Haichen Nie - Academia.edu (original) (raw)

Papers by Haichen Nie

Research paper thumbnail of CCDC 1501183: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Research paper thumbnail of Evaluation of Alternative Metallic Stearates as Lubricants in Pharmaceutical Tablet Formulation

Research paper thumbnail of High Bulk-Density Amorphous Dispersions to Enable Direct Compression of Reduced Tablet Size Amorphous Dosage Units

Journal of Pharmaceutical Sciences

Research paper thumbnail of A novel approach to mechanical characterization of pharmaceutical lyospheres

Research paper thumbnail of Tableting process-induced solid-state polymorphic transition

Journal of Pharmaceutical Investigation

Background Polymorphism is that a substance exists into more than two crystalline forms with diff... more Background Polymorphism is that a substance exists into more than two crystalline forms with different molecular arrangements and/or conformations. It has been reported that the polymorphic transition significantly influences several important qualities of a solid drug product such as physical properties of dosage form, physicochemical stability, dissolution rate, permeability and absorption, bioavailability, manufacturability, and commercial scalability. Polymorphic transition can be altered by several pharmaceutical processes. Area covered This review paper discussed the tableting process-induced solid-state polymorphic transition in detail. In particular, the basic principles of solid-state polymorphic transition, theoretical hypotheses for their mechanism, solid-state characterization methods for the analysis of polymorphic transition, and research cases for various drugs in relation to polymorphic transition were reviewed. Expert opinion For the proper selection of the solid phase of raw materials, formulation design, and robust production process to assure the quality and performance of a final tablet product, the following are essential: (i) an in-depth knowledge based on fundamental understanding of the polymorphic transition mechanisms, (ii) development of a promising analytical technology as a process analytical technology (PAT) available for in situ and in-die real-time measurement of a very small quantity of polymorphic transformation with high sensitivity, and iii) development of a complete technology in the formulation and process that can finely control the undesired polymorphic transition.

Research paper thumbnail of A comparative study of applying backscattering and transmission Raman spectroscopy to quantify solid-state form conversion in pharmaceutical tablets

International Journal of Pharmaceutics, 2022

Selecting appropriate Raman measurement and data processing method are of importance to enable ef... more Selecting appropriate Raman measurement and data processing method are of importance to enable effective quantification of solid form conversions upon processing or storage. Therefore, a comparative evaluation is presented herein on using backscattering and transmission Raman spectroscopy to quantify salt disproportionation in tablet matrices. The second part focuses on different spectra processing approaches and calibration models for quantifications. Finally, samples under different mechanical stresses were comprehensively analyzed using different Raman measurements. Much as transmission Raman spectrometry may provide accuracy on bulk measurements by having large sampling volume, it has the drawback of signal attenuation and may overlook process-induced phase transitions occurring on local regions of tablet surface. To overcome this limitation, backscattering Raman with deliberate subsampling can be used as an orthogonal method to probe the existence of low-level form conversion distributed over a tablet's surface. In the present case, different levels of the form conversions were found at the edge and the center of tablets due to the uneven shear stress distribution invoked during tablet compression. In such a scenario, it would be beneficial to apply deliberate-focused backscattering and transmission Raman spectrometry together as complementary techniques to capture chemical information both locally and within the bulk of the tablet.

Research paper thumbnail of Polymorphism and Phase Transitions

Pharmaceutical Crystals, 2018

Research paper thumbnail of CCDC 1501184: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Research paper thumbnail of Acid-Base Reactions in Different Solid-State Forms

are acknowledged for providing me an excellent platform to facilitate this work. I would also lik... more are acknowledged for providing me an excellent platform to facilitate this work. I would also like to thank my friends and family for their warmth and companionship. Finally, my sincerest appreciation goes to my amazing parents and Zhiyi Cui for their love, encouragement, understanding, and constant support.

