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Spray Drying: Solving solubility issues with amorphous solid dispersions

3 September 2015  •  Author(s): Yin-Chao Tseng, Boehringer Ingelheim

Amorphous solid dispersions are increasingly being used as a means of improving bioavailability of poorly water-soluble compounds in research and development, and spray drying technology has been recognised as one of the useful methods to generate amorphous solid dispersions. Although the application of spray drying for the production of amorphous solid dispersions in the drug discovery stage is still limited, amorphous solid dispersions prepared with a small-scale spray drying process can be an effective approach to deliver high doses of poorly water-soluble compounds and to enhance their plasma exposure in in vivo studies for early drug discovery efforts. This article reviews the application of this technology for the production of amorphous solid dispersions in a single process, and the use of small-scale spray dryers to produce amorphous solid dispersions as early preclinical formulations using only milligram quantities of drug substances.

Spray Drying: Solving solubility issues with amorphous solid dispersions

Early preclinical formulations

It is estimated that 40 to 60% of drug compounds in today’s drug discovery phases exhibit poor aqueous solubility, and these compounds frequently have certain delivery limitations. Early preclinical formulations are developed for in vivopharmacology, safety pharmacology and toxicology studies in drug discovery. The main purpose of these formulations is to obtain sufficient plasma exposure in in vivostudies for optimising, selecting and advancing compounds to the clinic. However, inadequate plasma exposure does not sufficiently provide safety margins surrounding the predicted efficacious dose in animal models.

Oral gavage is the most common route in animal dosing, and in general, solution formulations are preferred due to their simplicity, dose accuracy and dose flexibility. For poorly water-soluble compounds, enabling solution formulations with solubility enhancement using a co-solvent, cyclodextrin, surfactant, lipid-based product, or the combination formulations, are employed to yield improved plasma exposures. However, these enabling solution formulations often have limitations, such as poorly soluble compounds failing to reach target drug concentrations. Drug precipitation and vehicle-related side effects can also occur. These issues limit the amount of the poorly soluble compounds that can be administered to animals as a solution…

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