Surface responses and desirability functions to determine optimal granulation domains.

Background: Single pot mixer-granulator-dryer (high-shear granulator with in situ double jacket vacuum drying) and multiphase equipment (high-shear granulator associated with fluid bed dryer) are classically used for wet granulation. At present time, industrial production imperatives may require to switch one formulation from one equipment to another.

Method: To compare the two processes and to define, for each of them, the optimal formulation domain, experiments were organized according to Doehlert experimental designs.

Comparison of single pot and multiphase granulation. Part 2: Effect of the drying process on granules manufactured in a single pot granulator and dried either in situ or in a fluid bed dryer.

The aim of this study was to highlight the effect of the drying process on granules manufactured in a pilot scale single pot granulator and dried either in situ or in a fluid bed dryer, for formulations differing in drug substance and its concentration (1%; 25%). Although most of raw data were within specifications, single pot drying tended to improve granule comprimability and seemed less sensitive to formulation. Moreover, it was demonstrated that the formulation impacted on granule median diameter, packing ability, comprimability, residual lower punch pressure and tablet dissolution kinetics.

Comparison of single pot and multiphase granulation. Part 1: Effect of the high shear granulator on granule properties according to the drug substance and its concentration.

Pharmaceutical granulations are usually developed with regard to a specific manufacturing process but switching from one piece of equipment to another can be necessary to comply with the available industrial equipment. Investigations were undertaken on formulations differing in the drug substance and in its concentration. Our aim was to highlight the effect of the granulation process on granules manufactured in a pilot scale Moritz Turbosphere TS50 or in Fielder PMA 65 and dried in a Glatt GPCG1 fluid bed dryer.

Comparison of single pot and multiphase high shear wet granulation processes related to excipient composition.

At present time, industrial production imperatives can require the transposition of a formulation from one equipment to another. In order to evaluate the impact of such a switch on the properties of granules and tablets, investigations were undertaken on formulations manufactured both in a single pot mixer-granulator-dryer (high shear granulator with in situ double jacket vacuum drying) and in a multiphase equipment (high shear granulator/fluid bed dryer). Principal component analysis highlighted the major contribution of the binder ratio on granule size distribution, flow and packing ability whereas the relative ratio of mannitol and lactose, used as fillers, mainly impacted on compressibility and tablet cohesion.

Drug/lactose co-micronization by jet milling to improve aerosolization properties of a powder for inhalation.

The aim of this work was to formulate a powder for inhalation with fusafungine, a drug substance initially highly cohesive. The classical approach based on micronization by jet milling to prepare respirable drug particles and then blending with a carrier was first applied. A fractional factorial experimental design was implemented to screen six formulation parameters.