Rahul Surana - Academia.edu (original) (raw)

Papers by Rahul Surana

Pharmaceutical Research, 2002

Purpose. To characterize the phase transitions in a multicomponent system during the various stag... more Purpose. To characterize the phase transitions in a multicomponent system during the various stages of the freeze-drying process and to evaluate the crystallization behavior below Tg' (glass transition temperature of maximally freeze-concentrated amorphous phase) in frozen aqueous solutions and during freeze-drying.

AAPS PharmSciTech, 2003

The goal of this research was a phenomenological study of the effect of environmental factors on ... more The goal of this research was a phenomenological study of the effect of environmental factors on the dehydration behavior of carbamazepine dihydrate. Dehydration experiments were performed in an automated vapor sorption apparatus under a variety of conditions, and weight loss was monitored as a function of time. In addition to lattice water, carbamazepine dihydrate contained a significant amount of physically bound water. Based on the kinetics of water loss, it was possible to differentiate between the removal of physically bound water and the lattice water. The activation energy for the 2 processes was 44 and 88 kJ/mol, respectively. As expected, the dehydration rate of carbamazepine dihydrate decreased with an increase in water vapor pressure. While dehydration at 0% relative humidity (RH) resulted in an amorphous anhydrate, the crystallinity of the anhydrate increased as a function of the RH of dehydration. A method was developed for in situ crystallinity determination of the anhydrate formed. Dehydration in the presence of the ethanol vapor was a 2-step process, and the fraction dehydrated at each step was a function of the ethanol vapor pressure. We hypothesize the formation of an intermediate lower hydrate phase with unknown water stoichiometry. An increase in the ethanol vapor pressure first led to a decrease in the dehydration rate followed by an increase. In summary, the dehydration behavior of carbamazepine dihydrate was evaluated at different vapor pressures of water and ethanol. Using the water sorption apparatus, it was possible to (1) differentiate between the removal of physically bound and lattice water, and (2) develop a method for quantifying, in situ, the crystallinity of the product (anhydrate) phase.

Thermochimica Acta, 2003

Our object was to investigate the effect of annealing on the glass transition temperatures and en... more Our object was to investigate the effect of annealing on the glass transition temperatures and enthalpic recovery of frozen aqueous solutions of trehalose. Trehalose solutions were subjected to differential scanning calorimetry wherein they were first cooled from room temperature to −60 • C, and heated to the annealing temperature, which ranged between −34 and −48 • C. Following isothermal annealing for the desired time period, the glass transition temperatures and the enthalpic recovery were determined in the final heating scan. Frozen unannealed trehalose solutions were characterized by two glass transition events. At a heating rate of 2 • C/min, the observed Tg 1 and Tg 2 were ∼−45 and −31 • C, respectively. Annealing resulted in an increase in the lower transition temperature, Tg 1 , while the higher transition temperature, Tg 2 , was unaffected. Enthalpic recovery due to annealing was associated only with Tg 2. Annealing at −36 • C resulted in the highest value of Tg 1 and the maximum enthalpic recovery. Irrespective of the heating rates, the magnitude of enthalpic recovery and Tg 1 showed a similar trend (first an increase, followed by a decrease) as a function of annealing temperature. This suggests that annealing led to crystallization of ice and subsequently the system became maximally freeze-concentrated. Annealing, at temperatures higher than −36 • C, led to a reduction in enthalpic recovery associated with Tg 2 and a lowering of Tg 1. These observations are consistent with the hypothesis that the higher transition temperature coincides with the onset of ice melting. We have attempted to bridge two conflicting schools of thought regarding the origin of multiple glass transitions in frozen aqueous sugar solutions. The two glass transitions are attributed to the formation of two "populations" in the freeze-concentrated phase during "non-equilibrium" or rapid cooling-one, that is maximally freeze-concentrated and the other that contains a higher amount of water. The higher transition temperature also overlaps with the onset of ice melting.

Acta pharmaceutica, 2003

Based on the principles of an elementary osmotic pump (OP), OP tablets were designed and evaluate... more Based on the principles of an elementary osmotic pump (OP), OP tablets were designed and evaluated with the aim to deliver diclofenac sodium (DS) in a controlled manner. In vitro evaluation was done in various release media and kinetics was evaluated using the regression coefficient analysis. Effects of orifice size, coating membrane type, coating thickness, static and stirred conditions and pH variation were studied. In vivo evaluation was performed on six healthy human volunteers and various pharmacokinetic parameters (c(max), t(max), AUC(0-24), MRT) and relative bioavailability were calculated. The results were compared with the performance of two commercial tablets of DS. The drug release from OP tablets was dependent on the type and thickness of the coating membrane, but was independent of the orifice size and static and stirred conditions of the release medium. The OP tablets provided a prolonged and controlled DS release compared to commercial sustained-release and convention...

