Solid-State Stability Testing of Drugs by Isothermal Calorimetry
A new technique has been developed to calculate rapidly the solid-state room-temperature degradation rate of drugs and drug candidates. The technique utilizes measurements of the initial rate of heat output at several elevated temperatures by isothermal calorimetry and the degradation rate of the compound determined at a single elevated temperature by chromatography. The activation energies and degradation rates at 25°C calculated by conventional methods and by isothermal calorimetry are compared and discussed. The compounds studied were phenytoin, triamterene, digoxin, tetracycline, theophylline, diltiazem, and several proprietary ICI compounds.
Isothermal microcalorimetry: an analytical technique for assessing the dynamic chemical stability of UHMWPE.
In this work, isothermal microcalorimetry (IMC) was utilized to measure the exothermic heat flow from specimens of ultra-high-molecular-weight polyethylene (UHMWPE), that had been sterilized by various standard methods, under simulated shelf storage (air at 25 degrees C, 30% r.h.) and simulated implantation (phosphate buffered saline, PBS, at 37 degrees C) conditions. Gamma-radiation sterilized UHMWPE yielded initial heat flow rates approximately 7-10 times higher in simulated shelf storage and 2-3 times higher in simulated implantation (even after 1 month in PBS) than specimens which were unsterilized or sterilized using either ethylene oxide gas (ETO) or gas plasma (GP). These results show that gamma sterilization of UHMWPE produces many more unstable bonds in the polymer than is the case when ETO or GP is used, and that the net exothermic physico-chemical change proceeds steadily in a diffusion-limited manner in air or saline. In addition, gamma sterilization in nitrogen rather than in air did not prevent the creation of unstable bonds, but did defer physico-chemical change until the UHMWPE was exposed to oxygen. These results demonstrate the usefulness of IMC as a viable method for studying the stability of polymeric implant materials.
An Ultrasensitive Analytical Method Based on Chemiluminescence Sensing Electrochemical Parallel Catalytic Reaction Event
An ultrasensitive electrochemiluminescence (ECL) method on the combination of electrochemical parallel catalytic reaction and chemiluminesence signal sensing was proposed for improving ECL analytical characteristics using vanadate(V) as a representative. Vanadate(V) could be electrochemically reduced to generate vanadate(II) which could be chemically oxidized by potassium periodate to regenerate vanadate(V) and give parallel catalytic wave effect. Then, the reduced product of potassium periodate could react with butyl-rhodamine B to emit a sensitive chemiluminescence signal. The chemiluminescence intensity was correlative with vanadate(V) concentration. The investigation on the electrochemical reaction rate constant (k0) confirmed that the speed of electrochemical reaction was faster than that of the subsequent chemiluminescence reaction. The possibility of the combination of electrochemical parallel catalytic reaction with chemiluminescence signal sensing was proved. The similar ECL behaviors could be observed at zirconia nanowires-Nafion modified electrode. Because of the separation and enrichment effect of the modified electrode on vanadate(V), the selectivity and sensitivity was further improved greatly. Based on these findings, a new concept on the combination of electrochemical parallel catalytic reaction and chemiluminesence signal sensing was proposed and an ultrasensitive ECL method for the determination of vanadate(V) was developed at zirconia nanowires-Nafion modified electrode. Under the optimum experimental conditions, the ECL intensity was linear with the concentration of vanadate(V) in the range of 2.0×10−12 mol/L–2.0×10−10 mol/L. The detection limit was 8.0×10−13 mol/L, which was more than 6 orders of magnitude lower than that observed by electrochemical current transduction for electrochemical parallel catalytic reaction at zirconia nanowires-Nafion modified electrode.