title: Development of a Predictive Model for the Long-Term Stability Assessment of Drug-In-Adhesive Transdermal Films Using Polar Pressure-Sensitive Adhesives as Carrier/Matrix.
abstract: Drug crystallization in transdermal drug delivery systems is a critical quality defect. The impact of drug load and hydration on the physical stability of polar (acrylic) drug-in-adhesive (DIA) films was investigated with the objective to identify predictive formulation parameters with respect to drug solubility and long-term stability. Medicated acrylic films were prepared over a range of drug concentrations below and above saturation solubility and were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, polarized microscopy, and dynamic vapor sorption (DVS) analysis. Physical stability of medicated films was monitored over 4 months under different storage conditions and was dependent on solubility parameters, Gibbs free energy for drug phase transition from the amorphous to the crystalline state, and relative humidity. DVS data, for assessing H-bonding capacity experimentally, were essential to predict physical stability at different humidities and were used together with Gibbs free energy change and the Hoffman equation to develop a new predictive thermodynamic model to estimate drug solubility and stability in DIA films taking into account relative humidity.
authors.affiliation: Sunderland Pharmacy School, Faculty of Applied Sciences, University of Sunderland, Sunderland SR13SD, UK.
authors.forename: Clémence
authors.initials: C
authors.lastname: Chenevas-Paule
authors.affiliation: UCB Biosciences GmbH, Monheim 40789, Germany.
authors.forename: Hans-Michael
authors.initials: HM
authors.lastname: Wolff
authors.affiliation: Sunderland Pharmacy School, Faculty of Applied Sciences, University of Sunderland, Sunderland SR13SD, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Ashton
authors.affiliation: UCB Pharma S.A., Braine L'Alleud B-1420, Belgium.
authors.forename: Martin
authors.initials: M
authors.lastname: Schubert
authors.affiliation: Sunderland Pharmacy School, Faculty of Applied Sciences, University of Sunderland, Sunderland SR13SD, UK. Electronic address: kalliopi.dodou@sunderland.ac.uk.
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Dodou
mesh_terms: D000269:Adhesives / Q000008:administration & dosage / Q000737:chemistry*; D000279:Administration, Cutaneous; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D004355:Drug Stability; D005544:Forecasting; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry*; D011312:Pressure
chemical_list: D000269:Adhesives; D004337:Drug Carriers; D004364:Pharmaceutical Preparations
keywords: amorphous; crystallization; hydration; mathematical model; physical stability; polymeric drug delivery system; thermal analysis; thermodynamics; transdermal; water sorption