Micro‐ and Nanosizing of Poorly Soluble Drugs by Grinding Techniques

Scheler, Stefan

doi:10.1002/9781118444726.ch16

Cited by 2 publications

(3 citation statements)

References 95 publications

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“…Co-crystals of poorly soluble APIs have been reported to have a higher solubility as compared with pure API. ,− On the other hand, also a pure API, or its dispersion with a polymer, can be solubilized significantly, if prepared as a fine powder. The micronization can be achieved not only by freeze-drying, but also by mechanical treatment liquid-assisted grinding (LAG), ball-milling, ,, or wet-milling. − Up to now, LAG has been the main method of obtaining meloxicam co-crystals and improving meloxicam bioavailability. ,,,, In this work we compare the dissolution dynamics of fine powders of pure meloxicam, its co-crystal with succinic acid, prepared (a) mechanically, (b) by freeze-drying, as well as of the solid dispersion a M-SA co-crystal with polyethylenglycol, prepared by freeze-drying. Succinic acid is one of the most common coformers.…”

Section: Introductionmentioning

confidence: 99%

Cryosynthesis of Co-Crystals of Poorly Water-Soluble Pharmaceutical Compounds and Their Solid Dispersions with Polymers. The “Meloxicam–Succinic Acid” System as a Case Study

Myz

Ogienko

Nefedov

et al. 2018

Crystal Growth & Design

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Co-crystals of pharmaceutical compounds are widely used to improve the properties of drug formulations, such as dissolution behavior, bioavailability, or tabletability. The main methods of their synthesis include co-crystallization from solution, melt, or cogrinding. Only a few examples have been documented when co-crystals have been obtained by freeze-drying, namely, in systems where the components of a target co-crystal had similar aqueous solubilities. This work illustrates the potential of freeze-drying for obtaining pharmaceutical cocrystals when the solubilities of individual components differ drastically. Co-crystals of a model system meloxicam and succinic acidcould be obtained both as a pure crystalline phase and forming a solid dispersion with a polymeric carrier. We show that even for pharmaceutical compounds with very low aqueous solubility, co-crystals with wellsoluble coformers can be successfully produced under well-optimized conditions of cooling and subsequent freeze-drying. The rate of release of meloxicam from the fine solid dispersion of its cocrystal with succinic acid in polyethylenglycol obtained by freeze-drying was significantly higher than dissolution rates of (a) pure meloxicam cocrystals with succinic acid obtained by different variants of freeze-drying (thin film freezing, TFF, and spray freeze-drying, SFD), (b) the powder of meloxicam cocrystal with succinic acid obtained by liquid-assisted cogrinding. The possibility to obtain co-crystals of components with very different aqueous solubilities not only by TFF or SFD techniques but also by freezing solutions in vials at temperatures significantly higher than that of liquid nitrogen is shown.

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Section: Introductionmentioning

confidence: 99%

Cryosynthesis of Co-Crystals of Poorly Water-Soluble Pharmaceutical Compounds and Their Solid Dispersions with Polymers. The “Meloxicam–Succinic Acid” System as a Case Study

Myz

Ogienko

Nefedov

et al. 2018

Crystal Growth & Design

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“…Surfactants are often employed as grinding aids for reducing particle size during ball-milling processes (comminution), 36,37 but to our knowledge grinding is not widely used for micelle formation and encapsulation. However, solid-state mixing in the absence of solvent has been applied for the supramolecular encapsulation of fullerenes and other polyaromatic hydrocarbons.…”

Section: Resultsmentioning

confidence: 99%

“…Three methods for encapsulating GNPs by SB micelles in water and 1 M NaCl were investigated: (a) the addition of citrate-stabilized GNPs to preformed SB micelles containing C12-SH; (b) the gradual removal of co-solvent from microemulsions of C12-SH coated GNPs mixed with SB micelles; and (c) the solid-state mixing of SB surfactants and C12-SH coated GNPs using mechanochemical (grinding) methods (Figure ). Surfactants are often employed as grinding aids for reducing particle size during ball-milling processes (comminution), , but to our knowledge grinding is not widely used for micelle formation and encapsulation. However, solid-state mixing in the absence of solvent has been applied for the supramolecular encapsulation of fullerenes and other polyaromatic hydrocarbons. , We thus compared mechanochemical encapsulation against solution-based methods.…”

Section: Resultsmentioning

confidence: 99%

Micellization and Single-Particle Encapsulation with Dimethylammoniopropyl Sulfobetaines

2017

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Sulfobetaines (SBs) are a class of zwitterionic surfactants with a reputation for enhancing colloidal stability at high salt concentrations. Here, we present a systematic study on the self-assembly of SB amphiphiles (sultaines or hydroxysultaines) in aqueous solutions, as a function of chain length and composition, ionic strength, and in the presence of alkanethiol-coated Au nanoparticles (GNPs). The diameters of the micelles assembled from SB and amidosulfobetaine (ASB) generally increase monotonically with chain length, although ASB micelles are smaller relative to alkyl SB micelles with similarly sized tailgroups, and oleyl sulfobetaine (OSB) micelles are slightly larger. SB amphiphiles can stabilize alkanethiol-coated GNPs in physiologically relevant buffers at concentrations well below their CMC, with size increases corresponding to single-particle encapsulation. SB-encapsulated GNPs were prepared by three different methods with SB:GNP weight ratios of 10:1, followed by dispersion in water or 1 M NaCl. The low hydrodynamic size of the SB micelles and SB-coated NPs is within the range needed for efficient renal clearance.

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Micro‐ and Nanosizing of Poorly Soluble Drugs by Grinding Techniques

Cited by 2 publications

References 95 publications

Cryosynthesis of Co-Crystals of Poorly Water-Soluble Pharmaceutical Compounds and Their Solid Dispersions with Polymers. The “Meloxicam–Succinic Acid” System as a Case Study

Cryosynthesis of Co-Crystals of Poorly Water-Soluble Pharmaceutical Compounds and Their Solid Dispersions with Polymers. The “Meloxicam–Succinic Acid” System as a Case Study

Micellization and Single-Particle Encapsulation with Dimethylammoniopropyl Sulfobetaines

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