An innovative carrier for the formulation of amorphous solid dispersion by hot-melt extrusion with no further downstream processes: a case study with indomethacin.

The aim of this work was to study the possibility to use SepitrapTM as a carrier for the formulation of amorphous solid dispersions by HME (hot melt extrusion) processing aiming solubility enhancement of poorly water-soluble drugs. SepitrapTM is a microencapsulated powder solubilizer designed to simplify the manufacture of drugs in oral solid forms, not yet tested for this purpose. The performance of SepitrapTM was evaluated in HME processing for amorphous solid dispersions of poorly-water soluble drugs with indomethacin as a model drug. The study was conducted using a twin-screw extruder, two compositions of SepitrapTM and different loads of indomethacin, demonstrating that SepitrapTM could represent a new range of carriers for amorphous solid dispersions for HME processing, reducing necessary downstream steps such as grinding.

Comparison study of physicochemical and biopharmaceutics properties of hydrophobic drugs ground by two dry milling processes.

This study focuses on the dry milling of biopharmaceutical classification system (BCS) class II molecules. These molecules have a limited bioavailability because of their low aqueous solubility, poor water wettability and low dissolution rate. In order to improve these properties, indomethacin (IND) and niflumic acid (NIF) were milled using two different types of equipment: Pulverisette 0® and CryoMill®. Milled samples were characterized and compared to commercial molecules. IND shows a modified solid state, like surface crystallinity reduction and an increase in water vapor adsorption from to 2- up to 5-fold due to milling processes. The obtained solubility data resulted in an improvement in solubility up to 1.2-fold and an increase in initial dissolution kinetics: 2% of dissolved drug for original crystals against 25% for milled samples. For NIF no crystallinity reduction, no change of surface properties and no solubility improvement after milling were noticed. In addition, milled particles seemed more agglomerated resulting in no changes in dissolution rate compared to the original drug. IND solubility and dissolution enhancement can be attributed to the modification of surface area, drug crystallinity reduction, and water sorption increase due to specific behavior related to the drug crystal disorder induced by milling process.

Preparation and characterization of carnauba wax nanostructured lipid carriers containing benzophenone-3.

Nanostructured lipid carriers (NLCs) are potential active delivery systems based on mixtures of solid lipids and liquid oil. In this paper, aqueous dispersions of NLCs were prepared by a hot high-pressure homogenization technique using carnauba wax as the solid lipid and isodecyl oleate as the liquid oil. The preparation and stability parameters of benzophenone-3-loaded NLCs have been investigated concerning particle size, zeta potential and loading capacity to encapsulate benzophenone-3, a molecular sunscreen. The current investigation illustrates the effect of the composition of the lipid mixture on the entrapment efficiency, in vitro release and stability of benzophenone-3-loaded in these NLCs. A loading capacity of approximately 5% of benzophenone-3 (m(BZ-3) /m(lipids) ) was characteristic of these systems.