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Papers by Estevao Macaringue

Research paper thumbnail of Preparation and Formation Mechanism of l-Valine Spherulites via Evaporation Crystallization

Industrial & Engineering Chemistry Research, 2021

Research paper thumbnail of Discovering inhibitor molecules for pathological crystallization of CaOx kidney stones from natural extracts of medical herbs

Journal of Ethnopharmacology, 2021

ETHNOPHARMACOLOGICAL RELEVANCE Kidney stones is one of the common diseases of the urinary system.... more ETHNOPHARMACOLOGICAL RELEVANCE Kidney stones is one of the common diseases of the urinary system. The primary cause of kidney stone formation is the thermodynamic supersaturation of lithogenic solutes in urine, which desaturates by nucleation, crystal growth and aggregation of minerals and salts, mainly Calcium oxalate (CaOx). One of the potential therapies is to develop drug molecules to inhibit or prevent CaOx crystallization in urine. Traditional Chinese medicines (TCMs) provided an efficient approach for the treatment of kidney stones with a specialized-designed recipe of medicinal herbs. But the action details of these herbs were poorly understood due to their complex components, and whether the effective constituents of herbs have an inhibitory effect on the process of stone formation has not been evaluated. AIM OF THE STUDY This study aims to develop and identify inhibitor substitutes from a library of kidney stone prescriptions in traditional Chinese medicines to prevent pathological kidney stone formation. MATERIALS AND METHODS As many as twenty Chinese medicines were extracted and separated into five different polar extracts, the inhibition performance of which on CaOx crystallization was explored by recording and comparing crystallization kinetics. The potential inhibitor molecules in the inhibitory extracts were confirmed by HPLC and their retardation efficacy was evaluated by quantifying nucleation and growth kinetics using colorimetry. Then the inhibitor-COM crystal interactions and specificity were examined by morphology evolution and surface structure analysis. In vitro inhibition performance of inhibitors on crystal growth and attachment of CaOx crystals to human renal epithelial cells were further evaluated by recording the nucleation and adhesive crystal numbers. RESULTS AND CONCLUSION Water- and n-butanol- soluble extracts from 20 kinds of herbs show almost 100% inhibition percentage, and the n-butanol extracts was found better than commercial drug citrate. Twenty-one molecule substitutes were identified from these extracts, and among them polyphenols display the best inhibition efficacy to retard CaOx crystallization. The high-throughput colorimetric assay and morphology examinations reveals thirteen out of 21 molecules show inhibition potential and disrupt growth of CaOx monohydrate crystals by interacting with exposed Ca2+ and C2O42- on the (100) and (010) surfaces. Moreover, these inhibitors also display pronounced performance in protecting renal epithelial cells by inhibiting nucleation and adhesion of CaOx crystals to cells, thus reducing stone formation. The structure-performance correlation among 19 screened molecules that inhibitors having pKa<3.5, logD (pH = 6) <0, H-number>0.1 mmol are the best in suppressing CaOx crystallization. Our findings provide a novel solution to design and manufacture inhibitor drugs from Chinese medicines for preventing pathological kidney stones formation.

Research paper thumbnail of Recent Progress in Continuous Crystallization of Pharmaceutical Products: Precise Preparation and Control

Organic Process Research & Development, 2020

Crystallization, as a solid-liquid separation process, is employed to purify and isolate a great ... more Crystallization, as a solid-liquid separation process, is employed to purify and isolate a great diversity of crystalline pharmaceutical products. In recent years, continuous crystallization has attracted increasing attention due to the product and process robustness as well as higher productivity. In this work, we review the use of novel continuous crystallizers or modified conventional continuous crystallizers for the preparation of polymorphs, chiral enantiomers, solvates/hydrates, cocrystals, and spherical crystals. In addition, theoretical framework and verification for the model-based control approaches have been demonstrated. The application of the PAT tools in classical feedback loop control strategies in continuous crystallization has also been focused on. Despite all this, the application of continuous crystallization still remains challenging due to the existence of the drawbacks, such as fouling and blockages. Therefore, a systematic discussion should be done before the wider application of continuous crystallization.

