Solid-state transformations of ribavirin as a result of high-shear mechanical processing

Vasa, Dipy M.; Wildfong, Peter L.D.

doi:10.1016/j.ijpharm.2017.04.002

Cited by 17 publications

(24 citation statements)

References 45 publications

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“…It is noteworthy that the mole-fraction solubility of ribavirin (II) in water at 298.15 K determined in this work is 0.01741, which is a little larger than 0.0103 (142 mgÁmLl À1 ) reported by Benet [19], Goodarzi [20], Dave [21] and Chen [22], 0.0109 (149 mgÁmL À1 ) reported by Vasa [23], and 0.0124 (169.99 mgÁmL À1 ) reported by Prasanthi [24]. The difference may be due to many factors, such as determination method, equilibration time, purity, sampling, analysis method and so on.…”

Section: Solubility Resultscontrasting

confidence: 50%

“…The difference may be due to many factors, such as determination method, equilibration time, purity, sampling, analysis method and so on. Based on study made by Vasa and Wildfong [23], ribavirin (II) reached a maximum solubility within 30 min. On the other hand, it can also be seen from the plots of the ribavirin (II) concentrations in distilled water as a function of time that, when the dissolution time is 180 min, the concentration of ribavirin (II) in water remains increased obviously.…”

Section: Solubility Resultsmentioning

confidence: 99%

“…Due to its good properties, ribavirin has been received great attention. Nevertheless, in spite of the usefulness of this drug, the physicochemical properties of ribavirin in aqueous and organic solutions have not been studied systematically in the previous works [19][20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

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Thermodynamic modelling of solubility and preferential solvation for ribavirin (II) in co-solvent mixtures of (methanol, n -propanol, acetonitrile or 1,4-dioxane) + water

Cong

et al. 2017

The Journal of Chemical Thermodynamics

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a b s t r a c tThe equilibrium solubility of ribavirin in solvent mixtures of {methanol (1) + water (2)}, {n-propanol (1) + water (2)}, {acetonitrile (1) + water (2)} and {1,4-dioxane (1) + water (2)} was determined experimentally by using isothermal dissolution equilibrium method within the temperature range from (278.15 to 318.15) K under atmospheric pressure (101.1 kPa). At the same temperature and mass fraction of methanol (n-propanol, acetonitrile or 1,4-dioxane), the mole fraction solubility of ribavirin is greater in (methanol + water) than in the other three solvent mixtures. The preferential solvation parameters were derived from their thermodynamic solution properties by means of the inverse Kirkwood-Buff integrals. The preferential solvation parameters for methanol, n-propanol, acetonitrile or 1,4-dioxane (dx 1,3 ) were negative in the four solvent mixtures with a very wide compositions, which indicated that ribavirin was preferentially solvated by water. Temperature had little effect on the preferential solvation magnitudes. The higher solvation by water could be explained in terms of the higher acidic behaviour of water interacting with the Lewis basic groups of the ribavirin. Besides, the solubility of the drugs was mathematically represented by using the Jouyban-Acree model, van't Hoff-Jouyban-Acree model and Apelblat-Jouyban-Acree model obtaining average relative deviations lower than 1.57% for correlative studies. It is noteworthy that the solubility data presented in this work contribute to expansion of the physicochemical information about the solubility of drugs in binary solvent mixtures and also allows the thermodynamic analysis of the respective dissolution and specific solvation process.

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Section: Solubility Resultscontrasting

confidence: 50%

Section: Solubility Resultsmentioning

confidence: 99%

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Thermodynamic modelling of solubility and preferential solvation for ribavirin (II) in co-solvent mixtures of (methanol, n -propanol, acetonitrile or 1,4-dioxane) + water

Cong

et al. 2017

The Journal of Chemical Thermodynamics

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“…Ribavirin raw material (batch #001-RIB-0908) was kindly donated by Euticals S.p.A. (Lodi, MI, Italy). The micronized powder was demonstrated to be exclusively the crystalline polymorph R-I by X-ray diffraction (data not shown) and DSC ( T m =180 °C), probably as a result of the milling process as reported by Vasa (Vasa & Wildfong, 2017 ). RBV analytical standard was purchased from Sigma Chemical Company (St. Louis, MO).…”

