The Noyes Whitney equation, dC/dT = kS(Cs-Ct) describes the change in concentration over time (dC/dT) as a function of the dissolution rate constant k, surface area S, solubility Cs, and concentration in the bulk fluid Ct. It is evident that ‘Cs’ cannot be significantly changed, that ‘Ct’ is often under sink conditions and ‘k’ comprises many factors, such as agitation and temperature. This leaves ‘S’, the surface area, as a factor that can affect the rate of dissolution. Micronization is a widely employed pharmaceutical technique of decreasing particle size in order to maximize the surface area for a given mass of drug as a means of increasing dissolution. This is indeed a very valuable process for effective oral delivery of poorly soluble drugs and for the production of parenteral solutions. However, long-acting injectable drugs do not need to be formulated in solution. We utilize large particle size (in association with novel coating technologies) to permit formulation of sustained-release injectable suspensions for a broad range of drugs. The concept of large particle size for parenteral sustained release is not new. Large particle size has been used as the basis for sustained drug delivery systems for insulin, corticosteroids and penicillin. However, this concept has not been applied to drug delivery for atypical antipsychotics, and significantly, has not been combined with coating technology.
The basis for our Plexis patents is the use of large crystal or amorphous particles of required dimensions, which are then appropriately coated. Large crystals or amorphous particles have three principal advantages for sustained release drug delivery: they dissolve slowly, enabling delivery systems to be developed based on dissolution; they can be manufactured simply and reproducibly; and they can be coated with conventional spray coating technologies, rather than relying on coacervation techniques for encapsulation. This will allow for greater drug loading.