Erythromycin particle formation with RESS process

In the pharmaceutical industry many of substances are insoluble or slightly soluble in aqueous media. Their application is limited by this solubility. Dissolution rate is a function of the surface area of the particles and solubility. Particle size is a critical parameter in the determining of surface area , and thus has significant effect on bioavailability. Therefore the bioavailability of the insoluble drugs in water can be improved by reduction in their particle size. Conventional techniques have been used for reduction of particle size such as crushing, grinding, milling, spray drying, freeze-drying and recrystallization of the solute particles from solutions using liquid antisolvents. Particle formation and design of pharmaceutical substances is major a development of SCF applications. Supercritical processes enhance micro or nano particles with narrow size distribution. The methods of fine particles formation using supercritical fluids are: RESS (Rapid Expansion of Supercritical Solutions), GAS/SAS (Gas Anti-Solvent/ Supercritical Anti- Solvent), ASES (Aerosol Solvent Extraction System), SEDS (Solution Enhanced Dispersion by Supercritical Fluids) and PGSS (Particles from Gas-Saturated Solutions/ Suspensions) In the RESS process, the solute to be precipitated is first dissolved in the supercritical solvent, and then the supercritical solution is expanded through a fine diameter nozzle or capillary. The rapid expansion of supercritical mixture leads to the high supersaturation ratios (the ratio of the solute mole fraction at the extraction temperature and pressure to the equilibrium mole fraction value at the given temperature and pressure) and consequently the fine particles are precipitated with narrow broad particle size distributions (PSDs) and to provide a solvent-free product. The morphology and size distributions of the precipitated materials are related to preexpansion, expansion conditions, extraction parameters and nozzle design. In this work, erythromycin is micronized by the RESS and effects of the process parameters such as extraction temperature (40, 50 and 60°C) and pressure (200, 300, 400, 500 and 600 bar), pre-expansion temperature (80, 100 and 120°C), flow rate of supercritical solution (5, 7.5 and 10 ml CO2/min), distance of spraying (3, 5, 7.5 and 10 cm) and type of nozzle on the size and morphology (orifis and capillary) of the precipitated erythromycin were investigated. HPLC, LC-MS, XRD, DSC and SEM analysis were done for erythromycin samples. End of this PhD thesis, the particle size of erythromycin was decreased from 13x8 ?m ? 45.2x20.8 ?m to ~2 ?m. According to bioactivity analysis there is not any degradation on the erythromycin structure during RESS process. Key Words: RESS, erythromycin, process of micronization