Arestat-T™ and Arestat-C™ technologies are based upon a number of
specific innovations that address the principal heat and concentration related
degradation pathways of proteins, vaccines and other biologics. The
technologies are used to produce bespoke stabilised formulations of biologics
both for therapeutic and diagnostic
applications. Arestat-T™ and Arestat-C™ technologies are applied
as a set of tools to extend the range of basic, conventional formulation approaches.
The physical stability of proteins is undermined by a number of reversible
reactions that take place at the equilibrium between the protein and its
surrounding environment. An example of such reversible reaction is the
trafficking of protons between the protein and surrounding excipients. The
consequence of these reactions is a continuous fluctuation of the charge
distribution in proteins. Such charge fluctuation allows proteins to explore
extreme states during storage that can initiate a series of conformational changes
leading to instability. A unique feature of the technologies is the use of
conventional buffering species in an unconventional manner in order to stabilise
the target molecule through controlling the protein exchange at its surface.
Another formulation tool of the Arestat-T™ & Arestat-C™ technologies
is based on inclusion of excipients that help to maintain an optimal balance between
metal ions and the protein molecules. Such balance is essential for maintaining the
native structure of proteins and other macromolecules and preventing their
degradation and aggregation.
Another formulation tool is aimed at controlling the hydrophobic interactions between
proteins and other biological molecules in order to minimise the rate of their
aggregation. This can be achieved by inclusion of specific ionic species in unique
combinations with other formulation parameters.
An additional feature of the technologies allows an efficient control of the rate
of hydrolysis in biological molecules. This particular tool allows control of
acid-base hydrolysis by specific combinations of excipients. Hydrolysis can thus be
controlled to a considerably larger extent compared with a simple pH optimisation.
When these and a number of other proprietary Arestat-T™ & Arestat-C™
formulation tools are applied together, they stabilise proteins by minimising the
rate of a number of processes, such as chemical modifications, protein-protein
interactions or fluctuation of the tertiary structure. The stability achieved is
typically markedly greater compared with that achieved by conventional formulation
tools. Experimental validation is required to ensure that the appropriate tools and
excipients addressing the relevant degradation pathways are applied in a complementary way.
Arestat-T™ & Arestat-C™ can achieve long shelf-stability of biologics
previously considered unstable in aqueous phase. Dry powders of hormones, recombinant
proteins, enzymes and vaccines can be readily transformed to stable liquids that can
be stored at elevated temperatures. This step change eliminates the requirement for a
cold-chain with the added benefits of reduced cost of production and transportation.
Exciting new concepts of the technology also allow proteins to be formulated at high
concentrations hitherto made difficult due to unacceptable levels of aggregation or viscosity.