Formulation and characterization of ternary solid dispersions made up of Itraconazole and two excipients, TPGS 1000 and PVPVA 64, that were selected based on a supersaturation screening study

Janssens, Sandrien; Nagels, Sophie; Armas, Héctor Novoa de; D'Autry, Ward; Schepdael, Ann Van; Mooter, Guy Van den

doi:10.1016/j.ejpb.2007.11.004

Cited by 91 publications

(39 citation statements)

References 16 publications

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“…The impact of surfactant addition in solid dispersions has been extensively studied by the group of Dr. Van den Mooter (71)(72)(73)(74). In one study, the surfactant TPGS 1000 was incorporated into solid dispersions containing an experimental antiviral compound, UC781, and either PVP VA64 or HPMC 2910 resulting in more rapid dissolution rates as the surfactant concentration was increased in solid dispersion granules (75).…”

Section: Thermal Processing Strategies Incorporation Of Plasticizers mentioning

confidence: 99%

“…In one study, the surfactant TPGS 1000 was incorporated into solid dispersions containing an experimental antiviral compound, UC781, and either PVP VA64 or HPMC 2910 resulting in more rapid dissolution rates as the surfactant concentration was increased in solid dispersion granules (75). TPGS 1000 was also evaluated in solid dispersions containing itraconazole and PVP VA64 (73). Itraconazole was found to have improved the maintenance of supersaturation relative to the presence of PVP VA64 or TPGS 1000 alone and, thus, was formulated together in a ternary solid dispersion.…”

Section: Thermal Processing Strategies Incorporation Of Plasticizers mentioning

confidence: 99%

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Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

2015

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Abstract. Thermal processing of amorphous solid dispersions continues to gain interest in the pharmaceutical industry, as evident by several recently approved commercial products. Still, a number of pharmaceutical polymer carriers exhibit thermal or viscoelastic limitations in thermal processing, especially at smaller scales. Additionally, active pharmaceutical ingredients with high melting points and/or that are thermally labile present their own specific challenges. This review will outline a number of formulation and process-driven strategies to enable thermal processing of challenging compositions. These include the use of traditional plasticizers and surfactants, temporary plasticizers utilizing sub-or supercritical carbon dioxide, designer polymers tailored for hot-melt extrusion processing, and KinetiSol® Dispersing technology. Recent case studies of each strategy will be described along with potential benefits and limitations.

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Section: Thermal Processing Strategies Incorporation Of Plasticizers mentioning

confidence: 99%

Section: Thermal Processing Strategies Incorporation Of Plasticizers mentioning

confidence: 99%

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

2015

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“…This involves adding a small volume of a concentrated solution of the poorly soluble test compound in an organic solvent to a relevant test medium in the presence or absence of various potential stabilizers. [92,93] It is important that the thermodynamic solubility of the test compound into the mixture of the organic solvent and the test medium is exceeded to create supersaturation. The influence of the formulation compounds on the generation and stabilization of supersaturation is then determined from the time-concentration profiles.…”

Section: Crystal Growthmentioning

confidence: 99%

“…[58,94,95] Some polymers that have been thoroughly investigated for their stabilizing characteristics are PVP, PEG, methylcellulose (MC) and HPMC. [57][58][59]93] Above their critical micellar concentration, surfactants will solubilize poorly soluble compounds and thereby decrease the degree of supersaturation. Apart from that, they are also capable of delaying the nucleation and crystal growth process.…”

Section: Crystal Growthmentioning

confidence: 99%

Review: physical chemistry of solid dispersions

2009

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Objectives With poorly soluble drug candidates emerging in the drug discovery pipeline, the importance of the solid dispersion formulation approach is increasing. This strategy includes complete removal of drug crystallinity, and molecular dispersion of the poorly soluble compound in a hydrophilic polymeric carrier. The potential of this technique to increase oral absorption and hence bioavailability is enormous. Nevertheless, some issues have to be considered regarding thermodynamic instability, as well in supersaturated solutions that are formed upon dissolution as in the solid state. Key findings After a brief discussion on the historical background of solid dispersions and their current role in formulation, an overview will be given on the physical chemistry and stability of glass solutions as they form supersaturated solutions, and during their shelf life. Conclusions Thorough understanding of these aspects will elicit conscious evaluation of carrier properties and eventually facilitate rational excipient selection. Thus, full exploitation of the solid dispersion strategy may provide an appropriate answer to drug attrition due to low aqueous solubility in later stages of development.

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“…To increase the bioavailability researchers formulated binary mixtures with various polymers creating either solid dispersions or solid solutions with enhanced dissolution rate [5,[8][9]. Solid dispersions containing ternary systems of the drug with polymers were also evaluated with successful increase in the dissolution of itraconazole [10][11][12]. Itraconazole dissolution was also enhanced by complexation with cyclodextrin derivatives or even by adsorption on ordered mesoporous silica .…”

Section: Introductionmentioning

confidence: 99%

Synergistic Enhancement of Itraconazole Dissolution by Ternary System Formation with Pluronic F68 and Hydroxypropylmethylcellulose

Maghraby

2009

Sci. Pharm.

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Pluronic F68 is a surfactant which can inhibit CYP3A4, an enzyme responsible for hepatic metabolism of many drugs including itraconazole. This study investigated the effect of incorporation of Pluronic F68 as a ternary component in solid dispersions of itraconazole with hydroxypropyl-methylcellulose (HPMC) on the dissolution rate of itraconazole. Binary solid dispersions with HPMC, reduced the drug crystallinity, increased the equilibrium solubility but showed slow dissolution. Binary dispersions with Pluronic produced eutectic systems but the increase in solubility and dissolution was lower than that of HPMC systems. Ternary system comprising optimum proportions of drug with Pluronic and HPMC enhanced the dissolution rate showing dissolution efficiency comparable to that obtained with the marketed product of itraconazole. The study thus presented a system capable of increasing the dissolution rate of itraconazole with a potential for increased oral bioavailability by inhibiting its pre-systemic metabolism as well.

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Formulation and characterization of ternary solid dispersions made up of Itraconazole and two excipients, TPGS 1000 and PVPVA 64, that were selected based on a supersaturation screening study

Cited by 91 publications

References 16 publications

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

Review: physical chemistry of solid dispersions

Synergistic Enhancement of Itraconazole Dissolution by Ternary System Formation with Pluronic F68 and Hydroxypropylmethylcellulose

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