Modulating drug release profiles by lipid semi solid matrix formulations for BCS class II drug--an in vitro and an in vivo study.
The main objective of the study was to alter the dissolution profile of a practically insoluble Biopharmaceutics Classification System class II drug, aceclofenac, by formulating into lipid semisolid matrix (SSM) formulations using liquid filling technology in hard gelatin capsules, for both immediate and sustained release. SSM formulations of aceclofenac were prepared by melt fusion technique, using Gelucires (44/14, 50/13, 33/01 and 43/01), polyethylene glycols (4000 and 6000) and Poloxamer 188 at different levels. Role of additives like docusate sodium, Tween 80, Aerosil 200 and polyvinylpyrrolidone K-30 in enhancement of drug release was investigated. The optimized immediate and sustained SSM capsules were characterized in terms of assay, in vitro drug release, moisture uptake and differential scanning calorimetry. More than 80% of the drug was released within 15 min in various dissolution media studied, from Gelucire 44/14-based immediate release formulations. Incorporation of docusate sodium and Tween 80 provided further enhancement in drug dissolution when compared to plain drug and marketed tablet. SSM formulations based on Gelucire blends of 50/13 and 43/01 and 44/14 and 43/01 sustained the release of the drug for a period of 24 h following zero-order kinetics. The in vivo study of the optimized immediate release and sustained release formulations revealed significant enhancement in anti inflammatory activity (p < 0.01) in rats. From these findings, liquid fill technique in hard gelatin capsules using Gelucire and their blends might be an efficacious approach for designing immediate or sustained drug release profiles for poorly soluble drugs like aceclofenac.
Sri Venkateshwara College of Pharmacy , Hitech City, Hyderabad, Andhra Pradesh , India .
Kalpana
K
M
Ramakrishna
R
Sistla
Nalini R
NR
Shastri
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry* / Q000145:classification / Q000627:therapeutic use; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000145:classification / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D004487:Edema / Q000188:drug therapy; D005079:Excipients / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D008956:Models, Chemical; D051381:Rats; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D008055:Lipids; D004008:Diclofenac; D005780:Gelatin; C056498:aceclofenac
Aceclofenac; gelucire; hard gelatin capsule; liquid fill technology; semi solid matrix; zero order kinetics