PREDICTIVE MODELING OF LONG-TERM STABILITY OF DRUG-IN-ADHESIVE TRANSDERMAL DRUG DELIVERY SYSTEMS

PREDICTIVE MODELING OF LONG-TERM STABILITY OF DRUG-IN-ADHESIVE TRANSDERMAL DRUG DELIVERY SYSTEMS K DODOU University of Sunderland, Sunderland SR1 3SD, UK Transdermal patches are medicated dosage forms that are applied on the skin for the delivery of the active ingredient to the systemic circulation. The attachment of the patch on the skin is due to the adhesive ability of the pressure-sensitive adhesive (PSA) polymer1. With my research group we focused on the drug-in-adhesive patch design, where the active ingredient is incorporated in the PSA, and we have explored the following challenges: • Effect of drug incorporation on the adhesive performance of the PSA. My research findings increased knowledge and understanding on how rheological parameters translate to adhesive performance criteria for different types of pressure sensitive adhesives, and provided new insights and practices on the incorporation of drugs in the adhesive films. Via this work, we established how the rheological properties of adhesives can be used as a quality control indicator for the adhesive performance of transdermal patches2,3. • Long-term stabilisation of drug against crystallisation in the PSA via polymeric amorphous solid dispersions. Drug crystallisation in dosage forms is a formulation defect because it hinders drug release. My research identified formulation and manufacturing approaches to prevent drug crystallisation in transdermal films via amorphous solid dispersions4. Drug stabilisation in lipophilic PSAs (such as silicones and polyisobutylenes) requires the addition of a stabiliser polymer that would form H-bonding interactions with the drug. Whereas drug stabilisation in polar PSAs (ie acrylic) could be feasible via H-bonding interaction with the PSA. We therefore developed predictive models for the estimation of the required polymer amount to stabilise a given drug concentration in lipophilic PSAs5 and for the long-term stability assessment of the drug in polar PSAs6. I would like to acknowledge the financial support from IChemE, Schwarz Pharma and UCB Pharma. 1. K Dodou (2011) The use of adhesive films in transdermal and mucoadhesive dosage forms. In: Adhesive Properties in Nanomaterials, Composites and Films. Nova Science Publishers, New York, pp. 83-93. 2. KY Ho, K Dodou, Rheological studies on pressure sensitive silicone adhesives and drug-in-adhesive layers as a means to characterise adhesive performance, Int.J.Pharm. 333(1-2), 24-33 (2007) 3. HM Wolff, Irsan, K Dodou, Investigations on the viscoelastic performance of pressure sensitive adhesives in drug-in-adhesive type transdermal films, Pharm.Res. 31(8), 2186-2202 (2014) 4. K Dodou, W Saddique, Effect of manufacturing method on the in-vitro drug release and adhesive performance of drug-in-adhesive films containing binary mixtures of ibuprofen with poloxamer 188. Pharm.Dev.Tech. 17(5), 552-561 (2012) 5. C Chenevas-Paule, HM Wolff, M Ashton, M Schubert, K Dodou, Development of a predictive model for the stabilizer concentration estimation in microreservoir transdermal drug delivery systems (MTDDS) using lipophilic pressure sensitive adhesives as matrix/carrier. J.Pharm.Sci. 106(5), 1371-1383 (2017) 6. C Chenevas-Paule, HM Wolff, M Ashton, M Schubert, K Dodou, 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. J.Pharm.Sci. 106(5), 1293-1301 (2017