Plasticization, a common method of reducing the polymer melt viscosity in plastics extrusion, was investigated to improve the processability of a pharmaceutical formulation during twin-screw melt granulation. The thermolabile drug gabapentin was used as a model compound given previous work showed the benefit of preparing 80% drug loading gabapentin granules with hydroxypropyl cellulose as thermal binder. The plasticizer triethyl citrate was selected based on physicochemical compatibility with both the thermal binder and gabapentin by assessing polymer melt rheology and drug stability, respectively. Gabapentin was melt granulated at 80% drug loading with pre-plasticized binder using a co-rotating twin-screw extruder. The chemical stability and tabletability of the pre-plasticized granules were assessed to evaluate granule tabletability, drug stability, and process robustness. The granulation of gabapentin was facilitated by pre-plasticization, showing both increased granule growth and the ability to optimize processing conditions by lowering processing temperature. Pre-plasticization of thermal binder was therefore shown to be beneficial during melt granulation as a method of optimizing processing conditions while maintaining granule robustness.

In this study we have developed a high-dose dry powder inhaler formulation of indomethacin using a novel approach to carrier-based formulations. Specifically, larger drug particles serve as the carrier for the smaller micronized drug particles, such that an inhaled dose is combined with an oral dose. To study this system, the aerosol performance of a standard indomethacin–lactose formulation was compared to carrier-free micronized indomethacin and a drug-as-carrier formulation (a micronized indomethacin–coarse indomethacin blend). Indomethacin with lactose showed a very poor aerosol performance, indicating high adhesion between the drug and carrier. The performance of the carrier-free micronized drug was significantly better, indicating low cohesion. Coarse drug particles as a carrier allowed improved powder flow and aerosol performance while also providing a potential secondary route of absorption of indomethacin, namely oral. An optimal formulation ratio of 1:1 (w/w) fine indomethacin–coarse indomethacin was developed in this study.

Inhaled biologics to treat lung diseases have an extensive history. This is counterbalanced by the limited products that have reached the commercialization stage of development despite the numerous disease states and targets that may be suitable for the delivery of proteins, peptides, or nucleic acid therapeutics. These opportunities are reviewed alongside current and past clinical and preclinical studies that highlight both successful and discontinued programs, providing key lessons for future development. Although there are physical, biological, and technical barriers that must be overcome to successfully deliver these relatively fragile moieties to the lung, there are commercial and clinical reasons why success has not always been realized. This review captures the current landscape of inhaled biologics, and as the field advances, we expect the inhaled route to expand rapidly given its distinct pharmacokinetic advantages for local lung diseases.