Partitioning behavior of carbamazepine between supercritical carbon dioxide and polyvinylpyrrolidone using in situ spectroscopy

Purpose. Supercritical CO2 (scCO2) processing of drug/polymer mixtures is a favorable means of enhancing the aqueous dissolution rate of drugs that exhibit poor water solubility. However, the role of drug solubilization and its interaction with the polymer during processing on the extent and rate of dissolution has been ambiguous. In this study, we examine the solubility of carbamazepine (CBZ), a hydrophobic drug for treating epilepsy, in scCO2 and its partitioning into polyvinylpyrrolidone (PVP) in situ using the UV-vis spectroscopy. Methods. CBZ and physical mixtures of PVP-CBZ (10 and 29K MW) were prepared by mixing CBZ-PVP in the ratio of 1:1 (w/w). The samples were placed in a high-pressure optical cell and CO2 was introduced using an ISCO syringe pump. All the measurements were carried out isothermally (35oC and 45oC) and at a constant pressure of 200 bar. These are the equilibrium solubility conditions for CBZ determined apriori. The equilibrium absorbance of CBZ was used to calculate the partition coefficient (K). One-way ANOVA (α = 0.05) was performed on the K values, and the means were further compared using the Tukey-Kramer (HSD) test. Results. The partitioning of CBZ was highest in PVP 29K processed at 45oC (K = 14.8) whereas the least partitioning of CBZ was observed in PVP 10K processed at 35oC (K = 4.3). The partition coefficients for samples of PVP 10K-CBZ processed at 45oC and PVP 29K-CBZ processed at 35oC were equal at 10.0. The results indicate that an increase in the molecular weight of the polymers and rise in the processing temperature yields greater partitioning of CBZ. The supporting SEM studies show plasticization in PVP 10K samples and swelling in PVP 29K samples after CO2 processing. The results from particle size measurements showed a marked increase in the particle size of PVP 29K as compared to the PVP 10K. Conclusions. As temperature increases, the chain mobility of PVP increases as characterized by plasticization and swelling. This leads to an increase in the surface area of the polymers. At a higher temperature (45oC), PVP 29K has relatively high surface area, which results in both a greater rate and extent of CBZ adsorption. Our results suggest that temperature, polymer molecular weight, and polymer particle size are key determinants in partitioning behavior of CBZ between scCO2 and PVP. Using this technique we can determine equilibrium solubility of drug compounds in CO2 and measure their partitioning behavior in the presence polymer formulators. The extent of drug partitioning into polymer phases during processing dictates therapeutic efficacy