Xiancheng Zhan

New heating controller and computation for linear heating stability experiment

Abstract A digital linear heating controller with pulse counter and a new computation with optimization and Simpson integration for linear heating experiments have been introduced. This controller is simple, reliable and inexpensive. Its temperature range is 0–97°C for the water bath or 0–200°C for the oven. The accuracy and precision of temperature are ≤ 0.5°C at 0–100°C or ≤ 1% at 100–200°C; the resolution is ±0.1°C; the fluctuation is ±0.1°C for the water bath or ≤ 0.5°C for the oven; and time is accurate to ≤ 5 s per month. Comparison of new and conventional computations is discussed. The results indicate that there is no approximation in the new computation and, therefore, that the deficiencies of the conventional computation have been overcome.

Computer-controlled heating system and new computation for reciprocal heating stability experiment

Abstract A computer-controlled heating system and a new computation with optimization for reciprocal heating experiment have been introduced. In the heating system, a pocket computer was used to control a common thermostat to obtain different heating models. This system is simple, reliable and inexpensive. Its temperature range is 0–97°C for the water bath or 0–200°C for the oven. The accuracy and precision of temperature are ≤ 0.5°C in the range 0–100°C or ≤ 1% in the range 100–200°C; the resolution is 0.05°C; the fluctuation is 0.05°C for the water bath or ≤ 0.5°C for the oven; and time is accurate to ≤ 5 s per month. A comparison of the new and conventional computations is discussed. The results indicate that the deficiencies of the conventional computation have been overcome.

Determining critical relative humidity by measuring air humidity in equilibrium directly

A method that simply, accurately and directly determines the critical relative humidity (H(cr)) of drugs by the measurement of the relative air humidity in equilibrium with saturated solution of drugs is presented. A new pocket humidity meter with a calibrated humidity sensor has been devised. The work of the humidity meter including the sensor is described. The principle for the proposed method is more rational and much simpler than that for both conventional methods and dynamic vapour sorption (DVS) methods. Compared with conventional methods, the proposed method is simple, prompt and can save sample; compared with the DVS system, the pocket humidity meter is significantly simpler and cheaper. The H(cr) of eleven salts and drugs measured by the proposed method and conventional methods serves as a model. The results of two-tailed two samples t-test indicate that there is no significant difference between the new method and the conventional ones.

Evaluation of the stability of aspirin in solid state by the programmed humidifying and non-isothermal experiments

The influence of both moisture and heat on the stability of aspirin was investigated by a single pair of experiments, one with programmed humidity control and the other non-isothermal, rather than many standard isothermal studies, each at constant relative humidity. In experiments, we adopted the acid-base back titration method to measure the content of aspirin in the presence of its degradation products. It was found that the degradation of aspirin could be expressed as ln[(c0−c)/c]=kt+D, where D was a lag time item not related to humidity and temperature. The relationship between the degradation rate constant k and humidity Hr and temperature T could be described as Arrhenius equation multiplied by an exponential item of relative humidity: k = A · exp(mHr) · exp(−(Ea/RT)), where A, Ea and m were the pre-exponential factor, observed activation energy, and a parameter related to humidity, respectively. The results obtained from the programmed humidifying and non-isothermal experiments, A=(1.09±2.04)×1012 h−1, Ea=(93.5±2.2) kJ · mol−1 and m=1.18±0.19, were comparable to those from isothermal studies at constant humidity, A=(1.71±0.35)×1012 h−1, Ea=(94.9±0.7) kJ · mol−1 and m=1.20±0.02. Since the programmed humidifying and non-isothermal experiments save time, labor and materials, it is suggested that the new experimental method can be used to investigate the stability of drugs unstable to both moisture and heat, instead of many classical isothermal experiments at constant humidity.

