# Predicting Drug Loading Capacity for PLA-Amorphous Drug System Using Hansen Solubility Parameters

## TL;DR

This paper uses solubility parameters to predict how much drug can be loaded into a polymer system to form a stable amorphous drug phase.

## Contribution

The novel use of Hansen solubility parameters to estimate amorphous drug saturation in polymer systems is introduced.

## Key findings

- A strong linear correlation (R2 0.85–0.93) was found between drug concentration and HSP distance.
- Amorphous drug phases were successfully created and confirmed using X-ray diffraction and HPLC.
- Both solvent casting and vacuum compression molding methods showed consistent results.

## Abstract

Objective: In this work, we look at Hansen solubility parameters (HSPs) to predict drug miscibility with polymers, in order to create a saturated amorphous drug phase. Methods: We used the Yamamoto molecular break (Y-MB) group contribution method (GCM) and solvent experiments to establish HSPs for PLA and 12 model drugs. Drug-loaded samples were made using solvent casting (SC) and vacuum compression moulding (VCM) in incremental drug concentrations until a saturated amorphous drug load was achieved. The amorphous drug phase was confirmed by X-ray diffraction after 24 h. These amorphous samples were further analysed by HPLC to confirm drug concentration. These drug concentrations were expressed as volume concentration in PLA, and they correlate with linearised HSP distance between drug and polymer. Results: This gives a statistically significant linear correlation between drug concentration and HSPs with R2 values ranging from 0.85 to 0.93 for SC and VCM methods. Conclusions: This work entails a possible concept for novel application of HSPs to predict miscible drug–polymer pairs and to estimate amorphous saturation concentration.