Preparation, in vitro, preclinical and clinical evaluations of once daily sustained release tablets of aceclofenac.
The objective of the present study was to develop "once daily" sustained release tablets of aceclofenac by direct compression using hydroxypropyl methylcellulose-K4M (HPMC). The solubility studies of aceclofenac were conducted to select suitable dissolution media. The drug-excipient mixtures were subjected to preformulation studies. The tablets were subjected to physicochemical, in vitro drug release and stability studies. Preclinical (anti-inflammatory, analgesic, pharmacokinetic and toxicity studies) and clinical pharmacokinetic studies were conducted for optimized tablets. Based on the preformulation results, microcrystalline cellulose (MCC), dicalcium phosphate and spray dried lactose (SDL) were selected as directly compressible vehicles. Because of the incompatibility with aceclofenac, SDL was excluded from the study. The physicochemical properties of tablets were found within the limits. By comparing the dissolution profiles with the marketed product, the tablet containing HPMC (45%) and MCC (30%) along with talc and magnesium stearate (1% w/w, each) (Tablet B7) was considered as a better formulation. This tablet exhibited almost similar drug release profile in different dissolution media as that of marketed tablet. Tablet B7 was stable in accelerated conditions for 6 months. The composition of this tablet showed almost similar preclinical pharmacological activities compared to marketed tablet composition and did not exhibit any toxicity in rats and mice with respect to tested haematological and biochemical parameters along with body weight, food and water intake. The pharmacokinetic study in healthy human volunteers indicated that B7 tablet produced an extended drug release of drug upto 24 h as that of marketed product with almost identical pharmacokinetic parameters.
Mutalik
S
S
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal 576 104, Karnataka State, India, Karnataka. srinivas.mutalik@manipal.edu
Naha
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A
Usha
A N
AN
Ranjith
A K
AK
Musmade
P
P
Manoj
K
K
Anju
P
P
Prasanna
S
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D019540:Area Under Curve; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D004334:Drug Administration Schedule; D004339:Drug Compounding; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D004487:Edema / Q000188:drug therapy; D005079:Excipients / Q000737:chemistry; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D010146:Pain / Q000188:drug therapy; D051381:Rats; D012995:Solubility; D013607:Tablets; D036401:Toxicity Tests, Chronic
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D005079:Excipients; D013607:Tablets; D004008:Diclofenac; C056498:aceclofenac