Development of a Spray Dried Tacrolimus Formulation Suitable for Delivery via a Dry Powder Inhaler

Iain G. Davidson, Fiona Dey, Karen Western

Tacrolimus is used as an immunosuppressant following transplant surgery. A dry powder inhaled form could be of advantage to lung transplant patients by improved targeting of the therapy and the reduction of systemic side effects. The aim of the research was to produce spray dried tacrolimus formulations, investigating the effects of the addition of a bulking agent and of blowing agents. Batches were manufactured from 50:50 vol% aqueous ethanol solution using Vectura’s bespoke small scale spray drier. The performance of the formulations was then assessed by cascade impactor testing using Vectura’s unit dose device or multi-unit dose Gyrohaler® device. Inclusion of trehalose or a blowing agent in the formulation greatly improved blister clearance and doubled the FPF (≤3.3 μm) compared to a pure tacrolimus powder. Comparable results were achieved using both devices. The two lead formulations – tacrolimus (20% blowing agent) and tacrolimus /trehalose 1:1 (20% blowing agent) – were filled into unit dose blisters and sealed in foil pouches for six months with little change in the performance at 25°C/60%RH with only a small decrease in FPF and FPM at 40°C/75%RH.
Spray dried powder formulations of tacrolimus have been successfully developed at a small scale using Vectura’s spray drying and formulation technology. The resulting formulations were successfully tested with both unit dose and multi-unit dose devices.

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