Critical Quality Attributes of Control Drug Release Systems and Their Impact on Rational Polymer Selection

Abstract

The aim of this paper is to select the appropriate polymer for the soluble agents encapsulation as Naloxone HCl, by understanding the impact of formulation on the critical quality attributes (CQAs) using a quality-by-design approach. The aim of our research is to develop a clear understanding of the physical, chemical or physical-chemical parameters which must be considered as CQAs in order to rationally select a suitable polymer for the design of an injectable biomedical system with Naloxone HCl. The definition of CQAs is within the concept of Quality by Design (QbD) of medicines. Drug-polymer compatibility, drug-polymer solubility, in vitro drug release from the control release system (CRS) and CRS drug loading proved to be the most useful parameters contributing to a rational polymer selection. A better understanding of these influences on the critical quality attributes (CQAs) of the final product is of prime importance. Poly(lactide-co-glycolide) and lactic acid polymers (PLGA and PLA) were included in the study since they are biodegradable and biocompatible (suitable characteristics for parenteral administration). The best results were obtained by using poly(lactide-co-glycolide) polymers: PLGA RG 504 and PLGA RG 502. Taking under consideration these selected polymers; this paper describes the development of innovative control release formulations for a Naloxone HCl delivery with the clinical purpose of discouraging opioid use and preventing relapse. The quality target product profile (QTTP) is to release effective amounts of Naloxone HCl during a week. The determination of the solubility of the crystalline drug in the polymer is interesting to assess the physical state of the drug in the CRS matrix, which is related to CQAs of the injectable biomedical system such as drug loading or drug controlled release. This work shows that the measurement of drug-polymer solubility by DSC is a rapid and simple technique that provides this information and, then, helps to select the most suitable polymer.