Controlled delivery of aspirin: effect of aspirin on polymer degradation and in vitro release from PLGA based phase sensitive systems.
The objective of this study was to develop poly (d,l-lactide-co-glycolide) (PLGA) based injectable phase sensitive in situ gel forming delivery system for controlled delivery of aspirin, and to characterize the effect of drug/polymer interaction on the in vitro release of aspirin and polymer degradation. Aspirin was dissolved into PLGA solution in 1-methyl-2-pyrrolidone. Poly(ethylene glycol)400 was used as plasticizer to reduce initial burst release. The solution formulation was injected into aqueous release medium to form a gel depot. Released samples were withdrawn periodically and assayed for aspirin content by high performance liquid chromatography. The effect of aspirin on the degradation of PLGA matrix was evaluated using Proton Nuclear Magnetic Resonance and Gel Permeation Chromatography. PLGA based in situ gel forming formulations controlled the in vitro release of aspirin for 7 days only. Analysis of PLGA matrix residuals revealed that PLGA in aspirin loaded formulations exhibited a significantly (p<0.05) faster degradation compared to blank formulations. These findings suggest that aspirin causes an unusually faster degradation of PLGA. Such faster degradation of PLGA has not been noticed for any other drugs reported in the literature.
Tang
Yu
Y
Department of Pharmaceutical Sciences, College of Pharmacy, Nursing, and Allied Sciences, North Dakota State University, Fargo, ND 58105, USA.
Singh
Jagdish
J
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001241:Aspirin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D002850:Chromatography, Gel; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005079:Excipients; D019344:Lactic Acid / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D005079:Excipients; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D001241:Aspirin