The Pharmaceutical Use of Captisol®: Some Surprising Observations

Abstract

The purpose of this paper is to share some recent observations on the pharmaceuticaluses and properties of Captisol® or SBE7M-β-CD in controlled porosity osmotic pump tablets (CP-OPT) and the underlying mechanism/sthat lead to apparent zero-order drug release pattern. It would have been simple toattribute the apparent zero-order release mechanism/s of poorly water-soluble drugsfrom CP-OPTs and pellets utilizing Captisol®as both a solubilizing andosmotic agent, to purely osmotic and diffusional components. However, the mechanismmay be more related to a counterbalancing of physical properties as the concentration of Captisol®changes within the matrix. Specifically, the initial concentration of Captisol®within a core is 0.3–0.4M. When this drops to lower values an osmotic pressure drop occurs across the membrane. Therefore, drug release should not follow apparent zero-order kinetics if all the drug is solubilized. However, as the viscosity within the tablet also drops, the apparent diffusion coefficient of both Captisol® and drug increases. Therefore, it appears that there is an initial resistance (hydraulic pressure) to fluid flow from the tablet through the rate-limiting microporous membrane. This resistance decreases so that even as osmotic pressure and concentration differences drop with time, counterbalancing faster release occurs. Osmotic driving force appears to be the most important initial driving force but a diffusional component becomes more significant with time.