Pharmaceutical research, 2003

To use an inverse gas chromatographic (IGC) method to determine the glass transition temperature ... more To use an inverse gas chromatographic (IGC) method to determine the glass transition temperature (Tg) of some amorphous pharmaceuticals and to extend this technique for the in situ study of the plasticizing effect of water on these materials. Amorphous sucrose and colyophilized sucrose-PVP mixtures were the model compounds. Both IGC and differential scanning calorimetry (DSC) were used to determine their Tg. By controlling the water vapor pressure in the IGC sample column, it was possible to determine the Tg of plasticized amorphous phases. Under identical temperatures and vapor pressures, the water uptake was independently quantified in an automated water sorption apparatus. The Tg of the dry phases, determined by IGC and by DSC, were in very good agreement. With an increase in the environmental relative humidity (RH), there was a progressive decrease in Tg as a result of the plasticizing effect of water. Because the water uptake was independently quantified, it was possible to use...

Powder Diffraction, 2000

The first object was to develop an X-ray diffractometric method for the detection and quantificat... more The first object was to develop an X-ray diffractometric method for the detection and quantification of crystalline sucrose when it occurs as a mixture with amorphous sucrose. Standards consisting of amorphous sucrose physically mixed with 1 to 5 weight percent crystalline sucrose were prepared. The sum of the background subtracted integrated intensities of the 12.7°2θ (6.94 Å) and 13.1°2θ (6.73 Å) sucrose diffraction peaks were linearly related to the weight percent crystalline sucrose. The limits of detection and quantitation of crystalline sucrose were 0.9% and 1.8% w/w, respectively. The second object was to study the kinetics of crystallization of sucrose as a function of temperature (at 102, 105 and 110 °C under a water vapor pressure of 0 Torr) and water vapor pressure (17.4, 19.8 and 21.4 Torr at 27 °C). In all cases, the crystallization kinetics was best described by the Avrami-Erofe’ev model (three-dimensional nucleation).

Thermochimica Acta, 2005

Differential scanning calorimetry (DSC) is the most commonly used technique for studying enthalpi... more Differential scanning calorimetry (DSC) is the most commonly used technique for studying enthalpic relaxation in amorphous systems. Our objective was to study the effect of experimental conditions, specifically heating and cooling rates, on the enthalpic relaxation measurement by differential scanning calorimetry. Amorphous trehalose was prepared by freeze-drying an aqueous solution of trehalose dihydrate. It was subjected to differential scanning calorimetry. The enthalpic recovery (ER) at the glass transition temperature (T g), for identically aged samples, depended on the heating rate (HR). The T g onset increased as a function of the heating rate and so did the completion of enthalpic recovery, i.e., the temperature at which the enthalpy curve meets the super-cooled liquid line after the glass transition. Therefore, the enthalpic recovery, and by extension the observed extent of relaxation, was influenced by the heating rate. As the aging time increased, there was an increase in the T g onset as well as the completion of enthalpic recovery. Since the calculated enthalpic recovery value is strongly dependent on this endpoint, there is a potential for overestimation of the relaxation below T g. This is particularly important for longer aging times and higher heating rates. It is generally believed that the enthalpic recovery can be minimized by keeping the cooling and heating rates identical. This observation can also be explained by the effect of heating rate on T g onset and the endpoint of enthalpic recovery. The enthalpic recovery at T g may not reflect the state of the sample, and may be strongly influenced by the experimental conditions. Thus, the effects of experimental conditions need to be carefully evaluated in order to obtain meaningful results.