Cumulative illuminometer and shelf life of drugs in daylight indoors

Abstract An instrument used for measuring cumulative illuminance via pulse counting method was introduced. Photodegradation of drugs in daylight and various lamplights was studied. The shelf life of drugs in daylight indoors was predicted with hydroxyprogesterone caproate injection as a model. The cumulative illuminance of unsteady daylight was measured with the patented pulse counting method in the experiment. The equivalent influences of light from different sources on the photostability of the model drug were observed. Results show that the daylight can be replaced by lamplight in photostability studies. The photodegradation of hydroxyprogesterone caproate injection obeys the zero order kinetics: c=cO−k(Et), and its shelf life in daylight indoors is about 1.1 years.

Determining osmotic pressure of drug solutions by air humidity in equilibrium method

Abstract Objective: To establish a new osmotic pressure measuring method with a wide measuring range. Method: The osmotic pressure of drug solutions is determined by measuring the relative air humidity in equilibrium with the solution. The freezing point osmometry is used as a control. Results: The data obtained by the proposed method are comparable to those by the control method, and the measuring range of the proposed method is significantly wider than that of the control method. Conclusion: The proposed method is performed in an isothermal and equilibrium state, so it overcomes the defects of the freezing point and dew point osmometries which result from the heterothermal process in the measurement, and therefore is not limited to diluted solutions.

Step Nonisothermal Method to Study Stability of Drugs

A step nonisothermal experiment under high oxygen pressure and a new computation with optimization for step nonisothermal experiment on stability study of drugs was introduced. The kinetics parameters of captopril oxidation in aqueous solution were determined by this method. It is reported that the reaction of captopril solution occurs under either aerobic or anaerobic condition, giving different products. Then the total rate constant ktotal can be expressed as where kanaerobic and kaerobic are the rate constants of anaerobic and aerobic degradations, respectively. The results indicated that the parameters obtained in the step nonisothermal experiment were comparable with those obtained in the isothermal–isobaric experiments. By a computer simulation, the estimates for the kinetic parameters (Ea and k0) obtained with step nonisothermal method were statistically evaluated. Results indicated that the estimates obtained with isothermal–isobaric method were somewhat more precise than those obtained with step nonisothermal method. However, the experimental period needed by isothermal–isobaric method was much longer than that needed by step nonisothermal method.

Improved stability of 25% vitamin C parenteral formulation

Abstract The rates of chemical degradation and coloration of 25% vitamin C aqueous solutions were studied in the temperature range of 60–90°C and pH range of 0.4–12.7. Curves of pH versus degradation or coloration rate at various temperatures (20–90°C) under anaerobic conditions indicated that the pH of optimal stability of a 25% vitamin C aqueous solution is 9–11, when determined by the degradation rate, compared to 8, when determined by the coloration rate. Adjustment of solutions with Na 2 CO 3 resulted in an accelerated rate of degradation and coloration in alkaline pH compared to adjustment by NaOH; pH of optimal stability when adjusted by Na 2 CO 3 was 6.5–7, as determined by the coloration rate. Based on the above studies, a parenteral formulation of 25% vitamin C with improved stability was developed. The shelf-life of the improved parenteral formulation is limited by its coloration, and was predicted to be 5 years.

Calculating osmotic pressure according to nonelectrolyte Wilson nonrandom factor model.

Abstract The osmotic pressure of NaCl solutions was determined by the air humidity in equilibrium (AHE) method. The relationship between the osmotic pressure and the concentration was explored theoretically, and the osmotic pressure was calculated according to the nonelectrolyte Wilson nonrandom factor (N-Wilson-NRF) model from the concentration. The results indicate that the calculated osmotic pressure is comparable to the measured one.

Calculating critical relative humidity from solubility according to nonelectrolyte Wilson nonrandom factor model

The critical relative humidity (Hcr) of 25 drugs and chemicals was determined by the air humidity in equilibrium (AHE) method. The relationship between the Hcr and the solubility was explored theoretically, and the Hcr was calculated according to the nonelectrolyte Wilson nonrandom factor (N-Wilson-NRF) model or Raoult’s law from their solubility. The results indicate that the calculated Hcr is comparable to the measured one.