Increasing numbers of drug candidates suffer from poor solubility issues. Various amorphous dispersion techniques have been developed that increase solubility. Much work remains to be done, however, to improve the performance of such methods. Enhancement of amorphous dispersions prepared using spray-drying is the focus of an exclusive collaboration between excipient producer The Dow Chemical Company (Dow) and CDMO Bend Research. The two companies are developing fully characterized polymers supported by complete quality-by-design (QbD) principles that can be tailored to meet the performance needs of specific drugs.
David Lyon, senior vice-president of research with Bend Research and Karen Coppens, senior R&D manager, Bob Schmitt, R&D fellow, and Brian Koblinski, strategic marketing manager at Dow, shared details about the new partnership with Pharmaceutical Sciences, Manufacturing & Marketplace Report.
Nature of the relationship
Pharmaceutical Sciences, Manufacturing & Marketplace Report: What specific capabilities does each company bring to the partnership?
Schmitt (Dow): Dow brings over 50 years of experience as one of the leading polymeric excipient suppliers worldwide. This materials-science experience is supported by high-throughput synthesis capabilities with API/polymer screening, laboratory-scale product development and structure/property optimization, a fully cGMP market development plant capable of supporting the clinical development of optimized solutions, and world-scale manufacturing capabilities.
Lyon (Bend Research): As one of the recognized leaders in spray-dried dispersions (SDDs), Bend Research brings proven feasibility screening, SDD formulation expertise, cGMP clinical manufacturing capabilities, and experience in successful technology transfer.
Pharmaceutical Sciences, Manufacturing & Marketplace Report: Why did choose to partner specifically with each other?
Coppens (Dow): We understand that successful solubility enhancement requires optimization of both the polymer and the formulation. In addition, it is imperative that QbD evaluations be incorporated early in the development cycle in order to facilitate robust formulations. Working jointly, we can seamlessly offer customers complete science-based support of their product development programs.
Rationale of the collaboration
Pharmaceutical Sciences, Manufacturing & Marketplace Report: How will the solid dosage industry benefit from the formation of this partnership?
Koblinski (Dow): The collaboration between Bend Research and Dow reduces drug-development risk by seamlessly combining materials development and optimization early in the formulation development process for spray-dried dispersions (SDDs) to achieve optimal clinical outcomes and robustness in drug-product manufacturability.
Lyon (Bend Research): Our two companies use rigorous science that is grounded in fundamentals to develop new excipients and processes that improve the performance of solubilization technologies. This collaboration further extends that effort to use cutting-edge research to enhance existing technologies and ensures that our clients have access to a reliable supply of solubilization excipients that meet the critical-to-quality properties that are key to the performance of their compounds.
Pharmaceutical Sciences, Manufacturing & Marketplace Report: What does the collaboration enable you to do together that you could not each do on your own?
Koblinski (Dow): The collaboration allows Dow and Bend Research to offer a complete SDD solution to the market. Dow’s ability to design, synthesize, and characterize polymers is coupled with Bend’s ability to formulate and manufacture SDDs. These complementary skills distinctly position the collaboration to rapidly develop robust formulations that meet the clients’ clinical requirements.
Incorporating QBD principles
Pharmaceutical Sciences, Manufacturing & Marketplace Report: Can you explain further why you believe that incorporating QbD into the collaborative effort is so important?
Lyon (Bend Research): A properly designed and executed QbD study is the best way to develop a robust SDD product. QbD should be included in formulation development as well as in process development. Studies presented by Dow and Bend Research demonstrate that some SDD performance attributes show a high sensitivity to variations in polymer substitution while others can tolerate a wider variability.
Schmitt (Dow): Dow is able to produce and characterize QbD samples in a design space broader than the currently available commercial product, which helps Dow tailor the material to best meet the needs of the compound.
Lyon (Bend Research): Bend Research’s expertise in SDD technology addresses the variability in SDD process parameters that a formulation can tolerate. Coupling the polymer and process reduces variability in performance and leads to a robust drug product.
Specific polymer and formulation advances
Pharmaceutical Sciences, Manufacturing & Marketplace Report: What types of polymers are you developing, and how are they differentiated from others on the market?
Coppens (Dow): Dow will provide hypromellose and hypromellose acetate succinate (HPMCAS), plus options to tailor these materials as well as next-generation cellulosic and noncellulosic polymers for enhanced performance. These new materials for SDDs will be developed and commercialized to address technology gaps in manufacturability and delivery, providing greater drug-product utility and therapeutic performance.
Pharmaceutical Sciences, Manufacturing & Marketplace Report: What new formulation processes are being investigated, and how do they advance SDD technology?
Lyon (Bend Research): Bend Research brings engineering solutions to SDD formation. For example, our patented hot-spray technology facilitates SDD production of API’s with low organic solubility at commercially relevant through-puts.
Pharmaceutical Sciences, Manufacturing & Marketplace Report: What have you been able to achieve through this collaboration? Have you had initial successes?
Koblinski (Dow): Initial results were presented in 2012 at the annual meeting of the American Association of Pharmaceutical Scientists (AAPS) and the American Association of Chemical Engineers (AIChE). These presentations highlighted the solubilization optimization of several model drugs from SDDs using Dow’s fully characterized Affinisol HPMCAS and Bend Research’s science-based formulation approach. QbD principles were used in the studies to determine the performance sensitivity of the SDDs with respect to variations in the substitution levels of the HPMCAS. The results indicate that the sensitivity varies among drugs, and that a QbD study is one of the best ways to develop a robust formulation for each SDD drug formulation. The pharmaceutical industry has since embraced this concept, and we have several ongoing projects supported by our collaboration.