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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.
Isreb, Abdullah
Isreb, Abdullah
Publication Date
2013-04-09
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The University of Bradford theses are licenced under a Creative Commons Licence.
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Accepted for publication
Institution
University of Bradford
Department
The School of Pharmacy.
Awarded
2012
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Abstract
Dispersing co-crystals in a polymeric carrier may improve their physicochemical
properties such as dissolution rate and solubility. Additionally co-crystal stability
may be enhanced. However, such dispersions have been little investigated to
date. This study focuses on the feasibility of dispersing co-crystals in a
polymeric carrier and theoretical calculations to predict their stability.
Acetone/chloroform, ethanol/water, and acetonitrile were used to load and grow
co-crystals in a HPMCAS film. Caffeine-malonic acid and ibuprofennicotinamide
co-crystals were prepared using solvent evaporation method. The
interactions between each of the co-crystals components and their mixtures
with the polymer were studied. A solvent evaporation approach was used to
incorporate each compound, a mixture, and co-crystals into HPMCAS films.
Differential scanning calorimetry data revealed a higher affinity of the polymer to
acidic compounds than their basic counterparts as noticed by the depression of
the glass transition temperature (Tg). Moreover, the same drug loading
produced films with different Tgs when different solvents were used. Solubility
parameter values (SP) of the solvents were employed to predict that effect on
the depression of polymer Tg with relative success. SP values were more
successful in predicting the preferential affinity of two acidic compounds to
interact with the polymer. This was confirmed using binary mixtures of
naproxen, flurbiprofen, malonic acid, and ibuprofen. On the other hand,
dispersing basic compounds such as caffeine or nicotinamide with malonic acid
in HPMCAS film revealed the growth of co-crystals. A dissolution study showed
that the average release of caffeine from films containing caffeine-malonic acid
was 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.
The 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
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Type
Thesis
Qualification name
PhD