Bioequivalence of Final Tablet Formulation and Research Tablet Formulation of Eslicarbazepine Acetate in Healthy Volunteers

Abstract

To investigate the bioequivalence of the final tablet formulation of eslicarbazepine acetate (ESL) and the tablet formulation used in pivotal clinical studies.Methods: Single centre (Algorithme Pharma, Quebec, Canada) study consisting of three single-dose, randomized, two-way crossover sub-studies in healthy subjects.In each sub-study (n=20), the bioavailability of BIA 2-005 (ESL active metabolite) following a given ESL tablet strength (400 mg, 600 mg or 800 mg) of the final formulation (Test) was compared with the corresponding tablet strength of the research formulation (Reference), under fasting conditions. The statistical method for testing bioequivalence was based upon the 90% confidence interval (90%CI) for the Test/Reference geometric mean ratio (GMR) for C max , AUC 0-t and AUC 0-∞ . Bioequivalence was to be assumed when the 90%CI fell within the recommended acceptance interval 80.00%; 125.00%. Results:The Test/Reference GMR and 90%CI for BIA 2-005 were as follows: 400 mg tablets -105.37% (99.57%; 111.52%), 102.83 (99.19%; 106.61%) and 102.83% (99.13%; 106.66%) for C max , AUC 0-t and AUC 0-∞ , respectively; 600 mg tablets -102.65% (97.27%; 108.33%), 102.40% (99.00%; 105.93%) and 102.38% (98.97%; 105.90%) for C max , AUC 0-t and AUC 0-∞ , respectively; 800 mg tablets -104.16% (95.44%; 113.67%), 100.34% (97.85%; 102.90%) and 99.88% (97.65%; 102.16%) for C max , AUC 0-t and AUC 0-∞ , respectively. Conclusion:The 90%CI of all pharmacokinetic parameters of interest (C max , AUC 0-t , and AUC 0-∞ ) fell within the acceptance range of 80.00%; 125.00%. Therefore, bioequivalence of the final tablet formulation and the tablet formulation used in the pivotal clinical trials of ESL has been demonstrated.

Role of Pharmacokinetic Studies in Drug Discovery

“…Typically [11,12] if two formulations are to be compared, a two-period, twosequence crossover design is the design of choice with the two phases of treatment separated by an adequate washout period which should ideally be equal to or more than five half life's of the moieties to be measured. For single formulation studies a single-centre, single dose, randomized, open labeled, cross-over study is the design of choice [13][14][15].…”

Recent Trends in Analytical Techniques for the Development of Pharmaceutical Drugs

“…• Some liquid chromatographic (LC) methods for determination of milnacipran combined with other antidepressants in human plasma have already been published [47][48][49][50][51]. A micellar electrokinetic capillary chromatographic method was developed for separation and determination of antidepressants and their metabolites in biological fluids [52] and LC enantioseparation of milnacipran was investigated on different cellulose-based chiral stationary phases [53].…”

Role of Novel Hole Technology in Fast Dissolving Tablets

“…Post compression parameters: All the prepared tablets were subjected to various physical characteristics like Crushing strength, Friability, Thickness, Diameter, Hole depth, Disintegration time, Wetting time, Weight variation, Drug content [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35].…”