Research paper thumbnail of Understanding Dynamics of Polymorphic Conversion during the Tableting Process Using In Situ Mechanical Raman Spectroscopy

Molecular Pharmaceutics, 2020

20 The objective of this study is to achieve a fundamental understanding of polymorphic 21 interc... more 20 The objective of this study is to achieve a fundamental understanding of polymorphic 21 interconversion during the tableting process, including during compaction, dwell, 22 decompression/unloading and ejection using an in situ mechanical Raman spectroscopy. The fitfor-purpose in situ mechanical Raman spectroscopy developed herein can provide simultaneous 24 measurement of Raman spectra and densification for the powder compacts. Chlorpropamide 25 (CPA), an anti-diabetic drug, was selected as a model pharmaceutical compound because of its 26 mechanical shear-induced polymorphic conversions. The results confirm that CPA polymorph A 27 (CPA-A) was transformed to CPA polymorph C (CPA-C) under different compaction stresses. 28 We also observed that the converted polymorph CPA-C could be reverted to the CPA-A due to the 29 elastic recovery of powder compacts as detected during dwelling and unloading. This study is the 30 first depiction of the dynamics of CPA polymorphic interconversion during compression, dwell, 31 unloading, and ejection. Mechanistically, this study illustrates a correlation between the change in 32 the powder compact's relative density and polymorphic interconversion of drug substance in 33 different solid-state forms. The present research suggests that the process-induced polymorph 34 conversion is a complicated dynamic process which could be affected by the compaction pressure, 35 the elasticity/plasticity of material, the level of elastic recovery, and the dissipation of residual 36 stress. In summary, this study demonstrates that the in situ mechanical Raman spectroscopy 37 approach enables the simultaneous detection of mechanical and chemical information of the 38 powder compact throughout the tableting process.

Research paper thumbnail of Quantifying Pharmaceutical Formulations from Proton Detected Solid-State NMR under Ultrafast Magic Angle Spinning

Journal of Pharmaceutical Sciences, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Single Crystal Growth Induced by a Copper Wire

Research paper thumbnail of Phytosome-nanosuspensions for silybin-phospholipid complex with increased bioavailability and hepatoprotection efficacy

European Journal of Pharmaceutical Sciences, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Investigating the Physicochemical Stability of Highly Purified Darunavir Ethanolate Extracted from PREZISTA® Tablets

AAPS PharmSciTech, 2018

Understanding physicochemical stability of darunavir ethanolate is expected to be of critical imp... more Understanding physicochemical stability of darunavir ethanolate is expected to be of critical importance for the development and manufacturing of high-quality darunavirrelated pharmaceutical products. However, there are no enabling monographs for darunavir to illustrate its solid-state chemistry, impurity profile, and assay methods. In addition, the US Pharmacopeia reference standard of darunavir is still not commercially available. It has been also challenging to find reliable vendors to obtain highly purified darunavir ethanolate crystals to conduct the physicochemical stability testing. In the present research, we developed a straightforward and cost-effective approach to extract and purify darunavir ethanolate from PREZISTA® tablets using reverse-engineering and crystallization. Using these highly purified crystals, we thoroughly evaluated the potential risks of degradation and form conversions of darunavir ethanolate at stressed conditions to define the manufacturing and packaging specifications for darunavir-related products. Amorphization was observed under thermal storage caused by desolvation of darunavir ethanolate. The ethanolate-tohydrate conversion of darunavir was observed at high relative humidity conditions. Moreover, acid/base-induced degradations of darunavir have been investigated herein to determine the possible drug-excipient compatibility issues in formulations. Furthermore, it is of particular interests to allow the production of high-quality darunavir-ritonavir fixed dose combinations for marketing in Africa. Thus, a validated HPLC method was developed according to ICH guideline to simultaneously quantify assays of darunavir and ritonavir in a single injection. In summary, the findings of this study provide important information for pharmaceutical scientists to design and develop reliable formulations and processings for darunavir-related products with improved stability.

