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Solid-state transformations of ribavirin as a result of high-shear mechanical processing
Dipy M Vasa1, Peter L D Wildfong1
1Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA 15282, USA.
International Journal of Pharmaceutics
|April 6, 2017
Summary
Ribavirin (R-I) is kinetically stable, while the R-II polymorph converts to R-I upon milling. Milling-induced defects and heat facilitate this transformation, impacting antiviral drug stability.
Area of Science:
- Solid-state chemistry
- Materials science
- Crystallography
Background:
- Ribavirin, an antiviral agent, exists in multiple solid forms.
- Understanding polymorph stability is crucial for drug formulation and efficacy.
Purpose of the Study:
- To investigate the solid-state transformations of ribavirin polymorphs.
- To determine the influence of mechanical processing on polymorph conversion.
Main Methods:
- Calorimetry (isobaric heat capacity, heat of transition) to determine transition temperature (Ttr).
- Polymorph characterization via milling (cryogenic and impact) and isothermal storage.
- Analysis of crystallinity and amorphous content.
Main Results:
- Two phase-pure ribavirin polymorphs (R-I and R-II) were identified, with R-I being kinetically stable at ambient temperature.
- Unprocessed R-II did not convert to R-I above Ttr, but milled R-II transformed rapidly.
- Cryomilling led to amorphous ribavirin, while impact milling at ambient temperature converted R-II to R-I.
Conclusions:
- Mechanical processing, particularly milling, significantly impacts ribavirin polymorph stability.
- Defects and localized heating during milling lower the energy barrier for R-II to R-I transformation.
- Cryomilling preserves amorphous forms due to limited molecular mobility, whereas impact milling promotes R-I formation.