Chemical Structural Effects of Amphipathic and Water-soluble Phospholipid Polymers on Formulation of Solid Dispersions.

For the polymeric carriers of solid dispersions, it is important that carriers themselves dissolve quickly and maintain the supersaturated state of amorphous drugs during their dissolution period to improve bioavailability. Amphipathic 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers can be dissolved in water, owing to the extremely high hydrophilicity of the MPC units, and are used as an ideal feeder for drug molecules to form aggregates in aqueous conditions. We synthesized amphipathic MPC copolymers with different hydrophobic side chains and molar ratios of MPC units, and evaluated the effect of the polymers on dissolution rate and supersaturation maintenance of solid dispersions of indomethacin.

Quantitative analysis of an impact of P-glycoprotein on edoxaban's disposition using a human physiologically based pharmacokinetic (PBPK) model.

The purpose of this study was to evaluate the impact of P-glycoprotein (P-gp) efflux on edoxaban absorption in gastrointestinal tracts quantitatively by a physiologically based pharmacokinetic (PBPK) model constructed with clinical and non-clinical observations (using GastroPlus™ software). An absorption process was described by the advanced compartmental absorption and transit model with the P-gp function. A human PBPK model was constructed by integrating the clinical and non-clinical observations.

Scale-Free Soft Sensor for Monitoring of Water Content in Fluid Bed Granulation Process.

In-line monitoring of granule water content during fluid bed granulation is important to control drug product qualities. In this study, a practical scale-free soft sensor to predict water content was proposed to cope with the manufacturing scale changes in drug product development. The proposed method exploits two key ideas to construct a scale-free soft sensor.

Application of void forming index (VFI): Detection of the effect of physical properties of dry powder inhaler formulations on powder cohesion.

Dry powder inhaler (DPI) is an attractive alternative for non-invasive drug administration and can make the use of critical biopharmaceutical formulations more convenient for patients. Inhalation of biopharmaceutical formulations can provide targeted delivery to the lungs as well as systemic delivery. Generally, biopharmaceutical DPI formulations consist of highly cohesive powders that tend to agglomerate.

Effects of inner polarity and viscosity of amphiphilic phospholipid polymer aggregates on the solubility enhancement of poorly water-soluble drugs.

We quantitatively evaluated the properties of aggregates of amphiphilic polymers formed in an aqueous medium and clarified the effect of the inside polarity and viscosity of the polymer aggregate on the solubilization of poorly water-soluble drugs. Three water-soluble amphiphilic 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers with various hydrophobic monomer units, namely, n-butyl methacrylate (BMA), 2-methacryloyloxyethyl butylurethane (MEBU), and 2-methacryloyloxyethyl benzylurethane (MEBZU), were synthesized. The different molecular interactions between the hydrophobic monomer units, such as hydrophobic interactions, hydrogen bonding, and dispersion force between the aromatic rings, were considered.

Establishment of a clinically relevant specification for dissolution testing using physiologically based pharmacokinetic (PBPK) modeling approaches.

This paper presented how to establish a clinically relevant specification (CRS) using in silico physiologically based pharmacokinetic (PBPK) modeling. Three different formulations of model drug products were used in the clinical studies in order to distinguish between bioequivalent (BE) batches from non-BE batches. A human PBPK model was constructed by integrating the clinical and non-clinical observations by using GastroPlus software.

Integration of In Silico Pharmacokinetic Modeling Approaches Into In Vitro Dissolution Profiles to Predict Bioavailability of a Poorly Soluble Compound.

The objective of present study is to develop pharmacokinetic (PK) prediction methods using in silico PK model for oral immediate release drug products (i.e. solution, suspension, and amorphous solid dispersion).

Influence of particle size and blender size on blending performance of bi-component granular mixing: A DEM and experimental study.

The effect of particle size enlargement and blender geometry down-scaling on the blend uniformity (BU) was evaluated by Discrete Element Method (DEM) to predict the blending performance of a binary granular mixture. Three 10 kg blending experiments differentiated by the physical properties specifically particle size were performed as reference for DEM simulations. The segregation behavior observed during the diffusion blending was common for all blends, while the sample BU, i.

Preparation and Characterization of Itraconazole- or Miconazole-Loaded PLGA Microspheres.

The purpose of this study was to prepare poly(lactide-co-glycolide) (PLGA) microspheres (MS) loaded with itraconazole (ITCZ) or miconazole (MCZ) under different evaporation temperatures (25 or 40°C) using an oil-in-water emulsion solvent evaporation method in order to evaluate the initial burst release of drug. Loading efficiencies were comparatively good and the diameters of prepared drug-loaded PLGA MS were around 20 µm in all formulations. The release rates of ITCZ-PLGA MS prepared at 40°C showed a significantly restricted release profile compared with the corresponding ITCZ-PLGA MS prepared at 25°C.

Selection of a round convex tablet shape that mitigates the risk of chipping and capping based on systematic evaluation by utilizing multivariate analysis.

Selecting a tablet shape that minimizes the risk of chipping and capping during manufacture is important in pharmaceutical industry. Here, the selection was performed based on systematic evaluation for the first time. Abrasion and stress relaxation time were utilized as indices of the occurrences of chipping and capping, respectively.

Effect of preparation method on properties of orally disintegrating tablets made by phase transition.

In order to evaluate the effect of preparation method on the properties of orally disintegrating (OD) tablets, OD tablets were prepared by compressing a mixture of high melting point sugar alcohol (HMP-SA) and low melting point sugar alcohol (LMP-SA) and subsequent heating. In the direct compression method (DCM) where the LMP-SA was added as a powder, both hardness and disintegration time were increased by decreasing the particle size of the LMP-SA. In the wet granule compression method (WGCM), where the LMP-SA was added as an aqueous binder solution, the tablets became harder with less heating compared to tablets prepared by DCM.

Evaluation of rapidly disintegrating tablets manufactured by phase transition of sugar alcohols.

The aim of the present study was to assess the properties of rapidly disintegrating (RD) tablets manufactured by the phase transition method. RD tablets were produced by compressing powder containing erythritol (melting point: 122 degrees C) and xylitol (melting point: 93 approximately 95 degrees C), and then heating at about 93 degrees C for 15 min. The hardness and oral disintegration time of the heated tablets increased with an increase of the xylitol content.