Comparative in vitro dissolution study of carbamazepine immediate-release products using the USP paddles method and the flow-through cell system

Abstract

Dissolution profiles of four carbamazepine immediate-release generic products (200 mg tablets) and the reference product Tegretol® were evaluated using the USP paddles method and an alternative method with the flow-through cell system, USP Apparatus 4. Under official conditions all products met the Q specification, dissolution profiles of generic products were similar to the dissolution profile of the reference product (f 2 > 50) and model-independent parameters showed non significant differences to the reference product except mean dissolution time for product A (p < 0.05). On the other hand, when the flow-through cell system was used, none of the products met the pharmacopeial specification at 15 min and product A did not reach dissolution criteria at 60 min, dissolution profiles of all generic products were not similar to the reference product profile (f 2 < 50) and all model-independent parameters showed significant differences compared to the reference product (p < 0.05). Weibull's model was more useful for adjusting the dissolution data of all products in both USP apparatuses and Td values showed significant differences compared to the reference product (p < 0.05) when USP Apparatus 4 was used. These results indicate that the proposed method, using the flow-through cell system, is more discriminative in evaluating both, rate and extent of carbamazepine dissolution process from immediate-release generic products.

In Vitro Release Studies of Carbamazepine Tablets and Benzoyl Metronidazole Suspensions Using the Flow-Through Cell Apparatus and Simulated Gastrointestinal Fluids

“…An adequate dissolution test allows differentiation between drug products before clinical problems occur. The flow-through cell method (16 ml/min) with 1.0% sodium lauryl sulphate aqueous solution as dissolution medium was reported to be more discriminative for carbamazepine generic products than the use of USP Apparatus 2 [31]. In another report, rapid dissolution was observed when several carbamazepine formulations were tested under official conditions (USP basket apparatus and 1.0% sodium lauryl sulphate aqueous solution); however, SIF showed better discriminative capability between drug products [32].…”

Design and In Vivo Anti-Inflammatory Effect of Ketoprofen Delayed Delivery Systems

“…Differences between the two apparatus may be explained by the different hydrodynamic conditions that characterize the flow-through cell system, where no agitation mechanisms occur and the dosage form is continuously exposed to a uniform laminar flow, similar to the natural environment of the gastrointestinal tract. 34,35 F20 performance may be explained by considering alginate pH-dependent solubility, zinc cross-linking properties, and high structural density of matrix in F20; beads did not swell or erode in SGF and still keep intact matrix, whereas in SIF (at pH 6.8) they started to swell and further erode due to the ion exchange. 36…”

The Evaluation of In Vitro Drug Dissolution of Commercially Available Oral Dosage Forms for Itraconazole in Gastrointestinal Simulator With Biorelevant Media

“…2 However, formulation development has often been misled when those formulations for low-soluble drugs are assessed in conventional in vitro dissolution tests using United States Pharmacopeia (USP) apparatus I and II. 3,4 It is because these dissolution tests use a constant fluid volume, pH, and buffer species, which are not physiologically relevant in human gastrointestinal (GI) tract. As a result, it is difficult to predict in vivo performance of oral drug products and to obtain good in vitroein vivo correlation.…”