Comparative in-vitro equivalence studies of some locally manufactured and imported generic BCS Class III drug products against their comparator counter products
| dc.contributor.advisor | Gebre-Mariam,Tsige(Prof.) | |
| dc.contributor.author | Nigussie,Tsegaye | |
| dc.date.accessioned | 2024-04-23T10:59:13Z | |
| dc.date.available | 2024-04-23T10:59:13Z | |
| dc.date.issued | 2023 | |
| dc.description.abstract | According to the Biopharmaceutical classification system (BCS), active pharmaceutical ingratiate (API) classified into four classes (BCS Class I-IV) based on aqueous solubility and intestinal permeability. BCS Class III medications are highly soluble and poorly permeable, and they are among the drug products that require documented evidence of bioequivalence study. In addition to the permeability problems, there may be differences between generic and innovator products in terms of the type, source, and quantity of ingredients, manufacturing method and process, and machinery used for production, and these factors can bring major differences in dissolution and bioavailability. The objective of this study was therefore to compare the in vitro equivalence of four locally manufactured and imported BCS Class III drug products, namely, Metoclopramide hydrochloride 10 mg tablets, Cloxacillin sodium 500 mg capsules, Metformin hydrochloride 500 mg tablets, and Enalapril maleate 5 mg tablets against their comparator counter products (MTF3, CLX3, MCP3, and ENA3), respectively. The selected drug products and their comparator counter products were purchased from retail pharmacies found in Addis Ababa, Ethiopia. For each drug product, physical properties such as weight uniformity, hardness, thickness, diameter, and friability were determined using appropriate equipment as per the USP monograph. The assay content and content uniformity for each drug product were also determined as per their respective procedures in the USP monograph and validated methods. In vitro dissolution profiles were performed according to monograph methods and validated methods, and in vitro drug release tests were also done to assess equivalence of the products investigated. The results of weight variation content uniformity, and assay content indicated that all the investigated drug products were within the pharmacopeia requirements. Similarly, all products investigated complied disintegration time tests (i.e., ≤ 30 min) of immediate- release drug products. Except for two generic products of metformin hydrochloride tablets MTF2 (62.66%±9.74), and MTF4 (78.71%±6.86), all the drug products included in this study fulfilled the acceptance criteria for dissolution (i.e., Q ≥ 80% at 30 min). The in-vitro equivalence of these products was assessed by statistical, model- independent, and mode-dependent methods. One generic products of metformin hydrochloride (MTF2) and all generic products of metoclopramide hydrochloride showed significant difference (p < 0.05) in dissolution profiles with comparator II products. Of the five generic products of metformin hydrochloride film coated tablets [MTF2 (32.88), MTF4 (39.80) and MTF6 (49.94)] and generic products of metoclopramide hydrochloride [MCP1 (37.04) and MCP2 (41.56)] failed to meet the f2 acceptance criteria. This means that these products are not interchangeable. However, cloxacillin sodium capsules and enalapril maleate tablets complied with the f2 > 50 acceptance criteria. In conclusion, this study showed that all the generic products of metformin hydrochloride tablets, metoclopramide hydrochloride tablets, enalapril maleate tablets, and cloxacillin sodium capsules complied the quality specifications of weight uniformity, hardness, friability, disintegration, and assay. Three generic products brands of metformin hydrochloride MTF2, MTF4, and MTF6, and both generic products brands of metoclopramide hydrochloride (MCP1 and MCP2) did not show in-vitro equivalence with their comparator products. All generic products of cloxacillin sodium capsules and enalapril maleate tablets included in this study met model independent fitting factor specifications, were statistically insignificant (P>0.05) in dissolution profiles and can be considered equivalent to their comparator counter product. | |
| dc.identifier.uri | https://etd.aau.edu.et/handle/123456789/2814 | |
| dc.language.iso | en_US | |
| dc.publisher | Addis Ababa University | |
| dc.subject | BCS Class III drugs | |
| dc.subject | Generic products | |
| dc.subject | Comparator pharmaceutical products | |
| dc.subject | In-vitro dissolution | |
| dc.subject | In-vitro equivalence | |
| dc.subject | Bioequivalence | |
| dc.title | Comparative in-vitro equivalence studies of some locally manufactured and imported generic BCS Class III drug products against their comparator counter products | |
| dc.type | Thesis |