Dissolution mechanism of poorly water-soluble drug from extended release solid dispersion system with ethylcellulose and hydroxypropylmethylcellulose.

Analytical Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 2-1-6 Kashima, Osaka 532-8514, Japan.
International Journal of Pharmaceutics (Impact Factor: 3.99). 10/2005; 302(1-2):95-102. DOI: 10.1016/j.ijpharm.2005.06.019
Source: PubMed

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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Over 40% of active pharmaceutical ingredients (API) under development pipelines are poorly water-soluble drugs which limit formulation approaches, clinical application and marketability because of their low dissolution and bioavailability. Solid dispersion has been considered one of the major advancements in overcoming these issues with several successfully marketed products. A number of key references that describe state-of-the-art technologies have been collected in this review, which addresses various pharmaceutical strategies and future visions for the solubilization of poorly water-soluble drugs according to the four generations of solid dispersions. This article reviews critical aspects and recent advances in formulation, preparation and characterization of solid dispersions as well as in-depth pharmaceutical solutions to overcome some problems and issues that limit the development and marketability of solid dispersion products.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 09/2013; · 3.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Devising directions for surfactant assisted effective controlled release of drugs requires a quantitative and qualitative understanding of the drug-protein, drug-surfactant, and surfactant-protein interactions. In this work, the effect of micellar environment on the binding of naproxen and diclofenac sodium with bovine serum albumin has been studied. The isothermal titration calorimetric (ITC) results suggest that the binding of naproxen is reduced with the protein when it is delivered from micellar media. However, the binding is observed to be strengthened for diclofenac sodium. The differential scanning calorimetric results suggest that the integrity of the binding sites is not altered under the employed micellar conditions. The ITC results further suggest that the numbers of naproxen and diclofenac sodium molecules partitioning/binding per micelle of HTAB are 15 and 38, respectively. In the micelles, naproxen is restricted to the surface of the micelles whereas diclofenac sodium is able to partition in the palisade layers. A detailed understanding of the energetics of the drug-protein interactions under different conditions helps in devising directions for effective drug delivery. The ITC and DSC results have shown that the micelles assisted drug-protein interactions are modified depending on the hydrophobic content of the drug.
    Journal of Colloid and Interface Science 01/2014; 413:118-26. · 3.55 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Solid dispersions are considered as the one of the most emerging technologies for improving the practically water insoluble drugs dissolution profile thereby increasing the bioavailability of hydrophobic drugs. This article review provides the information about different types of solid dispersions based on their molecular arrangement and type of matrix material employed. Different methods of preparations of solid dispersions and recent advances in preparation methods have been highlighted. Various analytical tools employed in the characterization of solid dispersions are discussed.
    International Journal o f Advance d Chemical Science and Applications. 09/2014;