Investigation of the release of carbamazepine from polyvinyl pyrrolidone matrices processed using near-critical and super critical carbon dioxide
Introduction. The work embodied in this dissertation is a result of the continued effort of the study which was published previously by our group (Ugaonkar et al., 2007) and which is also documented in the M.S. Thesis, 2006, titled “The effect of n-scCO2 (near supercritical carbondioxide) on the crystallinity of carbamazepine”. The results prompted us to investigate the effect of supercritical carbon dioxide (scCO2) on the carbamazepine (CBZ)-polyvinylpyrrolidone (PVP) mixtures with an objective of enhancing the dissolution of CBZ from PVP 10,000 (10K) and 29,000 (29K) matrix. By the end of this investigation, we expected to determine the factors responsible for release of CBZ from PVP matrices. We conducted the partitioning studies of CBZ and PVP with the goal of understanding the major components that ultimately drive the CBZ release from PVP matrices.^ Methods. CBZ and PVPs were mixed in (1:1) w/w and subjected to scCO2 (4000 pi, 35°C, 45°C and 5200 psi, 45°C). An untreated counterpart from the same batch served as a control against which the measurements of the treated samples were made. The samples were characterized using powder X-ray diffraction (PXRD), differential scanning calorimtery (DSC), scanning electron microcopy (SEM), optical microscopy and fourier transform infrared spectroscopy (FTIR). For the partitioning studies, CBZ-PVPs 10K and 29K of 0.3mg each were mixed and placed in a high pressure optical cell. CO 2 was charged at 200 bar, at 35°C and 45°C and in-situ absorbance of CBZ was measured at 285 nm until an equilibrium was reached.^ Results and conclusions. On transitioning from n-scCO 2 to scCO2 processing states, further improvement in the dissolution of CBZ from 14.06 ± 1.78% to 29.42 ± 5.15% was observed for CBZ released from PVP 10K matrix but not from the PVP 29K matrix. CBZ partitioned more into PVP 29K compared to PVP 10K, but that did not translate into greater release of CBZ from PVP 29K matrix indicating that polymer properties such as the morphology and polymer dissolution itself dictates the process of CBZ dissolution from PVP matrices rather than dissolution due to the molecularly dispersed CBZ in PVP matrix which in turn plays a minor role. ^
Health Sciences, Pharmacy
"Investigation of the release of carbamazepine from polyvinyl pyrrolidone matrices processed using near-critical and super critical carbon dioxide"
Dissertations and Master's Theses (Campus Access).