Calculating osmotic pressure of glucose solutions according to ASOG model and measuring it with air humidity osmometry.

The osmotic pressure of glucose solution at a wide concentration range was calculated using ASOG model and experimentally determined by our newly reported air humidity osmometry. The measurements from air humidity osmometry were compared with the well-established freezing point osmometry and ASOG model calculations at low concentrations and with only ASOG model calculations at high concentrations where no standard experimental method could serve as a reference for comparison. Results indicate that air humidity osmometry measurements are comparable to ASOG model calculations at a wide concentration range, while at low concentrations freezing point osmometry measurements provide better comparability with ASOG model calculations.

[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.

Calculating osmotic pressure of xylitol solutions from molality according to UNIFAC model and measuring it with air humidity osmometry.

The osmotic pressure of xylitol solution at a wide concentration range was calculated according to the UNIFAC model and experimentally determined by our newly reported air humidity osmometry. The measurements from air humidity osmometry were compared with UNIFAC model calculations from dilute to saturated solution. Results indicate that air humidity osmometry measurements are comparable to UNIFAC model calculations at a wide concentration range by two one-sided test and multiple testing corrections.

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.

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

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.

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

The critical relative humidity (H(cr)) of 25 drugs and chemicals was determined by the air humidity in equilibrium (AHE) method. The relationship between the H(cr) and the solubility was explored theoretically, and the H(cr) 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 H(cr) is comparable to the measured one.

Relationship between critical relative humidity and solubility of drugs.

Both the critical relative humidity (H(cr)) and the solubility are important physicochemical properties that affect the quality of drugs. However, the relationship between them is not noticed yet. By an analysis of interaction between molecules of drug and water, the conclusion logically obtained is: the higher the solubility is, the lower the H(cr) will be.

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.

Calculating critical relative humidity from solubility according to Pitzer ion interaction model.

The solubility and the critical relative humidity (H(cr)) of 14 drugs and inorganic salts were determined, the relationship between the H(cr) and the solubility was explored theoretically, and the H(cr) was calculated in the light of Raoult's law and Pitzer ion interaction model from their solubility. The results indicate that the H(cr) values calculated by Raoult's law in high humidity (H(cr)>80%) and by Pitzer ion interaction model in low humidity (H(cr)<80%) are comparable to the measured ones.

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.

Calculating the critical relative humidity from the solubility of electrolyte according to extended non-random two liquid model.

According to thermodynamic principle, the critical relative humidity of electrolytes is closely related to their solubility. The authors explored the relationship theoretically and calculated the critical relative humidity of 21 electrolytes in the light of Raoult's law, modified Debye-Hückel model and extended non-random two liquid (NRTL) model from their solubility. 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 high concentration range; the values calculated by modified Debye-Hückel model still can not accord with the reported ones well although without systematic error; and the values calculated by extended NRTL 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.

Compressed oxygen in drug stability experiments.

A drug stability experiment accelerated by compressed oxygen was established. The stability of 10% ascorbic acid solution as a model was studied and the kinetic parameters were obtained with the newly established experimental method. Because ascorbic acid degrades under both anaerobic and aerobic conditions, the total rate constant k(total) can be expressed as: k(total)=k(anaerobic) + k(aerobic), where k(anaerobic) and k(aerobic) are the rate constants of anaerobic and aerobic degradations, 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.

Programmed humidifying in drug stability experiments.

The stability of penicillin potassium, as a solid state model, was investigated by a programmed humidity and temperature controlled method. An optimization calculational approach to data handling is suggested. The stability of drugs which are unstable to both heat and moisture could be studied by a single pair of experiments, one with programmed humidity control and one non-isothermal, rather than many standard isothermal studies, each at constant relative humidity.

Determination of promethazine hydrochloride and its preparations by highly accurate nephelometric titration.

A highly accurate nephelometric titration for the determination of promethazine hydrochloride and its preparations was presented. The titration operating conditions were studied and the solubility product constant of promethazine tetraphenylboron precipitation was determined. The result of the titration is comparable to those of control experiments.

[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.