Dissolution mechanism of poorly water-soluble drug from extended release solid dispersion system with ethylcellulose and hydroxypropylmethylcellulose
ABSTRACT The purpose of this study is to investigate the release mechanism of poorly water-soluble drug from the extended release solid dispersion systems with water-insoluble ethylcellulose (EC) and water-soluble hydroxypropylmethylcellulose (HPMC) (1:1). Indomethacin (IND) was used as a model of poorly water-soluble drug. Two kinds of solid dispersions were prepared by the solvent evaporation methods, which consist of the same formulation but exhibit different physical performance. It appeared that the dissolution behavior of IND depended on the structures of EC-HPMC matrices, which were governed by the preparation method. In addition, the dissolution behavior showed pH dependency that the dissolution rate of IND was slower in acidic medium than that in neutral medium. The experimental results revealed that the hydrophobic interaction between IND and EC occurred under lower pH and strongly delayed the dissolution rate of IND. The relationship between this hydrophobic interaction and the dissolution rate of IND was also proposed.
SourceAvailable from: Hirofumi Takeuchi[Show abstract] [Hide abstract]
ABSTRACT: To enhance the dissolution of poorly water-soluble drugs using a twin-screw kneader as a completely solvent-free method. Completely dry process was performed using a twin-screw kneader with hydrophilic porous silica in order to make solid dispersions of indomethacin, risperidone and fenofibrate at melting temperature of each drug. Changes in the molecular state of the drugs were investigated using the powder X-ray diffractometry and differential scanning calorimetry analyses. The dissolution studies were performed using the puddle method. On the powder X-ray diffraction, nitrogen adsorption and differential scanning calorimetry analyses, indomethacin and risperidone in solid dispersion changed to an amorphous state to adsorb onto silica pores. However, crystalline form of fenofibrate in solid dispersion was maintained in spite of the adsorption of fenofibrate onto silica pores. It was indicated that no functional groups were found interacting with silanol groups of silica surface resulting in the detection of the crystal form remained. A remarkable dissolution enhancement of the drugs from kneaded products was achieved by making the solid dispersion system with porous silica. Improvement of wettability and dispersibility, resulting from adsorption onto hydrophilic porous silica, was substantially contributed to the dissolution enhancement. Melt kneading process to make solid dispersion with porous silica was an effective technology to enhance the dissolution rate.
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ABSTRACT: Solid dispersion has been a topic of interest in recent years for its potential in improving oral bioavailability, especially for poorly water soluble drugs where dissolution could be the rate-limiting step of oral absorption. Understanding the physical state of the drug and polymers in solid dispersions is essential as it influences both the stability and solubility of these systems. This review emphasizes on the classification of solid dispersions based on the physical states of drug and polymer. Based on this classification, stability aspects such as crystallization tendency, glass transition temperature (Tg), drug polymer miscibility, molecular mobility, etc. and solubility aspects have been discussed. In addition, preparation and characterization methods for binary solid dispersions based on the classification have also been discussed.Drug Development and Industrial Pharmacy 04/2015; DOI:10.3109/03639045.2015.1018274 · 2.01 Impact Factor
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ABSTRACT: Solid dispersion, defined as the dispersion of one or more active ingredient in a carrier or matrix at solid state, is an efficient strategy for improving dissolution of poorly water-soluble drugs for enhancement of their bioavailability. Compared to other conventional formulations such as tablets or capsules, solid dispersion which can be prepared by various methods has many advantages. However, despite numerous studies which have been carried out, limitations for com-mercializing these products remain to be solved. For example, during the manufacturing process or storage, amorphous form of solid dispersion can be converted into crystalline form. That is, the dissolution rate of solid dispersion would continuously decrease during storage, resulting in a product of no value. To resolve these problems, studies have been conducted on the effects of excipients. In fact, modification of the solid dispersions to overcome these disadvantages has progressed from the first generation to the recent third generation products. In this review, an overview on solid dispersions in general will be given with emphasis on the various manufacturing processes which include the use of polymers and on the stabilization strategies which include methods to prevent crystallization.06/2011; 41(3). DOI:10.4333/KPS.2011.41.3.125