The use of solubility parameters to predict the behaviour of a co-crystalline drug dispersed in a polymeric vehicle. Approaches to the prediction of the interactions of co-crystals and their components with hypromellose acetate succinate and the characterization of that interaction using crystallographic, microscopic, thermal, and vibrational analysis.

摘要

Dispersing co-crystals in a polymeric carrier may improve their physicochemicaludproperties such as dissolution rate and solubility. Additionally co-crystal stabilityudmay be enhanced. However, such dispersions have been little investigated touddate. This study focuses on the feasibility of dispersing co-crystals in audpolymeric carrier and theoretical calculations to predict their stability.udAcetone/chloroform, ethanol/water, and acetonitrile were used to load and growudco-crystals in a HPMCAS film. Caffeine-malonic acid and ibuprofennicotinamideudco-crystals were prepared using solvent evaporation method. Theudinteractions between each of the co-crystals components and their mixturesudwith the polymer were studied. A solvent evaporation approach was used toudincorporate each compound, a mixture, and co-crystals into HPMCAS films.udDifferential scanning calorimetry data revealed a higher affinity of the polymer toudacidic compounds than their basic counterparts as noticed by the depression ofudthe glass transition temperature (Tg). Moreover, the same drug loadingudproduced films with different Tgs when different solvents were used. Solubilityudparameter values (SP) of the solvents were employed to predict that effect onudthe depression of polymer Tg with relative success. SP values were moreudsuccessful in predicting the preferential affinity of two acidic compounds toudinteract with the polymer. This was confirmed using binary mixtures ofudnaproxen, flurbiprofen, malonic acid, and ibuprofen. On the other hand,uddispersing basic compounds such as caffeine or nicotinamide with malonic acidudin HPMCAS film revealed the growth of co-crystals. A dissolution study showedudthat the average release of caffeine from films containing caffeine-malonic acidudwas not significantly different to that of films containing similar caffeine concentration. The stability of the caffeine-malonic acid co-crystals in HPMC-AS was prolonged to 8 weeks at 95% relative humidity and 45°C.udThe theory developed in this project, that an acidic drug with a SP value closer to the polymer will dominate the interaction process and prevent the majority of the other material from interacting with the polymer, may have utility in designing co-crystal systems in polymeric vehicles