The influence of non-ionic surfactants on the rheological properties of drug/microcrystalline cellulose/water mixtures and their use in the preparation and drug release performance of pellets prepared by extrusion/spheronization.
The influence of adding two concentrations (5 and 25%) of non-ionic surfactants, one hydrophilic and the other hydrophobic, plus mixtures of equal parts of the two, on the rheological properties of a mixture of equal parts of microcrystalline cellulose and ibuprofen with water has been assessed by capillary rheometry. The mixtures were also used to form pellets by extrusion/spheronization and their in vitro dissolution in simulated intestinal fluid was measured. As with previous rheological studies of these types of pastes, the flow was non-Newtonian (shear thinning). Other rheological parameters were determined in terms of die entry angles, extensional flow and elastic parameters of recoverable shear and compliance. By comparisons with previous studies with the model drug, it was found that it was these latter parameters that were indicative of the ability of the formulations to produce satisfactory pellets. The experiments also identified that the level of surfactant as opposed to the type of surfactant determined the rheological properties of the wet mass. All the formulations were able to produce round pellets with a narrow size distribution, whereby their median size increased with the concentration of the surfactant. The 25% level of each of the surfactant formulations provided a rapid release of the drug (100% within 30min), but the 5% level and the mixed surfactant formulations provided lower drug release profiles.
Podczeck
Fridrun
F
Department of Mechanical Engineering, University College London, Torrington Place, London, WC1E 7JE, UK. f_podczeck@meng.ucl.ac.uk
Maghetti
Ana
A
Newton
J Michael
JM
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D004548:Elasticity; D005079:Excipients / Q000737:chemistry*; D006601:Hexoses / Q000737:chemistry; D007052:Ibuprofen / Q000008:administration & dosage / Q000737:chemistry; D007202:Indicators and Reagents; D008863:Microspheres; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D012212:Rheology; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D005079:Excipients; D006601:Hexoses; D007202:Indicators and Reagents; D011136:Polysorbates; D013501:Surface-Active Agents; D014867:Water; C018665:sorbitan monooleate; D002482:Cellulose; C109691:microcrystalline cellulose; D007052:Ibuprofen