DISSOLUTION BEHAVIOR OF CARBAMAZEPINE SUSPENSIONS USING THE USP DISSOLUTION APPARATUS 2 AND THE FLOW-THROUGH CELL METHOD WITH SIMULATED GI FLUIDS


Jose Raul Medina, Erik Aguilar, Marcela Hurtado

Abstract


Objective: To characterize the dissolution behaviour of carbamazepine generic suspensions using the USP Dissolution Apparatus 2 and the flow-through cell method with simulated gastrointestinal fluids as dissolution media.

Methods: Tegretol® suspension and two generic formulations were tested. Dissolution studies were performed using the USP Apparatus 2 (75 rpm and 900 ml of dissolution medium) and the flow-through cell method (laminar flow at 16 ml/min). Simulated gastric fluid (SGF) (with and without pepsin) and simulated intestinal fluid (SIF) (without pancreatin) at 37.0±0.5 °C, was used as dissolution media. The quantity of dissolved carbamazepine was determined at 5 min intervals until reaching 60 min, at 285 nm. Percentage dissolved at 60 min, mean dissolution time, dissolution efficiency values (model-independent parameters), as well as t50% and t63.2% were calculated (model-dependent parameters). Values for all parameters were compared between the reference and generic formulations using one-way analysis of variance (ANOVA) following a Dunnett’s multiple comparison test. Dissolution data were also fitted to different fit models.

Results: Since the first sampling time, the reference product had reached 100% of drug dissolved, which was determined using USP Apparatus 2. Nevertheless, significant differences in the three model-independent parameters of generic products were found (*P<0.05). Dissolution data obtained with the paddle apparatus were fitted to different kinetic equations; however, using the flow-through cell method and SIF without pancreatin, the three drug products were fitted to the same kinetic model (Gompertz). With ANOVA-based comparisons and the flow-through cell method, significant differences were found in dissolution data of generic product A versus reference at all sampling times (*P<0.05). The flow-through cell method and SGF with pepsin were the best options to discriminate among dissolution profiles.

Conclusion: The flow-through cell method seems to be an adequate dissolution apparatus to characterize in vitrodissolution performance of Class II drugs manufactured as suspensions. For carbamazepine suspensions, SGF and laminar flow at 16 ml/min were the most appropriate conditions to discriminate among generic formulations. Given the physicochemical characteristics of carbamazepine and the environment in which the drug products were tested, these differences could be of clinical relevance.

 


Keywords


Carbamazepine, Flow-through cell apparatus, Simulated gastrointestinal fluids, Suspensions, USP Apparatus 2

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About this article

Title

DISSOLUTION BEHAVIOR OF CARBAMAZEPINE SUSPENSIONS USING THE USP DISSOLUTION APPARATUS 2 AND THE FLOW-THROUGH CELL METHOD WITH SIMULATED GI FLUIDS

Keywords

Carbamazepine, Flow-through cell apparatus, Simulated gastrointestinal fluids, Suspensions, USP Apparatus 2

DOI

10.22159/ijpps.2017v9i11.21201

Date

01-11-2017

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 9, Issue 11, 2017 Page: 111-116

Online ISSN

0975-1491

Statistics

34 Views | 7 Downloads

Authors & Affiliations

Jose Raul Medina
Departamento Sistemas Biologicos, Universidad Autonoma Metropolitana-Xochimilco, Mexico City, Mexico
Mexico

Erik Aguilar
Departamento Sistemas Biologicos, Universidad Autonoma Metropolitana-Xochimilco, Mexico City, Mexico
Mexico

Marcela Hurtado
Departamento Sistemas Biologicos, Universidad Autonoma Metropolitana-Xochimilco, Mexico City, Mexico
Mexico


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