Various extended release carbamazepine (CBZ) formulations have been developed previously, in order to reduce the frequency of dosing in chronic therapy and to decrease the variability in drug plasma concentration. In the present study, the suitability of different grades of Gelucires (G, glyceride based excipients) to formulate CBZ extended release capsules by the application of semisolid matrix (SSM) filling capsule technology was investigated. The possible modification of CBZ release kinetics by using Gelucire blends or inclusion of hydrophilic additives in the SSM was studied. The effect of ageing on some selected formulations was also evaluated, using scanning electron microscopy and differential thermal analysis. Twenty-one capsule formulations were prepared and assessed for their release characteristics. The mechanism of drug release from the test formulations was studied. The following results were obtained: a) Release data could not be correlated to the melting point (mp) of Gelucires used, pointing to relative lipophilicity of the base as a more important determinant of drug release. Among Gelucire grades having melting points higher than 37 degrees C, the release rate proved to be highly dependent on the HLB value and matrix composition. b) CBZ release occurred by different mechanisms, including matrix disintegration, diffusion and or erosion depending on the vehicle employed. c) Zero order release profiles of CBZ were obtained from SSM-based on G50/13, G53/10 and their blends in ratios higher than 1:1 and G53/10 containing croscarmellose sodium. d) The ageing study revealed that these latter formulations, except those based on G50/13, also showed high dissolution stability during one year of shelf ageing. e) PVP, as a polymorphic transformation inhibitor, can be used to reduce the storage-induced changes of some grades of Gelucires. From the above data, it can be concluded that different grades of Gelucires and their blends as well as hydrophilic additives could be successfully used to formulate CBZ extended release SSM filled capsules with various release kinetics.
The aim of this study was to develop a dissolution medium for assessment of various carbamazepine (CBZ) formulations with different strengths. The design of a system inhibiting transformation of the anhydrous CBZ (CBZ A) to the dihydrate form (CBZ D), with minimum surface-active properties and suitable sink was investigated. The effect of pH, different concentrations of sodium lauryl sulphate (SLS), polyvinylpyrrolidone (PVP), and methyl cellulose (MC) on dissolution rate, solubility, dissolution solubility, and polymorphic transformation of CBZ was assessed. Solution-mediated transformation of CBZ A into CBZ D was monitored using optical microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry. Results showed that different strengths (100, 200, 400 mg) of the same CBZ tablet formulation exhibited different dissolution patterns, in 1% SLS (USP system). Such differences were reduced in 0.5% SLS solution which provided sufficient sink for up to 200 mg CBZ. It was also shown that solubility of CBZ A could not be detected in the media under study (water, SGF, SIF, and SLS solutions) due to its rapid transformation into CBZ D. The use of 3% PVP solution protected CBZ A from conversion for 75 min, while 0.01% MC completely inhibited the transformation up to 24 h. Therefore, a medium consisting of 0.5% SLS and 0.01% MC was selected. The medium provided: a) protection against transformation of CBZ A to CBZ D, b) increased solubility of CBZ A (204 mg % compared to 128 mg % of CBZ D in 0.5% SLS), c) suitable sink for up to 400 mg CBZ and d) overlapping dissolution profiles of various strengths of the same CBZ formulation. The suggested system may be a step in the way of solving CBZ dissolution problems that forced the USP to specify two similar dissolution tests with two different limits for conventional 200 mg CBZ tablets.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.