Research paper thumbnail of A novel approach for measuring room temperature enthalpy of mixing and associated solubility estimation of a drug in a polymer matrix

Polymer, 2018

The utility of amorphization of drug molecules, such as enhanced solubility, dissolution rate and... more The utility of amorphization of drug molecules, such as enhanced solubility, dissolution rate and oral bioavailability, has been well exemplified in the literature. Yet, the application of this technique is often hindered by the crystallization liability of the drug. Amorphous solid dispersions (ASD), in which polymers are mixed with the amorphous drug, are often utilized to maintain the amorphous form. Several approaches have been illustrated in the literature to quantify the degree of mixing of drug and polymer. Although successful quantification has been demonstrated, all of these approaches probe the mixing energies at temperatures close to the melting temperature and, thus, require an extrapolation to room/storage temperature. Hence, an approach to directly estimate the drug-polymer extent of mixing at room temperature would enable a more accurate prediction of the physical stabilities. Herein, solution calorimetry was used to determine enthalpies of mixing of drug and polymer dispersions. These are necessary for the estimation of the Flory-Huggins interaction parameter, and associated free energy of mixing function. The estimated free energy of mixing, in turn, enabled the calculation of the drug solubility in the polymer system, which is a critical thermodynamic parameter in predicting the physical stability of an ASD.

Research paper thumbnail of {"__content__"=>"Quantifying Disproportionation in Pharmaceutical Formulations with Cl Solid-State NMR.", "sup"=>{"__content__"=>"35"}}

Molecular pharmaceutics, Jan 2, 2018

Reliable methods for the characterization of drug substances are critical for evaluating stabilit... more Reliable methods for the characterization of drug substances are critical for evaluating stability and bioavailability, especially in dosage formulations under varying storage conditions and usage. Such methods must also give information on the molecular identities and structures of drug substances and any potential byproducts of the formulation process, as well as providing a means of quantifying the relative amounts of these substances. For example, active pharmaceutical ingredients (APIs) are often formulated as ionic salts to improve the pharmaceutical properties of dosage forms; however, exposure of such formulations to elevated temperature and/or humidity can trigger the conversion of an ionic salt of an API to a neutral form with different properties, through a process known as disproportionation. It is particularly challenging to identify changes of pharmaceutical components in solid dosage formulations, which are complex heterogeneous mixtures of the API and excipient compo...

Research paper thumbnail of Correction to: Effects of Moisture-Induced Crystallization on the Aerosol Performance of Spray Dried Amorphous Ciprofloxacin Powder Formulations

Pharmaceutical research, Jan 8, 2018

Research paper thumbnail of Effects of Moisture-Induced Crystallization on the Aerosol Performance of Spray Dried Amorphous Ciprofloxacin Powder Formulations

Pharmaceutical research, Jan 2, 2018

This study aims to investigate the influence of different storage humidity conditions on crystall... more This study aims to investigate the influence of different storage humidity conditions on crystallization and aerosol performance of inhalable spray dried amorphous powder formulations (Ciprofloxacin hydrochloride as the model drug). The spray dried samples were stored at 20%, 55% and 75% relative humidity (RH). Crystallinity was monitored by Powder X-ray diffraction (PXRD), and particle morphology was measured by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Aerosol performance was evaluated using a multi-stage liquid impinger (MSLI). PXRD diffractograms showed the spray dried Ciprofloxacin stored at 20% RH for three weeks were amorphous; whereas those stored at 55% RH and 75% RH started crystallizing after one hour. Fine particle fraction (FPF) of the particles was improved from 28% to 42% after storage at 55% RH for three days. Such improvement was attributed to the crystallization of amorphous powders, which led to increased particle roughness and reduced ...

Research paper thumbnail of Unexpected Single Crystal Growth Induced by a Wire and New Crystalline Structures of Lapatinib

Crystal Growth & Design, 2016

Single crystal growth of lapatinib free base was induced by immersion of a copper wire into a sup... more Single crystal growth of lapatinib free base was induced by immersion of a copper wire into a supersaturated methanolic aqueous solution yielding monoclinic anhydrous plates (space group P2 1 /c, Form 1) and needles of a previously unknown channel hydrate (in P4 2 2 1 2). Also, a new method has been developed herein to obtain anhydrous Form 1 via acid-base reaction of lapatinib ditosylate and sodium methoxide, avoiding the usage of an aqueous solution and hydrate formation. Anhydrous Form 2 as well as new solvates were produced via solution

Research paper thumbnail of To Differentiate End-Point of Wet Granulation for Various Grades of Hydroxypropyl Methylcellulose by Utilizing Thermal and Rheological Approaches

