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

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 CO2 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 CO2. The addition of mPEG facilitated the distribution of the drug into the bulk matrix of the polymer. Paired with supercritical CO2 processing, the drug release profile showed a slow, sustained release throughout the 4 months of the study.

Formulation Considerations for Autologous T Cell Drug Products.

Genetically modified autologous T cells have become an established immunotherapy in the fight against cancer. The manufacture of chimeric antigen receptor (CAR) and αß-T cell receptor (TCR) transduced T cells poses unique challenges, including the formulation, cryopreservation and fill-finish steps, which are the focus of this review. With an increasing number of marketing approvals for CAR-T cell therapies, comparison of their formulation design and presentation for administration can be made. These differences will be discussed alongside the emergence of automated formulation and fill-finish processes, the formulation design space, Monte Carlo simulation applied to risk analysis, primary container selection, freezing profiles and thaw and the use of dimethyl sulfoxide and alternative solvents/excipients as cryopreservation agents. The review will conclude with a discussion of the pharmaceutical solutions required to meet the simplification of manufacture and flexibility in dosage form for clinical treatment.