Formulation and Evaluation of Mouth Dissolving Tablets of Tramadol Hydrochloride

摘要

Purpose: To prepare, and evaluate in vitro and in vivo tramadol hydrochloride mouth dissolving tablets (MDT). Methods: Tramadol HCl MDT were prepared by direct compression using Pharmaburst as co- processed excipient and compared with a reference product (Rybix ODT, 50 mg). Physicochemical parameters including hardness, friability, weight variation, disintegration time and dissolution studies were determined for all the formulations. In-vivo studies were performed for the optimized formulation (F13), using as reference, a commercial product (Trambax IR, 50 mg), by a two-way crossover design under fasting conditions on eight healthy adult human subjects. Drug-plasma concentrations obtained from the bioequivalence study for test and reference products were analyzed in each subject by high performance liquid chromatography (HPLC), and basic pharmacokinetic parameters, including C_max, T_max, AUC_0-t, AUC_0-∞, t_1?2 and λ_z, were calculated. Results: The tablet formulation prepared with Pharmaburst (F13) showed good flow properties, low disintegration time (15 s) and improved drug release (99 % at 30 min) compared with those of the reference product (88 % at 30 min) and passed 6 months accelerated stability test. Bioequivalence of the test product with that of the reference product under fasting conditions was established by computing 90 % confidence interval for the In-transformed pharmacokinetic parameters of C_max, AUC_0-t and AUC_0-∞ for tramadol. The 90 % confidence intervals for C_max were 99.70 - 114.31, for AUC_0-t 97.31 - 108.87 and for AUC_0-∞ 97.17 - 109.75. This confidence interval, in each case, was within bioequivalence criteria limit Conclusion: A suitable preparation of tramadol HCl MDT that is bioequivalent with a reference commercial product under fasting condition can be obtained when Pharmaburst is used as a disintegrant.