Deng X.,Johnson and Johnson Pharmaceutical Research and Development LLC |
Liang J.T.,Johnson and Johnson Pharmaceutical Research and Development LLC |
Peterson M.,Amgen Inc. |
Rynberg R.,Johnson and Johnson Pharmaceutical Research and Development LLC |
And 2 more authors.
Journal of Organic Chemistry | Year: 2010
"Chemical Equation Presented" A "redox economical" strategy resulted in a concise, modular synthesis of compound 1, a potent Cathepsin S inhibitor. Starting from three building blocks, crude drug substance was prepared, in a two-step sequence in high yield. Efficient purification of the crude drug substance was accomplished via the formation of an unusual monoethyl oxalate salt. © 2010 American Chemical Society.
Oliveira M.A.,TransForm Pharmaceuticals |
Oliveira M.A.,University of Manchester |
Oliveira M.A.,Alkermes |
Peterson M.L.,Amgen Inc. |
Davey R.J.,University of Manchester
Crystal Growth and Design | Year: 2011
Enthalpy of formation values for 1:1 carbamazepine:saccharin (CBZ:SAC), cyheptamide:saccharin (CYH:SAC), and 10,11-dihydrocarbmazepine:saccharin (HCBZ:SAC) co-crystals and relative enthalpy differences between polymorphs of the co-crystal formers - CBZ(P21/c, P1̄), CYH (P21/c, P1̄), and HCBZ (P21/c, Pbca) - were calculated from enthalpy of solution measurements. The results showed that the co-crystals were enthalpically stabilized and the more stable polymorphs of the co-formers were CBZ-P21/c, CYH-P21/c, and HCBZ-Pbca. The differences in enthalpies between polymorphs were related to the differences in the packing of the molecules. Likewise, the heats of formation of the co-crystals were related to differences in molecular and crystal structures. The transfer enthalpies for the components were assessed and included in the enthalpy of formation calculation. The free energy of formation of CBZ:SAC calculated from the ternary CBZ-SAC-methanol phase diagram showed that the co-crystal was the stable thermodynamic form, and the kinetics of crystallization followed the thermodynamics of crystallization. © 2010 American Chemical Society.
Schlehuber L.D.,TransForm Pharmaceuticals |
Schlehuber L.D.,Avaxia Biologics, Inc. |
McFadyen I.J.,TransForm Pharmaceuticals |
Shu Y.,TransForm Pharmaceuticals |
And 18 more authors.
Vaccine | Year: 2011
As a result of thermal instability, some live attenuated viral (LAV) vaccines lose substantial potency from the time of manufacture to the point of administration. Developing regions lacking extensive, reliable refrigeration (" cold-chain" ) infrastructure are particularly vulnerable to vaccine failure, which in turn increases the burden of disease. Development of a robust, infectivity-based high throughput screening process for identifying thermostable vaccine formulations offers significant promise for vaccine development across a wide variety of LAV products. Here we describe a system that incorporates thermal stability screening into formulation design using heat labile measles virus as a prototype. The screening of >11,000 unique formulations resulted in the identification of liquid formulations with marked improvement over those used in commercial monovalent measles vaccines, with <1.0. log loss of activity after incubation for 8. h at 40 °C. The approach was shown to be transferable to a second unrelated virus, and therefore offers significant promise towards the optimization of formulation for LAV vaccine products. © 2011 Elsevier Ltd.
Remenar J.F.,TransForm Pharmaceuticals |
Tawa M.D.,TransForm Pharmaceuticals |
Peterson M.L.,TransForm Pharmaceuticals |
Almarsson O.,TransForm Pharmaceuticals |
And 2 more authors.
CrystEngComm | Year: 2011
Crystalline hydrates and propylene glycol solvates of celecoxib sodium salt (Cel-Na) were prepared and characterized with the aim of improving oral drug absorption by breaking up the H-bonding interactions present in crystals of the poorly soluble marketed form of the drug (Cel-III). The hydrate grows rapidly from aqueous alkaline solution, forming a thick slurry of thin plates. Thicker plates for structure determination were successfully grown by adding up to 1% benzyl alcohol to the solution. The structure of the pentahydrate of the sodium salt is comprised of a bilayer motif where three waters are coordinated to sodium ions in a discrete layer, while the other two waters reside in a one-dimensional channel. At a given temperature, the hydration state changes rapidly and reversibly as a function of relative humidity (RH). The hydrated salt is physically stable in a sealed vial, but reverts rapidly to the crystalline free base if exposed to ambient CO2 in air at 40% RH or higher. The propylene glycol (PG) solvate of Cel-Na exists in an anhydrous and trihydrate form. The trihydrated PG solvate of Cel-Na is physically stable above ∼15% RH and does not react measurably with CO2 at 66% RH over 4 days, making it the most suitable form for use in solid pharmaceutical formulations. © The Royal Society of Chemistry 2011.