 San Juan de Alicante, Spain.
Pharmaceutics
|December 23, 2022
Summary
Excipients can impact drug absorption, contrary to previous beliefs. This study found that specific disintegrants in silodosin formulations altered drug permeability, explaining bioequivalence failure.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery
- Bioavailability Studies
Background:
- Excipients were historically considered inert, but emerging evidence suggests they can influence drug absorption.
- Understanding excipient roles is crucial for successful drug formulation and bioequivalence.
Purpose of the Study:
- To investigate the reasons behind a bioequivalence failure between two silodosin formulations.
- To identify specific excipient effects on silodosin absorption and bioavailability.
Main Methods:
- Biopharmaceutics Classification System (BCS) classification of silodosin.
- In vitro dissolution testing under various conditions (pH, agitation speeds, apparatus).
- In vitro permeability studies and analysis of excipient impact on drug absorption.
Main Results:
- Dissolution tests at pH 4.5 and 6.8 using paddle apparatus detected formulation differences missed by basket methods.
- Specific disintegrants (Crospovidone, Povidone) in the test product, unlike the reference product's pregelatinized corn starch, altered silodosin permeability.
- Polyvinylpyrrolidone (PVP) derivatives were shown to increase silodosin absorption.
Conclusions:
- Excipients, particularly disintegrants like PVP derivatives, significantly affect silodosin permeability and absorption.
- The increased absorption due to PVP likely explains the higher Cmax observed in the bioequivalence study, leading to formulation failure.
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