Therapeutic Equivalence of Multisource Drugs Assessed by In Vitro Dissolution Studies: Amoxicillin/Clavulanic Acid Tablets

The objective of this study was to determine the in vitro therapeutic equivalence of multisource amoxicillin/clavulanic acid (875 mg/125 mg) tablets to establish their interchangeability with the reference product. Six multisource products manufactured in Peru, Colombia, Argentina, Mexico, and India were analyzed. The reference product was Augmentin (875/125 mg) coated tablets (Smithkline Beecham LTD, UK) purchased from pharmaceutical establishments in Peru. Quality control and dissolution tests were performed. For dissolution tests, we use a validated ultraviolet -visible spectrophotometry method to determine the percentage of drugs released. Similarity factor (f2) analysis was used to establish therapeutic equivalence of the dissolution profiles, which were considered equivalent if f2 values were between 50 and 100. Amoxicillin content was 101.3% for the reference product and 97.0-105.0% for the multisource products. Clavulanic acid content was 104.0% for the reference and 99.0-109.0% for the multisource products. For amoxicillin, five of the six multisource products passed the f2 test at pH 4.5 and four passed the f2 test at pH 6.8. For clavulanic acid, five of the six multisource products passed the f2 test at pH 6.8. In conclusion, two out of six multisource amoxicillin/clavulanic acid tablets (manufactured in Peru and Colombia) are not interchangeable with the reference product based on comparison of in vitro drug release profiles.