Softgel Technology Advances Offer New Opportunities for Challenging Therapeutics

Pharmaceutical companies are increasingly turning to innovative softgel and lipid-based formulations to enhance the performance of challenging therapeutics. Recent developments in this technology are providing solutions for drugs with poor solubility, stability issues, and bioavailability concerns.

Lipid-Based Formulations Improve Drug Performance

Lipid-based softgel formulations are proving to be a valuable tool for pharmaceutical developers looking to optimize their therapeutics. These formulations can significantly enhance the bioavailability of drugs with poor aqueous solubility, a common challenge in drug development.

Catalent, a leading provider of advanced delivery technologies, has been at the forefront of this innovation. Benoit Hilbold, scientific development lead at Catalent, explains, "We are equipped to tackle the challenges associated with APIs, including poor solubility, permeability issues, stability, and scalability. Our expertise extends to processing complex formulations, including liquid and highly potent APIs, ensuring uniformity and safety in each dose."

In a recent case study, Catalent worked with a client developing a potent inhibitor of Bruton Tyrosine Kinase (BTK) for treating hematologic malignancies with central nervous system involvement. The drug faced challenges with low aqueous solubility and high sensitivity to light and oxidation. By implementing a self-emulsifying lipid-based formulation, Catalent was able to improve bioavailability and decrease the coefficient of variation from 21.6% to 7.5% in preclinical pharmacokinetic studies.

Amruta Mhashilkar, associate director of product development at Catalent, noted, "Thanks to these improvements, we were able to reduce the estimated maximum clinical dose to 10 times lower than the dose used in the GLP toxicology study. And, because the softgel formulation decreased exposure to light and oxidation, we were able to enhance stability as well."

Enhancing Stability Through Advanced Shell Formulations

Stability is a critical factor in pharmaceutical development, and softgel technologies are offering new ways to improve shelf-life and maintain drug efficacy. One of the main challenges in softgel formulations has been cross-linking, which can affect dissolution and release rates of active pharmaceutical ingredients (APIs).

Catalent's scientists have been working on developing more stable shell formulations to address this issue. Through extensive research, they have identified optimal combinations of gelatin types, plasticizers, and antioxidants that can significantly reduce cross-linking, even under accelerated storage conditions.

"Based on the trending analysis of stability data for soft gelatin capsules, it seems that we can avoid cross-linking issues by carefully choosing the right fill and shell composition," Hilbold stated. "Additionally, selecting specific grades of excipients can help prevent this problem even further."

In a recent study, Catalent assessed five types of gelatin with varied plasticizer compositions to identify the best fit for reducing cross-linking under accelerated storage conditions. The results were promising, with Hilbold reporting, "We found we could improve stability with the right combination of antioxidants and plasticizers. Combined with optimizations to the gelatin content of the capsule, the resulting softgels would resist cross-linking even after six months of storage at 40°C and 75% relative humidity."

These advancements in softgel technology are providing pharmaceutical companies with new tools to overcome formulation challenges and bring more effective and stable drugs to market. As the industry continues to face increasingly complex therapeutic candidates, innovations in drug delivery systems like softgels are likely to play a crucial role in the successful development of future medications.