Rositza Petrova - Academia.edu (original) (raw)
Papers by Rositza Petrova
Journal of Pharmaceutical Sciences, Nov 1, 2009
Related Article: John Y. L. Chung, Benjamin Marcune, Hallena R. Strotman, Rositza I. Petrova, Jef... more Related Article: John Y. L. Chung, Benjamin Marcune, Hallena R. Strotman, Rositza I. Petrova, Jeffrey C. Moore, Peter G. Dormer|2015|Org.Process Res.Dev.|19|1418|doi:10.1021/acs.oprd.5b00259
Organic Process Research & Development, Sep 28, 2015
An asymmetric synthesis of orexin receptor antagonist MK-6096 piperidine core, ((3R,6R)-6-methylp... more An asymmetric synthesis of orexin receptor antagonist MK-6096 piperidine core, ((3R,6R)-6-methylpiperidin-3-yl)methanol (3), is described. The target is synthesized in four steps and 40% overall yield from methyl vinyl ketone and diethyl malonate. The key operation is a practical crystallization-induced dynamic resolution for the conversion of a trans/cis mixture of lactam acid 17 into the desired trans-lactam acid salt in >95% de and 91% yield. The substrate lactam acid mixture was prepared via a solvent-free Michael reaction and a practical biocatalytic transamination process.
Crystal Growth & Design, Oct 24, 2006
Crystal growth of a model molecular crystal system, asparagine monohydrate (Asn‚H 2 O), was explo... more Crystal growth of a model molecular crystal system, asparagine monohydrate (Asn‚H 2 O), was explored in a variety of hydrogel media. Morphologies of crystals grown in agarose, carrageenan, and gelatin gels were compared with those of crystals grown from pure aqueous solutions, as well as those grown from solutions containing various concentrations of related monomers, ions, and cosolvents. The morphological differences were analyzed and interpreted on the basis of complementary interactions at various gel/crystal interfaces. In many cases, the gel polymers were found to have a greater impact on the crystal habit than when solution growth occurred in the presence of comparable concentrations of monomeric or ionic species. These studies clearly indicate that gel methods can provide (at least some systems) a viable alternative means to generate novel crystal morphologies of small molecules that may not be attainable under more conventional solution growth methods.
Crystal Growth & Design, Sep 18, 2002
Agarose, gelatin, and silica gel media have been surveyed as appropriate matrixes for the crystal... more Agarose, gelatin, and silica gel media have been surveyed as appropriate matrixes for the crystal growth of sodium bromate (NaBrO 3). From pure aqueous solution, NaBrO 3 crystallizes with a characteristic tetrahedral habit. We have demonstrated that a greater variety of habits (e.g., cubic, tetrahedral, polyhedral, and dendritic) can be reliably obtained from the growth in these gel media by controlling the solute concentration and the gel density. Agarose and silica matrixes suppress the nucleation as the gel density increases, while increasing gelatin concentrations seem to enhance crystal nucleation rates. These observations support the general hypothesis that the gel media influences the relative growth rates by controlling the solute nucleation and diffusion; however, little can be concluded about the possible chemical interaction between the polymeric backbone and the solute.
Journal of the American Chemical Society, Jan 3, 2004
The crystallization of sodium chlorate (NaClO3) is a classic example of spontaneous chirality, si... more The crystallization of sodium chlorate (NaClO3) is a classic example of spontaneous chirality, since it is achiral in solution but adopts a chiral form in the solid state. While crystal growth of NaClO3 from pure aqueous solutions yields a 50:50 statistical distribution of dand l-crystals, large enantiomeric excesses of either dand l-crystals can be achieved by crystal growth in agarose gel, a naturally occurring chiral polysaccharide. The influence of gel density (0.1-0.75 wt %), temperature, and the diffusion of cosolvents on crystal distribution was discerned from statistical data obtained from 752 gel-mediated crystallization experiments yielding 12,384 individual crystals. These studies demonstrate that the magnitude and direction of the bias can be selectively engineered toward either dor l-forms by changing the gelation conditions. Aqueous agarose gels infused with 48 wt % NaClO3 at 6°C, favored the growth of d-NaClO3 crystals, with ee's reaching 22% at the highest gel concentrations. Crystal growth under methanol diffusion favored deposition of the opposite enantiomorph, l-NaClO3. The bias in the crystal distribution is enhanced at higher temperatures. Aqueous gels at 24°C infused with methanol cosolvent favored l-NaClO3, with ee's reaching 53%. The changing magnitude and direction of the enantiomorph bias can be ascribed to differences in the agarose conformation and intermolecular interactions between the gel and crystal surfaces that inhibit the formation of the two enantiomers to different extents.