Journal of Pharmaceutical Sciences and Pharmacology, 2015

Research paper thumbnail of CCDC 1501183: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Research paper thumbnail of Evaluation of Alternative Metallic Stearates as Lubricants in Pharmaceutical Tablet Formulation

Research paper thumbnail of High Bulk-Density Amorphous Dispersions to Enable Direct Compression of Reduced Tablet Size Amorphous Dosage Units

Journal of Pharmaceutical Sciences

Research paper thumbnail of A novel approach to mechanical characterization of pharmaceutical lyospheres

Research paper thumbnail of Tableting process-induced solid-state polymorphic transition

Journal of Pharmaceutical Investigation

Background Polymorphism is that a substance exists into more than two crystalline forms with diff... more Background Polymorphism is that a substance exists into more than two crystalline forms with different molecular arrangements and/or conformations. It has been reported that the polymorphic transition significantly influences several important qualities of a solid drug product such as physical properties of dosage form, physicochemical stability, dissolution rate, permeability and absorption, bioavailability, manufacturability, and commercial scalability. Polymorphic transition can be altered by several pharmaceutical processes. Area covered This review paper discussed the tableting process-induced solid-state polymorphic transition in detail. In particular, the basic principles of solid-state polymorphic transition, theoretical hypotheses for their mechanism, solid-state characterization methods for the analysis of polymorphic transition, and research cases for various drugs in relation to polymorphic transition were reviewed. Expert opinion For the proper selection of the solid phase of raw materials, formulation design, and robust production process to assure the quality and performance of a final tablet product, the following are essential: (i) an in-depth knowledge based on fundamental understanding of the polymorphic transition mechanisms, (ii) development of a promising analytical technology as a process analytical technology (PAT) available for in situ and in-die real-time measurement of a very small quantity of polymorphic transformation with high sensitivity, and iii) development of a complete technology in the formulation and process that can finely control the undesired polymorphic transition.

Research paper thumbnail of A comparative study of applying backscattering and transmission Raman spectroscopy to quantify solid-state form conversion in pharmaceutical tablets

International Journal of Pharmaceutics, 2022

Selecting appropriate Raman measurement and data processing method are of importance to enable ef... more Selecting appropriate Raman measurement and data processing method are of importance to enable effective quantification of solid form conversions upon processing or storage. Therefore, a comparative evaluation is presented herein on using backscattering and transmission Raman spectroscopy to quantify salt disproportionation in tablet matrices. The second part focuses on different spectra processing approaches and calibration models for quantifications. Finally, samples under different mechanical stresses were comprehensively analyzed using different Raman measurements. Much as transmission Raman spectrometry may provide accuracy on bulk measurements by having large sampling volume, it has the drawback of signal attenuation and may overlook process-induced phase transitions occurring on local regions of tablet surface. To overcome this limitation, backscattering Raman with deliberate subsampling can be used as an orthogonal method to probe the existence of low-level form conversion distributed over a tablet's surface. In the present case, different levels of the form conversions were found at the edge and the center of tablets due to the uneven shear stress distribution invoked during tablet compression. In such a scenario, it would be beneficial to apply deliberate-focused backscattering and transmission Raman spectrometry together as complementary techniques to capture chemical information both locally and within the bulk of the tablet.

Research paper thumbnail of Polymorphism and Phase Transitions

Pharmaceutical Crystals, 2018

Research paper thumbnail of CCDC 1501184: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Research paper thumbnail of Acid-Base Reactions in Different Solid-State Forms

are acknowledged for providing me an excellent platform to facilitate this work. I would also lik... more are acknowledged for providing me an excellent platform to facilitate this work. I would also like to thank my friends and family for their warmth and companionship. Finally, my sincerest appreciation goes to my amazing parents and Zhiyi Cui for their love, encouragement, understanding, and constant support.

