Academic CRO/Industrial collaborations in drug discovery (Track)



Challenges in Parenteral Dosage Form Preparations of Slightly Water-Soluble Drugs: Dantrolene Sodium’s Successful Example of Academic-Industrial Collaboration

Abeer M. Al-Ghananeem
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, USA

Abstract:

The making of a drug usually starts with an interesting observation made by a scientist, and ends with an FDA-approved product. In between, there is a wide gap with years of painstaking and costly work. In order to bridge the gap between the discoveries achieved at the ‘bench’ and therapies at the ‘bedside’, academia is increasingly investing in moving basic research into its ultimate goal: clinical application.

The solubility behavior of drugs remains one of the most challenging aspects in formulation development.  Dantrolene sodium (DS) is a hemiheptahydrate salt that has been used successfully in the treatment of malignant hyperthermia and neuroleptic malignant syndrome.  The main difficulty in DS drug development is its poor water solubility.

Various techniques, described in this study, were successfully utilized to enhance DS solubility and dissolution in both lab and industrial scale; API size reduction, use of co-solvent, and nanoparticle formulation has shown great promise to hasten the dissolution of slightly water soluble drug like DS.  These techniques provided valuable formulation alternative to the traditional formulation approach to ensure full drug solubility before intravenous administration.