Research paper thumbnail of Crystal Structures and Phase Behavior of Sulfadiazine and a Method for the Preparation of Aggregates with Good Performance

Chemical Engineering & Technology, 2018

This article has been accepted for publication and undergone full peer review but has not been th... more This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the final Version of Record (VOR). This work is currently citable by using the Digital Object Identifier (DOI) given below. The final VoR will be published online in Early View as soon as possible and may be different to this Accepted Article as a result of editing. Readers should obtain the final VoR from the journal website shown below when it is published to ensure accuracy of information. The authors are responsible for the content of this Accepted Article.

Research paper thumbnail of Influence of Solvent Content on Phase Transformation of Sulfadiazine N‐Methyl Pyrrolidone Solvate

Chemical Engineering & Technology, 2019

This article has been accepted for publication and undergone full peer review but has not been th... more This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the final Version of Record (VOR). This work is currently citable by using the Digital Object Identifier (DOI) given below. The final VoR will be published online in Early View as soon as possible and may be different to this Accepted Article as a result of editing. Readers should obtain the final VoR from the journal website shown below when it is published to ensure accuracy of information. The authors are responsible for the content of this Accepted Article.

Research paper thumbnail of Organic solvent effects on solid-liquid phase equilibrium of d -mannitol and aqueous binary solvents: An experimental and computational study

Journal of Molecular Liquids, 2017

Gong , Organic solvent effects on solid-liquid phase equilibrium of d-mannitol and aqueous binary... more Gong , Organic solvent effects on solid-liquid phase equilibrium of d-mannitol and aqueous binary solvents: An experimental and computational study. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Molliq(2017),

Research paper thumbnail of Crystallization behavior of citric acid based on solution speciation and growth kinetics

CrystEngComm, 2020

The work reports the crystallization study of citric acid in aqueous solutions, using a large var... more The work reports the crystallization study of citric acid in aqueous solutions, using a large variety of methods. The results are compared to Ostwald's rule of stages, leading to some contradictory results between the experiments and the rule.

Research paper thumbnail of Preparation and Formation Mechanism of l-Valine Spherulites via Evaporation Crystallization

Industrial & Engineering Chemistry Research, 2021

Research paper thumbnail of Discovering inhibitor molecules for pathological crystallization of CaOx kidney stones from natural extracts of medical herbs

Journal of Ethnopharmacology, 2021

ETHNOPHARMACOLOGICAL RELEVANCE Kidney stones is one of the common diseases of the urinary system.... more ETHNOPHARMACOLOGICAL RELEVANCE Kidney stones is one of the common diseases of the urinary system. The primary cause of kidney stone formation is the thermodynamic supersaturation of lithogenic solutes in urine, which desaturates by nucleation, crystal growth and aggregation of minerals and salts, mainly Calcium oxalate (CaOx). One of the potential therapies is to develop drug molecules to inhibit or prevent CaOx crystallization in urine. Traditional Chinese medicines (TCMs) provided an efficient approach for the treatment of kidney stones with a specialized-designed recipe of medicinal herbs. But the action details of these herbs were poorly understood due to their complex components, and whether the effective constituents of herbs have an inhibitory effect on the process of stone formation has not been evaluated. AIM OF THE STUDY This study aims to develop and identify inhibitor substitutes from a library of kidney stone prescriptions in traditional Chinese medicines to prevent pathological kidney stone formation. MATERIALS AND METHODS As many as twenty Chinese medicines were extracted and separated into five different polar extracts, the inhibition performance of which on CaOx crystallization was explored by recording and comparing crystallization kinetics. The potential inhibitor molecules in the inhibitory extracts were confirmed by HPLC and their retardation efficacy was evaluated by quantifying nucleation and growth kinetics using colorimetry. Then the inhibitor-COM crystal interactions and specificity were examined by morphology evolution and surface structure analysis. In vitro inhibition performance of inhibitors on crystal growth and attachment of CaOx crystals to human renal epithelial cells were further evaluated by recording the nucleation and adhesive crystal numbers. RESULTS AND CONCLUSION Water- and n-butanol- soluble extracts from 20 kinds of herbs show almost 100% inhibition percentage, and the n-butanol extracts was found better than commercial drug citrate. Twenty-one molecule substitutes were identified from these extracts, and among them polyphenols display the best inhibition efficacy to retard CaOx crystallization. The high-throughput colorimetric assay and morphology examinations reveals thirteen out of 21 molecules show inhibition potential and disrupt growth of CaOx monohydrate crystals by interacting with exposed Ca2+ and C2O42- on the (100) and (010) surfaces. Moreover, these inhibitors also display pronounced performance in protecting renal epithelial cells by inhibiting nucleation and adhesion of CaOx crystals to cells, thus reducing stone formation. The structure-performance correlation among 19 screened molecules that inhibitors having pKa<3.5, logD (pH = 6) <0, H-number>0.1 mmol are the best in suppressing CaOx crystallization. Our findings provide a novel solution to design and manufacture inhibitor drugs from Chinese medicines for preventing pathological kidney stones formation.

