title: In vitro release of levonorgestrel from phase sensitive and thermosensitive smart polymer delivery systems.
abstract: The objective of this research is to develop injectable controlled delivery systems for the contraceptive hormone, levonorgestrel (LNG), using phase sensitive and thermosensitive polymers. A combination of poly (lactide) (PLA) and a solvent mixture of benzyl benzoate (BB) and benzyl alcohol (BA) was used in the phase-sensitive polymer delivery systems. The effects of solvent systems and polymer concentrations on the in vitro LNG release were evaluated. In the case of thermosensitive polymer delivery systems, a series of low-molecular-weight poly (lactide-co-glycolide)-poly (ethylene glycol)-poly (lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers with varying ratios of lactide/glycolide (LA/GA, 2.0-3.5) were used. The effects of varying block length of copolymers 1, 2, 3, and 4 on the in vitro LNG release were evaluated. Phosphate buffer saline (pH 7.4) containing 0.5% w/v Tween-80 was used as in vitro release medium. The amount of the released LNG was determined by an high pressure liquid chromatography (HPLC) method. A controlled (zero-order) in vitro release of LNG was observed from both phase-sensitive and thermosensitive-polymer delivery systems. Increasing the concentration of the phase-sensitive polymer from 5% to 30% significantly (p < 0.05) decreased the release rate of LNG from 38.32 microg/day to 31.45 microg/day; and increasing the hydrophilic fraction of the solvents mixture (i.e., BA) significantly (p < 0.05) increased the release rate of LNG. In the case of the thermosensitive polymer delivery system, increasing the hydrophobic PLGA block length of copolymers significantly (p < 0.05) decreased the release rate of LNG (98.65 microg/day to 67.60 microg/day). It is evident from this study that both the phase sensitive and thermosensitive polymers are suitable for developing prolonged-release injectable delivery systems for the contraceptive hormone.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, ND 58105, USA.
authors.forename: Sibao
authors.initials: S
authors.lastname: Chen
authors.forename: Jagdish
authors.initials: J
authors.lastname: Singh
mesh_terms: D001565:Benzoates / Q000737:chemistry; D019905:Benzyl Alcohol / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D006358:Hot Temperature; D007267:Injections; D019344:Lactic Acid; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D012995:Solubility; D012997:Solvents
chemical_list: D001565:Benzoates; D003280:Contraceptives, Oral, Synthetic; D011091:Polyesters; D011108:Polymers; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D016912:Levonorgestrel; D019905:Benzyl Alcohol; C006723:benzyl benzoate