Dissolution Testing Combined With Computer Simulation Technology To Evaluate The Bioequivalence Of Domestic β-lactam Antibiotic

Re-evaluation of bioequivalence of generic drugs is one of the key research focuscurrently，and bioequivalence may be affected by the changes of drug prescription andpreparation technology. As a means to ensure consistency of the therapeuticperformance of drug products, clinical bioequivalence has been widely accepted as agold standard test. In vitro dissolution testing based on the theory of the BCS is thebest alternative to in vivo bioequivalence study.The Biopharmaceutical Classification System (BCS) guidance issued by theFDA allows waivers for in vivo bioavailability and bioequivalence studies forimmediate-release(IR) solid oral dosage forms only for BCS class I drugs. However,both the WHO and the EMA extend biowaivers to some class III drug compounds.Most β-lactam antibiotics oral preparations belong to BCS class III drugs with highsolubility and low permeability, their permeability is the rate-limiting step for oraldrug absorption. If the drug can be quickly dissolved in physiological environments,they behave would more similarly to an oral solution in vivo.In this article, the different dissolution methods were used to investigate thedissolution profiles of domestic amoxicillin capsules and cefdinir capsules in differentdissolution medias, and the absorption behavior of the drugs with different releaserates in the gastrointestinal tract was predicted by Gastro PlusTM. The results ofdissolution test show that domestic amoxicillin capsules have different dissolutioncharacteristics in vitro: It can be divided into3types in four different dissolutionmediums by the conventional dissolution method and2types by the flow-through cellmethod. The behave of domestic cefdinir capsules in four different dissolutionmediums were faster than the reference capsule recorded in Japanese Orange Book,and more similarly to the reference granules. The predicted results of Gastro PlusTMshow that amoxicillin capsules and cefdinir capsules regard to the release rates up to45min (T85%=45min) were having a satisfied bioequivalence with the oral solutionaccording to the Cmaxand AUC. The computer simulation indicated that domesticamoxicillin capsules with different dissolution characteristics were probablybioequivalent each other, and domestic cefdinir capsules probably were not bioequivalent with the reference capsule recorded in Japanese Orange Book, but werebioequivalent with the reference granules, and they all were available.