In Vitro dissolution similarity as a surrogate for in Vivo bioavailability and therapeutic equivalence

Abstract

Generic immediate-release solid oral dosage forms containing BCS Class I and III drugs that have similar in vitro dissolution profiles might receive market authorization without in vivo bioequivalence testing. The objective was to investigate whether the different immediate-release generic products containing BCS Class I drugs (fluoxetine and linezolid) and a Class III drug (fluconazole) fulfill the requirements of 85% or more drug release in 15 or 30 min in all three buffers (pH 1.2, pH 4.5, and pH 6.8) using in vitro dissolution testing in accordance with WHO requirements. The dissolution profiles were compared statistically to the relevant reference product by calculating the fit factors (f1 and f2), dissolution efficiencies, and mean dissolution time. The amount of drug dissolved in all dissolution media was determined by a validated UV spectrophotometric method. All investigated products of fluoxetine and linezolid met the biowaiver criteria for BCS Class I drugs and would be considered in vitro equivalent. Only one product of the BCS Class III drug fluconazole did not pass the WHO guideline for in vitro equivalence; however, all the products released fluconazole satisfactorily, with at least 80% dissolved within 30 min. Pharmaceutical equivalence together with in vitro dissolution similarity could be considered suitable to ensure in vivo bioequivalence and, hence, therapeutic equivalence of BCS Class I and III drugs. Not all generic products containing the same drug (BCS Class I or III) in similar strengths and dosage forms are in vitro equivalent.