[Air humidity solubility assay].

Measurement of drug solubility is one of the key elements of compound characterization during the drug discovery and development process. A broad variety of solubility assay methods have been developed, including equilibrium method which requires analysis of the equilibrium composition and kinetic method which monitors the concentration of a compound dynamically at the time when a precipitate first appears or disappears in the solution. Despite the numerous experimental methods, precise drug solubility values are hard to obtain for time-consuming, sample size and manual work.

Cross-validation of the osmotic pressure based on Pitzer model with air humidity osmometry at high concentration of ammonium sulfate solutions.

The osmotic pressure of ammonium sulfate solutions has been measured by the well-established freezing point osmometry in dilute solutions and we recently reported air humidity osmometry in a much wider range of concentration. Air humidity osmometry cross-validated the theoretical calculations of osmotic pressure based on the Pitzer model at high concentrations by two one-sided test (TOST) of equivalence with multiple testing corrections, where no other experimental method could serve as a reference for comparison. Although more strict equivalence criteria were established between the measurements of freezing point osmometry and the calculations based on the Pitzer model at low concentration, air humidity osmometry is the only currently available osmometry applicable to high concentration, serves as an economic addition to standard osmometry.

Using extended Wilson model to study the relationship between critical relative humidity and solubility of electrolytes.

Based on thermodynamic principle, the critical relative humidity of electrolytes is closely related to their solubility. The authors explored the relationship theoretically and calculated critical relative humidity of 21 electrolytes from their solubility in the light of Raoult's law and extended Wilson model. The results indicate that the critical relative humidity values calculated by Raoult's law can not accord with the reported ones and there is a systematic error in the high concentration range; while these calculated by extended Wilson model are comparable to the reported ones.

Single time point isothermal drug stability experiments at constant humidity.

A single time point isothermal drug stability experiments at constant humidity is introduced. In the new method, kinetic parameters related to both moisture and temperature were obtained by a single pair of experiments: these related to moisture by one with a group of testing humidities and a fixed temperature, those related to temperature by the other with a group of testing temperatures and a constant humidity. By a simulation, the estimates for the kinetic parameters (E(a), m, A) obtained by the proposed method and the reported programmed humidifying and heating method were statistically evaluated and were compared with those obtained by the isothermal measurements at constant humidity.

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.

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.

Step nonisothermal method in kinetics studies of captopril oxidation under compressed oxygen.

A step nonisothermal experiment under high oxygen pressure and a computation with optimization for a step nonisothermal experiment on a stability study of drugs are introduced. The kinetics parameters of captopril oxidation in aqueous solution were determined with this method. It is reported that the reaction of captopril solution occurs under either aerobic or anaerobic conditions, giving different products.

[Stability of penicillin potassium with linear degradation programmed humidifying experiments].

A linear degradation humidifying model for drug stability experiment is introduced. This new humidifying model is presented as: H(r) = -M1-ln {exp(- MH(r,0)) - [exp(-MH(r,0)) -exp(-MH(r-m)) t(m)-t}. Where H(r) is the relative humidity; t is the time; H(r,m) and t(m) are the final relative humidity and time of the experiment, respectively.

Application of highly accurate nephelometric titration in the assaying of phenytoin sodium.

Aim: To determine phenytoin sodium by a highly accurate nephelometric titration.

Methods: The titration operating conditions were optimized and the solubility product constant of phenytoin silver precipitation was determined.

Results: The result of the titration is comparable to those of control experiments.

Determination of phenytoin sodium injection and tablets by highly accurate nephelometric titration.

A highly accurate nephelometric titration method was developed for the quantitative analysis of phenytoin sodium injection and tablets. The titration operating conditions and the validation of the method were studied. Five batches of phenytoin sodium injection and tablets were determined by the proposed method and the control experiment methods, respectively.

[Kinetic study on the degradation of penicillin potassium at different temperature and relative humidity].

Objective: To perform a kinetic analysis and formulation of the degradation of penicillin potassium in the solid phase at different temperature and relative humidity.

Methods: Penicillin potassium was incubated in a temperature-and-humidity-controlled oven at different temperature and relative humidity, and was determined by HPLC at suitable time intervals during the incubation.

Results: The reaction rate was expressed as -dc/dt=k(c0-c+B), where c is the residual concentration, k degradation rate constant, c0 original concentration and B a constant related to original concentration of degradant.

[Effect of programmed humidification and temperature on drug stability].

Aim: To simplify the study on the effect of relative humidity and temperature on drug stability.

Methods: The stability of penicillin potassium as a model was studied with programmed humidifying and heating.

Results: Results of our programmed humidifying and heating experiments are comparable to those of traditional experiment at constant humidity and temperature.

Influence of light and temperature on the stability of procaine hydrochloride injection.

Aim: To study the influence of light and heat on the stability of procaine hydrochloride injection.

Methods: Accelerated tests upon exposure to light at high temperatures were employed.

Results: In experiments with either isothermal heating or exposure to light at high temperatures, the drug degradation rate obeys first-order kinetics.

[Influence of illuminance on the photo-reaction rate order of nitrofurazone solution].

Objective: To explore the relationship between the illuminance and the observed order of reaction of photodegradation of nitrofurazone solution.

Methods: Studying the observed order of reaction of photodegradation of nitrofurazone solution exposed to light with three illuminance values at three concentration values respectively.

Results: The observed order of reaction of photodegradation increased with the decrease of concentration when the illuminance kept constant and, on the other hand, the observed order increased with the increase of illuminance when the concentration kept constant.

[Highly-accurate nephelometric titrimetry].

Aim: To indicate the titration end-point of precipitation reaction by measuring the relative intensity of the scattered light in the titrate for use in pharmaceutical analysis.

Methods: A visible light-emitting diode (LED) was used as a light source and a photodiode was used as the optical detector. Light on the detector creates an electric current through the diode.

[Effect of light and heat on the stability of furacilin aqueous solution].

Aim: To study the effect of both light and heat on the stability of furacilin aqueous solution and the probability of substituting for isothermal accelerated tests by nonisothermal accelerated tests upon exposure to light at high temperatures.

Methods: The isothermal and nonisothermal accelerated tests were employed. The accelerated tests were proceeded in the dark and exposed to light at high temperature.