Abstract
Objective: To perform an in vitro equivalence study of two doses of carbamazepine reference tablets sold in the local market under hydrodynamic conditions of USP Apparatus 4, a dissolution apparatus that better simulates the human gastrointestinal tract. Results were compared with dissolution official conditions using USP Apparatus 2.
 Methods: Dissolution profiles of both formulations were carried out with an automated USP Apparatus 2 at 75 rpm and 900 ml of dissolution medium. USP Apparatus 4 with laminar flow at 16 ml/min and 22.6 mm cells were used. 1% lauryl sulfate aqueous solution at 37.0±0.5 °C was used as dissolution medium. Spectrophotometric determination of drug at 285 nm was carried out during 60 min. Dissolution profiles were compared with model-independent and-dependent approaches.
 Results: When comparing dissolution profiles of low vs. high dose similar profiles were found (f2>50) in each dissolution apparatus, however, when the same dose was compared, USP 2 vs. USP 4, opposite results were obtained. Comparison of mean dissolution time and dissolution efficiency data corroborates these results. Weibull function was the best mathematical model that described the in vitro dissolution performance of carbamazepine. No significant differences were found in Td values (low vs. high dose) but opposite results were also found with USP 2 vs. USP 4.
 Conclusion: Equivalent dissolution performance of two doses of carbamazepine reference tablets were found in each USP dissolution apparatus. The main problem identified in this comparative study is the low dissolution rate and extent found with USP Apparatus 4. More research on this field is necessary for all available doses of reference drug products since the quality of generic formulations depends on the quality of references.
Highlights
Dissolution test is an important tool to ensure lot-to-lot good quality and after some manufacture, changes as well as for determination of interchangeability among generic formulations
The study was carried out with 1% sodium lauryl sulfate aqueous solution as dissolution medium. If this performance is observed with dissolution media of physiological relevance it is possible to suggest waiver of in vivo studies for lower carbamazepine dose since bioavailability will be proportional to the highest dose. More research on this field is necessary for all available doses of reference drug products since the quality of generic formulations depends on the quality of references
Similar dissolution performance of two doses of carbamazepine reference tablets was found in each United States Pharmacopoeia (USP) dissolution apparatus used
Summary
Dissolution test is an important tool to ensure lot-to-lot good quality and after some manufacture, changes as well as for determination of interchangeability among generic formulations. These formulations have the same pharmacological effect with the benefit of lower costs for patients and hospitals. Due to the high cost of bioequivalence studies and information of Biopharmaceutics Classification System (BCS) about solubility and permeability of some drugs, Guidelines for Industry-based on BCS have established criteria by which bioequivalence studies can be replaced by in vitro dissolution studies [1]. Some biowaiver monographs have been published for class I and III drugs (high solubility drugs) [3] but for its physicochemical and clinical characteristics, no biowaiver monograph has been published for carbamazepine
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