Composite microparticles with in vivo reduction of the burst release effect.
The aim of this study was to develop microparticles containing nanoparticles (composite microparticles) for prolonged drug delivery with reduced burst effect in vitro and in vivo. Such composite microparticles were prepared with hydrophobic and biodegradable polymers [poly(epsilon-caprolactone), poly(lactic-co-glycolic) acid]. Ibuprofen was chosen as the model drug, and microparticles were prepared by the extraction technique with ethyl acetate as the solvent. Nanoparticles and microparticles and an ibuprofen solution (Pedea) were administered subcutaneously at the dose of 1 mg of ibuprofen per kg to overnight-fasted rats (male Wistar). Composite microparticles showed prolonged ibuprofen release and less burst effect when compared to simple microparticles (without nanoparticles inside) or nanoparticles both in vitro (PBS buffer) and in vivo. Moreover, ibuprofen was still detected in the plasma after 96 h with composite microparticles. Consequently, it has been demonstrated that composite microparticles were able to reduce burst release and prolong the release of ibuprofen for a long period of time.
Sheikh Hassan
A
A
Nancy-Université, Faculty of Pharmacy, Laboratory of Pharmaceutical Technology, Nancy Cedex, France.
Sapin
A
A
Lamprecht
A
A
Emond
E
E
El Ghazouani
F
F
Maincent
P
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D057927:Hydrophobic and Hydrophilic Interactions; D007052:Ibuprofen / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007279:Injections, Subcutaneous; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008863:Microspheres; D053758:Nanoparticles; D011091:Polyesters / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C016240:polycaprolactone; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007052:Ibuprofen