title: A systemic evaluation of drug in acrylic pressure sensitive adhesive patch in vitro and in vivo: The roles of intermolecular interaction and adhesive mobility variation in drug controlled release.
abstract: Though acrylic pressure sensitive adhesives (PSAs) are widely used in transdermal drug delivery system, molecular details of drug-PSA interactions, PSA molecular mobility variations and their influences on drug skin permeation are unclear. In this study, three classes of acrylic PSAs containing hydroxyl (AAOH), carboxyl (AACOOH) and non-functional group (AAnone) were synthesized. Their abilities of controlling drug release were evaluated using propranolol (PRO) and zaltoprofen (ZAL) in vitro and in vivo. Interaction details were identified by FT-IR, solid-state NMR and molecular modeling. Thermodynamic activity of drug and strength of drug-PSA interaction were characterized using miscibility study. PSA mobility was characterized using thermal analysis and rheology study. Thus, ionic interaction reduced the thermodynamic activity of PRO and mobility of AACOOH, which made PRO-AACOOH obtain a significant lower bioavailability (11.8±0.7%) than these of PRO-AAnone (40.7±2.5%) and PRO-AAOH (42.3±2.9%). Though thermodynamic activity of ZAL in AACOOH was lower than that in AAOH due to the hydrogen bonding, bioavailability of ZAL-AAOH (19.0±4.1%) exhibited no significant difference with ZAL-AACOOH (15.4±2.8%), mainly because AAOH mobility was decreased by ZAL. In conclusion, the strength, types and involved functional groups of drug-PSA interactions were identified. On this basis, it was found that different control patterns of drug release were not only caused by the thermodynamic or kinetic hindrance effects of drug-PSA interactions, but also influenced by the interactions introduced PSA mobility variations, which was an innovative mechanism of controlled release in transdermal patch. The conclusions extended our understanding about the mechanism of controlled drug release of drug-in-adhesive patch. In addition, they contributed to the design of TDDS and custom acrylic PSAs.
authors.affiliation: Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Quan
authors.affiliation: School of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: School of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China. Electronic address: zhao09081@163.com.
authors.forename: Yongshan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China. Electronic address: fangliang2003@yahoo.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
mesh_terms: D000179:Acrylates / Q000737:chemistry*; D000269:Adhesives / Q000737:chemistry*; D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage* / Q000494:pharmacology; D003692:Delayed-Action Preparations; D065546:Drug Liberation; D005079:Excipients; D006801:Humans; D008297:Male; D008958:Models, Molecular; D011312:Pressure; D011422:Propionates / Q000008:administration & dosage* / Q000494:pharmacology; D011433:Propranolol / Q000008:administration & dosage* / Q000494:pharmacology; D017208:Rats, Wistar; D013816:Thermodynamics; D057968:Transdermal Patch
chemical_list: D000179:Acrylates; D000269:Adhesives; D001578:Benzopyrans; D003692:Delayed-Action Preparations; D005079:Excipients; D011422:Propionates; C043940:pyranoprofen; D011433:Propranolol; C036658:acrylic acid
keywords: Adhesive mobility; Drug-in-adhesive patch; Intermolecular interaction; Pressure sensitive adhesives; Transdermal drug delivery system