This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Active pharmaceutical ingredients (APIs), including many anti-tumor drugs, are frequently delivered to the patient in the solid-state as part of an approved dosage type (e.g. tablets, capsules, etc.). Solids provide a convenient, compact and generally stable format to store a drug product. APIs can exist in a variety of distinct solid forms where each form may display unique physicochemical properties such as melting point and sensitivity to moisture. Most importantly, each physical form will have a profound impact on two of the most important properties that are essential to the successful development of drug candidates: solubility and stability. Unfortunately, a vast number of potentially useful compounds with highly desirable molecular pharmacological properties never make it through trials and onto the market because the physical properties of the bulk material may result in very unfavorable bioavailability, undesirable processing characteristics and unacceptable shelf-life. How can we then alter and control solid-state properties without changing desirable molecular behavior? In this project, we will set out to address this question through the deliberate design and synthesis of molecular co-crystals of several families of anti-cancer compounds. Co-crystals of drugs and drug candidates represent new types of materials for pharmaceutical development, and this approach will facilitate the incorporation of an API within a solid """"""""casing"""""""" that may offer enhanced mechanical or thermal stability, reduced hygroscopicity, or modified solubility (thus bioavailability). Furthermore, co-crystallizations allow such properties to be realized without making or even requiring any changes at the molecular level of the API. This is an essential consideration, as the active component derives its specific reactivity or function from what is frequently a carefully and painstakingly constructed molecular structure.
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