| Different SCF processes are being developed to design composite particles with several purposes: Preparation of sustained-release drugs by incorporating the active in a slowdissolving (bio-degradable or bio-erodable) matrix, stabilization of fragile molecules (mainly bio-molecules) in solid form, and bio-availability enhancement of poorly-soluble compounds by incorporating the active in a fast-dissolving hydrophilic excipient. For this latter purpose, many works are focused on the preparation of particles consisting in a complex of the active drug inserted in a cyclodextrin-type molecule : the cyclodextrin “cage” presents a hydrophilic character on its outside, leading to a very fast dissolution in aqueous media, but a hydrophobic character on its inside, permitting a stable inclusion of poorly-soluble molecules of an adapted size. This explains that these inclusion compounds are widely considered for designing delivery systems adapted to poorly-soluble drugs, although these complexes are generally considered as new chemical entities with specific pharmacological properties different from the neat drug ones.
Moreover, impregnation of hydrophilic porous carriers can be operated using a supercritical fluid as vector of the active ingredient. The choice of the carrier and the choice of the process are correlated, as summarized on the Table 18. One might be surprised as we do not list some other SCF processes applicable when the active compound is not soluble and the fluid and the carrier is soluble, like SCF deposition leading to micro-capsules; in fact, these processes seem not applicable when hydrophilic carriers are concerned for dissolution enhancement.
Table 18: Formation of composite micro-particles for dissolution enhancement
Composite particle generation by SCF processes looks as a very promising solution to enhance the dissolution of poorly-soluble compounds. It is strongly believed that amphiphilic carriers could supply valuable alternatives as the hydrophobic moiety will permit a labile association of the excipient with the active compound by formation of a sort of cluster around each active molecule (or nano-aggregate of molecules), meanwhile the hydrophilic moiety will induce a rapid dispersion at the molecular scale in the aqueous media, inducing a micellar-like solubilization that may lead to a high bioavailability of the active molecule associated with this amphiphilic excipient. Notwithstanding these attractive results, it is certainly not wise to deduct that dissolution rate enhancement of these SCF-processed materials signifies a comparative enhancement of the bio-availability of the final drug, especially when dissolution tests were performed in pure water instead of “representative” artificial media. And finally, only animal or human tests could quantify the improvement, case-by-case. |