Study of polymer properties that influence crystal disruption of the model drug piroxicam

The present study identified specific properties of polymers, critical to creating and stabilizing an amorphous dispersion of drug in polymer. The solid-state miscibility of drug in polymer was investigated as a function of difference in their solubility parameter. The effectiveness of polymers as inhibitors of drug crystallization were quantified and compared by determination of disruptive indices. Specific heats of solution for the amorphous systems were used to explain dissolution rate increases. A short-term study of physical stability of amorphous solids as a function of moisture was undertaken to help establish appropriate storage conditions. The influence of common solvent on solvent evaporation process variables was studied.;Piroxicam was chosen as the model drug with low aqueous solubility (BCS Class II compound). Three polymers, namely polyvinyl pyrrolidone (PVP K29-32), vinyl pyrrolidone-vinyl acetate copolymer (PVP/VA S630) and hydroxypropyl cellulose (HPC), were used as amorphous polymers based on differences in their solubility parameters, molecular weight and hydrophilicity.;In general, the three polymers showed varying propensity to inhibit crystallization of piroxicam in solid dispersions. Inhibition was dependent on polymer-loading in the solid dispersions. Drug-polymer hydrogen bonding, determined using I.R. spectroscopy, was critical to creating and stabilizing amorphous systems. Polymer hydrophobicity did not influence crystal disruption of piroxicam as quantified by disruptive indices. A similarity in the solubility parameter of piroxicam and polymer enhanced solid-state miscibility of the two. This was over-ridden by increases in molecular weight of polymer which reduced miscibility due to steric hindrance and consequent inability to hydrogen bond. Dispersions with maximum solid-state miscibility (powder x-ray diffraction), crystal disruption (thermal analysis) and negative specific heats of solution (solution calorimetry) showed the greatest improvement in dissolution profiles compared to pure piroxicam. Physical mixtures of drug in polymer showed dissolution rates lower than pure piroxicam. Polymer hydrophilicity and molecular weight controlled drug release from physical mixtures. Cumulative drug fractions released were best fitted using the Peppas (power law) model and release exponent, n, were used to gain insight into dissolution mechanisms. Dispersions containing 1:4 w/w piroxicam in PVP/VA and PVP K29-32 were identified as stable amorphous systems. A critical relative humidity of glass transition (60% RH) was determined (isothermal moisture uptake) for the two polymers at room temperature (25°C). Reductions in glass transition temperature (modulated DSC) were a function of polymer hydrophilicity. Storage at 25°C/60% RH over thirty days did not induce recrystallization of piroxicam or significantly change the dissolution rate profiles.