(W1230-07-40) Expanding the Design Space of Swellable Core Technology (SCT) for Delivery of Higher Doses and Patient Centric Dosage Form

Purpose: Osmotic systems for controlled drug-delivery applications are well established and preferred systems owing to their robustness in performance. Swellable Core technology (SCT) based formulations, an osmotic delivery system, consist of a core tablet that contains two layers; an active layer and a water-swellable layer and performs robustly producing an excellent in vitro/in vivo correlation. Until now, the bilayer SCT’s challenging manufacturability and release performance has limited this platform to a maximum unit dose of approximately 50 mg, often requiring multiple tablets to be needed for clinical studies. The purpose of this work was to systematically study the feasibility of increasing the drug load in the SCT system and reduce patient bill burden.

Methods: Five model compounds with different aqueous solubilities ranging by more than 10 times were chosen. The drug load in the active layer for each compound varied from 10-50%. In addition to drug loading, other formulation variables such as tablet size and coating thickness was varied to achieve different duration of release; short duration (t80 of 6-8 hours) and long duration (t80 of 12-14 hours). Different manufacturing processes: direct compression (DC) and dry granulation (DG) were also evaluated. The active layer consisted of drug, PEO, and lubricant, and the amount of PEO was reduced to balance the increased active. The weight of the active layer and swell layer was kept constant for each formulation. The swell layer was the same for all compounds and tablet sizes, and contained PEO, MCC, sodium chloride, and lubricant, as well as blue dye for easy distinction of active and swell layers. Bilayer tablet cores were then coated using a usual CA:PEG coating in a water/acetone solvent system. Dissolution was performed on the final dosage form.

Results: The dissolution profiles were analyzed for rate and extent of dissolution, T80 (time required to release 80% of the total drug) and the amount retained within the tablet or not released from the tablet. This value (% retained) is plotted for each compound and related to drug load and their aqueous solubility (Figure 1). Additionally, the performance of different drug loaded SCT tablets were evaluated for effect of release duration (short/long), tablet size, and process conditions (DC and DG). Drug loading in active layer coupled with aqueous solubility of the compound had the most influence on the in vitro performance of an SCT formulation. When the solubility of the compound is very high, then the effect of API properties and formulation variables are minimal. On the other hand, depending on the aqueous solubility from low to medium, the API properties and formulation variables may have varying level of impact.

Conclusion: The tablets had more residual material when they had high drug load and less solubility. High solubility compounds did not show a trend across other parameters, but low solubility ones did: % drug load and release duration had an impact on the extent of drug release from the SCT tablet. Manufacturing process and tablet size had a smaller and variable impact depending on the compound.

Figure 1. Relationship between log aqueous solubility, drug load and fraction retained in each formulation