Research paper thumbnail of Understanding Dynamics of Polymorphic Conversion during the Tableting Process Using In Situ Mechanical Raman Spectroscopy

Molecular Pharmaceutics, 2020

20 The objective of this study is to achieve a fundamental understanding of polymorphic 21 interc... more 20 The objective of this study is to achieve a fundamental understanding of polymorphic 21 interconversion during the tableting process, including during compaction, dwell, 22 decompression/unloading and ejection using an in situ mechanical Raman spectroscopy. The fitfor-purpose in situ mechanical Raman spectroscopy developed herein can provide simultaneous 24 measurement of Raman spectra and densification for the powder compacts. Chlorpropamide 25 (CPA), an anti-diabetic drug, was selected as a model pharmaceutical compound because of its 26 mechanical shear-induced polymorphic conversions. The results confirm that CPA polymorph A 27 (CPA-A) was transformed to CPA polymorph C (CPA-C) under different compaction stresses. 28 We also observed that the converted polymorph CPA-C could be reverted to the CPA-A due to the 29 elastic recovery of powder compacts as detected during dwelling and unloading. This study is the 30 first depiction of the dynamics of CPA polymorphic interconversion during compression, dwell, 31 unloading, and ejection. Mechanistically, this study illustrates a correlation between the change in 32 the powder compact's relative density and polymorphic interconversion of drug substance in 33 different solid-state forms. The present research suggests that the process-induced polymorph 34 conversion is a complicated dynamic process which could be affected by the compaction pressure, 35 the elasticity/plasticity of material, the level of elastic recovery, and the dissipation of residual 36 stress. In summary, this study demonstrates that the in situ mechanical Raman spectroscopy 37 approach enables the simultaneous detection of mechanical and chemical information of the 38 powder compact throughout the tableting process.

Research paper thumbnail of Quantifying Pharmaceutical Formulations from Proton Detected Solid-State NMR under Ultrafast Magic Angle Spinning

Journal of Pharmaceutical Sciences, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Single Crystal Growth Induced by a Copper Wire

Research paper thumbnail of Phytosome-nanosuspensions for silybin-phospholipid complex with increased bioavailability and hepatoprotection efficacy

European Journal of Pharmaceutical Sciences, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Investigating the Physicochemical Stability of Highly Purified Darunavir Ethanolate Extracted from PREZISTA® Tablets

AAPS PharmSciTech, 2018

Understanding physicochemical stability of darunavir ethanolate is expected to be of critical imp... more Understanding physicochemical stability of darunavir ethanolate is expected to be of critical importance for the development and manufacturing of high-quality darunavirrelated pharmaceutical products. However, there are no enabling monographs for darunavir to illustrate its solid-state chemistry, impurity profile, and assay methods. In addition, the US Pharmacopeia reference standard of darunavir is still not commercially available. It has been also challenging to find reliable vendors to obtain highly purified darunavir ethanolate crystals to conduct the physicochemical stability testing. In the present research, we developed a straightforward and cost-effective approach to extract and purify darunavir ethanolate from PREZISTA® tablets using reverse-engineering and crystallization. Using these highly purified crystals, we thoroughly evaluated the potential risks of degradation and form conversions of darunavir ethanolate at stressed conditions to define the manufacturing and packaging specifications for darunavir-related products. Amorphization was observed under thermal storage caused by desolvation of darunavir ethanolate. The ethanolate-tohydrate conversion of darunavir was observed at high relative humidity conditions. Moreover, acid/base-induced degradations of darunavir have been investigated herein to determine the possible drug-excipient compatibility issues in formulations. Furthermore, it is of particular interests to allow the production of high-quality darunavir-ritonavir fixed dose combinations for marketing in Africa. Thus, a validated HPLC method was developed according to ICH guideline to simultaneously quantify assays of darunavir and ritonavir in a single injection. In summary, the findings of this study provide important information for pharmaceutical scientists to design and develop reliable formulations and processings for darunavir-related products with improved stability.

