Background/Objectives: The aim of our research was to understand how excipients, unit operations, and process parameters impact processability and resulting properties, performance, and stability of tablets containing bovine lactoferrin, a cohesive biomacromolecule. Methods: Microcrystalline cellulose (MCC), croscarmellose (xCMC), lactose (LAC), hydroxypropyl methylcellulose (HPMC), and sodium stearyl fumarate (SSF) were used to produce various tablet formulations containing lactoferrin across a concentration range of 5 to 45%, targeting immediate- or controlled release performance. Tablets were made either by direct compression or via dry granulation followed by tableting. In addition to release performance, tablet attributes were characterized for tensile strength, friability, weight uniformity, and content uniformity. Results: Acceptable tablet tensile strength, friability, and performance were obtained for lactoferrin concentrations ranging from 15 to 45%, using a variety of excipients and manufacturing approaches. In several cases, dry granulation improved content uniformity. Excipient choice and tablet compression force impacted drug release, particularly when MCC alone was used as dry binder for immediate release. Dry granulation impacted tablet tensile properties, but did not significantly impact release performance. Lactoferrin–excipient compatibility was demonstrated for up to 2 years in ambient laboratory conditions. Conclusions: The study demonstrates that robust tablets can be produced using excipients and processes amenable to scale-up for industrial production. Consistent, stable, and suitably performing tablets were successfully produced using a variety of excipients, processing approaches, and across a broad concentration range with this cohesive biomacromolecule active pharmaceutical ingredient (API). Both immediate- and controlled release performance modes were possible.

Background/Objectives: A push–pull osmotic pump (PPOP) tablet is a controlled-release delivery system consisting of a bilayer tablet (push layer/pull (drug) layer), coated within a selectively permeable barrier membrane, and containing a laser-drilled orifice in the pull layer side of the barrier. Aqueous media permeates across the barrier membrane and into the bilayer tablet core. The push layer swells axially, creating force and acting like a piston to drive the active pharmaceutical ingredient (API) dosage through the laser-drilled orifice. The primary purpose of this study was to develop a method to quantitate swelling force generated by the PPOP push layer. Methods: A key challenge was devising measurement methodology that most closely represented continuous PPOP push-layer swelling force exerted in the axial dimension over time, so the method setup was adjusted until attaining what closely approximated PPOP push-layer swelling-force dynamics within the delivery system. After some adjustments, swelling forces were measured from PPOP push layers containing various polyethylene oxide (PEO) molecular weight (MW) grades. Results: The most representative configuration was a cylindrical holder fully submerged in water with the push-layer compact situated at the bottom of the holder. This setup constrained the push layer to swell in the axial dimension. The optimal setup also allowed the texture analyzer to continuously measure push-layer swelling force over 24 h, representing typical duration of functionality. Quantitative analysis of the swelling force vs. time profiles demonstrated comparable force generation over 24 h from the 4, 5, and 7,000,000 MW grades of PEO. Swelling force decreased in near-linear fashion, from push layers formulated with PEO 4,000,000 down to PEO 100,000. Conclusions: The optimal setup enabled discriminatory quantification of push-layer swelling force for PEO MW grades spanning from 100,000 up to 4,000,000 Daltons. Furthermore, the method demonstrated why the 4, 5, and 7,000,000 MW grades of PEO are recommended for use in the PPOP push layer, given that these three highest MW grades delivered comparable swelling force over 24 h. Finally, the method provides new quantitative insight into the push-layer swelling force that is necessary, over the duration of the dosing interval, to deliver the active dosage from the PPOP tablet.