Formulation of rate-modulating pellets for the release of ibuprofen: an extrusion-spheronization process.
OBJECTIVE
To develop a stable and reproducible modified release pellet formulation containing ibuprofen.


METHODS
Using extrusion-spheronization technology to produce pellets.


RESULTS
The percentage yield, size distribution and overall pellet shape within the desired size range of 1000-1400 microm was found to be dependent on various process variables. These include extrusion and spheronization speed, spheronization time and composition of the granulation fluid. Formulation factors such as viscosity grade of hydroxypropylmethylcellulose and concentration of microcrystalline cellulose were shown to influence the drug release rate of the pellets. In vitro dissolution studies revealed that the pellets behaved in a pH-dependent manner. Pellets exposed to different drying techniques exhibited an increase in drug release rate in the order corresponding to oven-dried, vacuum-dried, fluid bed-dried and freeze-dried pellets. In conjunction with scanning electron microscopy, kinetic modelling and statistical treatment of dissolution data, it was confirmed that the predominant release rate-controlling mechanism was diffusion, as evidenced from the power law expressions incorporating Fickian and relaxational parameters (M(t) /M(infinity) = K(1)t(n); M(t) /M(infinity) = K(1)t(2n)). Matrix swelling and erosion were not significant factors in modulating the drug release rate.


CONCLUSIONS
The pH-dependent property of the pellets may be strategically employed towards development of a site-specific drug delivery system for non-steroidal anti-inflammatory agents. In general, targeting the delivery of an agent with potential for gastric irritation to the proximal intestine/colon may effectively reduce its ulcerogenic effect and ultimately contribute towards improved patient compliance.
Lutchman
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School of Pharmacy and Pharmacology, University of KwaZulu-Natal, Durban, South Africa. lutchmand@ukzn.ac.za
Dangor
C M
CM
Perumal
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D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002482:Cellulose; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004343:Drug Implants; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000008:administration & dosage*; D007785:Lactose / Q000031:analogs & derivatives / Q000737:chemistry; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D010316:Particle Size; D011109:Polymethacrylic Acids; D014783:Viscosity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004343:Drug Implants; D011109:Polymethacrylic Acids; C509290:hydroxypropylmethylcellulose-lactose matrix; C012553:spherons; D002482:Cellulose; D008747:Methylcellulose; D007785:Lactose; D007052:Ibuprofen