Modulating Drug Release from Short Poly(ethylene glycol) Block Initiated Poly(L-lactide) Di-block Copolymers

• Published in: Pharmaceutical research 2023-07, Vol.40 (7), p.1697-1707
• Main Authors: Azhari, Zein, Smith, Patricia, McMahon, Sean, Wang, Wenxin, Cameron, Ruth E.
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Carbon Dioxide; Controlled release; Crystals; Delayed-Action Preparations; Drug Carriers - chemistry; Drug interaction; Drug Liberation; FDA approval; Injection; Injection molding; Medical Law; Original; Original Research Article; Pharmacology/Toxicology; Pharmacy; Poly(L-lactide); Polyesters - chemistry; Polyethylene glycol; Polyethylene Glycols - chemistry; Polylactic acid; Polymers; Polymers - chemistry; Propranolol
• ISSN: 0724-8741; 1573-904X; 1573-904X
• DOI: 10.1007/s11095-022-03228-8

This paper investigates drug release from a novel series of mPEG-functionalised PLLA polymers whose individual components (PEG and PLLA) have regulatory FDA approval. Two processing methods were explored to understand their effect on the morphology and drug release profiles of the polymers, with and without mPEG functionalisation. In the first method the polymer and Propranolol.HCl drug powders were mixed together before injection moulding. In the second method, supercritical CO 2 was used to mix the polymer and drug before injection moulding. When non-functionalised PLLA was processed through injection moulding alone, there were no signs of polymer-drug interaction, and the drug was confined to crystals on the surface. This resulted in up to 85 wt% burst release of propranolol.HCl after one day of incubation. By contrast, injection moulding of mPEG-functionalised polymers resulted in the partial dissolution of drug in the polymer matrix and a smaller burst (50 wt% drug) followed by sustained release. This initial burst release was completely eliminated from the profile of mPEG-functionalised polymers processed via supercritical CO 2 . The addition of mPEG facilitated the distribution of the drug into the bulk matrix of the polymer. Paired with supercritical CO 2 processing, the drug release profile showed a slow, sustained release throughout the 4 months of the study.