Pratibhash Chattopadhyay

PubMed2006

Particle size analysis in pharmaceutics: principles, methods and applications.

Physicochemical and biopharmaceutical properties of drug substances and dosage forms can be highly affected by the particle size, a critical process parameter in pharmaceutical production. The fundamental issue with particle size analysis is the variety of equivalent particle diameters generated by different methods, which is largely ascribable to the particle shape and particle dispersion mechanism involved. Thus, to enable selection of the most appropriate or optimal sizing technique, cross-correlation between different techniques may be required. This review offers an in-depth discussion on particle size analysis pertaining to specific pharmaceutical applications and regulatory aspects, fundamental principles and terminology, instrumentation types, data presentation and interpretation, in-line and process analytical technology. For illustration purposes, special consideration is given to the analysis of aerosols using time-of-flight and cascade impactor measurements, which is supported by a computational analysis conducted for this review.

Aerosols↗

PubMed2006

Nanoparticles of poorly water-soluble drugs prepared by supercritical fluid extraction of emulsions.

PURPOSE: The aim of the study was to develop and evaluate a new method for the production of micro- and nanoparticles of poorly soluble drugs for drug delivery applications. METHODS: Fine particles of model compounds cholesterol acetate (CA), griseofulvin (GF), and megestrol acetate (MA) were produced by extraction of the internal phase of oil-in-water emulsions using supercritical carbon dioxide. The particles were obtained both in a batch or a continuous manner in the form of aqueous nanosuspensions. Precipitation of CA nanoparticles was used for conducting a mechanistic study on particle size control and scale-up. GF and MA nanoparticles were produced in several batches to compare their dissolution behavior with that of micronized materials. The physical analysis of the particles produced was performed using dynamic light scattering (particle size), scanning electron microscopy (morphology), powder X-ray diffraction (crystallinity), gas chromatography (residual solvent), and a dissolution apparatus. RESULTS: Particles with mean volume diameter ranging between 100 and 1000 nm were consistently produced. The emulsion droplet size, drug solution concentration, and organic solvent content in the emulsion were the major parameters responsible for particle size control. Efficient and fast extraction, down to low parts-per-million levels, was achieved with supercritical CO2. The GF and MA nanoparticles produced were crystalline in nature and exhibited a 5- to 10-fold increase in the dissolution rate compared with that of micronized powders. Theoretical calculations indicated that this dissolution was governed mainly by the surface kinetic coefficient and the specific surface area of the particles produced. It was observed that the necessary condition for a reliable and scalable process was the sufficient emulsion stability during the extraction time. CONCLUSION: The method developed offers a viable alternative to both the milling and constructive nanoparticle formation processes. Although preparation of a stable emulsion can be a challenge for some drug molecules, the new technique significantly shortens the processing time and overcomes the current limitations of the conventional precipitation techniques in terms of large waste streams, product purity, and process scale-up.

Algorithms↗