New Perspectives for Fixed Dose Combinations of Poorly Water-Soluble Compounds: a Case Study with Ezetimibe and Lovastatin.

Purpose: Aiming to improve the dissolution rate of ezetimibe (EZE) and lovastatin (LOV) in a fixed dose combination (FDC), co-amorphous systems and ternary solid dispersions were prepared by quench cooling and spray drying, respectively.

Methods: Formulations were characterized through X-ray diffraction, modulated differential scanning calorimetry, infrared spectroscopy, scanning electron microscopy and laser diffraction, and evaluated by 'in vitro' dissolution. Stability studies were conducted at different conditions during 30 days with the ternary solid dispersion composed of 75% of Soluplus® (ELS 1:1 75%).

Agglomeration of mesoporous silica by melt and steam granulation. Part I: a comparison between disordered and ordered mesoporous silica.

The objective of this study was to compare agglomerations by melt and steam granulation of ordered, COK-12, and disordered, Syloid(®) 244 FP (244), mesoporous silica material. Poloxamer 188 (P188) and polyvinylpyrrolidone K25 (PVP) were chosen as binders for melt and steam granulation, respectively. The poorly water-soluble compound, itraconazole (ITZ), was selected for the development of an immediate-release oral dosage form.

Agglomeration of mesoporous silica by melt and steam granulation. part II: screening of steam granulation process variables using a factorial design.

The objectives of this study were to identify the key process parameters during steam granulation of disordered mesoporous silica material Syloid® 244 FP (244) and to compare two different binders: polyvinylpyrrolidone (PVP) K25 and hydroxypropylmethyl cellulose (HPMC). Itraconazole (ITZ) was selected as the model compound for the development of an oral dosage form for enhanced release. Six factors: binder content, steam amount, mixing time, impeller speed, spray pause time, and filler content were investigated using a two-level quarter-fraction factorial design of experiment (DOE) for each binder type.

Drug release modification by interpolymer interaction between countercharged types of Eudragit® RL 30D and FS 30D in double-layer films.

Interpolymer interactions between the countercharged methacrylate copolymers Eudragit(®) RL 30D (polycation) and Eudragit(®) FS 30D (polyanion), were investigated in conditions mimicking the gastrointestinal environment. The formation of inter-macromolecular ionic bonds between Eudragit(®) RL 30D and Eudragit(®) FS 30D was investigated using FT-IR spectroscopy and modulated DSC. The FT-IR spectra of the tested polymeric matrices are characterized by visible changes in the observed IR region indicating the interaction between chains of two oppositely charged copolymers.

Effect of compression on non-isothermal crystallization behaviour of amorphous indomethacin.

Purpose: To evaluate the effect of tablet compression on the physical stability of amorphous indomethacin.

Methods: The amorphous indomethacin generated by melt cooling, rapid (5°C/min) or slow (0.2°C/min) cooling, was evaluated by PXRD, mDSC and FTIR analysis.

Influence of preparation methods on solid state supersaturation of amorphous solid dispersions: a case study with itraconazole and eudragit e100.

Purpose: The present study aims to determine the drug / polymer miscibility level as a function of the preparation method for an amorphous solid dispersion model system containing itraconazole and eudragit E100. This value was compared to the theoretical crystalline drug solubility in the amorphous polymer and the miscibility of the amorphous drug in the amorphous polymer.

Methods: The amorphous solid dispersions were prepared via spray drying and film casting in order to evaluate the influence of the solvent drying rate.

Spray drying from complex solvent systems broadens the applicability of Kollicoat IR as a carrier in the formulation of solid dispersions.

The presented study aims to explore the feasibility of preparing solid dispersions of the poorly soluble drug, itraconazole, with Kollicoat IR via spray drying, in order to broaden the application window of the polymer. In order to circumvent the need for a common solvent, Kollicoat IR was dissolved in a 50/50 (v/v) water/ethanol mixture and itraconazole was dissolved in a 50/50 (v/v) dichloromethane/ethanol mixture. In a first approach these two solutions were simultaneously spray dried via a spray nozzle with two inlets.

Influence of polyethylene glycol chain length on compatibility and release characteristics of ternary solid dispersions of itraconazole in polyethylene glycol/hydroxypropylmethylcellulose 2910 E5 blends.

The present study aims to elucidate the influence of the polyethylene glycol chain length on the miscibility of PEG/HPMC 2910 E5 polymer blends, the influence of polymer compatibility on the degree of molecular dispersion of itraconazole, and in vitro dissolution. PEG 2000, 6000, 10,000 and 20,000 were included in the study. Solid dispersions were prepared by spray drying and characterized with MDSC, XRPD and in vitro dissolution testing.

The effect of pressurized carbon dioxide as a temporary plasticizer and foaming agent on the hot stage extrusion process and extrudate properties of solid dispersions of itraconazole with PVP-VA 64.

The aim of the current research project was to explore the possibilities of combining pressurized carbon dioxide with hot stage extrusion during manufacturing of solid dispersions of itraconazole and polyvinylpyrrolidone-co-vinyl acetate 64 (PVP-VA 64) and to evaluate the ability of the pressurized gas to act as a temporary plasticizer as well as to produce a foamed extrudate. Pressurized carbon dioxide was injected into a Leistritz Micro 18 intermeshing co-rotating twin-screw melt extruder using an ISCO 260D syringe pump. The physicochemical characteristics of the extrudates with and without injection of carbon dioxide were evaluated with reference to the morphology of the solid dispersion and dissolution behaviour and particle properties.

Comparative evaluation of co-processed lactose and microcrystalline cellulose with their physical mixtures in the formulation of folic acid tablets.

In this study, a new co-processed filler-binder ingredient for direct compression, MicroceLac 100, was compared with three different lactoses mixed with microcrystalline cellulose. The aim was to improve a folic acid tablet formulation. Therefore, the influence of drug addition to these mixtures was studied with regard to flow and binding properties.