(T1230-07-43) Advancing Oral Delivery of Biologic Drugs: Strategies to Overcome Formulation Challenges with Permeation Enhancers

Purpose: Oral delivery of biologics is long considered the holy grail. Permeation enhancers (PEs) are the leading strategy, with two approved oral peptide drugs utilizing PEs to support drug delivery are Rybelsus® and Mycapssa. Sodium caprate (SC) is being widely evaluated to improve the intestinal absorption of peptides via the paracellular and transcellular pathways. However, the poor flow and compression characteristics of SC have limited its utility in direct-compression tablet processing, particularly for oral biologic formulations. To overcome these limitations, a new process-engineered SC with improved flow and compaction to ease processing and yield more robust tablets than existing SC was developed and compared with commercially available SC in model peptide tablet formulations.

Methods: The flowability and flow function of each sodium caprate grade was evaluated using Flowdex™ and Brookfield^® powder flow testers, respectively. Peptide (collagen) tablet formulations with 70% SC were compressed at 25kN using 7/16” standard concave tooling on a Styl’One Evolution Compaction Simulator (Table 1). Tablet hardness was measured along the long axis of tablets using a Key International hardness tester HT-550S. The potential of each sodium caprate formulation to promote permeation across rat colonic mucosae was evaluated by measuring the Trans-Epithelial Electrical Resistance (TEER) using the mounted tissue chamber method.

Results: Material characterization revealed that the new process-engineered sodium caprate has intrinsically superior powder properties, such as low cohesion and higher bulk density, leading to a better flow profile when tested on a shear cell. The peptide tablet formulation with optimized SC yielded three times stronger tablets than the standard material (Figure 1). In the permeability test, all products showed similar Trans-Epithelial Electrical Resistance (TEER) trends (Figure 2), indicating the optimized Sodium caprate provides permeation enhancement similar to commercially available material.

Conclusion: SC is among the commonly used permeation enhancers to improve the permeation of biological molecules administered by the oral route, but until now, its poor flow and compression behavior have limited its use in direct compression tableting. The new process-engineered sodium caprate offers significant improvements in flowability and compaction compared to the standard grades. The optimized SC provides superior tableting, offering improved ease of handling and more robust tablets than existing commercially available grades while still providing comparable permeation enhancement.

References: Fattah, S., Salcaprozate sodium (SNAC) enhances permeability of octreotide across isolated rat and human intestinal epithelial mucosae in Ussing chambers. EJPS, 154, 105509


Table 1: Peptide tablet formulation


Figure 1: Crushing strength of peptide tablets


Figure 2: Trans-Epithelial Electrical Resistance (TEER) values across rat colonic mucosae exposed to apical 10mM Sodium Caprate