Formulation of Chewable Tablets Containing Carbamazepine-β-cyclodextrin Inclusion Complex and F-Melt Disintegration Excipient. The Mathematical Modeling of the Release Kinetics of Carbamazepine

Pharmaceutics

Constantin Mircioiu¹  George Mihai Nitulescu²  Iulian Sarbu³  Mirela Adriana Mitu⁴  Emma Adriana Ozon⁴  Valentina Anuta⁵  Adina Magdalena Musuc⁶  Vlad Tudor Popa⁶  Cornel Munteanu⁶  Irina Atkinson⁶ 

[1] Department of Applied Mathematics and Biostatistics, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 020956 Bucharest, Romania;Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 020956 Bucharest, Romania;Department of Pharmaceutical Physics and Biophysics, Drug Industry and Pharmaceutical Biotechnologies, Faculty of Pharmacy, “TituMaiorescu” University, 004051 Bucharest, Romania;Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 020956 Bucharest, Romania;Department of Physical and Colloidal Chemistry, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 020956 Bucharest, Romania;“Ilie Murgulescu” Institute of Physical Chemistry, Romanian Academy, 202 Spl. Independentei, 060021 Bucharest, Romania;

关键词: carbamazepine;    β-cyclodextrin;    release kinetics;    inclusion complex;    F-Melt excipient;    chewable tablets;   

DOI  :  10.3390/pharmaceutics13060915

来源: DOAJ

【 摘 要 】

Due to its low solubility, carbamazepine (CBZ) exhibits slow and incomplete release in the gastrointestinal tract and, hence, variable pharmacokinetics and pharmacodynamic effect. Lots of methods have been devised to improve its solubility, the large number of proposed solutions being a sign that the problem is not yet satisfactorily solved. The persistent problem is that predictable release kinetics, an increased rate but within defined limits, are required to avoid high absorption variability. This paper presents a synthesis of a carbamazepine-β-cyclodextrin inclusion complex (CBZ-β-CD), the characterization of the physical mixture, CBZ, β-CD and the CBZ-β-CD inclusion complex using Fourier transform infrared spectroscopy, scanning electron microscopy, simultaneous thermal analysis and X-ray diffraction, formulation of chewable tablets, determination of the dissolution of carbamazepine in medium containing 1% sodium lauryl sulfate (LSS), and in simulated saliva (SS), mathematical modeling of release kinetics. The kinetics of total CBZ release from tablets containing CBZ-β-CD and super-disintegrant F-Melt in both SS and LSS followed two steps: a burst release in the first minutes and a slower release in intervals up to 60 min. The release in the second phase has been well described by the Higuchi and Peppas models, which advocate a controlled release by combined diffusion and with some phenomena of swelling and relaxation of the matrix generated by the crospovidone component of the F-Melt excipient.

【 授权许可】

Unknown