Section: Methodsmentioning

confidence: 57%

In vivo nose-to-brain delivery of the hydrophilic antiviral ribavirin by microparticle agglomerates

et al. 2018

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Nasal administration has been proposed as a potential approach for the delivery of drugs to the central nervous system. Ribavirin (RBV), an antiviral drug potentially useful to treat viral infections both in humans and animals, has been previously demonstrated to attain several brain compartments after nasal administration. Here, a powder formulation in the form of agglomerates comprising micronized RBV and spray-dried microparticles containing excipients with potential absorption enhancing properties, i.e. mannitol, chitosan, and α-cyclodextrin, was developed for nasal insufflation. The agglomerates were characterized for particle size, agglomeration yield, and ex vivo RBV permeation across rabbit nasal mucosa as well as delivery from an animal dry powder insufflator device. Interestingly, permeation enhancers such as chitosan and mannitol showed a lower amount of RBV permeating across the excised nasal tissue, whereas α-cyclodextrin proved to outperform the other formulations and to match the highly soluble micronized RBV powder taken as a reference. In vivo nasal administration to rats of the agglomerates containing α-cyclodextrin showed an overall higher accumulation of RBV in all the brain compartments analyzed as compared with the micronized RBV administered as such without excipient microparticles. Hence, powder agglomerates are a valuable approach to obtain a nasal formulation potentially attaining nose-to-brain delivery of drugs with minimal processing of the APIs and improvement of the technological and biopharmaceutical properties of micronized API and excipients, as they combine optimal flow properties for handling and dosing, suitable particle size for nasal deposition, high surface area for drug dissolution, and penetration enhancing properties from excipients such as cyclodextrins.

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“…The conversion of a stable ribavirin polymorph R-II into its metastable enantiotrope R-I has been investigated using mechanochemistry [ 89 – 90 ]. LAG in an improvised planetary mill using lead balls gave limited phase conversion [ 89 ] but dry milling R-II in a commercial mixer mill at 30 Hz gave 100% conversion within 15 minutes [ 90 ]. Three crystal polymorphs of the antiviral nucleoside prodrug clevudine were characterised and a large scale preparation of the most stable form from commercial material was performed using LAG in a mortar [ 91 ].…”

Section: Reviewmentioning

confidence: 99%

Mechanochemistry of nucleosides, nucleotides and related materials

Eguaogie¹,

Vyle²,

Conlon³

et al. 2018

Beilstein J. Org. Chem.

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The application of mechanical force to induce the formation and cleavage of covalent bonds is a rapidly developing field within organic chemistry which has particular value in reducing or eliminating solvent usage, enhancing reaction rates and also in enabling the preparation of products which are otherwise inaccessible under solution-phase conditions. Mechanochemistry has also found recent attention in materials chemistry and API formulation during which rearrangement of non-covalent interactions give rise to functional products. However, this has been known to nucleic acids science almost since its inception in the late nineteenth century when Miescher exploited grinding to facilitate disaggregation of DNA from tightly bound proteins through selective denaturation of the latter. Despite the wide application of ball milling to amino acid chemistry, there have been limited reports of mechanochemical transformations involving nucleoside or nucleotide substrates on preparative scales. A survey of these reactions is provided, the majority of which have used a mixer ball mill and display an almost universal requirement for liquid to be present within the grinding vessel. Mechanochemistry of charged nucleotide substrates, in particular, provides considerable benefits both in terms of efficiency (reducing total processing times from weeks to hours) and by minimising exposure to aqueous conditions, access to previously elusive materials. In the absence of large quantities of solvent and heating, side-reactions can be reduced or eliminated. The central contribution of mechanochemistry (and specifically, ball milling) to the isolation of biologically active materials derived from nuclei by grinding will also be outlined. Finally non-covalent associative processes involving nucleic acids and related materials using mechanochemistry will be described: specifically, solid solutions, cocrystals, polymorph transitions, carbon nanotube dissolution and inclusion complex formation.

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Solid-state transformations of ribavirin as a result of high-shear mechanical processing

Cited by 17 publications

References 45 publications

Thermodynamic modelling of solubility and preferential solvation for ribavirin (II) in co-solvent mixtures of (methanol, n -propanol, acetonitrile or 1,4-dioxane) + water

Thermodynamic modelling of solubility and preferential solvation for ribavirin (II) in co-solvent mixtures of (methanol, n -propanol, acetonitrile or 1,4-dioxane) + water

In vivo nose-to-brain delivery of the hydrophilic antiviral ribavirin by microparticle agglomerates

Mechanochemistry of nucleosides, nucleotides and related materials

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