Pharmaceutical Research, 2000

Pharmaceutical Research, 2000

The purpose of this investigation was i) to study the effect of physical aging on crystallization... more The purpose of this investigation was i) to study the effect of physical aging on crystallization and water vapor sorption behavior of amorphous anhydrous trehalose prepared by freeze-drying, and ii) to determine the effects of water sorption on the relaxation state of the aged material. Methods. Freeze-dried trehalose was aged at 100°C for varying time periods to obtain samples with different degrees of relaxation. The glass transition temperature (T g) and enthalpic relaxation were determined by differential scanning calorimetry, and the rate and extent of water uptake at different relative humidity values were quantified using an automated vapor sorption balance. Results. Annealing below the T g caused nucleation in the amorphous trehalose samples, which decreased the crystallization onset temperature on subsequent heating. However, no crystallization was observed below the T g even after prolonged annealing. Physical aging caused a decrease in the rate and extent of water vapor sorption at low relative humidity values. Moreover, the water sorption removed the effects of physical aging, thus effectively causing enthalpic recovery in the aged samples. This recovery occurred gradually in the glassy phase and was not associated with a glass to rubber transition. We believe this aging reversal to be due to volume expansion during water sorption in the amorphous structure. Conclusions. Thermal history of amorphous materials is a crucial determinant of their physical properties. Aging of amorphous trehalose led to nucleation below the T g , and decrease in rate and extent of water sorption. Sorption of water resulted in irreversible changes in the relaxation state of the aged material.

Archives of Pharmacal Research, 2007

... Silymarin (the content of silybin: 43%, Galena Opava, Czech Republic), polyethylene glycol 20... more ... Silymarin (the content of silybin: 43%, Galena Opava, Czech Republic), polyethylene glycol 200 (PEG 200) and polyethylene glycol 400 (PEG ... Constantinides and Scalart (1997) reported that a small droplet size of the oil phase provides a thermodynamically stable microemul ...

Acta Pharmaceutica, 2000

Extended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was deve... more Extended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was developed and evaluated. Target release profile was selected and different variables were optimized to achieve it. Formulation variables such as the level of swellable polymer, plasticizer and the coat thickness of semipermeable membrane (SPM) were found to markedly affect drug release. TRH release was directly proportional to the levels of plasticizer but inversely proportional to the levels of swellable polymer and coat thickness of SPM. Drug release from developed formulations was independent of pH and agitation intensity but dependent on osmotic pressure of the release media. In vivo study was also performed on six healthy human volunteers and various pharmacokinetic parameters (cmax, tmax, AUC0-24, MRT) and relative bioavailability were calculated. The in vitro and in vivo results were compared with the performance of two commercial TRH tablets. The developed formulation provided more prolonged and controlled TRH release compared to the marketed formulation. In vitro-in vivo correlation (IVIVC) was analyzed according to the Wagner-Nelson method. The optimized formulation (batch IVB) exhibited good IVIV correlation (R = 0.9750). The manufacturing procedure was found to be reproducible and formulations were stable over 6 months of accelerated stability testing.

Pharmaceutical Research, 2002

Purpose. To characterize the phase transitions in a multicomponent system during the various stag... more Purpose. To characterize the phase transitions in a multicomponent system during the various stages of the freeze-drying process and to evaluate the crystallization behavior below Tg' (glass transition temperature of maximally freeze-concentrated amorphous phase) in frozen aqueous solutions and during freeze-drying.

AAPS PharmSciTech, 2003

The goal of this research was a phenomenological study of the effect of environmental factors on ... more The goal of this research was a phenomenological study of the effect of environmental factors on the dehydration behavior of carbamazepine dihydrate. Dehydration experiments were performed in an automated vapor sorption apparatus under a variety of conditions, and weight loss was monitored as a function of time. In addition to lattice water, carbamazepine dihydrate contained a significant amount of physically bound water. Based on the kinetics of water loss, it was possible to differentiate between the removal of physically bound water and the lattice water. The activation energy for the 2 processes was 44 and 88 kJ/mol, respectively. As expected, the dehydration rate of carbamazepine dihydrate decreased with an increase in water vapor pressure. While dehydration at 0% relative humidity (RH) resulted in an amorphous anhydrate, the crystallinity of the anhydrate increased as a function of the RH of dehydration. A method was developed for in situ crystallinity determination of the anhydrate formed. Dehydration in the presence of the ethanol vapor was a 2-step process, and the fraction dehydrated at each step was a function of the ethanol vapor pressure. We hypothesize the formation of an intermediate lower hydrate phase with unknown water stoichiometry. An increase in the ethanol vapor pressure first led to a decrease in the dehydration rate followed by an increase. In summary, the dehydration behavior of carbamazepine dihydrate was evaluated at different vapor pressures of water and ethanol. Using the water sorption apparatus, it was possible to (1) differentiate between the removal of physically bound and lattice water, and (2) develop a method for quantifying, in situ, the crystallinity of the product (anhydrate) phase.

