Formulation, characterization, and evaluation of ketorolac tromethamine-loaded biodegradable microspheres.
Ketorolac tromethamine has to be given every 6 hr intramuscularly in patients for acute pain, so to avoid frequent dosing and patient inconvenience we found it to be a suitable candidate for parenteral controlled delivery by biodegradable microspheres for the present study. Ketorolac tromethamine-loaded microspheres were prepared by o/w emulsion solvent evaporation technique using different polymers: polycaprolactone, poly lactic-co-glycolic acid (PLGA 65/35), and poly lactic-co-glycolic acid (PLGA 85/15). To tailor the release profile of drug for several days, blends of PLGA 65/35 and PLGA 85/15 were prepared with polycaprolactone (PCL) in different ratios. The results revealed that microspheres made with 1:3 (PLGA65/35:PCL) blend released 97% of the drug in 5 days as compared 97% in 30 days in with pure PLGA65/35 microspheres. Microspheres made with 1:1 (PLGA65/35:PCL) and 3:1 (PLGA65/35:PCL released 98% of the drug in 30 days. In microspheres made with 1:3 (PLGA85/15:PCL), almost the entire drug was released in a week whereas in batches made with pure PLGA85/15 and 3:1 (PLGA 85/15:PCL) more than 80% of the drug was released in 60 days as compared with 96% in 60 days in 1:1 (PLGA85/15:PCL). Higher encapsulation efficiency was obtained with microspheres made with pure PLGA 65/35. These formulations were characterized for particle size analysis by Malvern mastersizer that revealed particle size in range of 12-15 micron and 12-22 micron for microspheres made with polymer blends of PLGA 65/35:PCL and PLGA85/15:PCL, respectively. In pure PLGA65/35 and PLGA85/15, particle size was 28 micron and 8 micron, respectively. Surface topography was studied by scanning electron microscopy that revealed a spherical shape of microspheres. From our study it as concluded that with careful selection of different polymers and their combinations, we can tailor the release of ketorolac tromethamine for long periods.
Sinha
Vivek Ranjan
VR
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India. vr_sinha@yahoo.com
Trehan
Aman
A
D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001673:Biodegradation, Environmental; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D007279:Injections, Subcutaneous; D020911:Ketorolac Tromethamine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010147:Pain Measurement / Q000187:drug effects; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D013623:Tail / Q000503:physiopathology; D013678:Technology, Pharmaceutical / Q000379:methods*; D013997:Time Factors
D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C016240:polycaprolactone; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020911:Ketorolac Tromethamine