Pharmaceutical Development of an Amorphous Solid Dispersion Formulation of Elacridar Hydrochloride for Proof-of-Concept Clinical Studies.

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Pharmaceutical Development of an Amorphous Solid Dispersion Formulation of Elacridar Hydrochloride for Proof-of-Concept Clinical Studies.

Drug Dev Ind Pharm. 2016 Dec 23;:1-40

Authors: Sawicki E, Schellens JH, Beijnen JH, Nuijen B

Abstract
OBJECTIVE: A novel tablet formulation containing an amorphous solid dispersion (ASD) of elacridar hydrochloride was developed with the purpose to resolve the drug's low solubility in water and to conduct proof-of-concept clinical studies.
SIGNIFICANCE: Elacridar is highly demanded for proof-of-concept clinical trials that study the drug's suitability to boost brain penetration and bioavailability of numerous anticancer agents. Previously, clinical trials with elacridar were performed with a tablet containing elacridar hydrochloride. However, this tablet formulation resulted in poor and unpredictable absorption which was caused by the low aqueous solubility of elacridar hydrochloride.
METHODS: 24 different ASDs were produced and dissolution was compared to crystalline elacridar hydrochloride and a crystalline physical mixture. The formulation with highest dissolution was characterized for amorphicity. Subsequently, a tablet was developed and monitored for chemical/physical stability for 12 months at +15-25°C, +2-8°C and -20°C.
RESULTS: The ASD powder was composed of freeze dried elacridar hydrochloride-povidone K30-sodium dodecyl sulfate (1:6:1, w/w/w), appeared fully amorphous and resulted in complete dissolution whereas crystalline elacridar hydrochloride resulted in only 1% dissolution. The ASD tablets contained 25 mg elacridar hydrochloride and were stable for at least 12 months at - 20°C.
CONCLUSIONS: The ASD tablet was considered feasible for proof-of-concept clinical studies and is now used as such.

PMID: 28010129 [PubMed - as supplied by publisher]

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