Improved bioavailability of aceclofenac from spherical agglomerates: development, in vitro and preclinical studies.
The objective of present study was to improve the solubility, dissolution rate, micromeritic properties and bioavailability of aceclofenac (NSAID) by formulating its spherical agglomerates. They were prepared with different water soluble polymers (polyvinylpyrrolidone-K30, polyvinylpyrrolidone-K90 and sodium alginate) by using acetone-water-dichloromethane solvent system. The agglomerates were subjected to various physicochemical properties, DSC, IR spectroscopy, scanning electron microscopy (SEM), micromeritic properties and dissolution studies. The in vivo studies (anti-inflammatory, analgesic and pharmacokinetic studies) were conducted in Wistar rats and Swiss albino mice. SEM studies showed that agglomerates were spherical in structure and formed by cluster of small crystals. The agglomerates prepared with polyvinylpyrrolidone-K90 exhibited improved solubility, dissolution rate and micromeritic properties compared to those prepared with other polymers and pure drug. These optimized agglomerates showed rapid analgesic and anti-inflammatory activity besides exhibiting improved bioavailability of drug when compared to pure drug.
Muatlik
S
S
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal 576104, Karnataka State, India. ssmutalik@yahoo.com
Usha
A N
AN
Reddy
M S
MS
Ranjith
A K
AK
Pandey
S
S
D000464:Alginates; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002351:Carrageenan; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004008:Diclofenac / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D004655:Emulsions; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D066298:In Vitro Techniques; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010147:Pain Measurement; D010316:Particle Size; D011205:Povidone; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013055:Spectrophotometry, Infrared
D000464:Alginates; D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004655:Emulsions; D006603:Hexuronic Acids; D004008:Diclofenac; D020723:Glucuronic Acid; D002351:Carrageenan; D011205:Povidone; C056498:aceclofenac