Manufacturing of solid dispersions of poorly water soluble drugs by spray drying: Formulation and process considerations

Paudel, Amrit; Worku, Zelalem Ayenew; Meeus, Joke; Guns, Sandra; Mooter, Guy Van den

doi:10.1016/j.ijpharm.2012.07.015

Cited by 459 publications

(290 citation statements)

References 238 publications

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“…4 To overcome this difficulty, large quantities of crystallization-inhibiting polymers can be added. 5 Although drugs can be made amorphous, their use is still very limited as it is even more difficult to prevent crystallization during storage; this is especially the case if drugs are kept at temperatures close to their glass transition temperature, T g , as many drugs are. 6 This spontaneous phase transformation occurs even if they are stabilized with crystallization-inhibiting polymers; 7 it uncontrollably changes the bioavailability and limits the utility of amorphous drugs.…”

Section: Introductionmentioning

confidence: 99%

Crystallization of undercooled liquid fenofibrate

Amstad

Spaepen

Weitz

2015

Phys. Chem. Chem. Phys.

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Formulation of hydrophobic drugs as amorphous materials is highly advantageous as this increases their solubility in water and therefore their bioavailability. However, many drugs have a high propensity to crystallize during production and storage, limiting the usefulness of amorphous drugs. We study the crystallization of undercooled liquid fenofibrate, a model hydrophobic drug. Nucleation is the ratelimiting step; once seeded with a fenofibrate crystal, the crystal rapidly grows by consuming the undercooled liquid fenofibrate. Crystal growth is limited by the incorporation of molecules into its surface. As nucleation and growth both entail incorporation of molecules into the surface, this process likely also limits the formation of nuclei and thus the crystallization of undercooled liquid fenofibrate, contributing to the good stability of undercooled liquid fenofibrate against crystallization.

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Section: Introductionmentioning

confidence: 99%

Crystallization of undercooled liquid fenofibrate

Amstad

Spaepen

Weitz

2015

Phys. Chem. Chem. Phys.

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“…1,2 Since the poorly soluble drugs must be dissolved in the gastrointestinal lumen contents before oral absorption, improving the solubility and dissolution rate of poorly soluble APIs is rapidly becoming the leading hurdle for formulation scientists. 3,4 Consequently, a variety of strategies have been developed to overcome this obstacle for poorly water-soluble APIs, such as solid dispersions, 5,6 nanoemulsion, 7 salt formation, 8 melt extrusion, 9,10 liposomes, 11,12 nanostructured lipid carriers, 13,14 and micellar systems. 15,16 During the past several years, the use of particle size reduction methods to form stable nanosized particles has been proven to be an effective strategy to address this thorny problem.…”

Section: Introductionmentioning

confidence: 99%

Effect of particle size on oral absorption of carvedilol nanosuspensions: in vitro and in vivo evaluation

Liu¹,

Pan²,

He³

et al. 2015

IJN

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The purpose of this work was to explore the particle size reduction effect of carvedilol on dissolution and absorption. Three suspensions containing different sized particles were prepared by antisolvent precipitation method or in combination with an ultrasonication process. The suspensions were characterized for particle size, surface morphology, and crystalline state. The crystalline form of carvedilol was changed into amorphous form after antisolvent precipitation. The dissolution rate of carvedilol was significantly accelerated by a reduction in particle size. The intestinal absorption of carvedilol nanosuspensions was greatly improved in comparison with microsuspensions and solution in the in situ single-pass perfusion experiment. The in vivo evaluation demonstrated that carvedilol nanosuspensions and microsuspensions exhibited markedly increased C max (2.09- and 1.48-fold) and AUC 0− t (2.11- and 1.51-fold), and decreased T max (0.34- and 0.48-fold) in contrast with carvedilol coarse suspensions. Moreover, carvedilol nanosuspensions showed good biocompatibility with the rat gastric mucosa in in vivo gastrointestinal irritation test. The entire results implicated that the dissolution rate and the oral absorption of carvedilol were significantly affected by the particle size. Particle size reduction to form nanosized particles was found to be an efficient method for improving the oral bioavailability of carvedilol.

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“…This possible difference of solute deposition time might also influence the spatial distribution of the API (25).…”

Section: Discussionmentioning

confidence: 99%

Combination of (M)DSC and Surface Analysis to Study the Phase Behaviour and Drug Distribution of Ternary Solid Dispersions

et al. 2014

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den (2015) Combination of (M)DSC and surface analysis to study the phase behaviour and drug distribution of ternary solid dispersions. Pharmaceutical Research, 32 (4 A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. Results:The distribution of the API in the ternary solid dispersions depended on formulation parameters. The extent of API surface coverage and therefore the distribution of the API over both polymeric phases differed significantly for the three formulations. Conclusions:Combining (M)DSC and surface analysis rendered additional insights in the composition of mixed phases in complex systems, like ternary solid dispersions.3

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Manufacturing of solid dispersions of poorly water soluble drugs by spray drying: Formulation and process considerations

Cited by 459 publications

References 238 publications

Crystallization of undercooled liquid fenofibrate

Crystallization of undercooled liquid fenofibrate

Effect of particle size on oral absorption of carvedilol nanosuspensions: in vitro and in vivo evaluation

Combination of (M)DSC and Surface Analysis to Study the Phase Behaviour and Drug Distribution of Ternary Solid Dispersions

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Manufacturing of solid dispersions of poorly water soluble drugs by spray drying: Formulation and process considerations

Cited by 459 publications

References 238 publications

Crystallization of undercooled liquid fenofibrate

Crystallization of undercooled liquid fenofibrate

Effect of particle size on oral absorption of carvedilol nanosuspensions: in vitro and in&nbsp;vivo&nbsp;evaluation

Combination of (M)DSC and Surface Analysis to Study the Phase Behaviour and Drug Distribution of Ternary Solid Dispersions

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Effect of particle size on oral absorption of carvedilol nanosuspensions: in vitro and in vivo evaluation