A novel method for determination of drug solubility in polymeric matrices.
Crystallization of drugs in metastable, supersaturated adhesive polymeric matrices in transdermal drug delivery devices can be avoided by determination of the solubility of the drug in the adhesive polymer. A novel method is described to determine the solubility of the drug in polymeric matrices. Unlike existing methods, this method does not require a long and uncertain experimental time, and is accurate. In this study, an easy and accurate method is presented for the determination of solubility of drugs in polymers based on the relationship between thermodynamic activity of drugs and steady-state flux. In particular, the steady-state flux from a reference saturated solution across a test membrane was compared to an experimentally determined relationship between the polymeric loading concentration and the observed steady-state fluxes. The validity of this method was demonstrated by comparing the results to microscopic observation of crystallization and the study of aged drug-loaded adhesives for lidocaine as a model drug and an acrylate pressure-sensitive adhesive as a model polymer. The solubility of lidocaine was 20.8 +/- 0.5% (w/w) in the acrylate polymer.
Jasti
Bhaskara R
BR
Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, California 95211, USA.
Berner
Bret
B
Zhou
Sen-Lin
SL
Li
Xiaoling
X
D000269:Adhesives; D002851:Chromatography, High Pressure Liquid; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D012995:Solubility
D000269:Adhesives; D004364:Pharmaceutical Preparations; D011108:Polymers