title: Formulation and optimization of desogestrel transdermal contraceptive patch using crystallization studies.
abstract: Levonorgestrel (LNG) is the most commonly used progestin in contraception. In this study, we report the use of an alternative progestin, desogestrel, for transdermal contraception. The drug was found to be significantly more permeable as compared to LNG (p<0.05). Crystallization studies were used to select the best adhesive among acrylate (Duro-Tak 87-4098 and Duro-Tak 87-202A) and polyisobutylene (PIB, Duro-Tak 87-608A) pressure sensitive adhesives by determining the drug's saturation solubility in them. The use of copovidone and mineral oil as formulation excipients was investigated to increase drug loading in the PIB adhesive. Physical characterization of the patches was performed using in vitro drug release, content analysis, patch weight and thickness variations and rolling ball tack and peel adhesion studies. Optimized patches were evaluated for in vitro transdermal delivery across hairless rat skin. The saturation solubility of desogestrel was found to be approximately 49.3% (w/w) and 55.6% (w/w) in Duro-Tak 87-4098 and Duro-Tak 87-202A acrylate adhesives, respectively. The saturation solubility of desogestrel was significantly lower (3-4%, w/w) in the PIB adhesive. Mineral oil (10%, w/w) and copovidone (30%, w/w) were found to be optimum for increasing drug loading and patch cosmetics. Results from the physical characterization studies suggest that a uniform and reproducible 7 day drug-in-adhesive patch could be developed.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Mercer University, Atlanta, GA 30341, USA.
authors.forename: Vishal
authors.initials: V
authors.lastname: Sachdeva
authors.forename: Yun
authors.initials: Y
authors.lastname: Bai
authors.forename: Agis
authors.initials: A
authors.lastname: Kydonieus
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Banga
mesh_terms: D000269:Adhesives / Q000737:chemistry; D000818:Animals; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003460:Crystallization; D017135:Desogestrel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005079:Excipients / Q000737:chemistry*; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008899:Mineral Oil / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D051381:Rats; D054772:Rats, Hairless; D015203:Reproducibility of Results; D012869:Skin Absorption; D012995:Solubility; D057968:Transdermal Patch; D014753:Vinyl Compounds / Q000737:chemistry
chemical_list: D000269:Adhesives; D003280:Contraceptives, Oral, Synthetic; D005079:Excipients; D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D016912:Levonorgestrel; D008899:Mineral Oil; D017135:Desogestrel