Thermochimica Acta, 2003

Our object was to investigate the effect of annealing on the glass transition temperatures and en... more Our object was to investigate the effect of annealing on the glass transition temperatures and enthalpic recovery of frozen aqueous solutions of trehalose. Trehalose solutions were subjected to differential scanning calorimetry wherein they were first cooled from room temperature to −60 • C, and heated to the annealing temperature, which ranged between −34 and −48 • C. Following isothermal annealing for the desired time period, the glass transition temperatures and the enthalpic recovery were determined in the final heating scan. Frozen unannealed trehalose solutions were characterized by two glass transition events. At a heating rate of 2 • C/min, the observed Tg 1 and Tg 2 were ∼−45 and −31 • C, respectively. Annealing resulted in an increase in the lower transition temperature, Tg 1 , while the higher transition temperature, Tg 2 , was unaffected. Enthalpic recovery due to annealing was associated only with Tg 2. Annealing at −36 • C resulted in the highest value of Tg 1 and the maximum enthalpic recovery. Irrespective of the heating rates, the magnitude of enthalpic recovery and Tg 1 showed a similar trend (first an increase, followed by a decrease) as a function of annealing temperature. This suggests that annealing led to crystallization of ice and subsequently the system became maximally freeze-concentrated. Annealing, at temperatures higher than −36 • C, led to a reduction in enthalpic recovery associated with Tg 2 and a lowering of Tg 1. These observations are consistent with the hypothesis that the higher transition temperature coincides with the onset of ice melting. We have attempted to bridge two conflicting schools of thought regarding the origin of multiple glass transitions in frozen aqueous sugar solutions. The two glass transitions are attributed to the formation of two "populations" in the freeze-concentrated phase during "non-equilibrium" or rapid cooling-one, that is maximally freeze-concentrated and the other that contains a higher amount of water. The higher transition temperature also overlaps with the onset of ice melting.

Acta pharmaceutica, 2003

Based on the principles of an elementary osmotic pump (OP), OP tablets were designed and evaluate... more Based on the principles of an elementary osmotic pump (OP), OP tablets were designed and evaluated with the aim to deliver diclofenac sodium (DS) in a controlled manner. In vitro evaluation was done in various release media and kinetics was evaluated using the regression coefficient analysis. Effects of orifice size, coating membrane type, coating thickness, static and stirred conditions and pH variation were studied. In vivo evaluation was performed on six healthy human volunteers and various pharmacokinetic parameters (c(max), t(max), AUC(0-24), MRT) and relative bioavailability were calculated. The results were compared with the performance of two commercial tablets of DS. The drug release from OP tablets was dependent on the type and thickness of the coating membrane, but was independent of the orifice size and static and stirred conditions of the release medium. The OP tablets provided a prolonged and controlled DS release compared to commercial sustained-release and convention...

Pharmaceutical research, 2003

To use an inverse gas chromatographic (IGC) method to determine the glass transition temperature ... more To use an inverse gas chromatographic (IGC) method to determine the glass transition temperature (Tg) of some amorphous pharmaceuticals and to extend this technique for the in situ study of the plasticizing effect of water on these materials. Amorphous sucrose and colyophilized sucrose-PVP mixtures were the model compounds. Both IGC and differential scanning calorimetry (DSC) were used to determine their Tg. By controlling the water vapor pressure in the IGC sample column, it was possible to determine the Tg of plasticized amorphous phases. Under identical temperatures and vapor pressures, the water uptake was independently quantified in an automated water sorption apparatus. The Tg of the dry phases, determined by IGC and by DSC, were in very good agreement. With an increase in the environmental relative humidity (RH), there was a progressive decrease in Tg as a result of the plasticizing effect of water. Because the water uptake was independently quantified, it was possible to use...

Powder Diffraction, 2000

The first object was to develop an X-ray diffractometric method for the detection and quantificat... more The first object was to develop an X-ray diffractometric method for the detection and quantification of crystalline sucrose when it occurs as a mixture with amorphous sucrose. Standards consisting of amorphous sucrose physically mixed with 1 to 5 weight percent crystalline sucrose were prepared. The sum of the background subtracted integrated intensities of the 12.7°2θ (6.94 Å) and 13.1°2θ (6.73 Å) sucrose diffraction peaks were linearly related to the weight percent crystalline sucrose. The limits of detection and quantitation of crystalline sucrose were 0.9% and 1.8% w/w, respectively. The second object was to study the kinetics of crystallization of sucrose as a function of temperature (at 102, 105 and 110 °C under a water vapor pressure of 0 Torr) and water vapor pressure (17.4, 19.8 and 21.4 Torr at 27 °C). In all cases, the crystallization kinetics was best described by the Avrami-Erofe’ev model (three-dimensional nucleation).

