Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8514301 | Journal of Pharmaceutical Sciences | 2017 | 53 Pages |
Abstract
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 4Â 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
DVSAPIPVPPSASAATransdermalTDDsGibbs free energy of mixingASADSCAmorphousThermal analysisacetylsalicylic acidSalicylic acidThermodynamicsEquilibrium constantPhysical stabilityWater sorptiondynamic vapor sorptionMassEnthalpy of fusionTemperatureglass transition temperatureMelting TemperatureRelative humidityDIAPolymeric drug delivery systemTransdermal drug delivery systemsInteraction coefficientFTIRFourier transform infrared spectroscopyactivityIbuprofenIbuMathematical modelSEMActive Pharmaceutical IngredientDrug-in-adhesiveScanning electron microscopyHydrationMolecular weightFlory-Huggins interaction parameterSolubility parameterSolid dispersionpolyvinylpyrrolidonepressure-sensitive adhesiveDifferential scanning calorimetryVolume fractionMolar fraction
Related Topics
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Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Clémence Chenevas-Paule, Hans-Michael Wolff, Mark Ashton, Martin Schubert, Kalliopi Dodou,