Particle Characterization of Poorly Water-Soluble Drugs Using a Spray Freeze Drying Technique

Abstract

657Many newly developing compounds have been dropped out during the early stages of drug development process because of poorly water-soluble property. Poorly water-soluble drugs often demonstrate the low bioavailability when administered orally due to the low dissolution and absorption rate in the gastrointestinal tract. Therefore, improvement of the solubility of poorly water-soluble compounds is an important mission in drug development.Increasing the solubility and dissolution rate of poorly water-soluble drugs is a significant challenge to pharmaceutical scientists. Technologies that have been commonly used to achieve this task include mechanical milling, 1) coprecipitation, 2,3) spray-drying, 4) the complex formation with watersoluble excipients, 5) and freeze-drying. 6) Spray drying has also been widely used as a technique to improve water solubility. However, it is not always appropriate for thermolabile compounds because the spray-drying process requires elevated temperatures. Although lyophilization or freeze-drying is a promising technique to produce pharmaceutical powders with improved solubility, the freezing rate is so slow that this technique is often difficult to apply in the pharmaceutical industry.Spray freezing into liquid nitrogen (SFL) is a novel cryogenic atomization technology, developed by Williams et al. [7][8][9][10][11] in which either an aqueous or an aqueous-organic cosolvent solution containing an active pharmaceutical ingredient (API) and a pharmaceutical excipient is atomized directly into cryogenic liquid nitrogen. This method via atomization resulted in production of fine particles with a significant large specific surface area, with high yields, and has also been found to prevent interparticle aggregation. In addition, when insulin was atomized by this method, it was possible to obtain lower crystallinity while preventing protein aggregation.In our previous work, 12) the solid dispersions were prepared by rapidly cooling of melt drugs in ice or in liquid nitrogen, and it was found that liquid nitrogen was appropriate as a cryogenic source to prepare particle-shaped solid dispersion with amorphous drug. Based on these previous results, we devised new atomization with quick freezing drying (a novel spray freeze drying: SFD) process which combined the spray dryer with the freeze drying equipment. This SFD method is spraying the drug solution over the surface of liquid nitrogen using the nozzle of the spray drier unlike the SFL method. Mumenthaler and Leuenberger 13) use the spray dryer as well as us, however, the freezing temperature makes it freeze at Ϫ70-Ϫ90°C, comparatively high temperature.The objective of this study was to utilize SFD technology for the preparation of composite particles containing a watersoluble polymer and a poorly water-soluble drug. In addition, the particles obtained by SFD were physicochemically characterized in the viewpoint of solubility improvement. ExperimentalMaterials Tolbutamide (TBM), which was commercially purchased from Wako Pure Chemical Indust...

Novel Spray Freeze-Drying Technique Using Four-Fluid Nozzle-Development of Organic Solvent System to Expand Its Application to Poorly Water Soluble Drugs

“…It was found that 4N-SFD-MeCN particles (B-1, 2, 3) have porous and spherical structure, which is same characteristic morphology exhibited in 4N-SFD-aqua particles (A-1, 2, 3) as also reported in previous paper. 20,21) No difference in particle size was visually confirmed and Phe : Eud-L particles from both systems had 2-25 mm in diameter as shown in low-magnified photographs (A-3, B-3). However, the size and quantity of pores observed in the 4N-SFD-MeCN particles (B) are apparently smaller than those of 4N-SFD-aqua particles (A).…”

“…The resultant spray freeze-dried (SFD) composite particles were collected and stored in glass vials in a desiccator at room temperature before the characterization measurement. The detailed operational conditions of SFD preparation were basically same as those of previous experiments 20) except freeze-drying equipment.…”

“…In order to increase universality of unique lyophilization technique in SFL, authors have developed spray freeze-drying (SFD) technique before, which is combined the conventional spraydryer with freeze-dryer, both equipments are available in market. 20) In addition, SFD technique was further improved by adopting four-fluid nozzle (4N) to expand its application in pharmaceutical industry. 21) In the conventional process both API and a hydrophilic excipient, called drug and carrier in this report respectively, are necessary to be dissolved in common spray solution because two-fluid nozzle (2N) has only one liquid-supplying line.…”

Inorganic-polymer nanohybrid carrier for delivery of a poorly-soluble drug, ursodeoxycholic acid

“…Therefore, numerous approaches have been made to improve aqueous solubility of poorly soluble drugs in pharmaceutical industry and science. Most of strategies are based on particulating the drugs in small scale (nano-or micro-scale) through milling (Remenar et al, 2003;Choi et al, 2004;Hu et al, 2004), spray drying (Hu et al, 2004;Kondo et al, 2009) and nanoemulsification (Shakeel and Faisal, 2009) to increase the surface area-to-volume ratio of drug particles themselves, hence better interaction with the surrounding aqueous media. Many different types of delivery vehicles were also introduced to improve drug solubility, the approach of which was basically similar as distributing drug particles of small size inside of delivery vehicles (Chung et al, 2003;Denga et al, 2008).…”

Fabrication of biodegradable polyurethane microspheres by a facile and green process

“…Adjusting the solid content did not affect the size distribution, probably because the viscosity of dispersion was not affected by the different solid content. 33 The hypothetical mechanism for microsphere formation is illustrated in Figure 2. After spraying, the surface water of microbeads may quickly evaporate, which gives rise to the skin layer, in particular at high solid contents.…”