(463a) Advanced Formulation of Co-Processed Ionic Liquid Drugs Via Spray Drying for Incorporation into Solid Dosage Forms

Transforming active pharmaceutical ingredients (APIs) into analogous ionic liquid forms (API-ILs) holds the potential to concurrently solve the increasingly commonplace problems of poor aqueous solubility and solid state instability of APIs. However, as this class of compounds mostly exist as viscous oils or waxes, handling, processing, and formulation are extremely challenging. Therefore, before these promising forms of active pharmaceutical ingredients (APIs) can be routinely incorporated into oral solid dosage forms (OSDs), questions remain as to how best to overcome their particularly poor material properties.

To address this, spray drying API-ILs with other excipients was found to be an excellent solidification method. This can be achieved in one of two ways by the appropriate selection of carrier material to form single or two-phase solid forms and was applicable to a range of API-ILs. Selecting an API-IL insoluble polymer (ethyl cellulose) to form two-phase systems allows for up to 75% w/w API-IL to be loaded into the polymer and recovered as a fine powder, whilst up to 90% w/w API-IL content can be recovered as a solidified paste. Alternatively, an exceptionally high glass transition temperature (T_g) polysaccharide (maltodextrin) can be used to form a single-phase solid solution with the API-IL. Using this approach, however, only allowed for 50% w/w loading of the API-IL in the polysaccharide to be successfully produced. This was due to T_g suppression becoming too substantial at higher loadings for a viable product to be recovered. Perhaps counterintuitively, this points towards the immiscible approach being more desirable for solidification of API-ILs.

As the intended use for the spray dried materials is for incorporation into OSDs, dissolution studies were performed in representative dissolution media and showed that solidification of the API-IL in this manner had no detrimental effect on release characteristics, even when encapsulated in the immiscible (and water insoluble) polymer. The nature of the interactions between API-IL and carrier material were verified using modulated differential scanning calorimetry, hot-stage microscopy, powder X-ray diffraction, and attenuated total reflectance Fourier transform infrared spectroscopy.

These results demonstrate that API-ILs spray dried at high loadings in immiscible or high T_g materials preserve solubility and solid state stability enhancements of the API-IL form. At the same time, these approaches provide solid powders for processing and further formulation unit operations, and so represent an exciting new platform that allows API-ILs to fulfil their potential for formulating poorly soluble compounds as OSDs.