Hydrophobic ion pair formation between leuprolide and sodium oleate for sustained release from biodegradable polymeric microspheres. 2000

S H Choi, and T G Park
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373-1 Kusong-dong, Yusong-gu, 305-701, Taejon, South Korea.

Leuprolide acetate, an analogue of luteinizing hormone-releasing hormone (LH-RH), was hydrophobically ion paired with a long chain fatty acid, sodium oleate, in an aqueous solution. Solution behaviors of the complex formed between leuprolide and sodium oleate were investigated in terms of aqueous solubility, turbidity, particle size, and zeta potential as a function of molar ratio between the two species. It was found that with increasing the stoichiometric molar amounts of sodium oleate to leuprolide approached up to 2.5-3, the solution became gradually turbid with increasing particle sizes, indicating leuprolide precipitation as a result of hydrophobic ion pairing. On the other hand, beyond that critical molar ratio range, the solution turned into clear with much reduced particle size, indicative of micelle formation. The hydrophobically modified leuprolide-oleate complex was lyophilized and directly encapsulated within biodegradable poly(D, L-lactic-co-glycolic acid) (PLGA) microspheres via a single oil-in-water (O/W) emulsion method. Microsphere morphology, leuprolide release behavior, and polymer mass erosion profiles were examined in comparison to the PLGA microspheres prepared with free leuprolide.

UI MeSH Term Description Entries
D011100 Polyglycolic Acid A biocompatible polymer used as a surgical suture material. Polyglycolide,Biofix,Dexon (Polyester),Dexon-S,Dexon S,DexonS
D011108 Polymers Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., BIOPOLYMERS; PLASTICS). Polymer
D003692 Delayed-Action Preparations Dosage forms of a drug that act over a period of time by controlled-release processes or technology. Controlled Release Formulation,Controlled-Release Formulation,Controlled-Release Preparation,Delayed-Action Preparation,Depot Preparation,Depot Preparations,Extended Release Formulation,Extended Release Preparation,Prolonged-Action Preparation,Prolonged-Action Preparations,Sustained Release Formulation,Sustained-Release Preparation,Sustained-Release Preparations,Timed-Release Preparation,Timed-Release Preparations,Controlled-Release Formulations,Controlled-Release Preparations,Extended Release Formulations,Extended Release Preparations,Slow Release Formulation,Sustained Release Formulations,Controlled Release Formulations,Controlled Release Preparation,Controlled Release Preparations,Delayed Action Preparation,Delayed Action Preparations,Formulation, Controlled Release,Formulations, Controlled Release,Prolonged Action Preparation,Release Formulation, Controlled,Release Formulations, Controlled,Sustained Release Preparation,Timed Release Preparation,Timed Release Preparations
D000077182 Polylactic Acid-Polyglycolic Acid Copolymer A co-polymer that consists of varying ratios of polylactic acid and polyglycolic acid. It is used as a matrix for drug delivery and for BONE REGENERATION. PLGA Acid,LactoSorb,PL-PG Copolymer,PLG Polymer,PLGA Compound,Poly (D,L-lactic-co-glycolic Acid),Poly (Lactic-co-glycolic Acid) -,Poly(D,L-lactide-co-glycolide),Poly(DL-lactide-co-glycolic Acid),Poly(Glycolide-co-lactide),Poly(L-lactide)-co-glycolide,Poly(Lactic-co-glycolic Acid),Poly-L-lactic-polyglycolic Acid,Polylactic-co-glycolic Acid Copolymer,RG 502,Acid, PLGA,Acids, PLGA,Copolymer, PL-PG,Copolymer, Polylactic-co-glycolic Acid,Copolymers, PL-PG,Copolymers, Polylactic-co-glycolic Acid,PL PG Copolymer,PL-PG Copolymers,PLG Polymers,PLGA Acids,PLGA Compounds,Poly L lactic polyglycolic Acid,Poly-L-lactic-polyglycolic Acids,Polylactic Acid Polyglycolic Acid Copolymer,Polylactic co glycolic Acid Copolymer,Polylactic-co-glycolic Acid Copolymers,Polymer, PLG,Polymers, PLG
D012995 Solubility The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Solubilities
D016729 Leuprolide A potent synthetic long-acting agonist of GONADOTROPIN-RELEASING HORMONE that regulates the synthesis and release of pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE. Leuprorelin,A-43818,Enantone,Leuprolide Acetate,Leuprolide Monoacetate,Leuprolide, (DL-Leu)-Isomer,Leuprolide, (L-Leu)-Isomer,Lupron,TAP-144,A 43818,A43818,Acetate, Leuprolide,Monoacetate, Leuprolide,TAP 144,TAP144
D019301 Oleic Acid An unsaturated fatty acid that is the most widely distributed and abundant fatty acid in nature. It is used commercially in the preparation of oleates and lotions, and as a pharmaceutical solvent. (Stedman, 26th ed) 9-Octadecenoic Acid,Oleate,cis-9-Octadecenoic Acid,9 Octadecenoic Acid,cis 9 Octadecenoic Acid
D019344 Lactic Acid A normal intermediate in the fermentation (oxidation, metabolism) of sugar. The concentrated form is used internally to prevent gastrointestinal fermentation. (From Stedman, 26th ed) Lactate,2-Hydroxypropanoic Acid,2-Hydroxypropionic Acid,Ammonium Lactate,D-Lactic Acid,L-Lactic Acid,Propanoic Acid, 2-Hydroxy-, (2R)-,Propanoic Acid, 2-Hydroxy-, (2S)-,Sarcolactic Acid,2 Hydroxypropanoic Acid,2 Hydroxypropionic Acid,D Lactic Acid,L Lactic Acid,Lactate, Ammonium

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