Bioequivalence trials for the approval of generic drugs in Saudi Arabia: a descriptive analysis of design aspects.

BACKGROUND: This retrospective analysis aimed to comprehensively review the design and regulatory aspects of bioequivalence trials submitted to the Saudi Food and Drug Authority (SFDA) since 2017. METHODS: This was a retrospective, comprehensive analysis study. The Data extracted from the SFDA bioequivalence assessment reports were analyzed for reviewing the overall design and regulatory aspects of the successful bioequivalence trials, exploring the impact of the coefficient of variation of within-subject variability (CVw) on some design aspects, and providing an in-depth assessment of bioequivalence trial submissions that were deemed insufficient in demonstrating bioequivalence. RESULTS: A total of 590 bioequivalence trials were included of which 521 demonstrated bioequivalence (440 single active pharmaceutical ingredients [APIs] and 81 fixed combinations). Most of the successful trials were for cardiovascular drugs (84 out of 521 [16.1%]), and the 2 × 2 crossover design was used in 455 (87.3%) trials. The sample size tended to increase with the increase in the CVw in trials of single APIs. Biopharmaceutics Classification System Class II and IV drugs accounted for the majority of highly variable drugs (58 out of 82 [70.7%]) in the study. Most of the 51 rejected trials were rejected due to concerns related to the study center (n = 21 [41.2%]). CONCLUSION: This comprehensive analysis provides valuable insights into the regulatory and design aspects of bioequivalence trials and can inform future research and assist in identifying opportunities for improvement in conducting bioequivalence trials in Saudi Arabia.

Vision of bacterial ghosts as drug carriers mandates accepting the effect of cell membrane on drug loading.

The use of bacterial ghosts (BGs) for drug delivery is an extremely fascinating perspective especially with the inherited efficient target-ability to specialized tissues. Trafficking of drug molecules across the outer membrane of Gram-negative bacteria are important to be understood for both loading (influx) and drug release (efflux). In this study, Escherichia coli (E. coli) BGs were prepared using modified protocol sponge-like reduced protocol (SLRP) which was used for loading of doxorubicin (DOX). First time in the literature, different possible factors affecting DOX loading from BGs were examined in this study. These factors including drug concentration, temperature, pH gradient, incubation time and tonicity, are proposed to effect on drug loading into E. coli BGs. Results of optimum effect from accompanied factors were found to be 10 mg/mL as DOX concentration at pH 6 with tonicity of 0.7% incubated overnight at 4 °C. After gather all factors, the amount of DOX loaded inside the BGs was recorded as 37.58%. The in vitro release studies of DOX loaded BGs over time showed a burst initial release rate of 26.75% at the first 12 h followed by a period of sustained release lasting for 16 days to give maximum release rate of 58.04%. Remarkably, DOX loaded in BG showed more apoptosis (55%) than control and DOX solution. Overall, the results indicated the presence of some important factors to be controlled when loading drugs into BGs. Also, data showed the future possibility of utilizing BGs to deliver DOX to colon cancer cells.