Thermochimica Acta, 2005

Differential scanning calorimetry (DSC) is the most commonly used technique for studying enthalpi... more Differential scanning calorimetry (DSC) is the most commonly used technique for studying enthalpic relaxation in amorphous systems. Our objective was to study the effect of experimental conditions, specifically heating and cooling rates, on the enthalpic relaxation measurement by differential scanning calorimetry. Amorphous trehalose was prepared by freeze-drying an aqueous solution of trehalose dihydrate. It was subjected to differential scanning calorimetry. The enthalpic recovery (ER) at the glass transition temperature (T g), for identically aged samples, depended on the heating rate (HR). The T g onset increased as a function of the heating rate and so did the completion of enthalpic recovery, i.e., the temperature at which the enthalpy curve meets the super-cooled liquid line after the glass transition. Therefore, the enthalpic recovery, and by extension the observed extent of relaxation, was influenced by the heating rate. As the aging time increased, there was an increase in the T g onset as well as the completion of enthalpic recovery. Since the calculated enthalpic recovery value is strongly dependent on this endpoint, there is a potential for overestimation of the relaxation below T g. This is particularly important for longer aging times and higher heating rates. It is generally believed that the enthalpic recovery can be minimized by keeping the cooling and heating rates identical. This observation can also be explained by the effect of heating rate on T g onset and the endpoint of enthalpic recovery. The enthalpic recovery at T g may not reflect the state of the sample, and may be strongly influenced by the experimental conditions. Thus, the effects of experimental conditions need to be carefully evaluated in order to obtain meaningful results.

Pharmaceutical Research, 2000

Pharmaceutical Research, 2000

The purpose of this investigation was i) to study the effect of physical aging on crystallization... more The purpose of this investigation was i) to study the effect of physical aging on crystallization and water vapor sorption behavior of amorphous anhydrous trehalose prepared by freeze-drying, and ii) to determine the effects of water sorption on the relaxation state of the aged material. Methods. Freeze-dried trehalose was aged at 100°C for varying time periods to obtain samples with different degrees of relaxation. The glass transition temperature (T g) and enthalpic relaxation were determined by differential scanning calorimetry, and the rate and extent of water uptake at different relative humidity values were quantified using an automated vapor sorption balance. Results. Annealing below the T g caused nucleation in the amorphous trehalose samples, which decreased the crystallization onset temperature on subsequent heating. However, no crystallization was observed below the T g even after prolonged annealing. Physical aging caused a decrease in the rate and extent of water vapor sorption at low relative humidity values. Moreover, the water sorption removed the effects of physical aging, thus effectively causing enthalpic recovery in the aged samples. This recovery occurred gradually in the glassy phase and was not associated with a glass to rubber transition. We believe this aging reversal to be due to volume expansion during water sorption in the amorphous structure. Conclusions. Thermal history of amorphous materials is a crucial determinant of their physical properties. Aging of amorphous trehalose led to nucleation below the T g , and decrease in rate and extent of water sorption. Sorption of water resulted in irreversible changes in the relaxation state of the aged material.

Archives of Pharmacal Research, 2007

... Silymarin (the content of silybin: 43%, Galena Opava, Czech Republic), polyethylene glycol 20... more ... Silymarin (the content of silybin: 43%, Galena Opava, Czech Republic), polyethylene glycol 200 (PEG 200) and polyethylene glycol 400 (PEG ... Constantinides and Scalart (1997) reported that a small droplet size of the oil phase provides a thermodynamically stable microemul ...

Acta Pharmaceutica, 2000

Extended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was deve... more Extended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was developed and evaluated. Target release profile was selected and different variables were optimized to achieve it. Formulation variables such as the level of swellable polymer, plasticizer and the coat thickness of semipermeable membrane (SPM) were found to markedly affect drug release. TRH release was directly proportional to the levels of plasticizer but inversely proportional to the levels of swellable polymer and coat thickness of SPM. Drug release from developed formulations was independent of pH and agitation intensity but dependent on osmotic pressure of the release media. In vivo study was also performed on six healthy human volunteers and various pharmacokinetic parameters (cmax, tmax, AUC0-24, MRT) and relative bioavailability were calculated. The in vitro and in vivo results were compared with the performance of two commercial TRH tablets. The developed formulation provided more prolonged and controlled TRH release compared to the marketed formulation. In vitro-in vivo correlation (IVIVC) was analyzed according to the Wagner-Nelson method. The optimized formulation (batch IVB) exhibited good IVIV correlation (R = 0.9750). The manufacturing procedure was found to be reproducible and formulations were stable over 6 months of accelerated stability testing.