Organic Process Research & Development, Aug 18, 2015
Severe operational challenges were experienced during the delumping (via comilling) of a shear-se... more Severe operational challenges were experienced during the delumping (via comilling) of a shear-sensitive active pharmaceutical ingredient (API) during a pilot plant campaign. During the in-line comilling operation from the dryer, the API melted and blinded the screen, which compromised the equipment and called the batch fitness for formulation into question. These challenges instigated the investigation of comilling parameters and API physical properties and their respective effects on delumping performance as well as the final API attributes. Comil impeller speed, impeller type, screen hole size, and screen hole type were studied at both pilot plant and lab scale. The unique properties of the API were also studied in order to understand how this solid differed from others. Because solids with similar physical properties to the API in question are likely to behave in a similar way, the experimental approach described here for Comil and solid characterization should be applicable to other projects as well....
An asymmetric synthesis of orexin receptor antagonist MK-6096 piperidine core, ((3<i>R</... more An asymmetric synthesis of orexin receptor antagonist MK-6096 piperidine core, ((3<i>R</i>,6<i>R</i>)-6-methylpiperidin-3-yl)methanol (<b>3</b>), is described. The target is synthesized in four steps and 40% overall yield from methyl vinyl ketone and diethyl malonate. The key operation is a practical crystallization-induced dynamic resolution for the conversion of a trans/cis mixture of lactam acid <b>17</b> into the desired trans-lactam acid salt in >95% de and 91% yield. The substrate lactam acid mixture was prepared via a solvent-free Michael reaction and a practical biocatalytic transamination process
![Research paper thumbnail of Synthesis, structure and antimicrobial activities of meso silver(I) histidinate [Ag2(D-his)(L-his)]n (Hhis=histidine) showing different self-assembly from those of chiral silver(I) histidinates](https://attachments.academia-assets.com/104088100/thumbnails/1.jpg)
](Inorganica Chimica Acta, 2011
An achiral coordination polymer, [Ag 2 (D-his)(L-his)] n , DL-1 (Hhis = histidine), was prepared ... more An achiral coordination polymer, [Ag 2 (D-his)(L-his)] n , DL-1 (Hhis = histidine), was prepared by slow diffusion of two aqueous solutions of chiral complexes, {[Ag(D-his)] 2 } n (D-2) and {[Ag(L-his)] 2 } n (L-2). 1 The crystal structure of DL-1 consists of a linkage of meso-form dimer units through two kinds of AgÁ Á ÁAg contacts. Crystals of the achiral silver(I) histidinate complex DL-1 exhibited different self-assembly from those of chiral helical polymers (D-3 and L-3). The formation of DL-1 from the two aqueous solutions indicated that ligand exchange around silver(I) atoms took place in water. The antimicrobial activities of DL-1 against selected bacteria, yeasts and molds were evaluated by minimum inhibitory concentration (MIC).
Organic Process Research & Development, 2015
Severe operational challenges were experienced during the delumping (via comilling) of a shear-se... more Severe operational challenges were experienced during the delumping (via comilling) of a shear-sensitive active pharmaceutical ingredient (API) during a pilot plant campaign. During the in-line comilling operation from the dryer, the API melted and blinded the screen, which compromised the equipment and called the batch fitness for formulation into question. These challenges instigated the investigation of comilling parameters and API physical properties and their respective effects on delumping performance as well as the final API attributes. Comil impeller speed, impeller type, screen hole size, and screen hole type were studied at both pilot plant and lab scale. The unique properties of the API were also studied in order to understand how this solid differed from others. Because solids with similar physical properties to the API in question are likely to behave in a similar way, the experimental approach described here for Comil and solid characterization should be applicable to other projects as well....
