Solution and Solid State Characteristics in Captisol®
What are the solid state characteristics of Captisol®?
Captisol® is currently isolated by spray drying. Some characteristics of this spray dried material are:
Molecular Weight: average 2163 (based on average degree of substitution of 6.5)
Crystallinity: amorphous
Water Content: max. 10%
Melting point: decomposition at approximately 275°C
What are the properties of Captisol® solutions?
In addition to the information presented elsewhere:
At what concentration is Captisol® isotonic?
The plot below shows the solution osmolality as a function of Captisol® concentration and degree of substitution (DS). In general, aqueous Captisol® solutions in the range of 9.5 to 11.4% w/v are iso osmotic with blood and extracellular fluid (280-330 mOsM).
NOTE: Preclinical safety studies have been conducted at 30-40% w/v Captisol® without any adverse effects from the hypertonicity of the solution.
I would like to use a 30% w/v solution of Captisol® in my formulation. Will it be highly viscous?
The viscosity of Captisol® solutions does increase with an increase in concentration. However, for most practical applications, the viscosity is not an issue. The viscosity of various Captisol® solutions is shown below in w/v units.
Can Captisol® be autoclaved?
Yes. Captisol® is stable at autoclave temperatures and under a broad range of pH and other stress conditions.
Captisol® is noted to be hygroscopic - how should we handle the solid material?
Captisol® is a hygroscopic amorphous solid. Its moisture isotherm is shown in the figure below. Captisol® will reversibly take up moisture without any effect on the appearance of the material at humidities up to 60% RH. Equilibration at relative humidity values above 60% will result in deliquescence. Once in this state, the 3 material can be dried, but will give a glass-like product. This water absorption behavior is typical of amorphous hygroscopic materials.
Captisol® should be stored in a closed container to maintain its water content. The water content of Captisol® should be determined if material has been opened for an extended period of time.
What is the substitution pattern of Captisol®?
Captisol® is a mixture of both positional and regioisomers. There are three positions on each glucose unit available for modification, and seven glucose units in the parent β-cyclodextrin. Captisol® is a homogenous mixture of derivatives containing 1 through 10 substituents on each β-cyclodextrin molecule with the average being seven. The manufacturing process produces material with a well controlled substituent distribution. This distribution is well characterized, reproducible, and monitored by capillary electrophoresis (CE). A release specification has been developed for the CE "fingerprint" of Captisol®.
