This Small Business Innovation Research (SBIR) Phase I project will develop a drug delivery platform for drugs with poor water solubility. Poor water solubility significantly hinders the delivery of some drug compounds into the body, which leads to poor drug performance. Cocrystals are new materials that can improve the water solubility of a poorly water soluble drug compounds. In order to take advantage of the improved cocrystal properties, a suitable drug delivery system is required. The current drug delivery approaches for cocrystals are failing to control the parameters critical to optimizing performance of poorly soluble cocrystallized drugs. By tuning the effective cocrystal solubility using the innovative approaches proposed here, a robust delivery system for highly soluble cocrystals will be developed.
The broader/commercial impacts of this research are the potential to create a tunable drug delivery platform that can result in improvements in drug product performance. This technology will also create new product opportunities for existing drug products (e.g. rapid onset of pain relieving drugs), which can provide society with improved medicines. Cocrystal technology has significant advantages over competing technologies including: 1) the physical properties of cocrystals are superior to the physical forms used in competing technologies, and 2) intellectual property protection is stronger, which creates an increased commercial incentive for adopting cocrystal technology.
Society relies on the pharmaceutical industry to create new medicines to improve human health, but current pharmaceutical drug discovery efforts have yielded a significant number of development compounds that are very difficult to use as medicines because they will not dissolve in water. This poor water solubility limits the delivery of these compounds into the body, which leads to poor drug performance. This creates a need for a continuous effort to improve drug delivery technology for poorly soluble compounds. With the increasing number low solubility drugs in pharmaceutical development pipelines, it has been necessary to create advanced formulation technologies that can allow these compounds to be effectively developed. Meeting the societal expectation that the pharmaceutical industry will continue to produce new and effective medicines will be dependent on the ability to maintain innovation in the area of advanced drug delivery for poorly soluble compounds. The results from this research have established a new approach for overcoming this solubility problem that has unique benefits compared to existing formulation technologies. This benefit is primarily due to the improved chemical and physical stability of the ‘high energy form’ of the drug that is used in the technology developed in this project. A high energy form in this context is a a physical state of the drug that can overcome the limited solubility barrier present in the poorly soluble ‘low energy form’. The high energy form used in this project is called a ‘cocrystal’. Competing technologies typically use amorphous (non-crystalline) forms, drug dissolved in a liquid vehicle, or nano-sized particles to improve the solubility and absorption of the drug. Cocrystals are useful high energy forms because they are stable crystalline solids. This can make them easier to manufacture and process in addition to being more stable to degradation in use and storage. The use of cocrystals in the drug development pre-clinical (animal testing) phase has been limited because the current approach to using cocrystals in formulations suitable for dosing animals is not well developed. The most significant obstacle to the adoption of cocrystals as a platform to improve solubility is the lack of a reliable and generally applicable drug delivery platform. In this SBIR Phase I project it was demonstrated that using the newly developed formulation method, the amount of drug available in the blood was increased over 10 times compared to the original poorly soluble form of the drug. However, when the cocrystal was compared to the original drug form without the formulation, the blood levels for the cocrystal were only 1.7 times higher. The use of the formulation in parallel with the cocrystal was essential for success. The prevailing industry approach for evaluating cocrystals does not include an integrated formulation strategy and results have been very mixed. The industry has been slow to adopt cocrystals as a viable alternative to existing technologies as a result. Renovo will be communicating these results to the scientific community that is actively working with cocrystals in the pharmaceutical industry in the form of an academic publication in a peer reviewed journal and presentations of the results directly to key scientists in this field. With the increasing number low solubility drugs in pharmaceutical development pipelines, it will be necessary to create advanced formulation technologies that can allow these compounds to be effectively developed. Meeting the societal expectation that the pharmaceutical industry will continue to produce new and effective medicines will be dependent on the ability to maintain continuous innovation in the area of advanced drug delivery for poorly soluble compounds. The results from this Phase I SBIR project have established the framework for a new approach to drug delivery for poorly soluble compounds. The successful commercialization of this technology will result in medicines with improved performance, which in turn can lead to improved human health.