Journal of the American Chemical Society, 2004
The crystallization of sodium chlorate (NaClO3) is a classic example of spontaneous chirality, si... more The crystallization of sodium chlorate (NaClO3) is a classic example of spontaneous chirality, since it is achiral in solution but adopts a chiral form in the solid state. While crystal growth of NaClO3 from pure aqueous solutions yields a 50:50 statistical distribution of dand l-crystals, large enantiomeric excesses of either dand l-crystals can be achieved by crystal growth in agarose gel, a naturally occurring chiral polysaccharide. The influence of gel density (0.1-0.75 wt %), temperature, and the diffusion of cosolvents on crystal distribution was discerned from statistical data obtained from 752 gel-mediated crystallization experiments yielding 12,384 individual crystals. These studies demonstrate that the magnitude and direction of the bias can be selectively engineered toward either dor l-forms by changing the gelation conditions. Aqueous agarose gels infused with 48 wt % NaClO3 at 6°C, favored the growth of d-NaClO3 crystals, with ee's reaching 22% at the highest gel concentrations. Crystal growth under methanol diffusion favored deposition of the opposite enantiomorph, l-NaClO3. The bias in the crystal distribution is enhanced at higher temperatures. Aqueous gels at 24°C infused with methanol cosolvent favored l-NaClO3, with ee's reaching 53%. The changing magnitude and direction of the enantiomorph bias can be ascribed to differences in the agarose conformation and intermolecular interactions between the gel and crystal surfaces that inhibit the formation of the two enantiomers to different extents.
Crystal Growth & Design, 2002
Agarose, gelatin, and silica gel media have been surveyed as appropriate matrixes for the crystal... more Agarose, gelatin, and silica gel media have been surveyed as appropriate matrixes for the crystal growth of sodium bromate (NaBrO 3). From pure aqueous solution, NaBrO 3 crystallizes with a characteristic tetrahedral habit. We have demonstrated that a greater variety of habits (e.g., cubic, tetrahedral, polyhedral, and dendritic) can be reliably obtained from the growth in these gel media by controlling the solute concentration and the gel density. Agarose and silica matrixes suppress the nucleation as the gel density increases, while increasing gelatin concentrations seem to enhance crystal nucleation rates. These observations support the general hypothesis that the gel media influences the relative growth rates by controlling the solute nucleation and diffusion; however, little can be concluded about the possible chemical interaction between the polymeric backbone and the solute.
Journal of Pharmaceutical Sciences, 2009
Three anhydrous polymorphs, a monohydrate and a dihydrate of an active pharmaceutical ingredient,... more Three anhydrous polymorphs, a monohydrate and a dihydrate of an active pharmaceutical ingredient, N-{[(5S)-3-(4-{6-[(1R,5S)-6-cyano-3-oxabicyclo[3.1.0]hex-6yl]pyridin-3-yl}phenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide (Compound 1), have been crystallized and characterized. Slurry experiments and thermal data have been used to determine their relative thermodynamic stability. The hydrates of Compound 1 were found to be less stable than the most stable anhydrous Form I and converted into Form I in water within 15 min. The rate of conversion in a dry state was found to depend on the relative humidity (RH) and was highest at the two RH extremes examined, 5% and 97.5% RH.
Crystal Growth & Design, 2006
Crystal growth of a model molecular crystal system, asparagine monohydrate (Asn‚H 2 O), was explo... more Crystal growth of a model molecular crystal system, asparagine monohydrate (Asn‚H 2 O), was explored in a variety of hydrogel media. Morphologies of crystals grown in agarose, carrageenan, and gelatin gels were compared with those of crystals grown from pure aqueous solutions, as well as those grown from solutions containing various concentrations of related monomers, ions, and cosolvents. The morphological differences were analyzed and interpreted on the basis of complementary interactions at various gel/crystal interfaces. In many cases, the gel polymers were found to have a greater impact on the crystal habit than when solution growth occurred in the presence of comparable concentrations of monomeric or ionic species. These studies clearly indicate that gel methods can provide (at least some systems) a viable alternative means to generate novel crystal morphologies of small molecules that may not be attainable under more conventional solution growth methods.
Chemical Engineering Science, 2011
Two distinct laboratory methods have been developed to assess the propensity of active pharmaceut... more Two distinct laboratory methods have been developed to assess the propensity of active pharmaceutical ingredients to undergo particle breakage during agitated drying operations. In the first method, mechanical stress is applied to particles by mechanical agitation of powders compressed under an applied normal force. For the second, particles experience stresses as they are carried within a pressurized gas stream. These methods are simple, relatively compound-sparing, and are used to rank materials according to a quantitative breakage classification scale as hard, medium, or easy to break. Based on the results obtained using these methods at laboratory scale, recommendations and precautions for processing at larger scale are made. In this paper, these methods are described in detail, and the results, obtained for several pharmaceutical compounds, are presented.
