Improvement of the Dissolution Rate of Poorly Soluble Drugs by Solid Crystal Suspensions

We present a novel extrusion based approach where the dissolution rate of poorly soluble drugs (griseofulvin, phenytoin and spironolactone) is significantly accelerated. The drug and highly soluble mannitol are coprocessed in a hot melt extrusion operation. The obtained product is an intimate mixtur...

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Bibliographic Details
Published in:Molecular pharmaceutics 2011-06, Vol.8 (3), p.727-735
Main Authors: Thommes, Markus, Ely, David R, Carvajal, M. Teresa, Pinal, Rodolfo
Format: Article
Language:English
Subjects:
Drug Stability
Pharmaceutical Preparations - chemistry
Solubility
Suspensions - chemistry
Temperature
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Summary:We present a novel extrusion based approach where the dissolution rate of poorly soluble drugs (griseofulvin, phenytoin and spironolactone) is significantly accelerated. The drug and highly soluble mannitol are coprocessed in a hot melt extrusion operation. The obtained product is an intimate mixture of the crystalline drug and crystalline excipient, with up to 50% (w/w) drug load. The in vitro drug release from the obtained solid crystalline suspensions is over 2 orders of magnitude faster than that of the pure drug. Since the resulting product is crystalline, the accelerated dissolution rate does not bear the physical stability concerns inherent to amorphous formulations. This approach is useful in situations where the drug is not a good glass former or in cases where it is difficult to stabilize the amorphous drug. Being thermodynamically stable, the dissolution profile and the solid state properties of the product are maintained after storage at 40 °C, 75% RH for at least 90 days.
ISSN:1543-8384
1543-8392
DOI:10.1021/mp1003493