Research paper thumbnail of A novel approach for measuring room temperature enthalpy of mixing and associated solubility estimation of a drug in a polymer matrix

Polymer, 2018

The utility of amorphization of drug molecules, such as enhanced solubility, dissolution rate and... more The utility of amorphization of drug molecules, such as enhanced solubility, dissolution rate and oral bioavailability, has been well exemplified in the literature. Yet, the application of this technique is often hindered by the crystallization liability of the drug. Amorphous solid dispersions (ASD), in which polymers are mixed with the amorphous drug, are often utilized to maintain the amorphous form. Several approaches have been illustrated in the literature to quantify the degree of mixing of drug and polymer. Although successful quantification has been demonstrated, all of these approaches probe the mixing energies at temperatures close to the melting temperature and, thus, require an extrapolation to room/storage temperature. Hence, an approach to directly estimate the drug-polymer extent of mixing at room temperature would enable a more accurate prediction of the physical stabilities. Herein, solution calorimetry was used to determine enthalpies of mixing of drug and polymer dispersions. These are necessary for the estimation of the Flory-Huggins interaction parameter, and associated free energy of mixing function. The estimated free energy of mixing, in turn, enabled the calculation of the drug solubility in the polymer system, which is a critical thermodynamic parameter in predicting the physical stability of an ASD.

Research paper thumbnail of {"__content__"=>"Quantifying Disproportionation in Pharmaceutical Formulations with Cl Solid-State NMR.", "sup"=>{"__content__"=>"35"}}

Molecular pharmaceutics, Jan 2, 2018

Reliable methods for the characterization of drug substances are critical for evaluating stabilit... more Reliable methods for the characterization of drug substances are critical for evaluating stability and bioavailability, especially in dosage formulations under varying storage conditions and usage. Such methods must also give information on the molecular identities and structures of drug substances and any potential byproducts of the formulation process, as well as providing a means of quantifying the relative amounts of these substances. For example, active pharmaceutical ingredients (APIs) are often formulated as ionic salts to improve the pharmaceutical properties of dosage forms; however, exposure of such formulations to elevated temperature and/or humidity can trigger the conversion of an ionic salt of an API to a neutral form with different properties, through a process known as disproportionation. It is particularly challenging to identify changes of pharmaceutical components in solid dosage formulations, which are complex heterogeneous mixtures of the API and excipient compo...

Research paper thumbnail of Correction to: Effects of Moisture-Induced Crystallization on the Aerosol Performance of Spray Dried Amorphous Ciprofloxacin Powder Formulations

Pharmaceutical research, Jan 8, 2018

Research paper thumbnail of Effects of Moisture-Induced Crystallization on the Aerosol Performance of Spray Dried Amorphous Ciprofloxacin Powder Formulations

Pharmaceutical research, Jan 2, 2018

This study aims to investigate the influence of different storage humidity conditions on crystall... more This study aims to investigate the influence of different storage humidity conditions on crystallization and aerosol performance of inhalable spray dried amorphous powder formulations (Ciprofloxacin hydrochloride as the model drug). The spray dried samples were stored at 20%, 55% and 75% relative humidity (RH). Crystallinity was monitored by Powder X-ray diffraction (PXRD), and particle morphology was measured by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Aerosol performance was evaluated using a multi-stage liquid impinger (MSLI). PXRD diffractograms showed the spray dried Ciprofloxacin stored at 20% RH for three weeks were amorphous; whereas those stored at 55% RH and 75% RH started crystallizing after one hour. Fine particle fraction (FPF) of the particles was improved from 28% to 42% after storage at 55% RH for three days. Such improvement was attributed to the crystallization of amorphous powders, which led to increased particle roughness and reduced ...

Research paper thumbnail of Unexpected Single Crystal Growth Induced by a Wire and New Crystalline Structures of Lapatinib

Crystal Growth & Design, 2016

Single crystal growth of lapatinib free base was induced by immersion of a copper wire into a sup... more Single crystal growth of lapatinib free base was induced by immersion of a copper wire into a supersaturated methanolic aqueous solution yielding monoclinic anhydrous plates (space group P2 1 /c, Form 1) and needles of a previously unknown channel hydrate (in P4 2 2 1 2). Also, a new method has been developed herein to obtain anhydrous Form 1 via acid-base reaction of lapatinib ditosylate and sodium methoxide, avoiding the usage of an aqueous solution and hydrate formation. Anhydrous Form 2 as well as new solvates were produced via solution

Research paper thumbnail of To Differentiate End-Point of Wet Granulation for Various Grades of Hydroxypropyl Methylcellulose by Utilizing Thermal and Rheological Approaches

Journal of Pharmaceutical Sciences and Pharmacology, 2015