In vitro release of levonorgestrel from phase sensitive and thermosensitive smart polymer delivery systems.
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.
Chen
Sibao
S
Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, ND 58105, USA.
Singh
Jagdish
J
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
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