R Nair1, S Gonen, Stephen W Hoag. 1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 20 N. Pine Street, Baltimore, MD 21218, USA.
Abstract
PURPOSE: Influence of polymers on the polymorphic transition of drugs has received limited attention in the literature. The main objective of this study was to gain an understanding of the influence of polyethylene glycol and povidone on the crystalline modification and subsequently the solubility of carbamazepine in solid dispersions. METHODS: The physical state of the drug within the dispersions was determined using DSC and powder X-ray diffractometer. DSC and optical microscopy was used to study the kinetics and morphology of dihydrate formation, respectively. RESULTS: Both the polymeric dispersions showed an improved dissolution profile for carbamazepine. Carbamazepine was present in an amorphous form within the povidone dispersions. In contrast, the PEG dispersions showed the presence of crystalline drug. Higher ratios of drug/PEG resulted in the metastable form I of carbamazepine. Dihydrate formation from both the polymeric dispersions was higher compared with pure carbamazepine. The physical state of the drug and the amount of drug in solution accounted for the higher dihydrate formation from these dispersions. CONCLUSIONS: Knowledge of the factors contributing to enhanced solubility is critical to the stability of solid dispersions. Additionally, influence of polymers like povidone on the crystalline transitions of polymorphic drugs may be crucial during its use as a binder in granulation.
PURPOSE: Influence of polymers on the polymorphic transition of drugs has received limited attention in the literature. The main objective of this study was to gain an understanding of the influence of polyethylene glycol and povidone on the crystalline modification and subsequently the solubility of carbamazepine in solid dispersions. METHODS: The physical state of the drug within the dispersions was determined using DSC and powder X-ray diffractometer. DSC and optical microscopy was used to study the kinetics and morphology of dihydrate formation, respectively. RESULTS: Both the polymeric dispersions showed an improved dissolution profile for carbamazepine. Carbamazepine was present in an amorphous form within the povidone dispersions. In contrast, the PEG dispersions showed the presence of crystalline drug. Higher ratios of drug/PEG resulted in the metastable form I of carbamazepine. Dihydrate formation from both the polymeric dispersions was higher compared with pure carbamazepine. The physical state of the drug and the amount of drug in solution accounted for the higher dihydrate formation from these dispersions. CONCLUSIONS: Knowledge of the factors contributing to enhanced solubility is critical to the stability of solid dispersions. Additionally, influence of polymers like povidone on the crystalline transitions of polymorphic drugs may be crucial during its use as a binder in granulation.
Authors: Fang Wang; Wenbo Yu; Carmen Popescu; Ahmed Ashour Ibrahim; Dongyue Yu; Ryan Pearson; Alexander D MacKerell; Stephen W Hoag Journal: Pharm Dev Technol Date: 2022-04-25 Impact factor: 3.915