In Silico and Hansen Solubility Parameters-Guided HME-3D Printed Tablets: Boosting Aceclofenac Solubility and Dissolution

Abstract

Purpose

The restricted aqueous solubility of BCS-II drugs leads to significant biopharmaceutical variability, limiting dissolution and therapeutic efficacy. This study shows an integrated experimental-computational platform to improve the solubility of Aceclofenac (AF), where Hansen solubility and In-Silico binding efficiencies are checked to select the optimal polymer for stable and molecular-level Amorphous Solid Dispersions.

Methods

The drug and excipient screening was done using the in-silico binding energy and Hansen solubility parameters. Eudragit, PVA, and HPMC E5 showed better compatibility in the initial screening. AF, along with selected carriers, was processed in the Hot Melt Extrusion (HME). The prepared dispersions were subjected to 3D printing for the preparation of tablets. The solid dispersions and prepared tablets were subjected to various solid and liquid characterisations.

Results

From the characterizations data, it was noticed that the AF was no longer in the crystalline form. The HME processed the drug-polymer physical mixture into a uniform filament exhibiting maximum amorphous content, as confirmed by FTIR, DSC, XRD, solubility, and Dissolution studies. The HME-assisted AF dispersions were then converted to an oral tablet dosage form using a novel 3D printing technology. The ICH stability studies proved that there was less than 5% loss with a sustained supersaturation state.

Conclusion

The organic solvent-free HME, followed by 3D printing tablets, eliminates the conventional tablet formulation battle, delivering patient-centric and scalable tablets with guaranteed physical stability.

Graphical Abstract