Pharmacokinetics and bioequivalence assessment of optimized directly compressible Aceclofenac (100 mg) tablet formulation in healthy human subjects

• Published in: PloS one Vol. 15; no. 9; p. e0238951
• Main Authors: Bushra, Rabia, Shoaib, Muhammad Harris, Ali, Huma, Ghayas, Sana
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 08.09.2020; Public Library of Science (PLoS)
• Subjects: Acetonitrile; Analysis; Arthritis; Bioequivalence; Biology and Life Sciences; Compressibility; Computer and Information Sciences; Cost control; Deionization; Dosage and administration; Drug dosages; Engineering and Technology; Enzymes; Health sciences; High-performance liquid chromatography; Human subjects; Linearity; Liquid chromatography; Mathematical analysis; Medicine and Health Sciences; Nonsteroidal anti-inflammatory agents; Oral administration; Parameters; Pharmaceutical sciences; Pharmacokinetics; Pharmacology; Pharmacy; Physical Sciences; Product development; Research and Analysis Methods; Smoking; Variance analysis; Pakistan; United Kingdom > UK; United States > US; Japan; England; Karachi Pakistan; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0238951

The aim of the study was to determine the various pharmacokinetic parameters of the newly developed cost-effective aceclofenac 100 mg tablet formulation (F-15) and to establish the bioequivalence against the marketed brand (ACEMED). Both products (test and reference) were given to 12 healthy non-smokers male subjects with overnight fasting of >10hr. The study was a randomized, single-dose, open-label, two sequence, and two treatment crossover design, with a washout period of 2 weeks. Blood samples (5 mL) from the human subjects were collected before (0 hr) and after drug administration at 13different time points (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12 and 18 hrs). The drug plasma concentration was analyzed by a validated RP-HPLC method using a solvent system containing acetonitrile and deionized water (60:40% v/v). Linearity was found to be 0.999 over the drug concentration range of 50[mu]g/mL to 0.05[mu]g/mL with LLOQ and LOD of 0.05[mu]g/mL and 0.025[mu]g/mL respectively. Non-compartmental pharmacokinetic analysis was performed using Kinetica.sup.® (ver. 5.1) software. Using the log-transformed data C.sub.max, AUC.sub.0-t, AUC.sub.0-[infinity], AUMC.sub.tot, and MRT were calculated. The C.sub.max of the test and brand was found to be 8.629±1.251[mu]g/mL and 8.478±0.913[mu]g/mL. The AUC.sub.0-t and AUC.sub.0-[infinity] of the test and the reference were computed to be 20.890 ±2.2021[mu]g/mL.h, 23.272 ±1.914 [mu]g/mL.h and 19.850 ±2.911 [mu]g/mL.h, 22.890 ± 2.110 [mu]g/mL.h correspondingly. Two-way analysis of variance (ANOVA) test and two one-sided t-test (p>0.05; non-significant) were applied to assess the variation in the period, sequence, subjects, and treatment. Geometric mean ratios for above mentioned pharmacokinetic parameters of reference/test were found within the acceptable FDA limits of 80-125% using 90% CI. There was no inter and intrasubject variation (p> 0.05) that was observed. Therefore, the directly compressible aceclofenac (100 mg) test formulation and the commercial reference tablets were declared to be biosimilar.