PCMC TECHNOLOGY

Protein-coated microcrystals represent a novel particle engineering approach for the formulation of a wide range of biomolecules including proteins; peptides; DNA/RNA and vaccines. Protein-coated microcrystals (PCMC) are water-soluble micron-sized particles that consist of a core crystalline material, such as an amino acid, sugar or salt on which is coated the therapeutic biomolecule. PCMC are prepared in a 1-step process that simultaneously dehydrates these two components and results in the immobilisation of the protein on the surface of the carrier. Particle morphology, protein payload and particle size can all be tuned via the appropriate choice of dehydration conditions.

CHARACTERISTICS

DSC and x-ray powder diffraction analysis of a number of PCMC preparations using a range of amino acid carriers have shown the core to be crystalline. Coating of the crystalline core with a given biomolecule arrests crystal growth and particle morphology can thus be defined. Biomolecule payload is flexible, and can be tuned depending on the drug potency and dosing regime required. PCMC are therefore suitable for the delivery of both high and low potency biomolecules, and can be administered as an inhaleable dry powder, or for injectables, either as a suspension or redissolution of the dry powder.

FORMATION

The procedure involves dissolution of the appropriate crystal-forming carrier together with the given biomolecule. Rapid dehydration of the two components is facilitated by using a water miscible organic solvent, such as ethanol. There is immediate formation of the PCMC particles, which can then be subesquently dried to for free-flowing powders.

Co-immobilisation of the antigen and adjuvant (yellow) on the surface of a core carrier composed of a crystalline pharmaceutical excipient, such as an amino acid, sugar or polyol (blue).

Scanning electron microscopy (SEM) imaging of PCMCs show that particle morphology is retained and importantly remain as free-flowing crystalline powders when exposed to high humidity conditions (~75 % R.H.). Dynamic vapour sorption (DVS) of insulin-coated valine indicates that repeated hydration/dehydration cycling does not affect the core crystalline carrier and overall water adsorption to the particles is low, with the major contribution to hydration determined by the protein layer.