Key parameters affecting the initial release (burst) and encapsulation efficiency of peptide-containing poly(lactide-co-glycolide) microparticles. 2006

Xiaosong Luan, and Marc Skupin, and Jürgen Siepmann, and Roland Bodmeier
College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany.

The objective of this study was to identify key variables affecting the initial release (burst) and the encapsulation of leuprolide acetate-containing poly(lactide-co-glycolide) (PLGA) microparticles, which were prepared by the cosolvent evaporation method. Adjusting parameters, which affected the PLGA precipitation kinetics, provided efficient ways to increase the encapsulation efficiency and to control the initial release. Addition of 0.05M NaCl to the external aqueous phase increased the encapsulation efficiency and the initial release; in contrast, NaCl at high concentration (0.5M) delayed polymer precipitation and resulted in non-porous microparticles with a low initial release. The presence of ethanol in the external phase led to porous microparticles with an increased initial release but a decreased encapsulation efficiency. The initial release also decreased with decreasing volume of the external phase and homogenization speed, as well as with covering the preparation apparatus; however, these variations had no significant effect on the encapsulation efficiency. Scale-up of the laboratory size by a factor of 5 and 25 showed insignificant influence on the encapsulation efficiency, particle size, and drug release.

UI MeSH Term Description Entries
D010316 Particle Size Relating to the size of solids. Particle Sizes,Size, Particle,Sizes, Particle
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
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D012965 Sodium Chloride A ubiquitous sodium salt that is commonly used to season food. Sodium Chloride, (22)Na,Sodium Chloride, (24)NaCl
D014835 Volatilization A phase transition from liquid state to gas state, which is affected by Raoult's law. It can be accomplished by fractional distillation. Vaporization,Volatility
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
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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