In vitro-in vivo characterization of release modifying agents for parenteral sustained-release ketorolac formulation.
One of the prerequisites for a parenteral preparation is that the excipients incorporated are biocompatible and biodegradable. In the present study hydrophilic and hydrophobic excipients were investigated for developing an intramuscular sustained-release formulation of ketorolac. Kollidon 17 PF, Peceol (glyceryl monooleate), and castor oil were chosen as the potential release-retarding agents, each with a distinct mechanism of action. They were evaluated by in vitro drug-release profiles and in vivo pharmacodynamic and pharmacokinetic study in mice. Cumulative drug release was determined for standard and test formulations in modified Franz diffusion cell. Pharmacodynamic parameter, T = 70% response of peak analgesic response, was used to compare the performance of test formulations. Based on pharmacodynamic/pharmacokinetic correlation in the animal studies, Css(max) and Css(min) of 51.39 and 30.0 microg/mL, respectively, were determined and considered as performance markers for pharmacokinetic evaluation of test formulations. The study suggested that the sustained-release capability of glyceryl monooleate was maximum followed by that of castor oil and Kollidon 17 PF, when compared to conventional ketorolac tromethamine formulation. It was inferred that water soluble excipient, though, showed release retarding property in vitro but could not maintain it in the in vivo environment. Glyceryl monooloeate-based formulation produced the most favorable drug blood concentration vs. time profile.
Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research, SAS. Nagar, Punjab, India.
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Puri
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Bansal
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002368:Castor Oil / Q000737:chemistry / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D005079:Excipients / Q000737:chemistry / Q000494:pharmacology; D005989:Glycerides / Q000737:chemistry / Q000494:pharmacology; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D020911:Ketorolac Tromethamine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D010147:Pain Measurement; D010592:Pharmaceutic Aids / Q000737:chemistry / Q000494:pharmacology*; D011205:Povidone / Q000494:pharmacology; D012995:Solubility; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D005079:Excipients; D005989:Glycerides; D010592:Pharmaceutic Aids; D020911:Ketorolac Tromethamine; D002368:Castor Oil; C005953:monoolein; D011205:Povidone