ChemInform Abstract: Pharmaceutical Application of Supercritical Fluid Technique:

Abstract

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Surfactant-Free Solid Dispersions of Hydrophobic Drugs in an Amorphous Sugar Matrix Dried from an Organic Solvent

“…An alternate methodology for improving the water solubility of a hydrophobic drug is based on the amorphization of the drug . Namely, the amorphous state can be regarded as a frozen solid of the constituents in the amorphous material, and when the constituent molecules are dispersed in a solvent in which the constituents are poorly soluble, it follows that they would temporarily behave as dissolved materials, a phenomenon that is referred to as “super-saturation” − or “over-dissolution.” It has actually been demonstrated that the water solubility of a water-insoluble drug can be approximately doubled as the result of amorphization. ,− Since amorphous hydrophobic drugs are usually unstable and have a tendency to crystallize, they are often amorphized in the presence of carrier matrix forming agents. − This strategy is categorized as a solid dispersion. − In the solid dispersion of water-insoluble drugs, an amphiphilic polymer such as polyvinylpyrrolidone is frequently used as the carrier matrix, , and a combination of a surfactant with an amorphous carbohydrate matrix has also been reported to be effective for the stable dispersion of drugs. , …”

“…23−25 In the solid dispersion of water-insoluble drugs, an amphiphilic polymer such as polyvinylpyrrolidone is frequently used as the carrier matrix, 26,27 and a combination of a surfactant with an amorphous carbohydrate matrix has also been reported to be effective for the stable dispersion of drugs. 28,29 However, over-dissolution can also occur in a system that is composed of a water-soluble solute and a fat-soluble solvent, which permits the preparation of a surfactant-free solid dispersion of fat-soluble oily substances in a dried amorphous sugar matrix 19,30 as follows (Figure S1): (i) The sugar is amorphized and (ii) added to an organic solvent containing a hydrophobic substance, followed by homogenization. (iii) The homogenized solution is then dried to a solid (surfactant-free solid dispersion) under appropriate conditions.…”

Thermal stability of amorphous sugar matrix, dried from methanol, as an amorphous solid dispersion carrier

“…The concentration of the dissolved drug temporarily increases much above the equilibrium solubility (over-dissolution), possibly resulting in the improvement of the bioavailability of the hydrophobic drug [6]. In the solid dispersion of hydrophobic drugs, an amphiphilic polymer such as polyvinylpyrrolidone and hydroxypropyl methylcellulose is frequently used as the carrier matrix [6,7], and a combination of a surfactant with an amorphous carbohydrate matrix has also been reported to be effective for the stable dispersion of drugs [8,9]. On the other hand, we recently developed a new ASD technique that does not involve the use of a surface active agent [10].…”