Related Article: John Y. L. Chung, Benjamin Marcune, Hallena R. Strotman, Rositza I. Petrova, Jef... more Related Article: John Y. L. Chung, Benjamin Marcune, Hallena R. Strotman, Rositza I. Petrova, Jeffrey C. Moore, Peter G. Dormer|2015|Org.Process Res.Dev.|19|1418|doi:10.1021/acs.oprd.5b00259
Organic Process Research & Development, 2015
Journal of Pharmaceutical Sciences, Nov 1, 2009
Related Article: John Y. L. Chung, Benjamin Marcune, Hallena R. Strotman, Rositza I. Petrova, Jef... more Related Article: John Y. L. Chung, Benjamin Marcune, Hallena R. Strotman, Rositza I. Petrova, Jeffrey C. Moore, Peter G. Dormer|2015|Org.Process Res.Dev.|19|1418|doi:10.1021/acs.oprd.5b00259
Organic Process Research & Development, Sep 28, 2015
An asymmetric synthesis of orexin receptor antagonist MK-6096 piperidine core, ((3R,6R)-6-methylp... more An asymmetric synthesis of orexin receptor antagonist MK-6096 piperidine core, ((3R,6R)-6-methylpiperidin-3-yl)methanol (3), is described. The target is synthesized in four steps and 40% overall yield from methyl vinyl ketone and diethyl malonate. The key operation is a practical crystallization-induced dynamic resolution for the conversion of a trans/cis mixture of lactam acid 17 into the desired trans-lactam acid salt in >95% de and 91% yield. The substrate lactam acid mixture was prepared via a solvent-free Michael reaction and a practical biocatalytic transamination process.
Crystal Growth & Design, Oct 24, 2006
Crystal growth of a model molecular crystal system, asparagine monohydrate (Asn‚H 2 O), was explo... more Crystal growth of a model molecular crystal system, asparagine monohydrate (Asn‚H 2 O), was explored in a variety of hydrogel media. Morphologies of crystals grown in agarose, carrageenan, and gelatin gels were compared with those of crystals grown from pure aqueous solutions, as well as those grown from solutions containing various concentrations of related monomers, ions, and cosolvents. The morphological differences were analyzed and interpreted on the basis of complementary interactions at various gel/crystal interfaces. In many cases, the gel polymers were found to have a greater impact on the crystal habit than when solution growth occurred in the presence of comparable concentrations of monomeric or ionic species. These studies clearly indicate that gel methods can provide (at least some systems) a viable alternative means to generate novel crystal morphologies of small molecules that may not be attainable under more conventional solution growth methods.
Crystal Growth & Design, Sep 18, 2002
Agarose, gelatin, and silica gel media have been surveyed as appropriate matrixes for the crystal... more Agarose, gelatin, and silica gel media have been surveyed as appropriate matrixes for the crystal growth of sodium bromate (NaBrO 3). From pure aqueous solution, NaBrO 3 crystallizes with a characteristic tetrahedral habit. We have demonstrated that a greater variety of habits (e.g., cubic, tetrahedral, polyhedral, and dendritic) can be reliably obtained from the growth in these gel media by controlling the solute concentration and the gel density. Agarose and silica matrixes suppress the nucleation as the gel density increases, while increasing gelatin concentrations seem to enhance crystal nucleation rates. These observations support the general hypothesis that the gel media influences the relative growth rates by controlling the solute nucleation and diffusion; however, little can be concluded about the possible chemical interaction between the polymeric backbone and the solute.
Journal of the American Chemical Society, Jan 3, 2004
The crystallization of sodium chlorate (NaClO3) is a classic example of spontaneous chirality, si... more The crystallization of sodium chlorate (NaClO3) is a classic example of spontaneous chirality, since it is achiral in solution but adopts a chiral form in the solid state. While crystal growth of NaClO3 from pure aqueous solutions yields a 50:50 statistical distribution of dand l-crystals, large enantiomeric excesses of either dand l-crystals can be achieved by crystal growth in agarose gel, a naturally occurring chiral polysaccharide. The influence of gel density (0.1-0.75 wt %), temperature, and the diffusion of cosolvents on crystal distribution was discerned from statistical data obtained from 752 gel-mediated crystallization experiments yielding 12,384 individual crystals. These studies demonstrate that the magnitude and direction of the bias can be selectively engineered toward either dor l-forms by changing the gelation conditions. Aqueous agarose gels infused with 48 wt % NaClO3 at 6°C, favored the growth of d-NaClO3 crystals, with ee's reaching 22% at the highest gel concentrations. Crystal growth under methanol diffusion favored deposition of the opposite enantiomorph, l-NaClO3. The bias in the crystal distribution is enhanced at higher temperatures. Aqueous gels at 24°C infused with methanol cosolvent favored l-NaClO3, with ee's reaching 53%. The changing magnitude and direction of the enantiomorph bias can be ascribed to differences in the agarose conformation and intermolecular interactions between the gel and crystal surfaces that inhibit the formation of the two enantiomers to different extents.
