Development Process For Transforming A Liquid Protein Solution Into A Solid Oral Dosage Form

By Josh Miller, M.S. Pharm, Bend Bioscience

The oral delivery of protein therapeutics represents a groundbreaking advancement in medicine, providing patients with a convenient and non-invasive alternative to injections. However, achieving meaningful oral bioavailability for proteins remains a formidable challenge due to their inherent susceptibility to enzymatic degradation and poor permeability across the gastrointestinal (GI) epithelium. Even when protective formulations are developed to shield the protein and enhance absorption, the transition to a manufacturable oral dosage form introduces additional complexities.

The production of oral protein formulations requires innovative approaches to maintain stability throughout processing, storage, and passage through the harsh GI environment. Techniques such as encapsulation, lyophilization, and the incorporation of permeation enhancers or protective coatings are often necessary, demanding precise control over formulation parameters and manufacturing conditions. Ensuring consistent drug release, maintaining protein integrity, and scaling up production add further layers of complexity, requiring a multidisciplinary approach that integrates pharmaceutical sciences, engineering, and material science.

Despite these challenges, successfully developing oral protein therapeutics could significantly improve patient compliance, enhance accessibility, and broaden the therapeutic applications of biologics. In this paper, we present a case study detailing the conversion of a protein solution formulation into an oral solid dosage form using a fluid bed granulation process, highlighting key formulation and manufacturing hurdles and the strategies employed to overcome them.