Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs.
TL;DR: In this review, it is intended to discuss the recent advances related on the area of solid dispersions.
About: This article is published in Drug Discovery Today.The article was published on 2007-12-01. It has received 1329 citations till now. The article focuses on the topics: Bioavailability & Recrystallization (geology).
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TL;DR: The article provides an integrated and contemporary discussion of current approaches to solubility and dissolution enhancement but has been deliberately structured as a series of stand-alone sections to allow also directed access to a specific technology where required.
Abstract: Drugs with low water solubility are predisposed to low and variable oral bioavailability and, therefore, to variability in clinical response. Despite significant efforts to "design in" acceptable developability properties (including aqueous solubility) during lead optimization, approximately 40% of currently marketed compounds and most current drug development candidates remain poorly water-soluble. The fact that so many drug candidates of this type are advanced into development and clinical assessment is testament to an increasingly sophisticated understanding of the approaches that can be taken to promote apparent solubility in the gastrointestinal tract and to support drug exposure after oral administration. Here we provide a detailed commentary on the major challenges to the progression of a poorly water-soluble lead or development candidate and review the approaches and strategies that can be taken to facilitate compound progression. In particular, we address the fundamental principles that underpin the use of strategies, including pH adjustment and salt-form selection, polymorphs, cocrystals, cosolvents, surfactants, cyclodextrins, particle size reduction, amorphous solid dispersions, and lipid-based formulations. In each case, the theoretical basis for utility is described along with a detailed review of recent advances in the field. The article provides an integrated and contemporary discussion of current approaches to solubility and dissolution enhancement but has been deliberately structured as a series of stand-alone sections to allow also directed access to a specific technology (e.g., solid dispersions, lipid-based formulations, or salt forms) where required.
1,201 citations
TL;DR: Viable formulation options for poorly water-soluble drugs, such as crystal modification, micronization, amorphization, self-emulsification, cyclodextrin complexation, and pH modification are reviewed on the basis of the biopharmaceutics classification system of drug substances.
961 citations
Cites background from "Solid dispersions as strategy to im..."
...The ASD formulations can be prepared by spray drying, melt extrusion, lyophilization, and use of supercritical fluids with polymeric carriers and/or surfactant (Vasconcelos et al., 2007)....
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TL;DR: Methods and excipients associated with the development of supersaturating drug delivery systems are assessed and the future directions and factors likely to contribute to or detract from optimal dosage form selection are assessed.
807 citations
TL;DR: A melting temperature (Tm)/glass-transition temperature (K/K) versus log P map for 139 compounds formulated as SDDs provides a perspective on an appropriate formulation strategy for low-solubility drugs with various physical properties.
Abstract: Spray-dried dispersions (SDDs) of low-solubility drugs have been prepared using the polymer hydroxypropyl methylcellulose acetate succinate (HPMCAS). For a variety of drug structures, these SDDs provide supersaturation in in vitro dissolution determinations and large bioavailability increases in vivo. In bile-salt/lecithin in vitro solutions, these SDDs provide amorphous drug/polymer colloids and an increased concentration of free drug and drug in micelles relative to crystalline or amorphous drug. As dry powders, the SDDs are a single amorphous phase in which the drug remains amorphous and dispersed and does not crystallize over storage times relevant for practical drug products. A melting temperature (Tm)/glass-transition temperature (Tg) (K/K) versus log P map for 139 compounds formulated as SDDs provides a perspective on an appropriate formulation strategy for low-solubility drugs with various physical properties.
554 citations
TL;DR: 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 are reviewed.
510 citations
References
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TL;DR: The historical background and definitions of the various systems including eutectic mixtures, solid dispersions and solid solutions, as well as the production, the different carriers and the methods used for the characterization of solid dispersion are outlined.
2,695 citations
1,883 citations
TL;DR: Commercial use of solid dispersion systems during the past four decades has been very limited, primarily because of manufacturing difficulties and stability problems, but this has been changing in recent years because of the availability of surface-active and self-emulsifying carriers and the development of technologies to encapsulate solid dispersions directly into hard gelatin capsules as melts.
1,730 citations
TL;DR: A model is proposed whereby the release behaviour from the dispersions may be understood in terms of the dissolution or otherwise of the drug into the concentrated aqueous polymer layer adjacent to the solid surface, including a derivation of an expression to describe the release of intact particles from the dispersed particles.
960 citations