Organic Process Research & Development, Aug 18, 2015
Severe operational challenges were experienced during the delumping (via comilling) of a shear-se... more Severe operational challenges were experienced during the delumping (via comilling) of a shear-sensitive active pharmaceutical ingredient (API) during a pilot plant campaign. During the in-line comilling operation from the dryer, the API melted and blinded the screen, which compromised the equipment and called the batch fitness for formulation into question. These challenges instigated the investigation of comilling parameters and API physical properties and their respective effects on delumping performance as well as the final API attributes. Comil impeller speed, impeller type, screen hole size, and screen hole type were studied at both pilot plant and lab scale. The unique properties of the API were also studied in order to understand how this solid differed from others. Because solids with similar physical properties to the API in question are likely to behave in a similar way, the experimental approach described here for Comil and solid characterization should be applicable to other projects as well....
An asymmetric synthesis of orexin receptor antagonist MK-6096 piperidine core, ((3<i>R</... more An asymmetric synthesis of orexin receptor antagonist MK-6096 piperidine core, ((3<i>R</i>,6<i>R</i>)-6-methylpiperidin-3-yl)methanol (<b>3</b>), is described. The target is synthesized in four steps and 40% overall yield from methyl vinyl ketone and diethyl malonate. The key operation is a practical crystallization-induced dynamic resolution for the conversion of a trans/cis mixture of lactam acid <b>17</b> into the desired trans-lactam acid salt in >95% de and 91% yield. The substrate lactam acid mixture was prepared via a solvent-free Michael reaction and a practical biocatalytic transamination process
Inorganica Chimica Acta, 2011
An achiral coordination polymer, [Ag 2 (D-his)(L-his)] n , DL-1 (Hhis = histidine), was prepared ... more An achiral coordination polymer, [Ag 2 (D-his)(L-his)] n , DL-1 (Hhis = histidine), was prepared by slow diffusion of two aqueous solutions of chiral complexes, {[Ag(D-his)] 2 } n (D-2) and {[Ag(L-his)] 2 } n (L-2). 1 The crystal structure of DL-1 consists of a linkage of meso-form dimer units through two kinds of AgÁ Á ÁAg contacts. Crystals of the achiral silver(I) histidinate complex DL-1 exhibited different self-assembly from those of chiral helical polymers (D-3 and L-3). The formation of DL-1 from the two aqueous solutions indicated that ligand exchange around silver(I) atoms took place in water. The antimicrobial activities of DL-1 against selected bacteria, yeasts and molds were evaluated by minimum inhibitory concentration (MIC).
Organic Process Research & Development, 2015
Severe operational challenges were experienced during the delumping (via comilling) of a shear-se... more Severe operational challenges were experienced during the delumping (via comilling) of a shear-sensitive active pharmaceutical ingredient (API) during a pilot plant campaign. During the in-line comilling operation from the dryer, the API melted and blinded the screen, which compromised the equipment and called the batch fitness for formulation into question. These challenges instigated the investigation of comilling parameters and API physical properties and their respective effects on delumping performance as well as the final API attributes. Comil impeller speed, impeller type, screen hole size, and screen hole type were studied at both pilot plant and lab scale. The unique properties of the API were also studied in order to understand how this solid differed from others. Because solids with similar physical properties to the API in question are likely to behave in a similar way, the experimental approach described here for Comil and solid characterization should be applicable to other projects as well....
Journal of the American Chemical Society, 2004
The crystallization of sodium chlorate (NaClO3) is a classic example of spontaneous chirality, si... more The crystallization of sodium chlorate (NaClO3) is a classic example of spontaneous chirality, since it is achiral in solution but adopts a chiral form in the solid state. While crystal growth of NaClO3 from pure aqueous solutions yields a 50:50 statistical distribution of dand l-crystals, large enantiomeric excesses of either dand l-crystals can be achieved by crystal growth in agarose gel, a naturally occurring chiral polysaccharide. The influence of gel density (0.1-0.75 wt %), temperature, and the diffusion of cosolvents on crystal distribution was discerned from statistical data obtained from 752 gel-mediated crystallization experiments yielding 12,384 individual crystals. These studies demonstrate that the magnitude and direction of the bias can be selectively engineered toward either dor l-forms by changing the gelation conditions. Aqueous agarose gels infused with 48 wt % NaClO3 at 6°C, favored the growth of d-NaClO3 crystals, with ee's reaching 22% at the highest gel concentrations. Crystal growth under methanol diffusion favored deposition of the opposite enantiomorph, l-NaClO3. The bias in the crystal distribution is enhanced at higher temperatures. Aqueous gels at 24°C infused with methanol cosolvent favored l-NaClO3, with ee's reaching 53%. The changing magnitude and direction of the enantiomorph bias can be ascribed to differences in the agarose conformation and intermolecular interactions between the gel and crystal surfaces that inhibit the formation of the two enantiomers to different extents.
