Impact of a non-meltable additive on melt agglomeration with a hydrophobic meltable binder in high-shear mixer

The present study aims to investigate the behavior of melt agglomeration with a low-viscosity hydrophobic meltable binder by using a non-meltable additive. The size, crushing strength, and pore size distribution of resultant agglomerates, the rheological, surface tension, and wetting properties of the molten binder, as well as, the flow characteristics of preagglomeration powder blend were determined. The use of additive showed contradictory agglomerate growth-promoting and -retarding effects on the molten binder surface tension and the interparticulate frictional forces. Critical concentration effects of additive corresponded to threshold transition of agglomeration-promoting to -retarding behavior were discussed.     

Melt pelletization in high shear mixer using a hydrophobic melt binder: influence of some apparatus and process variables.

The effects of process conditions and the apparatus variables on the granulometric characteristics of a formulation containing a hydrophobic binder (stearic acid), lactose and paracetamol prepared by melt pelletization process were investigated in a 10-litre high shear mixer. The factors under investigation were: impeller speed, massing time, type of impeller blades and presence of the deflector and their reciprocal interactions. Two granule characteristics were analysed: the percentage of aggregates larger than 3000 microm (Y(1)) and the yield of the 2000-microm pellet size fraction (Y(2)). In order to estimate simultaneously the above-mentioned factors, a particular experimental design was adopted, that allowed the reduction of the number of trials from 378 to 35 and took into consideration other uncontrolled factors with the aid of a block variable. Using the postulated model, we found the optimal operating conditions to minimize Y(1) and increase Y(2) by selecting the type of impeller, and by using an impeller speed lower than 300 rpm, a massing time of 8-9 min and by not using the deflector. Finally, the validity of the adopted strategy has been proved with an additional check point.     

An investigation into the effect of formulation variables and process parameters on characteristics of granules obtained by in situ fluidized hot melt granulation

The aim of this study was to investigate the influence of binder content, binder particle size, granulation time and inlet air flow rate on granule size and size distribution, granule shape and flowability, as well as on drug release rate. Hydrophilic (polyetilenglycol 2000) and hydrophobic meltable binder (glyceryl palmitostearate) were used for in situ fluidized hot melt granulation. Granule size was mainly influenced by binder particle size. Binder content was shown to be important for narrow size distribution and good flow properties. The results obtained indicate that conventional fluid bed granulator may be suitable for production of highly spherical agglomerates, particularly when immersion and layering is dominant agglomeration mechanism. Granule shape was affected by interplay of binder content, binder particle size and granulation time. Solid state analysis confirmed unaltered physical state of the granulate components and the absence of interactions between the active and excipients. Besides the nature and amount of binder, the mechanism of agglomerate formation seems to have an impact on drug dissolution rate. The results of the present study indicate that fluidized hot melt granulation is a promising powder agglomeration technique for spherical granules production.     

Investigation on in vitro dissolution rate enhancement of indomethacin by using a novel carrier sucrose fatty acid ester

Background and the purpose of the study

The purpose of the present investigation was to characterize and evaluate solid dispersions (SD) of indomethacin by using a novel carrier sucrose fatty acid ester (SFE 1815) to increase its in vitro drug release and further formulating as a tablet.

Methods

Indomethacin loaded SD were prepared by solvent evaporation and melt granulation technique using SFE 1815 as carrier in 1:0.25, 1:0.5 1:0.75 and 1:1 ratios of drug and carrier. Prepared SD and tablets were subjected to in vitro dissolution studies in 900 mL of pH 7.2 phosphate buffer using apparatus I at 100 rpm. The promising SD were further formulated as tablets using suitable diluent (DCL 21, Avicel PH 102 and pregelatinised starch) to attain the drug release similar to that of SD.. The obtained dissolution data was subjected to kinetic study by fitting the data into various model independent models like zero order, first order, Higuchi, Hixon-Crowell and Peppas equations. Drug and excipient compatibility studies were confirmed by fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry and scanning electron microscopy.

Results

The in vitro dissolution data exhibited superior release from formulation S₆ with 1:0.5 drug and carrier ratio using solvent evaporation technique than other SDs prepared at different ratio using solvent evaporation and melt granulation technique. The in vitro drug release was also superior to that of the physical mixtures prepared at same ratio and also superior to SD prepared using common carriers like polyvinyl pyrollidone and PEG 4000 by solvent evaporation technique. Tablets (T₈) prepared with DCL21 as diluent exhibited superior release than the other tablets. The tablet formulation (T₈) followed first order release with Non-Fickian release.

Conclusion

SFE 1815 a novel third generation carrier can be used for the preparation of SD for the enhancement of in vitro drug release of indomethacin an insoluble drug belonging to BCS class II.     

Impact of a Non-meltable Additive on Melt Agglomeration with a Hydrophobic Meltable Binder in High-Shear Mixer

The present study aims to investigate the behavior of melt agglomeration with a low-viscosity hydrophobic meltable binder by using a non-meltable additive. The size, crushing strength, and pore size distribution of resultant agglomerates, the rheological, surface tension, and wetting properties of the molten binder, as well as, the flow characteristics of preagglomeration powder blend were determined. The use of additive showed contradictory agglomerate growth-promoting and -retarding effects on the molten binder surface tension and the interparticulate frictional forces. Critical concentration effects of additive corresponded to threshold transition of agglomeration-promoting to -retarding behavior were discussed.