Koustuv Chatterjee

Stabilization of a metastable polymorph of sulfamerazine by structurally related additives

Abstract The influence of structurally related additives, namely N4-acetylsulfamerazine (NSMZ), sulfadiazine (SD) or sulfamethazine (SM), on the rate of the solvent-mediated polymorphic transformation (I→II) of sulfamerazine in acetonitrile (ACN) at 24°C was studied. The transformation rate is controlled by the crystallization rate of the more stable Polymorph II. All three impurities exhibit inhibitory effects on the crystallization of Polymorph II and hence stabilize the metastable Polymorph I in ACN suspension. The rank order of the inhibitory effect (NSMZ⪢SD>SM) is the same as the rank order of the binding energy of the impurity molecule to the surface of the host crystal. The relationship between the concentration of the impurity and the inhibitory effect was fitted to various models and was found to be best described by a model based on the Langmuir adsorption isotherm.

A new application for the Antoine equation in formulation development

Characterization of formulation components in pre-formulation and formulation studies will be made easier if a rapid method to evaluate the evaporation characteristics of an ingredient in the formulation is developed. This study aims at providing a simple and rapid thermogravimetric method for estimating the vapor pressure characteristics using the Antoine equation as the analytical tool. The heat treatment for the majority of benzoic acid derivatives follows zero-order rate processes that are in good correlation with their evaporation process. The optimum conditions for the rising temperature experiments were found when the heating rate was 10 degrees C/min in an atmosphere of dry nitrogen (100 ml/min). Methyl paraben was taken as the calibration compound since its Antoine constants are reported in the literature, and its selected thermodynamic parameters were evaluated using the Langmuir equation. The coefficient of vaporization (k macro) was determined to be 124,525+/-0.8, with units being reported in the S.I. system. The corresponding vapor-pressure plots were obtained for the remaining compounds and their Antoine constants calculated.

Estimating vapor pressure curves by thermogravimetry: a rapid and convenient method for characterization of pharmaceuticals.

The purpose of this study was to investigate a rapid method for the evaluation of vaporization characteristics for selected benzoic acid derivatives. The compounds studied in this context were the ortho-, meta- and para-derivatives of hydroxy and amino benzoic acids. Calculations for the order of reaction were first carried out for each of the compounds using methyl paraben as the calibration standard. Those compounds undergoing zero order, non-activated evaporation processes, were analyzed by the Antoine and Langmuir equations, conjointly. The coefficient of vaporization was obtained as 1.2 x 10(5)+/-0.8 Pakg (0.5)mol(0.5)s(-1)m(-2)K(-0.5). The vapor pressure values were used to determine the Antoine constants using the SPSS 10.0 software. This study attempts to outline a comprehensive thermogravimetric technique for vapor pressure characterization of single-component systems.

Calculation of vapor pressure curves for hydroxy benzoic acid derivatives using thermogravimetry

This study aims at providing a simple thermogravimetric method in estimating the vapor pressure characteristics using the Antoine equation as the analytical tool. The heat treatment for the majority of benzoic acid derivatives follows zero order rate processes that are in good correlation with their evaporation process. The optimum conditions for the rising temperature experiments were found when the heating rate was 10 8C/min in an atmosphere of dry nitrogen (100 ml/min). Methyl paraben was taken as the calibration compound since its Antoine constants are reported in literature and its selected thermodynamic parameters were evaluated using the Langmuir equation. The coefficient of vaporization k was determined to be 124525 � 0:8, with units being reported in the SI system. The corresponding vapor pressure plots were obtained for the remaining compounds that followed a zero order evaporation process and their Antoine constants were calculated using the Levenberg‐Marquardt least square curve fit method. # 2002 Elsevier Science B.V. All rights reserved.

Crystalline to amorphous transition of disodium hydrogen phosphate during primary drying

AbstractPurpose. To monitor the phase transitions during freeze-drying of disodium hydrogen phosphate. Methods. The variable temperature sample stage of the X-ray diffractometer (XRD) was attached to a vacuum pump, which enabled the entire freeze-drying process to be carried out in the sample chamber. The phase transitions during the freeze-drying cycle were monitored in real time by XRD. Aqueous buffer solution (containing disodium hydrogen phosphate and sodium dihydrogen phosphate) was cooled at 2°C/min from room temperature to −70°C. It was then heated to −25°C and subjected to primary drying for 2 h at a chamber pressure of ∼100 mTorr, followed by secondary drying at −10°C. Results. In the frozen solution, disodium hydrogen phosphate had crystallized as the dodecahydrate (Na2HPO4⋅12H2O) as was evident from its characteristic lines at ∼5.37, 4.27, and 2.81 Å. Primary drying for 2 h resulted in ice sublimation, and the complete disappearance of the dodecahydrate peaks. Conclusion. The dehydration of the crystalline dodecahydrate resulted in an amorphous anhydrate. Thus the amorphous nature of the end product is a result of phase transitions during the process and do not reflect the solid-state of the ingredients during the entire process.

