Microreservoir-type transdermal drug delivery systems (MTDDS) can prevent drug crystallization; however, no current predictive model considers the impact of drug load and hydration on their physical stability. We investigated MTDDS films containing polyvinylpyrrolidone (PVP) as polymeric drug stabilizer in lipophilic pressure-sensitive adhesive (silicone). Medicated and unmedicated silicone films with different molar N-vinylpyrrolidone:drug ratios were prepared and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, microscopy, dynamic vapor sorption (DVS), and stability testing for 4 months at different storage conditions. Homogeneously distributed drug-PVP associates were observed when nonaqueous emulsions, containing drug-PVP (inner phase) and silicone adhesive (outer phase), were dried to films. DVS data were essential to predict physical stability at different humidities. A predictive thermodynamic model was developed based on drug-polymer hydrogen-bonding interactions, using the Hoffman equation, to estimate the drug-PVP ratio needed to obtain stable MTDDS and to evaluate the impact of humidity on their physical stability. This new approach considers the impact of polymorphism on drug solubility by using easily accessible experimental data (Tm and DVS) and avoids uncertainties associated with the solubility parameter approach. In conclusion, a good fit of predicted and experimental data was observed.
Keywords: amorphous; hydration; mathematical model; physical stability; polymeric drug delivery system; solid dispersion; thermal analysis; thermodynamics; transdermal; water sorption.
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