Effect of emulsifier blend on the characteristics of sustained release diclofenac microspheres.
This investigation involved the evaluation of the emulsifier blend effect on the development of sustained release diclofenac microspheres intended for use in a suspension formulation. The microspheres were prepared using the hydrophobic congealable disperse phase method. The emulsifier blend consisted of glycerol, monostearate (GMS), a hydrophobic emulsifier with HLB = 3.8, and Tween 80, a hydrophilic emulsifier with a HLB value of 15. The effect of this blend on the encapsulation efficiency, size distribution and drug release from the microspheres was studied. A critical amount of GMS (> 0.2 g) was found to be necessary for good encapsulation efficiency. X-ray diffractograms revealed that the drug retains its crystalline state within the microspheres, indicating that the drug is present as a dispersion within the wax matrix. Increasing amounts of Tween 80 caused an increase in the drug release while increased amounts of GMS retarded the release. The hydrophilic emulsifier and the emulsifier blend influenced the size distribution of the formed microspheres. With an increase in the amount of hydrophilic emulsifier, there was an initial increase in the percent of desired size fraction (137.5 microns) of microspheres followed by a decrease. Microspheres with a larger size released the drug slowly compared to smaller size microspheres, while increase in drug load increased the rate of drug release. The release pattern fitted the Higuchi dissolution kinetics for spherical matrices. Different impeller blade designs formed microspheres that exhibited different release rates. The microspheres (mean size 137.5 microns), had a release profile that made them suitable to be formulated as a sustained release suspension.
Lewis
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L
Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA.
Boni
R
R
Adeyeye
C M
CM
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002214:Capsules; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000008:administration & dosage*; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients; D005989:Glycerides; D006801:Humans; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011136:Polysorbates; D014961:X-Ray Diffraction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D003692:Delayed-Action Preparations; D005079:Excipients; D005989:Glycerides; D011136:Polysorbates; D004008:Diclofenac; C048159:glyceryl monostearate