Development of impact resistant immediate release amorphous solid dispersion via hot-melt extrusion and injection molding

Abstract

Immediate release (IR) amorphous solid dispersion (ASD) tablets are currently manufactured via a multi-step process which includes hot melt extrusion (HME), grinding of the extrudate, sieving to achieve narrow particle size, blending with other excipients, and finally, direct compression. Due to the multi-step nature of the process, the production time and costs are much higher for ASD tablets than conventional tablets. Thus, a new and more efficient method of IR-ASD tablet production using HME coupled with injection molding (IM) was explored as a viable alternative. Moxidectin, a low-dosage, high-potency BCS class II drug was used as a model API for formulation development. Interestingly, these tablets were also found to be porous (5.01 % φ) due to thermal decomposition of NaHCO₃. The IM tablets were measured against United States Pharmacopeia (USP) quality standards for content uniformity, tablet friability, and dissolution. The content uniformity of these tablets was ± 2 % of the label claim, and over 90 % API release was observed within 1 h in 0.74 % Tween 20 media. PXRD diffractograms revealed that the stability of the ASD at room temperature conditions was excellent. Placebo and API-loaded formulations were extruded and injection molded into circular and unique geometries using molds produced by stereolithography. Lastly, the HME-IM tablet formulations were observed to be extremely tough and would be an excellent candidate in the production of abuse-deterrent formulations for controlled substances.