# Phase Behavior of Potential Drug Delivery Systems, PolycaprolactoneNonsteroidal Anti-Inflammatory Drug in a Pressurized Carbon Dioxide Medium

## TL;DR

This study examines how high-pressure carbon dioxide affects the melting behavior of drug-polymer systems, which could improve drug delivery technologies.

## Contribution

The study provides new insights into the pressure-dependent phase behavior of drug-polymer systems in high-pressure CO₂ environments.

## Key findings

- Both ibuprofen–polycaprolactone and ketoprofen–polycaprolactone systems showed eutectic behavior under high-pressure CO₂.
- Eutectic and melting temperatures were highly pressure-dependent, but eutectic composition remained nearly constant.
- The findings could enhance high-pressure particle formation technologies like PGSS.

## Abstract

Although high-pressure technologies are widely used,
for example,
in the polymer and pharmaceutical industries, measuring phase equilibria
in high-pressure media is still challenging, especially for multicomponent
systems. Although the most reliable methods in solid–liquid­(-gas)
equilibrium measurements, also providing additional information, are
high-pressure differential scanning calorimetry (DSC) and transitiometry,
the most common techniques for detecting solid–liquid phase
transitions in pressurized media are visual observation-based methods.
In this research, the melting behavior of potential controlled-release
active pharmaceutical ingredient (API) polymer systems (ibuprofen–polycaprolactone,
ketoprofen–polycaprolactone) in the presence of high-pressure
carbon dioxide was investigated. First, the pressure-dependent behavior
of pure compounds was investigated by using two different methods.
One is based on differential pressure measurement, developed by the
research group, and the other is the widely used visual observation-based
process. The API polymer systems were investigated in a high-pressure
view-cell. Both systems showed eutectic behavior. According to the
measurement data, eutectic and melting temperatures of the system
were highly dependent on pressure, but the eutectic composition was
found to occur at a nearly constant value. The thermodynamic data
from the research could be applicable to high-pressure particle formation
technologies, such as the particle from gas saturated solutions (PGSS).