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

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.

Download the full article here: Formulation of Chewable Tablets Containing Carbamazepine-cyclodextrin Inclusion Complex and F-Melt Disintegration Excipient. The Mathematical Modeling of the Release Kinetics of Carbamazepine

or continue reading here: Musuc, A.M.; Anuta, V.; Atkinson, I.; Sarbu, I.; Popa, V.T.; Munteanu, C.; Mircioiu, C.; Ozon, E.A.; Nitulescu, G.M.; Mitu, M.A. 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 2021, 13, 915. https://doi.org/10.3390/pharmaceutics13060915

Conclusions
The properties of a novel inclusion complex of CBZ and β-CD were investigated as a promising candidate for the preparation of orodispersible tablets. The studied inclusion complex was obtained in a molar ratio of 1:1, using the kneading method of complexation, in a solid state. For comparison, a physical mixture between CBZ and β-CD, in the same molar ratio, was prepared and analyzed. The SEM images of the complex show aggregation into irregularly shaped more amorphous particles in which the morphology of both components has disappeared. This remarkable change indicates the formation of a binary inclusion complex between CBZ and β-CD. This is confirmed by FTIR, XRD and thermal analysis investigations. The formation of the CBZ-β-CD inclusion complex results in important modifications of the pharmacological properties (solubility, absorbability, and consequently bioavailability) of the active ingredient. These modifications may have a significant impact on the biological effects of the drug. Therefore, the natural development of this study was the preparation and characterization of several formulations of orodispersible tablets containing this new CBZ-β-CD inclusion complex. Tablet formulations that included the CBZ-CD complex and the super-disintegrant F-Melt® release CBZ faster compared to commercial CBZ Tegretol tablets. The kinetic release of total carbamazepine from tablets containing CBZ-CD and super-disintegrant F-Melt, in both SS and LSS, follows two stages: (i) a burst release in the initial minutes and (ii) a slower release at different time intervals up to 60 min. The release in the second phase is well described by the Higuchi and Peppas models, which support a diffusion-controlled release combined with some phenomena of swelling and relaxation of the matrix generated by the crospovidone component of the F-Melt excipient.