Effect of emulsifier blend on the characteristics of sustained release diclofenac microspheres

Abstract

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.

Development and in vitro evaluation of polar lipid based lipospheres for oral delivery of peptide drugs.

“…The value of coefficient of determination (R 2 ) in Higuchi equation was found to be >0.9 in alkaline buffer medium which again indicates the diffusion-controlled release. The result obtained is supported by the literatures reported on ibuprofen and diclofenac loaded wax microspheres [29,30]. The quicker drug release at low wax loads can be due to increased peptide positioned on the liposphere surface that remained exposed to the dissolution fluid.…”

“…Increase in peptide amount increased the drug loading with subsequent decrease in entrapment efficiency (Table 3). This may be explained by the fact that as the ratio of peptide to the lipid matrix increases, a reduced space becomes available for the peptide to be entrapped [29]. Inefficient encapsulation of peptide makes it possible to remain on the outer surface of the particles.…”

“…The faster dissolution with increased drug load can be explained by peptide present outside the LS and presumable increase in channels and number of pores (produced by the drug release) within the wax matrix. This effect caused a decrease in diffusion path length through the released part region and enhanced drug release [29,30]. Drug release kinetics from the STP formulations SLS1-SLS9 were examined at pH 7.4.…”

Alendronate PLGA microspheres with high loading efficiency for dental applications

“…Entrapment efficiency exceeding 100% could be explained by the loss of very small poorly loaded MS during the separation step, resulting in a higher proportion of drug to MS retained. A similar observation has been reported previously (Wan et al 1994, Lewis et al 1998). SEM of F 2 MS (Figure 1) indicates the presence of quite a large number of small microspheres.…”

Polymethacrylate Microparticles Gel for Topical Drug Delivery

“…The % IE exceeded 100% in some formulations (F3 and F4). This can be explained by the loss of very fine poorly drug-loaded or unloaded particles during MP separation or washing(41) or the loss of the dispersing agent to the external phase of the O/O emulsion. Both effects result in a higher proportion of drug to MPs.…”