Karbamazepinin polimorfları, katı dispersiyonları, mikrokristallendirilmesi ve bunlarla hazırlanan tabletlerin fiziko farmasötik özelliklerinin araştırılması

Abstract

- 132 - IX. SUMMARY Carbamazepin(CBZ) is one of the slightly soluble drugs and it shows polymorf izm.The microcrystals and solid dispersions of CBZ were prepared and some tablet formula tions were made from these microcrytals and solid dispet - sions by the direct compression method with Avicel PH 101, PVP-CL or Primogel and glidant-lubricants. In the case of the tablets of microcrystal CBZ and commercial CBZ.PVP or HPC and diluents are used in some formulations. In the case of the tablets formulation of solid dispersions of CBZ some diluents with Avicel are used to increase the porosity of the tablets. The physicopharmaceutical properties of these tablets were compared with each other. The influence of polymers on the solubility of CBZ were studied and the PVP was found to be the most effective polymer on the solubility of CBZ. The effect of polymers on the solubility increased as the temperature of the medium increased in the range of the temperature between 25-50 °C. Crosslinked PVP, which was used as the disintegrant, decreased the increasing effect of PVP and HPC on the solubility of CBZ. The CBZ microcrystals, which were produced through interaction with polymers and by sudden_decrease in temperature of the crystalization medium, showed different polymorfic modifications. These polymorphs were compared with the reference polymorphs, which were prepared in accordance with the lite-- 133 - rature, to identify them, by means of IR.DSC and X-ray powder diffractometry. The microcrystals, which were formed in the medium of methanol or ethanol with or without PVP.were found to be polymorf I; in the presence of PEG to be polymorf III and in the presence of HPMC or HPC to be pseudopolymorf dihidrate. The tablets, which were prepared from solid dispersion of the systems CBZ:PVP(1:1 and 1:3), did not disintegrate within 30 minutes. The dissolution rate of the tablet F5, which were prepared from commercial CBZ and PVP.were higher than those of other tablets and commercial tablets. The dissolution of the tablet which was prepared with the microcrystals which were formed in the presence of PVP.was lower than that of F5 although the particle size of the farmer was smaller than that of the latter. In friability tests, all the tablet formulations met the specifications, but the friability test results of two brands of commercial tablets was found to be too high in accordance with the specifications. Test results showed that the commercial CBZ was found to be polimoorf III, but the CBZ content of the commercial tablets was found to be turned to needle form or polymorf I and also the crystals growth occured during the tableting process. But two brands of commercial tablets didn't.

- 132 - IX. SUMMARY Carbamazepin(CBZ) is one of the slightly soluble drugs and it shows polymorf izm.The microcrystals and solid dispersions of CBZ were prepared and some tablet formula tions were made from these microcrytals and solid dispet - sions by the direct compression method with Avicel PH 101, PVP-CL or Primogel and glidant-lubricants. In the case of the tablets of microcrystal CBZ and commercial CBZ.PVP or HPC and diluents are used in some formulations. In the case of the tablets formulation of solid dispersions of CBZ some diluents with Avicel are used to increase the porosity of the tablets. The physicopharmaceutical properties of these tablets were compared with each other. The influence of polymers on the solubility of CBZ were studied and the PVP was found to be the most effective polymer on the solubility of CBZ. The effect of polymers on the solubility increased as the temperature of the medium increased in the range of the temperature between 25-50 °C. Crosslinked PVP, which was used as the disintegrant, decreased the increasing effect of PVP and HPC on the solubility of CBZ. The CBZ microcrystals, which were produced through interaction with polymers and by sudden_decrease in temperature of the crystalization medium, showed different polymorfic modifications. These polymorphs were compared with the reference polymorphs, which were prepared in accordance with the lite-- 133 - rature, to identify them, by means of IR.DSC and X-ray powder diffractometry. The microcrystals, which were formed in the medium of methanol or ethanol with or without PVP.were found to be polymorf I; in the presence of PEG to be polymorf III and in the presence of HPMC or HPC to be pseudopolymorf dihidrate. The tablets, which were prepared from solid dispersion of the systems CBZ:PVP(1:1 and 1:3), did not disintegrate within 30 minutes. The dissolution rate of the tablet F5, which were prepared from commercial CBZ and PVP.were higher than those of other tablets and commercial tablets. The dissolution of the tablet which was prepared with the microcrystals which were formed in the presence of PVP.was lower than that of F5 although the particle size of the farmer was smaller than that of the latter. In friability tests, all the tablet formulations met the specifications, but the friability test results of two brands of commercial tablets was found to be too high in accordance with the specifications. Test results showed that the commercial CBZ was found to be polimoorf III, but the CBZ content of the commercial tablets was found to be turned to needle form or polymorf I and also the crystals growth occured during the tableting process. But two brands of commercial tablets didn't.