Investigation of variability of primary materials on the intrinsic dissolution behavior of carbamazepine

摘要: Carbamazepine (CBZ) is a poorly water soluble drug, classified as class II according to the Biopharmaceutics Classification System and exhibits at least four polymorphic forms dihydrate. CBZ polymorphs have different crystal structures exhibit melting points, chemical reactivity, solubility compactibility, all of which can contribute differences in their bioavailability. In aqueous solution, anhydrous has ability convert dihydrate form, kinetic that conversion important for dissolution drug. Commercially available raw material contain mixture well amorphous parts. The aim present study was investigate effect variability commercially samples on intrinsic behavior order recommend strategy maintain product quality by monitoring critical parameters bulk Therefore, extensive physical characterization nine from three sources carried out. Polymorphism (by X-ray powder diffraction XRPD Fourier transformation infrared - FTIR microspectroscopy), thermal differential scanning calorimetry DSC, hot stage microscopy HSM), particle size/particle size distribution, morphology, were investigated. results showed commercial exhibited same but led variation kinetics form therefore solubility. detected suggested be attributed variations manufacturing processes, such use solvents crystallization and/or grinding crystals final manufacture CBZ. Furthermore, disc rate (DIDR) tests conducted if DIDR test provide information about its form. For purpose, compacts pure prepared using Zwick tester. imbedded paraffin leaving only one side free exposed media. CBZ behavior. Moreover examined within sample shown high standard deviation. Intrinsic dissolution determined with scope calculate transition point of anhydrous each sample, found vary among the CBZs obtained between 15 25 minutes. Carbamazepine crystallized order to tested characterized DSC to confirm complete formation. It previously detected variations significantly reduced, nine samples had constant characteristics. When investigated on intrinsic behavior, deviation group of samples reduced dihydrates anhydrous CBZ did not exist anymore. Considering excipients influence phase its dihydrate binary mixtures (from sources) Fast Flo® lactose were this study. Mixtures ratios drug excipient were compacted porosity, disintegration time dissolution behavior produced studied. selected excipient no anhydrate conversion. As step study, it proposed examine the transition used predict model formulation. formulations were prepared direct compaction process CBZs Ludipress®, which were subsequently analyzed dissolution. turned out the amount dissolved after minutes (CBZ B > A > CBZ P) being identical event intrinsic dissolution test, meaning earliest P latest point. Therefore, valuable simple monitoring tool materials, detect of primary material, employed determination be used estimation