Raffinose crystallization during freeze-drying and its impact on recovery of protein activity.

No HeadingPurpose.To study i) phase transitions in raffinose solution in the frozen state and during freeze-drying and ii) evaluate the impact of raffinose crystallization on the recovery of protein activity in reconstituted lyophiles.Methods.X-ray powder diffractometry (XRD) and differential scanning calorimetry (DSC) were used to study the frozen aqueous solutions of raffinose pentahydrate. Phase transitions during primary and secondary drying were monitored by simulating the entire freeze-drying process, in situ, in the sample chamber of the diffractometer. The activity of lactate dehydrogenase (LDH) in reconstituted lyophiles was determined spectrophotometrically.Results.Raffinose formed a kinetically stable amorphous freeze-concentrated phase when aqueous solutions were frozen at different cooling rates. When these solutions were subjected to primary drying without annealing, raffinose remained amorphous. Raffinose crystallized as the pentahydrate when the solutions were annealed at a shelf temperature of −10°C. Primary drying of these annealed systems resulted in the dehydration of raffinose pentahydrate to an amorphous phase. The phase separation of the protein from the amorphous raffinose in these two systems during freeze-drying resulted in a significant reduction in the recovery of LDH activity, even though the lyophile was amorphous.Conclusions.Annealing of frozen aqueous raffinose solutions can result in solute crystallization, possibly as the pentahydrate. The crystalline pentahydrate dehydrates during primary drying to yield an amorphous lyophile. Raffinose crystallization during freeze-drying is accompanied by a significant loss of protein activity.

A Thermal Analysis Study of Hydroxy Benzoic Acid Derivatives Using Rising Temperature Thermogravimetry

Hydroxy benzoic acids were subjected to rising temperature thermogravimetric analysis. After optimizing the procedural variables, the kinetics of decomposition was determined and methyl paraben was taken as the calibration compound to characterize the evaporation patterns for the ortho and meta derivatives. The Eact values for ortho, meta and para derivatives were 64.8, 78.2, and 119.1 kJ mol–1, respectively. The Antoine and Langmuir equations were utilized to determine the coefficient of evaporation k, which was 124525±0.8, units being in the SI system. The vapor pressure plots were generated for the ortho and meta derivatives; ΔHvap for these two compounds were obtained as 66.7 and 80.4 kJ mol–1, respectively.

CALCULATION OF VAPOR PRESSURE CURVES FOR ETHYL, PROPYL, AND BUTYL PARABENS USING THERMOGRAVIMETRY

The heat treatment of parahydroxy benzoic acid esters follows zero order rate processes that are in good correlation with their evaporation process. Rising temperature experiments were performed and the optimum conditions were found when the heating rate was 10°C/min in an atmosphere of dry nitrogen, the flow rate of which was maintained at 100 mL/min. The Antoine constants for methyl paraben were substituted into the Antoine equation to get the corresponding vapor pressures that were then used in the Langmuir equation to obtain the value for the coefficient of evaporation k . The Eact value, obtained from the Arrhenius plot, was 75.1 kJ mol−1; the enthalpy of vaporization (ΔHvap) was calculated to be 77.9 kJ mol−1, in very close agreement with the Eact value. Using the Antoine and Langmuir equations, the value of k was experimentally determined to be 124525 ± 0.8, units being in the S.I. system. Taking the value of k to be independent of the substance, the corresponding vapor pressures were obtained for ethyl, propyl, and butyl parabens to give their vapor pressure plots. The thermogravimetric data was obtained for all the compounds under the same experimental conditions. Using the Clausius Clapeyron equation, the enthalpy of vaporization (ΔHvap) of ethyl, propyl, and butyl parabens were calculated to be 72.6, 76.5, and 72.2 kJ mol−1.