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Solid Dispersions as Strategy to Improve Oral Bioavailability of Poor Water Soluble Drugs

01 Jan 2013-
TL;DR: Experience with solid dispersions over the last 20-30 years indicates that this is a very fruitful approach to improving the release rate and oral bioavailability of poorly water soluble drugs.
Abstract: A B S T R A C T Currently only 8% of new drug candidates have both high solubility and permeability. More than 60% of potential drug products suffer from poor water solubility. This frequently results in potentially important products not reaching the market or not achieving their full potential. Experience with solid dispersions over the last 20-30 years indicates that this is a very fruitful approach to improving the release rate and oral bioavailability of poorly water soluble drugs. So this article highlights technology various approaches for the preparation of solid dispersion, technology involved, detail description of poorly water soluble drugs & carriers.

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Citations
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Journal ArticleDOI
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


Cites background from "Solid Dispersions as Strategy to Im..."

  • ...Second-generation polymeric carriers—including PVP, PEG, polymethacrylates, and HPMC (and its derivatives) —and 3rd-generation carriers including self-emulsifying and surfactant-based excipients are now considerably more common (Serajuddin, 1999; Vasconcelos et al., 2007)....

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Journal ArticleDOI
TL;DR: Although differential scanning calorimetry is the most widely used thermal analytical technique applied to the characterization of amorphous solid dispersions, there are many established and emerging techniques which have been shown to provide useful information.

399 citations


Cites background or methods from "Solid Dispersions as Strategy to Im..."

  • ...Riegelman [9] as well as the review by Vasconcelos et al [7]....

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  • ...Two phase blends (sometimes termed solid suspensions), on the other hand, occurwhen thedrughas limitedmiscibility in the carrier and undergoes phase separation [7,9]....

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  • ...For a more comprehensive descriptions of these various types of systems, the readers are encouraged to read the classic review of Chiou and Riegelman [9] as well as the review by Vasconcelos et al [7]....

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  • ...formation [5], and complexation [6], rendering the drug amorphous is an attractive option [7]....

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Journal ArticleDOI
TL;DR: Formulation approaches such as the preparation of co-amorphous small-molecule mixtures and the use of mesoporous silicon and silica-based carriers are presented as potential means to increase the stability of amorphous pharmaceuticals.

370 citations


Cites background from "Solid Dispersions as Strategy to Im..."

  • ...…amorphous drugs (Janssens and Van den Mooter, 2009). morphous drug–polymer mixtures are often hygroscopic and in hat case the absorbed moisture reduces the Tg of the system, leadng to phase separation and recrystallization (Lu and Zografi, 1998; asconcelos et al., 2007; Rumondor and Taylor, 2010)....

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Journal ArticleDOI
TL;DR: The results showed that the effect in improving oral bioavailability of CUR may be associated with improved water solubility, higher release rate in the intestine juice, enhanced absorption by improved permeability, inhibition of P-glycoprotein (P-gp)-mediated efflux, and increased residence time in the intestinal cavity.
Abstract: The overall goal of this paper was to develop poly(lactic-co-glycolic acid) nanoparticles (PLGA-NPs) of curcumin (CUR), named CUR-PLGA-NPs, and to study the effect and mechanisms enhancing the oral bioavailability of CUR. CUR-PLGA-NPs were prepared according to a solid-in-oil-in-water (s/o/w) solvent evaporation method and exhibited a smooth and spherical shape with diameters of about 200 nm. Characterization of CUR-PLGA-NPs showed CUR was successfully encapsulated on the PLGA polymer. The entrapment efficiency and loading rate of CUR were 91.96 and 5.75%, respectively. CUR-PLGA-NPs showed about 640-fold in water solubility relative to that of n-CUR. A sustained CUR release to a total of approximately 77% was discovered from CUR-PLGA-NPs in artificial intestinal juice, but only about 48% in artificial gastric juice. After oral administration of CUR-PLGA-NPs, the relative bioavailability was 5.6-fold and had a longer half-life compared with that of native curcumin. The results showed that the effect in imp...

336 citations

Journal ArticleDOI
TL;DR: This review focuses on the application of IL methodologies to solve critical pharmaceutical problems, in particular, the low solubility and thus bioavailability of pharmaceutical compounds and the presence of polymorphs, which severely hamper the efficacy of important commercially available drugs.
Abstract: In the past several years, ionic liquids (ILs) have been at the cutting edge of the most promising science and technology. ILs not only have found applications in classical areas of knowledge but also are important candidates to solve classical problems within several societal challenges, such as clean and efficient energy, through the development of a broad swath of energy technologies, such as advanced batteries, dye-sensitized solar cells, double-layer capacitors, actuators, fuel cells, thermo-cells, and water splitting, essentially related to highly efficient carbon capture and storage technologies and resource efficiency to date. This review focuses on the application of IL methodologies to solve critical pharmaceutical problems, in particular, the low solubility and thus bioavailability of pharmaceutical compounds and the presence of polymorphs, which severely hamper the efficacy of important commercially available drugs. The development of strategies to use ILs as carriers of pharmaceutical active compounds is an extremely promising and wide avenue. Further, the synthesis of liquid salts through the discerning combination of cations and anions with several distinct pharmaceutical roles provides answers to some of today's pharmaceutical industrial challenges.

319 citations


Cites background from "Solid Dispersions as Strategy to Im..."

  • ...Among the many strategies attempted are prodrugs (1, 2), salt formation (3–5), crystal engineering (6–8), solid dispersions (9, 10), and micellar systems (11)....

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References
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Journal ArticleDOI
TL;DR: The results of this study show that provided Itraconazole is highly amorphous the addition of PEG 6000 to HPMC 2910 E5 leads to an increase in drug release.

78 citations

Journal ArticleDOI
TL;DR: Contrary to the original proposal of Sekiguchi and coworkers, dissolution rates of driseofulvin from solid dispersions were found to be markedly affected by the particle size ofSolid dispersions.

70 citations

Book ChapterDOI
25 Sep 2007

14 citations