Downstream drug product processing of itraconazole nanosuspension: Factors influencing drug particle size and dissolution from nanosuspension-layered beads

Parmentier, Johannes; Tan, En Hui; Low, Ariana; Möschwitzer, Jan P.

doi:10.1016/j.ijpharm.2017.04.012

Cited by 28 publications

(12 citation statements)

References 51 publications

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“…The crystallinity of the drug in nanocomposite particles is usually examined via X-Ray diffraction (XRD) (e.g., [ 183 , 208 ]) and differential scanning calorimetry (DSC) (e.g., [ 133 , 209 ]). The crystallinity of the drug in nanocomposites is affected by the nanosuspension preparation and drying method, as well as the formulation, especially drug–polymeric dispersant interactions.…”

Section: Preparation Characterization and Formulation Of Drug-lamentioning

confidence: 99%

“…Another disadvantage of such powders is the poor flowability and low bulk density, which requires further unit operations such as granulation and addition of a considerable amount of excipients to achieve suitable material characteristics for compression [ 55 , 245 ]. Most importantly, long processing/cycle times, i.e., on the order of day(s), as well as high cost and energy consumption [ 196 , 246 ], render freeze drying unfavorable for commercial-scale production for drying nanosuspensions of small molecule drugs [ 55 , 208 , 246 ]. Based on all these considerations, we maintain that freeze drying will not be of choice for large-scale development and manufacturing, unless the drug is thermally labile or extremely temperature/shear sensitive.…”

Section: Some Engineering Considerations For Rational Selection Ofmentioning

confidence: 99%

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Bioavailability Enhancement of Poorly Water-Soluble Drugs via Nanocomposites: Formulation–Processing Aspects and Challenges

et al. 2018

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Drug nanoparticles embedded in a dispersant matrix as a secondary phase, i.e., drug-laden nanocomposites, offer a versatile delivery platform for enhancing the dissolution rate and bioavailability of poorly water-soluble drugs. Drug nanoparticles are prepared by top-down, bottom-up, or combinative approaches in the form of nanosuspensions, which are subsequently dried to prepare drug-laden nanocomposites. In this comprehensive review paper, the term “nanocomposites” is used in a broad context to cover drug nanoparticle-laden intermediate products in the form of powders, cakes, and extrudates, which can be incorporated into final oral solid dosages via standard pharmaceutical unit operations, as well as drug nanoparticle-laden strip films. The objective of this paper is to review studies from 2012–2017 in the field of drug-laden nanocomposites. After a brief overview of the various approaches used for preparing drug nanoparticles, the review covers drying processes and dispersant formulations used for the production of drug-laden nanocomposites, as well as various characterization methods including quiescent and agitated redispersion tests. Traditional dispersants such as soluble polymers, surfactants, other water-soluble dispersants, and water-insoluble dispersants, as well as novel dispersants such as wet-milled superdisintegrants, are covered. They exhibit various functionalities such as drug nanoparticle stabilization, mitigation of aggregation, formation of nanocomposite matrix–film, wettability enhancement, and matrix erosion/disintegration. Major challenges such as nanoparticle aggregation and poor redispersibility that cause inferior dissolution performance of the drug-laden nanocomposites are highlighted. Literature data are analyzed in terms of usage frequency of various drying processes and dispersant classes. We provide some engineering considerations in comparing drying processes, which could account for some of the diverging trends in academia vs. industrial practice. Overall, this review provides rationale and guidance for drying process selection and robust nanocomposite formulation development, with insights into the roles of various classes of dispersants.

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Section: Preparation Characterization and Formulation Of Drug-lamentioning

confidence: 99%

Section: Some Engineering Considerations For Rational Selection Ofmentioning

confidence: 99%

Bioavailability Enhancement of Poorly Water-Soluble Drugs via Nanocomposites: Formulation–Processing Aspects and Challenges

et al. 2018

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“…[ 8 ] A recent article has studied the effect of these variables on the drug dissolution rate, using two different bead–solvent pairs, although in most places only the sucrose beads’ formulation is currently available. [ 9 ]…”

Section: Introductionmentioning

confidence: 99%

A pilot analysis of morphometric assessment of itraconazole brands using dermoscopy and its relevance in the current scenario

Sardana

Khurana

Singh

et al. 2018

Indian Dermatol Online J

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“…The addition of SLS as an electrostatic stabilizer in combination with HPMC is well known to be beneficial for the stabilization effect (Knieke et al, 2013;Knieke et al, 2015;Parmentier et al, 2017;Peltonen, 2018). The stabilizing effect is due to the adsorption on particle surfaces and, thereby, formation of surfaces with a charge sufficient for stabilization (Peltonen and Hirvonen, 2010).…”

Section: Effect Of Stabilizer Concentration and Bead Sizementioning

confidence: 99%

Nanosuspensions of a poorly soluble investigational molecule ODM-106: Impact of milling bead diameter and stabilizer concentration

Singhal

Baumgartner

Turunen

et al. 2020

International Journal of Pharmaceutics

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Aqueous solubility of a drug substance is an important attribute affecting oral bioavailability.Nanonization, particle size reduction to submicron level, is an elegant approach to improve drug solubility and dissolution by increasing the surface energy, which in turn necessitates the use of stabilizers. The purpose of this study was to develop a nanosuspension of a practically water-insoluble investigational molecule by nanomilling approach using wet media milling. A variety of polymeric and surface active excipients were tested for their wettability. A combination of hydroxypropyl methylcellulose and sodium lauryl sulfate (SLS) were selected as stabilizers on the bases of compatibility studies and efficient wettability behaviour in contact angle measurements (≈80˚). A factorial design set-up was used to study the effect of milling bead diameter and stabilizer concentration on the efficiency of particle size reduction.Nanonization outcome was different when milling beads of 0.5 mm and 1 mm diameter were used at different concentrations of the stabilizers, which demonstrated the complex nature of the whole system. Storage of the nanosuspensions under different temperature conditions resulted only in minor changes of the particle size fractions.

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Downstream drug product processing of itraconazole nanosuspension: Factors influencing drug particle size and dissolution from nanosuspension-layered beads

Cited by 28 publications

References 51 publications

Bioavailability Enhancement of Poorly Water-Soluble Drugs via Nanocomposites: Formulation–Processing Aspects and Challenges

Bioavailability Enhancement of Poorly Water-Soluble Drugs via Nanocomposites: Formulation–Processing Aspects and Challenges

A pilot analysis of morphometric assessment of itraconazole brands using dermoscopy and its relevance in the current scenario

Nanosuspensions of a poorly soluble investigational molecule ODM-106: Impact of milling bead diameter and stabilizer concentration

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