Pharmaceutical and Clinical Assessment of Multi-source Tegretol Sold in Egypt

Abstract

across generic Narrow therapeutic index (NTI) medications compared to brands. However, little attention has been given to possible inequality within the same brand due to transportation and storage conditions, production site, manufacturing condition, and product specification requested by different countries. Market surveys has shown that Egypt is one of the countries suffering from this problem, which consequently augments the need for comparing and evaluating brand products marketed under the same brand name, manufactured in different countries under its own licensing trademark™ and sold in Egypt. This work studies the drug carbamazepine (CBZ) available in Egypt as Tegretol® tablets used as an oral first-line anti-epileptic drug (AED). Objectives: The present work investigate and evaluate the pharmaceutical quality and clinical efficacy of Tegretol®, obtained from Egypt and Saudi Arabia and being marketed and sold in Egypt from 2020 to 21. Methods: In-vitro quality testing included potency and uniformity of content tests performed according to USP 2019 monograph. Dissolution rates were also carried by adopting USP dissolution test for the drug. Studies of stability were adjusted at 25°C/65% RH, 45°C/75% RH and 10°C/15% RH. The clinical efficacy was studied by evaluating the pharmacokinetics parameters and blood sodium level during six months of therapy. Results: Variability between multisource Tegretol® brand products were ensured. Potency results and uniformity of content revealed statistically significant difference between Tegretol® sources. Also, variations in dissolution rates were recognized in both Tegretol® sources when dissolved in HCL/KCL, Acetate and Phosphate Buffer dissolution media. Dissimilarities were obtained for hardness and friability testing. Furthermore, a pharmacokinetically and pharmacodynamically inequivalence was ensured. Hence, hyponatremia was more prominent in patients receiving Saudi Arabian Tegretol® compared to patients taking Egyptian Tegretol®. Conclusion: Interchangeability between multi-source Tegretol brand products should be limited.