Development of inhalable spray dried nalbuphine hydrochloride powders

Nalbuphine hydrochloride (NAL) is a potent opioid analgesic that has been used clinically for decades. However, current delivery methods are either invasive or inefficient due to low bioavailability. Therefore, an alternative route of administration is needed. Pulmonary delivery is a promising option as it can provide high bioavailability and a rapid onset of action. Beyond systemic analgesia, NAL has also shown local therapeutic benefits in the lungs. This study aimed to develop inhalable NAL powders using spray drying, with leucine and human serum albumin (HSA) as dispersion enhancers. The resulting powders were amorphous and contained <4 % residual solvent by mass. The spray dried particles were spherical, 3-4 µm large, and exhibited corrugated surface. Spray dried NAL alone were inhalable, with a fine particle fraction <5 µm (FPF) at 25 %. The addition of HSA improved the FPF to 33 % and 37 % for 10 % and 20 % w/w HSA, respectively. Similarly, the FPF increased to 39 % after adding 10 % w/w leucine, reaching a maximum of 47 % with 20 % w/w leucine. The latter formulation also demonstrated good chemical and physical stability after one month of storage at 25 °C under both 30 % and 60 % relative humidity. These formulations can be used as a platform to deliver NAL and other opioid analgesics by inhalation.