الفهرس 
General IntroductionOnly 14 pages are availabe for public view
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Abstract
At present about 40% of drugs in the development pipelines and approximately 70% of drugs coming from synthesis or high throughput screening are poorly soluble in aqueous media. Several formulation strategies have been developed to address low solubility/dissolution rate. Some well-known examples for oral drug delivery are the formulation of solid dispersions, self-microemulsifying drug delivery systems and micronization/nanonization. The use of nanocrystals as a way to formulate poorly soluble drugs has matured rapidly in recent years with new formulations coming onto the market. The oral bioavailability of poorly soluble drugs is improved due to the higher solubility and dissolution rate of the nanocrystals compared to the coarse drug particles. The increase in dissolution rate is the result of the high surface area of the nanocrystals. The higher solubility also has an additional positive effect on the dissolution rate. Other positive effects of the reduction in size are a reduced influence of the fasted/fed state after intake and less gastrointestinal irritation. Nanosuspensions can be produced using two distinct strategies: a top-down strategy
media milling or high-pressure homogenization) and a bottom-up strategy (precipitation). Nanosuspensions are thermodynamically unstable due to the large increase in surface area. The increase in surface area results in an increase in free energy, which the system will try to minimize by agglomeration. In an attempt to address these drawbacks, nanosuspensions are very often dried to obtain a powder that can be further processed into an oral formulation. A survey of the literature shows that two major techniques are currently used to dry nanosuspensions: spray drying and freeze drying. Itraconazole has been chosen as a model drug for this study. It is an orally active triazole antimycotic agent, which is active against a broad spectrum of fungal species. ITZ has been classified as a BCS Class II drug, and thus, the bioavailability of unformulated ITZ is extremely low. The mechanism of action of this compound is similar to all other azole antifungals. It inhibits cytochrome P450 of the fungi and thus interferes in sterol biosynthesis in cell membrane, leading to cell death. It became available on the market in 1986 in the form of pellets in which the drug is layered onto sugar beads (Sporanox®). However, there is no liquid dosage form of itraconazole for use by pediatrics, geriatrics or those with significant dysphagia.