(T1430-06-39) Effect of Formulation and Process Parameters on Fenofibrate Impregnation in Mesoporous Neusilin Particles

Purpose: Small-molecule active pharmaceutical ingredients (APIs) increasingly require solubility enhancement. Traditional and well-established approaches include spray drying, hot-melt extrusion, and micronization, among others. Despite its many advantages, API impregnation into mesoporous carriers (with pore sizes of 2–50 nm) remains a relatively underexplored approach. In this technology, an API is dissolved in an organic phase, impregnated into a mesoporous carrier, and (upon solvent evaporation) deposited as an amorphous material within the pores, conferring enhanced solubility and bioavailability. Using solvent impregnation conducted in a fluid bed dryer, this work explores the effect of formulation composition and process parameters on drug loading and dissolution of a fenofibrate-Neusilin drug product.

Methods: In this study, crystalline fenofibrate powder was dissolved in acetone at a concentration of 23 mg/L (Run 1) or 40 mg/mL (Runs 2-7), with varying amounts of sodium lauryl sulfate (SLS) within the solvent mixture. Mixtures were subsequently sprayed at a rate of 8 mL/min onto a Neusilin powder bed using a Mini-Glatt fluid bed dryer. Seven runs were conducted which varied API loading, SLS content, chamber loading, and nozzle size as process parameters of interest. The impregnated products were then characterized using XRPD to identify their structural state. UV-Vis Type II dissolution analyses were performed according to USP specifications to evaluate the dissolution performance of all samples.

Results: Results showed that the reduction of nozzle size from 1.0 mm to 0.4 mm,  successfully produced a fully amorphous drug with significantly improved dissolution rate compared to the crystalline API at 23% w/w loading.  The inclusion of SLS at the same drug loading and a 50 g scale resulted in partial crystallinity and reduced dissolution performance compared to the formulation without SLS. Moreover, increasing the drug loading from 23% to 33% and 43% while maintaining a constant SLS concentration of 5% w/w further decreased the dissolution performance. Notably, a 50g batch of a 23% FENO/5% SLS formulation processed at 0.9 bar atomization resulted in a crystalline product, whereas increasing the scale to 150 g and atomization pressure to 1.8 bar for the same formulation yielded an amorphous product with enhanced dissolution profile.

Conclusion: UV-vis dissolution and XRPD analyses illustrate that atomization pressure, nozzle size, and batch size are critical process parameters (CPP’s) influencing drug product performance during the impregnation of APIs into mesoporous material. With respect to formulation composition, depending on scale and drug loading, surfactants like sodium lauryl sulfate (SLS) variably impact amorphization and dissolution of the drug product; increasing drug loading generally results in decreased dissolution kinetics. Finally, this work illustrates that at small scales (50g) a drug product with API loading >20% w/w can be prepared which has enhanced solubility relative to the Crystalline API.


Dissolution Data of Run 1 (1.0 mm nozzle size) and Run 2 (0.4 mm nozzle size) with reference to Crystalline Fenofibrate.