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Atlanta, GA, United States

Lipert M.P.,University of Michigan | Roy L.,University of Michigan | Childs S.L.,Renovo Research LLC | Rodriguez-Hornedo N.,University of Michigan
Journal of Pharmaceutical Sciences | Year: 2015

This work examines cocrystal solubility in biorelevant media (FeSSIF, fed-state simulated intestinal fluid), and develops a theoretical framework that allows for the simple and quantitative prediction of cocrystal solubilization from drug solubilization. The solubilities of four hydrophobic drugs and seven cocrystals containing these drugs were measured in FeSSIF and in acetate buffer at pH 5.00. In all cases, the cocrystal solubility (Scocrystal) was higher than the drug solubility (Sdrug) in both buffer and FeSSIF; however, the solubilization ratio of drug, SRdrug = (SFeSSIF/Sbuffer)drug, was not the same as the solubilization ratio of cocrystal, SRcocrystal = (SFeSSIF/Sbuffer)cocrystal, meaning drug and cocrystal were not solubilized to the same extent in FeSSIF. This highlights the potential risk of anticipating cocrystal behavior in biorelevant media based on solubility studies in water. Predictions of SRcocrystal from simple equations based only on SRdrug were in excellent agreement with measured values. For 1:1 cocrystals, the cocrystal solubilization ratio (SR) can be obtained from the square root of the drug SR. For 2:1 cocrystals, SRcocrystal is found from (SRdrug)2/3. The findings in FeSSIF can be generalized to describe cocrystal behavior in other systems involving preferential solubilization of a drug such as surfactants, lipids, and other drug solubilizing media. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Strukil V.,Ruder Boskovic Institute | Igrc M.D.,Ruder Boskovic Institute | Fabian L.,University of East Anglia | Eckert-Maksic M.,Ruder Boskovic Institute | And 7 more authors.
Green Chemistry | Year: 2012

The mechanochemical click coupling of isothiocyanates and amines has been used as a model reaction to demonstrate that the concept of a solvent-free research laboratory, which eliminates the use of bulk solvents for either chemical synthesis or structural characterization, is applicable to the synthesis of small organic molecules. Whereas the click coupling is achieved in high yields by simple manual grinding of reactants, the use of an electrical, digitally controllable laboratory mill provides a rapid, quantitative and general route to symmetrical and non-symmetrical aromatic or aromatic-aliphatic thioureas. The enhanced efficiency of electrical ball milling techniques, neat grinding or liquid-assisted grinding, over manual mortar-and-pestle synthesis is demonstrated in the synthesis of 49 different thiourea derivatives. Comparison of powder X-ray diffraction data of mechanochemical products with structural information found in the Cambridge Structural Database (CSD), or obtained herein through single crystal X-ray diffraction, indicates that the mechanochemically obtained thiourea derivatives are pure in a chemical sense, but can also demonstrate purity in a supramolecular sense, i.e. in all structurally explored cases the product consisted of a single polymorph. As an extension of our previous work on solvent-free synthesis of coordination polymers, it is now demonstrated that such polymorphic and chemical purity of selected thiourea derivatives, the latter being evidenced through quantitative reaction yields, can enable the direct solvent-free structural characterization of mechanochemical products through powder X-ray diffraction aided by solid-state NMR spectroscopy. © 2012 The Royal Society of Chemistry.

Agency: NSF | Branch: Standard Grant | Program: | Phase: | Award Amount: 150.00K | Year: 2012

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.

Renovo Research LLC | Entity website

Contact Cocrystals behaving badly 2011 Renovo Research, LLC. All rights reserved ...

Renovo Research LLC | Entity website

Improving drug performance and intellectual property with cocrystal technology Cocrystals are novel, patentable, crystalline solid forms that can provide improved physical properties 2011 Renovo Research, LLC. All rights reserved ...

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