Chitosan and enteric polymer based once daily sustained release tablets of aceclofenac: in vitro and in vivo studies.
The purpose of this study was to develop a once daily sustained release tablet of aceclofenac using chitosan and an enteric coating polymer (hydroxypropyl methylcellulose phthalate or cellulose acetate phthalate). Overall sustained release for 24 h was achieved by preparing a double-layer tablet in which the immediate release layer was formulated for a prompt release of the drug and the sustained release layer was designed to achieve a prolonged release of drug. The preformulation studies like IR spectroscopic and differential scanning calorimetry showed the absence of drug-excipient interactions. The tablets were found within the permissible limits for various physicochemical parameters. Scanning electron microscopy was used to visualize the surface morphology of the tablets and to confirm drug release mechanisms. Good equivalence in the drug release profile was observed when drug release pattern of the tablet containing chitosan and hydroxypropyl methylcellulose phthalate (M-7) was compared with that of marketed tablet. The optimized tablets were stable at accelerated storage conditions for 6 months with respect to drug content and physical appearance. The results of pharmacokinetic studies in human volunteers showed that the optimized tablet (M-7) exhibited no difference in the in vivo drug release in comparison with marketed tablet. No significant difference between the values of pharmacokinetic parameters of M-7 and marketed tablets was observed (p > 0.05; 95% confidence intervals). However the clinical studies in large scale and, long term and extensive stability studies at different conditions are required to confirm these results.
Mutalik
Srinivas
S
Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104 Karnataka, India. ssmutalik@yahoo.com
Manoj
Krishnan
K
Reddy
Meka Sreenivasa
MS
Kushtagi
Pralhad
P
Usha
Achutha Nayak
AN
Anju
Parambil
P
Ranjith
Averineni Kumar
AK
Udupa
Nayanabhirama
N
D000284:Administration, Oral; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002152:Calorimetry, Differential Scanning; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013499:Surface Properties; D013608:Tablets, Enteric-Coated; D013678:Technology, Pharmaceutical / Q000379:methods; D013810:Therapeutic Equivalency
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D013608:Tablets, Enteric-Coated; D004008:Diclofenac; D002482:Cellulose; C011708:cellulose acetate phthalate; D008747:Methylcellulose; D048271:Chitosan; C053309:hydroxypropyl methylcellulose phthalate; C056498:aceclofenac