Microfluidics-assisted engineering of polymeric microcapsules with high encapsulation efficiency for protein drug delivery.

In this study, microfluidic technology was employed to develop protein formulations. The microcapsules were produced with a biphasic flow to create water-oil-water (W/O/W) double emulsion droplets with ultrathin shells. Optimized microcapsule formulations containing 1% (w/w) bovine serum albumin (BSA) in the inner phase were prepared with poly(vinyl alcohol), polycaprolactone and polyethylene glycol.

A new cocrystal and salts of itraconazole: comparison of solid-state properties, stability and dissolution behavior.

Cocrystallization and salt formation have been shown to entail substantial promise in tailoring the physicochemical properties of drug compounds, in particular, their dissolution and hygroscopicity. In this work, we report on the preparation and comparative evaluation of a new cocrystal of itraconazole and malonic acid and two new hydrochloric salts (dihydrochloride and trihydrochloride) of itraconazole. The intrinsic dissolution rate, hygroscopicity, and thermodynamic stability were determined for the obtained solid-state forms and compared to itraconazole-succinic acid (2:1) cocrystal.

Enhanced Dissolution and Oral Bioavailability of Piroxicam Formulations: Modulating Effect of Phospholipids.

Several biologically relevant phospholipids were assessed as potential carriers/additives for rapidly dissolving solid formulations of piroxicam (Biopharmaceutics Classification System Class II drug). On the basis of in vitro dissolution studies, dimyristoylphosphatidylglycerol (DMPG) was ranked as the first potent dissolution rate enhancer for the model drug. Subsequently, the solid dispersions of varying piroxicam/DMPG ratios were prepared and further investigated.

Nanodispersions of taxifolin: impact of solid-state properties on dissolution behavior.

Nanosizing is an advanced formulation approach to address the issues of poor aqueous solubility of active pharmaceutical ingredients. Here we present a procedure to prepare a nanoparticulate formulation with the objective to enhance dissolution kinetics of taxifolin dihydrate, a naturally occurring flavonoid with antioxidant, anti-inflammatory, and hepatoprotective activities. Polyvinylpirrolidone was selected as a carrier and the solid nanodispersions of varying compositions were prepared by a co-precipitation technique followed by lyophilization.

Pharmaceutical co-crystals-an opportunity for drug product enhancement.

By maximizing our understanding of materials and the relative importance of interactions on all levels (i.e., molecular, particle, powder, product), we can improve the manufacture of drug dosage forms and thus meet target specifications for mechanical durability, stability and biopharmaceutical performance.

Crystal morphology engineering of pharmaceutical solids: tabletting performance enhancement.

Crystal morphology engineering of a macrolide antibiotic, erythromycin A dihydrate, was investigated as a tool for tailoring tabletting performance of pharmaceutical solids. Crystal habit modification was induced by using a common pharmaceutical excipient, hydroxypropyl cellulose, as an additive during crystallization from solution. Observed morphology of the crystals was compared with the predicted Bravais-Friedel-Donnay-Harker morphology.

Phase transformation of erythromycin A dihydrate during fluid bed drying.

An in-line near infrared (NIR) spectrometer was employed to monitor phase transformations of erythromycin dihydrate during a miniaturized fluid bed drying process. The pellets, containing 50% (w/w) erythromycin dihydrate and 50% (w/w) microcrystalline cellulose, were dried at 30, 45, and 60 degrees C. Principal component analysis was used to determine solid-state changes.

A new insight into solid-state conformation of macrolide antibiotics.

Quantitative analysis of the molecular conformations of the 14-membered macrolide antibiotics erythromycin A and B, clarithromycin, and roxithromycin in the solid state was performed. While the erythronolide macrocycle adopts a very similar folded-out conformation in all the macrolides studied, the proximity of the monosaccharide moieties, L-cladinose and D-desosamine, to each other is demonstrated to be the distinctive feature of their molecular conformations, based on atom-atom interaction energy analysis. More surprisingly, the common features in the relative orientation of the monosaccharide moieties (in terms of non-bonded atom-atom interactions) were revealed between the 14- and 15-membered (azithromycin) macrolide antibiotics.

Solid-state properties and relationship between anhydrate and monohydrate of baclofen.

Baclofen, a widely used antispastic agent, has been found to exist in two crystalline forms, the anhydrate and monohydrate. The aim of this study was (1) to identify and characterize these two solid phases of baclofen, and (2) to examine the processing-induced phase transformations associated with wet granulation of baclofen. Using multiple techniques (powder X-ray diffraction, thermal analysis, vibrational spectroscopy and water vapor sorption analysis), a structural relationship has been established between the anhydrate and monohydrate of baclofen.

Phase transformations of erythromycin A dihydrate during pelletisation and drying.

An at-line process analytical approach was applied to better understand process-induced transformations of erythromycin dihydrate during pellet manufacture (extrusion-spheronisation and drying process). The pellets contained 50% (w/w) erythromycin dihydrate and 50% (w/w) microcrystalline cellulose, with purified water used as a granulating fluid. To characterise changes in solid-state properties during processing, near infrared (NIR) spectroscopy and X-ray powder diffraction (XRPD) were applied.

Understanding processing-induced phase transformations in erythromycin-PEG 6000 solid dispersions.

Since the quality and performance of a pharmaceutical solid formulation depend on solid state of the drug and excipients, a thorough investigation of potential processing-induced transformations (PITs) of the ingredients is required. In this study, the physical phenomena taking place during formulation of erythromycin (EM) dihydrate solid dispersions with polyethylene glycol (PEG) 6000 by melting were investigated. PITs were monitored in situ using variable temperature X-ray powder diffraction (VT-XRPD), differential scanning calorimetry (DSC), and hot-stage microscopy (HSM).

Multivariate data analysis as a fast tool in evaluation of solid state phenomena.

A thorough understanding of solid state properties is of growing importance. It is often necessary to apply multiple techniques offering complementary information to fully understand the solid state behavior of a given compound and the relations between various polymorphic forms. The vast amount of information generated can be overwhelming and the need for more effective data analysis tools is well recognized.

Influence of solvents on the variety of crystalline forms of erythromycin.

The influence of the organic solvents widely used in the pharmaceutical industry (acetone, methylethylketone, ethanol, and isopropanol) both in the presence and in the absence of water on the crystallization behavior of erythromycin (Em), a clinically relevant antibiotic of the macrolide group, was investigated. It was observed that despite a high preference for water as a guest molecule, Em rather easily forms solvates with the organic solvents studied. Consequently, 4 distinct solvates of Em have been isolated by recrystallization: acetonate, methylethylketonate, ethanolate, and isopropanolate.