Research paper thumbnail of Recent Progress in Continuous Crystallization of Pharmaceutical Products: Precise Preparation and Control

Organic Process Research & Development, 2020

Crystallization, as a solid-liquid separation process, is employed to purify and isolate a great ... more Crystallization, as a solid-liquid separation process, is employed to purify and isolate a great diversity of crystalline pharmaceutical products. In recent years, continuous crystallization has attracted increasing attention due to the product and process robustness as well as higher productivity. In this work, we review the use of novel continuous crystallizers or modified conventional continuous crystallizers for the preparation of polymorphs, chiral enantiomers, solvates/hydrates, cocrystals, and spherical crystals. In addition, theoretical framework and verification for the model-based control approaches have been demonstrated. The application of the PAT tools in classical feedback loop control strategies in continuous crystallization has also been focused on. Despite all this, the application of continuous crystallization still remains challenging due to the existence of the drawbacks, such as fouling and blockages. Therefore, a systematic discussion should be done before the wider application of continuous crystallization.

Research paper thumbnail of Crystal Structures and Phase Behavior of Sulfadiazine and a Method for the Preparation of Aggregates with Good Performance

Chemical Engineering & Technology, 2018

This article has been accepted for publication and undergone full peer review but has not been th... more This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the final Version of Record (VOR). This work is currently citable by using the Digital Object Identifier (DOI) given below. The final VoR will be published online in Early View as soon as possible and may be different to this Accepted Article as a result of editing. Readers should obtain the final VoR from the journal website shown below when it is published to ensure accuracy of information. The authors are responsible for the content of this Accepted Article.

Research paper thumbnail of Influence of Solvent Content on Phase Transformation of Sulfadiazine N‐Methyl Pyrrolidone Solvate

Chemical Engineering & Technology, 2019

This article has been accepted for publication and undergone full peer review but has not been th... more This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the final Version of Record (VOR). This work is currently citable by using the Digital Object Identifier (DOI) given below. The final VoR will be published online in Early View as soon as possible and may be different to this Accepted Article as a result of editing. Readers should obtain the final VoR from the journal website shown below when it is published to ensure accuracy of information. The authors are responsible for the content of this Accepted Article.

Research paper thumbnail of Organic solvent effects on solid-liquid phase equilibrium of d -mannitol and aqueous binary solvents: An experimental and computational study

Journal of Molecular Liquids, 2017

Gong , Organic solvent effects on solid-liquid phase equilibrium of d-mannitol and aqueous binary... more Gong , Organic solvent effects on solid-liquid phase equilibrium of d-mannitol and aqueous binary solvents: An experimental and computational study. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Molliq(2017),

Research paper thumbnail of Crystallization behavior of citric acid based on solution speciation and growth kinetics

CrystEngComm, 2020

The work reports the crystallization study of citric acid in aqueous solutions, using a large var... more The work reports the crystallization study of citric acid in aqueous solutions, using a large variety of methods. The results are compared to Ostwald's rule of stages, leading to some contradictory results between the experiments and the rule.