AIMTo determine phenytoin sodium by a highly accurate nephelometric titration.

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

RESULTSThe result of the titration is comparable to those of control experiments.

CONCLUSIONThe proposed method has been found to be accurate, precise, specific, reproducible, and linear.

Nephelometry and Turbidimetry ; methods ; Phenytoin ; analysis ; Reproducibility of Results ; Solutions ; Titrimetry ; methods

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.
Ammonium Sulfate ; chemistry ; Freezing ; Humidity ; Osmolar Concentration ; Osmometry ; methods ; Osmotic Pressure ; Solutions

AIMTo simplify the study on the effect of relative humidity and temperature on drug stability.

METHODSThe stability of penicillin potassium as a model was studied with programmed humidifying and heating.

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

CONCLUSIONProgrammed humidifying and heating experiments are applicable to drug stability study.

Drug Stability ; Hot Temperature ; Humidity ; Penicillins ; chemistry

AIMTo 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.

METHODSA 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. With the addition of the titrant, the titrate became turbid and the intensity of the scattered light in the solution increased gradually. If the precipitation reaction proceeded the completion and the solubility of the precipitate was small enough, the intensity of the scattered light will reach maximum at the stoichiometric point; thus, the titration end-point can be indicated. The accuracy of nephelometric titrimetry was discussed theoretically and the titration of NaCl with AgNO3 was used as a model. To demonstrate the applicability of the new titrimetry in pharmaceutical analysis, phenytoin sodium and procaine hydrochloride were titrated with AgNO3 and NaOH solutions, respectively.

RESULTSWith our new titrator and nephelometric sensor, the accuracy and precision of our new titrimetry can be better than 0.2% under suitable conditions.

CONCLUSIONThis new titrimetry can be used for pharmaceutical analysis.

Phenytoin ; analysis ; Procaine ; analysis ; Titrimetry ; instrumentation ; methods

AIMTo study the influence of light and heat on the stability of procaine hydrochloride injection.

METHODSAccelerated tests upon exposure to light at high temperatures were employed.

RESULTSIn experiments with either isothermal heating or exposure to light at high temperatures, the drug degradation rate obeys first-order kinetics. The total rate constant, ktotal, caused by both light and heat can be divided into two parts: ktotal = kdark + klight, where kdark and klight are the rate constants caused by heat and light, respectively. The klight can be expressed as klight = Alight x E x exp(-Ea,light/RT). Where E is the illuminance of light, Alight is an experimental constant related to light sources, and Ea,light is an experimental constant.

CONCLUSIONBecause the form of klight is similar to the Arrhenius equation, it is suggested that Ea,light might be the observed activation energy of the rate-determining step of the subsequent processes of the photochemical reaction. This viewpoint is supported by the fact that the Ea,light is independent of light sources.

Drug Stability ; Hot Temperature ; Injections ; Light ; Mathematics ; Procaine ; administration & dosage ; chemistry ; radiation effects

AIMTo 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.

METHODSThe isothermal and nonisothermal accelerated tests were employed. The accelerated tests were proceeded in the dark and exposed to light at high temperature. Tungsten, ultraviolet and fluorescent lamps were employed in exposure tests.

RESULTSThe degradation of furacilin aqueous solution in isothermal heating experiments or the exposure experiments to light at high temperatures obeys zero-order kinetics. The total degradation rate constant k caused by both light and heat can be divided into two parts: k = kdark + klight, where kdark and klight are the degradation rate constant caused by heat and light, respectively. The klight can be expressed as klight = Alight.exp(-Ea,light/RT).E, where E is the illuminance of light; Alight and Ea,light are both experimental constants. The parameters obtained in nonisothermal accelerated tests were comparable to those obtained in classic isothermal accelerated tests.

CONCLUSIONNonisothermal accelerated tests may substitute for isothermal accelerated tests during the study of the effects of both light and heat on the stability of drugs, in order to save time, labor and drugs.

Anti-Infective Agents, Local ; chemistry ; Drug Stability ; Hot Temperature ; Light ; Mathematics ; Nitrofurazone ; chemistry ; Solutions

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. M is humidifying constant used in the humidifying program. In the new programmed humidifying model, a linear relationship between the content function of drugs and the relative humidity is obtained, the degradation of drugs can be more uniform within different humidity ranges and the experimental results are more accurate than those in the reported linear humidifying model. The stability of penicillin potassium, as a solid state model, was investigated by the linear degradation programmed humidifying and the exponential heating experiments. The results indicated that the kinetic parameters obtained by the linear degradation programmed humidifying and the exponential heating models were significantly more precise than those obtained by the linear programmed humidifying and the reciprocal heating models.
Drug Stability ; Humidity ; Kinetics ; Mathematics ; Models, Chemical ; Penicillins ; chemistry ; Technology, Pharmaceutical ; methods ; Temperature

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.
Electrolytes ; chemistry ; Humidity ; Models, Chemical ; Solubility

OBJECTIVETo observe the effects of inhibiting stromal cell derived factor-1 (SDF-1) expression by RNA interference (RNAi) on adhesion and drug sensitivity of Jurkat cells co-cultured with bone marrow stromal cells.

