Our main areas of focus relate to the inherent strengths of mSAS® supercritical fluid technology, and in particular the following:
- Crystal and particle engineering
- Stabilisation of therapeutic agents derived from biotechnology
- Polymorph screening
- Improved performance of poorly soluble drugs
- Inhaled therapy
- Taste masking
- Crystallisation seeds
- Residual solvent elimination
Crystal and particle engineering
With growing demands on human medicines now being designed for delivery to patients via a range of alternative routes of administrations, the requirements for engineering specific characteristics of drug particles are ever increasing. Such desirable properties range across the spectrum of structural, physicochemical and surface features, for example solid state crystallography and particle size. SCF processing has been demonstrated to provide an enabling technology for achieving crystal and particle engineering of drug substances.
Stabilisation of therapeutic agents derived from biotechnology
A major challenge for efficient formulation and design of biopharmaceuticals is associated with their inherent lack of room temperature stability during processing or product storage (shelf-life). Many products are marketed as liquid products which need refrigeration or low temperature storage. Whilst spray and freeze drying processes can be used, these procedures are expensive and often involve complex operations therefore, new alternatives are required. Supercritical fluid (SCF) technologies, and the incorporation of stabilising and other regulatory acceptable agents during particle formation if required, have been shown to be a viable and attractive alternative.
The comprehensive examination of the range of polymorphs which can be prepared for specific drug compounds is of profound importance for pharmaceutical companies. There are major implications in discovering all potential forms for both commercial and regulatory reasons. Whilst many companies carry out ‘polymorph-mining’ procedures exploring the experimental space available to conventional crystallisation methods, studies using SCF technologies have demonstrated that new polymorphic forms, not identified during routine screening, can be formed in the supercritical fluid experimental region. Such information, and potential discovery of new polymorphic forms, provides critically important knowledge for pharmaceutical companies.
Improved performance of poorly soluble drugs
With over 40% of new drug substances exhibiting poor aqueous solubility, a major task for industrial pharmaceutical scientists has been to explore alternative procedures for overcoming this characteristic which can compromise the bioavailability, and thereby detract from optimising the clinical efficacy of these drug candidates. With SCF processing, micron sized particles with high surface areas can be readily produced, which provides the opportunity to maximise particle dissolution rates, and benefit from this particle engineering strategy.
Current technologies for preparing micron sized particles for respiratory drug delivery focus on high energy milling (fluid energy milling, micronisation). It is widely recognised that such processing operations can cause uncontrolled levels of chemical, crystallographic and/or surface damage to the fractured drug particles for many materials. Such changes can cause both downstream secondary processing problems as well as batch to batch variability issues. SCF processing, in contrast, is a single step operation with high yield of micron sized particles, which do not exhibit such damage, and the processes are highly reproducible delivering high levels of intra- and inter-batch consistency.
By incorporating regulatory acceptable excipient(s) into the fluid stream(s) prior to particle formation by the SCF antisolvent mechanism, the drug molecules can be dispersed in a ‘matrix type’ particulate structure, whereby distribution of the active in the matrix can be controlled thus enabling taste masking of poorly tasting drug substances.
In many conventional crystallisation processes, crystal seeds are used as ‘templates’ for additional growth to form crystalline particles of desired final particle size and size distribution. It has been shown that the crystallographic quality of such final particles can be highly dependent upon the crystallographic quality of the seed templates. As SCF particles exhibit exceptionally high quality crystallographic quality and purity, these fine (micron sized) crystals provide ideal seed materials.
Low residual solvent in SCF processed drug particles
It is an inherent feature of the SCF antisolvent process that drug particulate products will contain very low levels of residual organic solvents. This is a result of the rapid removal of the organic solvent used to prepare the drug solution when fed into the SCF fluid, since the organic solvents generally used in pharmaceutical crystallisation process are miscible in all proportions in the most frequently used carbon dioxide SCF.