Self-Assembly of Cyclodextrins and Their Complexes in Aqueous Solutions.

Cyclodextrins (CDs) are enabling pharmaceutical excipients that can be found in numerous pharmaceutical products worldwide. Because of their favorable toxicologic profiles, CDs are often used in toxicologic and phase I assessments of new drug candidates. However, at relatively high concentrations, CDs can spontaneously self-assemble to form visible microparticles in aqueous mediums and formation of such visible particles may cause product rejections.

Freeze-drying of nanosuspensions, part 3: investigation of factors compromising storage stability of highly concentrated drug nanosuspensions.

On the basis of a previously developed formulation and process guideline for lyophilized, highly concentrated drug nanosuspensions for parenteral use, it was the purpose of this study to demonstrate that the original nanoparticle size distribution can be preserved over a minimum period of 3 months, even if aggressive primary drying conditions are used. Critical factors were evaluated that were originally believed to affect storage stability of freeze-dried drug nanoparticles. It was found that the nature and concentration of the steric stabilizer, such as Poloxamer 338 and Cremophor EL, are the most important factors for long-term stability of such formulations, independent of the used drug compound.

Freeze drying of nanosuspensions, 2: the role of the critical formulation temperature on stability of drug nanosuspensions and its practical implication on process design.

The present study investigates whether controlling the product temperature below the critical formulation temperature (CFT) during primary drying in a freeze drying cycle is a prerequisite for the stabilization of drug nanoparticles. For that purpose, the CFT of four drug nanosuspensions stabilized with different types (amorphous and crystalline) and concentrations of steric stabilizers and either of the disaccharides, trehalose and sucrose, was determined by differential scanning calorimetry and freeze-dry microscopy. Freeze-drying experiments were performed such that product temperatures during primary drying remained either below or well above the CFT of individual mixtures.

Freeze-drying of nanosuspensions, 1: freezing rate versus formulation design as critical factors to preserve the original particle size distribution.

It has been recently reported in the literature that using a fast freezing rate during freeze-drying of drug nanosuspensions is beneficial to preserve the original particle size distribution. All freezing rates studied were obtained by utilizing a custom-made apparatus and were then indirectly related to conventional vial freeze-drying. However, a standard freeze-dryer is only capable of achieving moderate freezing rates in the shelf fluid circulation system.

Monoglyceride-based self-assembling copolymers as carriers for poorly water-soluble drugs.

To develop self-assembling polymers forming polymeric micelles and increasing the solubility of poorly soluble drugs, amphiphilic polymers containing a hydrophilic PEG moiety and a hydrophobic moiety derived from monoglycerides and polyethers were designed. The biodegradable copolymers were obtained via a polycondensation reaction of polyethylene glycol (PEG), monooleylglyceride (MOG) and succinic anhydride (SA). Polymers with molecular weight below 10,000 g/mol containing a minimum of 40 mol% PEG and a maximum of 10 mol% MOG self-assembled spontaneously in aqueous media upon gentle mixing.