Crystal Growth & Design, 2002
Agarose, gelatin, and silica gel media have been surveyed as appropriate matrixes for the crystal... more Agarose, gelatin, and silica gel media have been surveyed as appropriate matrixes for the crystal growth of sodium bromate (NaBrO 3). From pure aqueous solution, NaBrO 3 crystallizes with a characteristic tetrahedral habit. We have demonstrated that a greater variety of habits (e.g., cubic, tetrahedral, polyhedral, and dendritic) can be reliably obtained from the growth in these gel media by controlling the solute concentration and the gel density. Agarose and silica matrixes suppress the nucleation as the gel density increases, while increasing gelatin concentrations seem to enhance crystal nucleation rates. These observations support the general hypothesis that the gel media influences the relative growth rates by controlling the solute nucleation and diffusion; however, little can be concluded about the possible chemical interaction between the polymeric backbone and the solute.
Journal of Pharmaceutical Sciences, 2009
Three anhydrous polymorphs, a monohydrate and a dihydrate of an active pharmaceutical ingredient,... more Three anhydrous polymorphs, a monohydrate and a dihydrate of an active pharmaceutical ingredient, N-{[(5S)-3-(4-{6-[(1R,5S)-6-cyano-3-oxabicyclo[3.1.0]hex-6yl]pyridin-3-yl}phenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide (Compound 1), have been crystallized and characterized. Slurry experiments and thermal data have been used to determine their relative thermodynamic stability. The hydrates of Compound 1 were found to be less stable than the most stable anhydrous Form I and converted into Form I in water within 15 min. The rate of conversion in a dry state was found to depend on the relative humidity (RH) and was highest at the two RH extremes examined, 5% and 97.5% RH.
Crystal Growth & Design, 2006
Crystal growth of a model molecular crystal system, asparagine monohydrate (Asn‚H 2 O), was explo... more Crystal growth of a model molecular crystal system, asparagine monohydrate (Asn‚H 2 O), was explored in a variety of hydrogel media. Morphologies of crystals grown in agarose, carrageenan, and gelatin gels were compared with those of crystals grown from pure aqueous solutions, as well as those grown from solutions containing various concentrations of related monomers, ions, and cosolvents. The morphological differences were analyzed and interpreted on the basis of complementary interactions at various gel/crystal interfaces. In many cases, the gel polymers were found to have a greater impact on the crystal habit than when solution growth occurred in the presence of comparable concentrations of monomeric or ionic species. These studies clearly indicate that gel methods can provide (at least some systems) a viable alternative means to generate novel crystal morphologies of small molecules that may not be attainable under more conventional solution growth methods.
Chemical Engineering Science, 2011
Two distinct laboratory methods have been developed to assess the propensity of active pharmaceut... more Two distinct laboratory methods have been developed to assess the propensity of active pharmaceutical ingredients to undergo particle breakage during agitated drying operations. In the first method, mechanical stress is applied to particles by mechanical agitation of powders compressed under an applied normal force. For the second, particles experience stresses as they are carried within a pressurized gas stream. These methods are simple, relatively compound-sparing, and are used to rank materials according to a quantitative breakage classification scale as hard, medium, or easy to break. Based on the results obtained using these methods at laboratory scale, recommendations and precautions for processing at larger scale are made. In this paper, these methods are described in detail, and the results, obtained for several pharmaceutical compounds, are presented.
Related Article: John Y. L. Chung, Benjamin Marcune, Hallena R. Strotman, Rositza I. Petrova, Jef... more Related Article: John Y. L. Chung, Benjamin Marcune, Hallena R. Strotman, Rositza I. Petrova, Jeffrey C. Moore, Peter G. Dormer|2015|Org.Process Res.Dev.|19|1418|doi:10.1021/acs.oprd.5b00259
Organic Process Research & Development, 2015