Formulation development is a key step in the drug development process, and Ligand’s Captisol® technology has emerged as a versatile and indispensable tool in the formulation and development of many pharmaceutical products whether or not Captisol is retained for the final composition. Captisol is a patent protected, uniquely modified cyclodextrin, with a chemical structure that was designed to enable the creation of new products by significantly improving solubility, stability, bioavailability and dosing of active pharmaceutical ingredients (APIs). In this article, we explore the importance of Captisol and its impact on enhancing drug attributes.
- Solubility Enhancement: Poor solubility is a major challenge faced by pharmaceutical scientists during drug development. Many promising drug candidates have low aqueous solubility, leading to difficulties in formulation and reduced bioavailability. The molecular structure of Captisol enables it to encapsulate and interact with drug molecules, enhancing their solubility in aqueous solutions. This improved solubility allows for the development of more effective drug product presentations, including oral, injectable (both liquid and lyophilized), and topical dosage forms. These formulations using Captisol typically result in the reduction of additional excipients, shortened lead times for formulation development, and improved safety as several of the cosolvents and surfactants currently being used in the industry are toxic.
- Stability and Protection: Captisol plays a crucial role in stabilizing and protecting drug compounds. It forms inclusion complexes with drugs, preventing their degradation, hydrolysis, or oxidation. By encapsulating the drug molecule, Captisol shields it from environmental factors, such as light, moisture, and pH changes, thereby extending the shelf life and maintaining the drug’s potency. This stability enhancement enables the development of long-lasting and reliable pharmaceutical products to be used both in the clinic and for commercialization.
- Bioavailability Enhancement: Bioavailability refers to the extent and rate at which a drug is absorbed into the systemic circulation and becomes available at the site of action. The solubilizing properties provided by Captisol greatly improve drug bioavailability. By increasing the dissolution rate and maintaining drug concentration in the gastrointestinal tract, Captisol enhances drug absorption, ensuring a more predictable and effective therapeutic response. In the body, Captisol becomes freely eliminated, while the free API goes to the active site without any additional associated excipient or other conjugation. This bioavailability enhancement is especially beneficial for poorly soluble drugs, maximizing their therapeutic potential.
- Formulation Flexibility: Captisol offers formulation flexibility, allowing for the development of a wide range of drug delivery systems. It can be utilized in various dosage forms, including tablets, capsules, oral solutions, injectables (both liquid and lyophilized), inhaled dosage forms, and topical formulations. Captisol provides compatibility with different drug compounds from small molecules to large proteins and various industry standard excipients that enable the formulation of stable and effective pharmaceutical products across diverse therapeutic areas. This versatility makes Captisol a valuable tool for formulation scientists, offering creative solutions to overcome formulation challenges.
- Regulatory Compliance: Pharmaceutical manufacturing requires adherence to strict regulatory guidelines. Captisol has a well-established safety profile and is approved by regulatory authorities worldwide. Currently, there are 15 FDA-approved drug products that have been approved using Captisol in their formulation. Ligand has extensive toxicology data which provides reassurance to clients and regulatory agencies and streamlines the drug development process. By utilizing Captisol in pharmaceutical formulations, clients can ensure compliance with regulatory requirements, expediting the approval and commercialization process for their drug products.
CyDex has developed 3 of the 15 approved Captisol enabled products in house and helped make many of the other approved Captisol products possible by addressing these critical challenges related to solubility, stability, and bioavailability of drug compounds. Its solubility-enhancing capabilities, stability protection, and bioavailability enhancement significantly contribute to the development of effective and reliable drug formulations. Furthermore, formulation flexibility using Captisol, and regulatory acceptance make it an invaluable tool for pharmaceutical scientists and manufacturers. Captisol is globally accepted as a safe and versatile functional excipient with approvals in parenteral and oral formulations and soon to be approved ophthalmic and subcutaneous pump products. As the industry continues to seek innovative solutions, Captisol stands out as a key component in enhancing drug delivery and improving patient outcomes.
Singota® Solutions has worked side by side with the Captisol team and has in-depth knowledge when it comes to both formulating and testing Captisol. Over the years, Singota has helped improve, troubleshoot, customize and develop several formulations using Captisol as both a cosolvent and active pharmaceutical ingredient (API) for their clients. Currently, Singota has a dozen active clients using Captisol in their formulations. Because Captisol has become so widely used and well-established in the industry, both the United States Pharmacopeia (USP) – National Formulary (NF) and European Pharmacopeia (EP) have established robust testing methods for the characterization of Captisol. These tests are required for most regulatory submissions and universally benefit the pharmaceutical industry across the world to help develop safe products. Singota works directly with Ligand, manufacturer of Captisol, to validate and establish all the USP-NF and EP testing methods for Captisol. Singota continues to play an important role in keeping the methods up to date and optimized, routinely contributing to the methodologies provided by the organizations. With new Captisol products in development, Singota will be at the forefront for offering services related to formulating and testing both current and future Captisol products.
Singota Solutions is a US based CDMO in Bloomington, Indiana. Singota specializes in formulation development and aseptic fill finish for injectable projects. Once a formulation is established, Singota utilizes state of the art robotic filling technology and focuses on smaller batch size requirements. For more information, visit Singota.com to explore how Singota has established itself as a one-stop solution for all your developmental needs. Contact firstname.lastname@example.org to schedule a meeting with our business development team to further discuss your current or future projects.