Nanoseeded Desupersaturation and Dissolution Tests for Elucidating Supersaturation Maintenance in Amorphous Solid Dispersions

The impact of residual drug crystals that are formed during the production and storage of amorphous solid dispersions (ASDs) has been studied using micron-sized seed crystals in solvent-shift (desupersaturation) and dissolution tests. This study examines the impacts of the seed size loading on the s...

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Bibliographic Details
Published in:Pharmaceutics 2023-01, Vol.15 (2), p.450
Main Authors: Guner, Gulenay, Amjad, Ayesha, Berrios, Matthew, Kannan, Manisha, Bilgili, Ecevit
Format: Article
Language:English
Subjects:
amorphous solid dispersions
Analysis
Bioavailability
Cellulose
Composition
Crystallization
Crystals
desupersaturation
Drugs
Methods
Methylcellulose
Nanocrystals
nanoseeds
Performance evaluation
Pharmaceutical industry
Polymers
poorly soluble drugs
residual crystals
Seeds
solvent-shift method
Solvents
Surfactants
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Summary:The impact of residual drug crystals that are formed during the production and storage of amorphous solid dispersions (ASDs) has been studied using micron-sized seed crystals in solvent-shift (desupersaturation) and dissolution tests. This study examines the impacts of the seed size loading on the solution-mediated precipitation from griseofulvin ASDs. Nanoparticle crystals (nanoseeds) were used as a more realistic surrogate for residual crystals compared with conventional micron-sized seeds. ASDs of griseofulvin with Soluplus (Sol), Kollidon VA64 (VA64), and hydroxypropyl methyl cellulose (HPMC) were prepared by spray-drying. Nanoseeds produced by wet media milling were used in the dissolution and desupersaturation experiments. DLS, SEM, XRPD, and DSC were used for characterization. The results from the solvent-shift tests suggest that the drug nanoseeds led to a faster and higher extent of desupersaturation than the as-received micron-sized crystals and that the higher seed loading facilitated desupersaturation. Sol was the only effective nucleation inhibitor; the overall precipitation inhibition capability was ranked: Sol > HPMC > VA64. In the dissolution tests, only the Sol-based ASDs generated significant supersaturation, which decreased upon an increase in the nanoseed loading. This study has demonstrated the importance of using drug nanocrystals in lieu of conventional coarse crystals in desupersaturation and dissolution tests in ASD development.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics15020450