Rapid Room-Temperature Aerosol Dehydration Versus Spray Drying: A Novel Paradigm in Biopharmaceutical Drying Technologies.

To ensure the high quality of biopharmaceutical products, it is imperative to implement specialized unit operations that effectively safeguard the structural integrity of large molecules. While lyophilization has long been a reliable process, spray drying has recently garnered attention for its particle engineering capabilities for the pulmonary route of administration. However, maintaining the integrity of biologics during spray drying remains a challenge. To address this issue, we explored a novel dehydration system based on aerosol-assisted room-temperature drying of biological formulations recently developed at Princeton University, called Rapid Room-Temperature Aerosol Dehydration. We compared the quality attributes of the bulk powder of biopharmaceutical products manufactured using this drying technology with that of traditional spray drying. For all the fragment antigen-binding formulations tested, in terms of protein degradation and aerosol performance, we were able to achieve a better product quality using this drying technology compared to the spray drying technique. We also highlight areas for improvement in future prototypes and prospective commercial versions of the system. Overall, the offered dehydration system holds potential for improving the quality and diversity of biopharmaceutical products and may pave the way for more efficient and effective production methods in the biopharma industry.

Targeted Drug Delivery to Upper Airways Using a Pulsed Aerosol Bolus and Inhaled Volume Tracking Method.

The pulmonary route presents an attractive delivery pathway for topical treatment of lung diseases. While significant progress has been achieved in understanding the physical underpinnings of aerosol deposition in the lungs, our ability to target or confine the deposition of inhalation aerosols to specific lung regions remains meagre. Here, we present a novel inhalation proof-of-concept in silico for regional targeting in the upper airways, quantitatively supported by computational fluid dynamics (CFD) simulations of inhaled micron-sized particles (i.e. 1-10 µm) using an intubated, anatomically-realistic, multi-generation airway tree model. Our targeting strategy relies on selecting the particle release time, whereby a short-pulsed bolus of aerosols is injected into the airways and the inhaled volume of clean air behind the bolus is tracked to reach a desired inhalation depth (i.e. airway generations). A breath hold maneuver then follows to facilitate deposition, via sedimentation, before exhalation resumes and remaining airborne particles are expelled. Our numerical findings showcase how particles in the range 5-10 µm combined with such inhalation methodology are best suited to deposit in the upper airways, with deposition fractions between 0.68 and unity. In contrast, smaller (< 2 µm) particles are less than optimal due to their slow sedimentation rates. We illustrate further how modulating the volume inhaled behind the pulsed bolus, prior to breath hold, may be leveraged to vary the targeted airway sites. We discuss the feasibility of the proposed inhalation framework and how it may help pave the way for specialized topical lung treatments.

Development of drying-induced stresses in pharmaceutical granules prepared in continuous production line.

The phenomenon of development of drying-induced stresses has been given a through consideration in the literature on drying of many products. At the same time, to the best of our knowledge, the open published sources contain no information on drying stresses in pharmaceutical granules prepared by continuous manufacturing methods. To study the appearance and evolution of drying-induced stresses in pharmaceutical granules during their production, in this work a theoretical model of drying of single wet pharmaceutical granule has been developed and successively validated by published experimental data obtained on ConsiGma™ continuous from-powder-to-tablet production line (GEA Pharma Systems). The results demonstrate that elevated temperatures of drying air result in faster drying process (which reduces the specific cost of the final product), but, on the other hand, quick drying leads to substantial drying-induced stresses which may damage the granule microstructure, resulting in cracking or even breakage of granules. The drying-induced stresses increase with drying temperature, porosity and size of dense non-hollow granules. The negative effects promoted by the drying-induced stresses should be taken into consideration when choosing operating conditions of continuous production lines including drying of pharmaceutical granules.