METHODSSDF-1 specific short hairpin RNA (shRNA) expressing plasmid was transferred into cultured human acute leukemic bone marrow stromal cells, positive clones were isolated by screening G418 resistance (Group A) , SDF-1 protein level in culture supernatant was detected by enzyme-linked immunosorbent assay (ELISA). The adhesion rates to bone marrow stromal cells layer and the drug sensitivity to doxorubicin of co-cultured Jurkat cells were detected by cell counting and MTT assay, respectively. The un-transfected bone marrow stromal cells of acute leukemia patient (Group B) or normal subject (Group C) were taken as control.

RESULTSThe level of secreted SDF-1 protein (pg/10(5) cells/week) in the supernatants of Group A, B and C were 1920 +/- 205, 12,370 +/- 1355 and 6620 +/- 770, respectively. Of co-cultured Jurkat cells in Group A, B and C, the adhesion rates after 24 h co-culturing were (28.8 +/- 2.6)%, (57.4 +/- 3.8)% and (45.2 +/- 4.0)%, respectively, and the IC50 values of doxorubicin were 585, 6162 and 1758 nmol/L, respectively.

CONCLUSIONDown-regulating SDF-1 expression of bone marrow stromal cells by RNAi reduces adhesion rates and enhances drug sensitivity to doxorubicin of their co-cultured Jurkat cells.

Bone Marrow Cells ; metabolism ; Cell Adhesion ; Cells, Cultured ; Chemokine CXCL12 ; genetics ; metabolism ; Coculture Techniques ; Drug Resistance, Neoplasm ; Gene Expression ; Humans ; Jurkat Cells ; RNA Interference ; Stromal Cells ; metabolism

OBJECTIVETo study the effects of RNA interference inhibiting stromal cell derived factor-1 (SDF-1) expression on the proliferation and apoptosis of co-cultured Jurkat cells.

METHODInhibition of SDF-1 expression by RNA interference (RNAi) was achieved by transferring SDF-1 specific short hairpin RNA (shRNA) expressing plasmid into cultured human acute leukemic bone marrow stromal cells. Resistant clones were obtained by G418 selection (group A). The concentration of SDF-1 protein in culture supernatant was detected by enzyme-linked immunosorbent assay (ELISA). The population double time (PDT), cell cycles, apoptosis rates and the expressions of PCNA, Bcl-2/Bax, Fas/FasL of co-cultured Jurkat cells were detected by cells counting, flow cytometry. TdT-mediated dUTP nick-end labelling (TUNEL) and immunocytochemistry (ICC), respectively. The un-transfected acute leukemic (group B) and normal (group C) bone marrow stromal cells were taken as controls.

RESULTSThe content of SDF-1 protein in supernatant of group A\[(384 +/- 41) pg/ml] was significantly lower than that in group B[(2474 +/- 271) pg/ml] or group C[(1324 +/- 154) pg/ml]. As group A compared with group B and group C, the PDT of co-cultured Jurkat cells was prolonged (group A: 42 h, vs group B: 29 h, group C: 33 h), and G(0)/G(1) stage cells increased [group A: (28.47 +/- 2.39)%, vs group B: (19.43 +/- 2.80)%, group C: (27.15 +/- 2.07)%], S stage cells decreased [group A: (25.57 +/- 1.90)%, vs group B: (74.48 +/- 3.23)%, group C: (60.99 +/- 2.33)%], G(2)/M stage cells increased [group A: (45.96 +/- 3.24)%, vs group B: (6.09 +/- 1.96)%, group C: (11.86 +/- 1.98)%], the apoptosis rate increased [group A: (15.2 +/- 0.8)%, vs group B: (5.4 +/- 0.7)%, group C: (9.5 +/- 0.4)%], and the expressions of PCNA, Bcl-2, Fas decreased; whereas the expressions of Bax and FasL were increased.

CONCLUSIONThe inhibition of SDF-1 expression in bone marrow stromal cells inhibits the proliferation and promotes the apoptosis of co-cultured Jurkat cells.

Apoptosis ; genetics ; Bone Marrow Cells ; metabolism ; Cell Proliferation ; Cells, Cultured ; Chemokine CXCL12 ; genetics ; Coculture Techniques ; Gene Expression ; Humans ; Jurkat Cells ; RNA Interference ; Stromal Cells ; metabolism ; Transfection