Solving the Insoluble

Poor solubility remains a significant problem that the industry continues to battle. Pharmaceutical Technology spoke with Nathalie Knabe, global business communications leader, and Christophe Massip, global marketing director of Dow Pharma & Food Solutions, about the company’s innovations to solve solubility issues.

PharmTech: What advances have you seen in solubilization strategies?

Dow: Solubility enhancement strategies are increasingly utilizing amorphous solid dispersions. To meet this need an increasing number of polymers are being developed to support the creation of amorphous solid dispersions via hot melt extrusion (HME) and spray drying. As examples, Dow has developed AFFINISOL HPMC, a new extrudable grade of HPMC that does not require any additives or plasticizers for extrusion, and AFFINISOL HPMCAS for spray drying applications.

PharmTech: Can you tell us more about your new HPMCAS polymer? How does it address solubilization needs or enhance solubilization performance?

Dow: Dow’s AFFINISOL HPMCAS addresses the solubility enhancement of each individual API through the utilization of tailor-made QbD HPMCAS polymer sets that find the optimal acetyl and succinyl substitution levels as well as the ideal molecular weight of the HPMCAS. Each API is unique and may require an HPMCAS polymer outside of the current commercial offering. AFFINISOL HPMCAS addresses the unique needs of each API and allows for the best performance to be obtained. If required, customized HPMCAS can be scaled in Dow’s pilot plant and later commercially manufactured at CAMBREX for clinical trial and commercial drug needs.

In addition, novel AFFINISOL HPMCAS high productivity facilitates higher solids content in solution for higher throughput in spray-drying while maintaining solubility enhancement from HPMCAS. This innovative solution addresses technology gaps in manufacturability and delivery, offering process scale-up efficiencies and greater drug-product utility with expected solubility enhancement performance.

PharmTech: Why is structure-property important when designing solubilizing polymers?

Dow: Structure-property is a key element in the design of polymers for the solubility enhancement of an API. The polymer must balance the ability to be water soluble with the ability to interact and form a stable solid dispersion with a poorly soluble API. Our experience in polymer chemistry allows us to understand and modify the structure polymer performance of our polymers to obtain the most desirable performance for solubility enhancement.

PharmTech: Can you discuss the relationship between substitution levels and peak drug concentration and maintaining supersaturated drug concentration?

Dow: Each API has a unique performance with HPMCAS. This is why it is important to understand the HPMCAS substitution design space and utilize Dow’s QbD AFFINISOL tools to maximize the peak drug concentration and supersaturation maintenance. Often times, there is a balance between peak drug concentration and long term supersaturation of drug maintained in the supersaturated state that requires several HPMCAS substitution levels to be studied to maximize the combined performance of an API.