(T1330-02-11) Formulation of Cocrystal and Amorphous Solid Dispersion Printlets Developed by Hot Melt Extrusion Paired Fused Deposition Modeling for Dissolution Enhancement andStability of Ibuprofen

Purpose: In recent years, additive manufacturing has been widely investigated for developing on-demand patient-centric and complex medications. Additive manufacturing involves fabricating three-dimensional (3D) object layer by layer until the object of desired size and shape is printed. The current research is aimed to evaluate the stability of 3D printlets comprising of amorphous drug and its cocrystal fabricated using HME paired FDM 3D printing process. Ibuprofen (IBP), a non-steroidal anti-inflammatory drug belonging to BCS class II (poor solubility, high permeability), is selected as a model drug.

Methods: First, the optimum molar ratio of drug and coformer (nicotinamide; NIC) was determined using the conventional liquid-assisted grinding (LAG) approach. Then, the cocrystal and amorphous solid dispersion filaments were developed using the hot melt extrusion (HME) process (Table 1). The extrusion of filaments was performed using an 11 mm twin-screw extruder using a standard screw configuration with three mixing zones. The extrusion was carried at 75 rpm of screw speed with 3.0 – 3.5 g/min of feed rate by maintaining the barrel at 90 – 150 C of temperature. Then the printlets for all the extruded filaments were fabricated using a commercial FDM 3D printer (Figure 1). The milled extrudates were also compressed into tablets using microcrystalline cellulose 102, Kollidon CL, and magnesium stearate as reference samples to compare the in-vitro drug release. The formation of cocrystal and amorphous solid dispersion was characterized and confirmed using differential scanning calorimetry (DSC), Fourier transforms infrared spectroscopy (FTIR), and powder x-ray diffraction (PXRD) analysis.

Results: The cocrystal-loaded filaments and filaments of amorphous solid dispersion were successfully extruded using a combination of Kollicoat IR and Kollidon VA64 polymers. The cocrystal and amorphous solid dispersion filaments were successfully printed for 100% and 50% infill densities. The milled extrudates have resulted in poor compressibility and require more diluent to obtain tablets with acceptable mechanical strength. The in vitro drug release profiles of cocrystal printlets were faster when compared with the printlets of amorphous solid dispersion and compressed tablets. Figure 2 In vitro drug release profiles of 3D printlets (F3 & F6) and compressed tablets (CT3 & CT6) in water, 0.1N HCl, and pH 7.2 phosphate buffer solution. The cocrystal printlets, after storage at accelerated conditions, were stable for six months. At the same time, the printlets of amorphous solid dispersion and compressed tablets failed to retain stability attributing to the recrystallization of amorphous drug and loss in the mechanical properties of the tablet upon storage.

Conclusion: In conclusion, the present study shows the suitability of a cocrystal platform as a novel approach for developing stable formulations of poorly water-soluble drug substances over amorphous solid dispersions.

References: Strojewski D, Krupa A. Kollidon® VA 64 and Soluplus® as modern polymeric carriers
for amorphous solid dispersions. Polymers in Medicine. 2022;52:17–27.
2. Nyavanandi D, Narala S, Mandati P, Alzahrani A, Kolimi P, Almotairy A, et al. Twin
Screw Melt Granulation: Alternative Approach for Improving Solubility and
Permeability of a Non-steroidal Anti-inflammatory Drug Ibuprofen. AAPS
PharmSciTech. 2023;24:1–15.

In vitro drug release profiles of 3D printlets (F3 & F6) and compressed tablets
(CT3 & CT6) in water, 0.1N HCl, and pH 7.2 phosphate buffer solution.

Process flow diagram

List of formulations investigated for amorphous solid dispersion and cocrystal
formulations.