FDA-approved, Captisol-enabled® medications are marketed by partners including Amgen, Pfizer, Merck & Co., Melinta Therapeutics, Acrotech Biopharma L.L.C. and Baxter International. Ligand also has License and Supply Agreements (LSAs) in place with a number of other pharmaceutical companies worldwide with Captisol-enabled® product candidates. Routes of administration investigated include parenteral, oral, ophthalmic, nasal, topical, oral, and inhalation.
The regulatory acceptance of Captisol is supported by extensive safety studies demonstrating their excellent systemic safety profile. In 1999, a Type V Drug Master File (DMF) was filed with the FDA. This regulatory safety data package, which includes greater than 80 volumes, has been updated over time and now supports the use of Captisol cyclodextrins in parenteral formulations as well as support for other routes of delivery. In addition, there is a Type V US DMF for Chemistry, Manufacturing and Controls (CMC) and DMFs have also been established in China and Japan. Multiple FDA divisions and ex-US regulatory agencies have evaluated the data package and permitted the use of Captisol cyclodextrins in clinical trials.
Published in scientific articles and utilized in a number of ongoing clinical trials by leading pharmaceutical and biotech companies, Captisol is recognized as a valuable and vital delivery technology whose use could mean the success or failure of a development program.
Traditional formulation systems for very insoluble and/or unstable active pharmaceutical ingredients (APIs) have involved a combination of organic solvents, surfactants and extreme pH conditions. These formulations may precipitate upon injection, or may cause irritation and adverse reactions. At times, these approaches are inadequate for solubilizing enough active agent for a preferred formulation.
Neutral, cationic and anionic APIs have been effectively associated with Captisol®. Aqueous solubilities have increased by a factor of 10 to 25,000, depending on the compound. In contrast to other solubilization technologies, product or traditional formulation system, the feasibility and solubility effectiveness of Captisol® can be rapidly assessed with a few simple lab experiments.
Typically, the inherent pharmacokinetics and pharmacodynamics of the drug are unaffected by Captisol®, however onset may be manipulated and dose sparing maybe observed compared to classical formulations such as co-solvent based, emulsions or suspensions. Upon administration, Captisol® is readily and essentially completely renally eliminated. Captisol® formulations are biocompatible and can be administered parenterally, orally, ophthalmically, nasally, topically and via inhalation.
Captisol® was designed to maximize safety by eliminating the potentially damaging effects produced by the parent beta-cyclodextrin. In-vitro experiments and in-vivo acute, subchronic and chronic toxicity studies have provided safety data to support the development and approval of Captisol® drug formulations in man.
Interaction with Captisol® provides a beneficial and protected environment for the API in its lipophilic cavity, while Captisol's hydrophilic surface provides excellent water solubility- boosting both solubility and stability. Interaction of the API with Captisol® can reduce decomposition by protecting labile regions from the potential reactants in the aqueous environment.
Using Captisol® early in the development process can increase the number of candidates that can be evaluated, decrease development time and increase lead candidate survivability. Captisol® enables an aqueous formulation for many water insoluble APIs as oral, nasal, topical, ophthalmic or liquid-presented medications.
This is a representative listing of Captisol-enabled® partnerships