(41f) Continuous Manufacturing of Biological Drug Products for Pulmonary Drug Delivery

The traditional approaches that are being used in formulation of dry powder inhalers (DPI) are spray drying and blending. In spray drying, active pharmaceutical ingredient (API) is encapsulated within an excipient which improves the physical and chemical stability of the API. However, spray drying has the potential for protein denaturation due to high temperature and shear. On the other hand, in blending, Once the drug and carrier have been prepared individually to their desired states, they are mixed until reaching a homogeneous concentration of drug on all the particles. nevertheless, both of these methods are used for batch production of DPI formulations, which can lead to potential downtime, increased setup times, and higher labor costs.

In this study, A lab-scale continuous manufacturing (CM) platform was developed to produce complex biopharmaceutical formulations for pulmonary delivery. The system integrates an electrospray-based drying unit with a custom conveyor belt, enabling real-time generation and collection of engineered core–shell microparticles as dry powder inhaler (DPI) formulations. As a demonstration, microparticles containing bovine serum albumin (BSA) and insulin encapsulated in PLGA were fabricated and adhered to lactose carriers. Scanning electron microscopy (SEM) confirmed ~10 µm core–shell morphology, and fluorescence microscopy showed uniform protein distribution. Further characterization using Fourier-transform infrared (FTIR) spectroscopy and circular dichroism (CD) spectroscopy indicated an intact protein structure. Encapsulation efficiency and in vitro release were evaluated using UV–vis spectrophotometry, revealing approximately 78.2% encapsulation after formulation and nearly 75% cumulative release over three days. Compared to batch manufacturing methods, this CM approach enhances encapsulation control, scalability, and product uniformity while improving powder flow, aerosolization, and respiratory deposition. This study demonstrates that electrospray-based continuous manufacturing is a promising alternative for the large-scale production of stable, high-quality, inhalable biologic products.

References

Mehta T, Najafian S, Patel K, Lacombe J, Chaudhuri B. Optimization of Carrier-Based Dry Powder Inhaler Performance: A Review 2025;17:96.

Xie J, Lim LK, Phua Y, Hua J, Wang C-H. Electrohydrodynamic atomization for biodegradable polymeric particle production 2006;302:103–12.

Zamani M, Prabhakaran MP, San Thian E, Ramakrishna S. Protein encapsulated core–shell structured particles prepared by coaxial electrospraying: Investigation on material and processing variables 2014;473:134–43.