Dissolution profile evaluation of selected brands of amoxicillin-clavulanate potassium 625 mg tablets retailed in Hawassa town, Sidama Regional State, Ethiopia

Abstract

Poor quality amoxicillin-clavulanate potassium tablets have been recently discovered in generic drugs related to Augmentin-like medicines containing amoxicillin and clavulanic acid, as well as its derivatives containing falsified active ingredients. One of the most important dosage form characteristics are a detailed active pharmaceutical ingredients dissolution release profile evaluation obtained through dissolution testing. The dissolution test is used in the development of both brand-name and generic drugs. Prior to beginning bioequivalence studies, it is critical to compare the dissolution profiles of various pharmaceutical products. As a result, dissolution is a critical quality control parameter for drugs because it has a direct impact on absorption of pharmaceutical products. Dissolution profile evaluation of seven brands of amoxicillin-clavulanate potassium tablets is retailed in Hawassa town, Sidama Regional State, Ethiopia. The seven brands of amoxicillin-clavulanate potassium tablets were collected from Hawassa town, Sidama Regional State, Ethiopia. The dissolution study was conducted as per USP40-NF35. Then, the dissolution profile test results were compared by one-way ANOVA Dunnett’s test, model independent, and model dependent method. All of the included brand tablets complied with a single-point dissolution study specification. All brand tablets had similar dissolution profiles (p > 0.05), difference factor (f1) < 15%, and dissolution efficiency $$(\le 10\varvec{\%}$$ ). However, the f2 (similarity factor) value justifies that all brand tablets were not within USFDA specification ( $$\ge$$ 50%). The evaluated brands followed the Korsemeyer-Peppas followed by the Weibull curve models. All brand tablets passed the single point USP dissolution specification and the USFDA therapeutic interchangeability guideline. The similarity factor (f2), on the other hand, confirmed that none of the tested brand tablets were interchangeable with the innovator product. Therefore, researchers, national medicine regulatory bodies, and the manufacturer should conduct a properly designed dissolution test as proof of an in vitro bioequivalence study supported by in vivo bioavailability data. Dissolution profile evaluation of seven brands of amoxicillin-clavulanate potassium tablets retailed in Hawassa town, Sidama Regional State, Ethiopia. Why was the study done? Ever since a medicine must dissolve before it can be absorbed. Because the rate at which a drug dissolves from a dosage form generally influences the rate and amount of absorption. The Food and Drug Administration (FDA) should recommend that amoxicillin and clavulanate potassium are well absorbed from the gastrointestinal tract after oral administration of Augmentin with no significant difference in absorption after oral administration. When given orally, drugs with slow dissolution rates have intermittent and inadequate absorption, resulting in limited bioavailability. Aside from that, when a significant portion of the medicine fails to dissolve, only a tiny amount of active pharmaceutical ingredients (API) is available for absorption into the systemic circulation, resulting in the failure to produce the targeted therapeutic effect. The unabsorbed portion of the drug, on the other hand, causes the drug’s associated side effects. What did the researchers do? The researchers attempted to evaluate and compare the dissolution profiles of the different brands of amoxicillin-clavulanic acid collected from Hawassa town pharmaceutical market to determine the percentage drug release, the mechanism of drug release from the dosage form, and the bioequivalence status of the various brands included in the study. The researcher also attempts to examine dissolution challenges and provide scientific solutions to avoid them in the pharmaceutical environment in the future. What did the researchers find? The study endeavored to assess the seven brands of amoxicillin-clavulanate potassium tablets collected from the Hawassa town pharmaceutical market. All of the included brand tablets complied with a single-point dissolution study specification. All brand tablets had similar dissolution profiles (p > 0.05), difference factor (f1) < 15%, and dissolution efficiency $$(\le 10\varvec{\%}$$ ). However, the f2 (similarity factor) value justify that all brand tablets were not within USFDA specification ( $$\ge$$ 50%). The evaluated brands followed the Korsemeyer-Peppas followed by Weibull curve approaches. Furthermore, dissolution efficiency was considered to ascertain the interchangeability of all products with innovator product. All tested brands were pharmaceutically equivalent to the innovator product (AC001), with a dissolution efficiency value within ± 10%. The mean dissolution time (MDT) determined from accumulative curves of dissolved as a function of time revealed that brand code AC004 (1.3) had the smallest MDT while brand code AC007 (8.8) had the longest MDT from the tested amoxicillin brands, and brand code AC003 (1.02), and AC005 (1.03) had the smallest MDT while brands code AC001 (99.8) had the longest MDT from the tested clavulanate potassium brands. What do the findings mean? The study has identified some important quality control parameters for dissolution profile establishment during manufacturing of the pharmaceuticals for clinical purposes and market authorization. From a bioequivalence point of view, fit factors, mean dissolution time, and dissolution efficiency are not identical for the same dosage form that is produced in different brand forms from different manufacturing companies. Dissolution profile evaluation served as the foundational quality criteria for comprehending the product quality attributes because it was related to the medications’ bioavailability. It aims to offer general suggestions for dissolution testing, strategies for establishing dissolution specifications related to the biopharmaceutical’s properties of the drug substance, statistical techniques for comparing dissolution profiles, and a procedure to assist in determining when dissolution testing is sufficient to grant a waiver for an in vivo bioequivalence study.