scholarly journals The investigation of polymorph transition of erlotinib salts

2016 ◽  
Author(s):  
Wioleta Maruszak ◽  
Marta Łaszcz ◽  
Kinga Trzcińska ◽  
Wojciech Łuniewski ◽  
Krzysztof Bańkowski ◽  
...  
Keyword(s):  
Solid State ◽  
Kinase Inhibitor ◽  
Drug Product ◽  
Variable Temperature ◽  
Drug Substance ◽  
Crystalline Solid ◽  
Scanning Calorimetry ◽  
Thermal Methods ◽  
Polymorphic Transitions ◽  
Polymorphic Forms

Erlotinib is a reversible tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor (EGFR) and is used to treat non-small cell lung cancer (NSCLC), pancreatic cancer and several other types of cancer [1]. It is known that erlotinib forms different salts which can exist in multiple crystalline solid forms. This important property known as a polymorphism may have an impact on physical and chemical stability of the drug substance (API), processability during manufacturing in the final drug product and bioavailability of the drug to the patient. Changes in the crystal structure of API can lead to the undesired changes in properties. Hence, the control of the polymorphic form is essential during the drug substance manufacture and requires a thorough understanding of solid-state changes that may occur in pharmaceutical materials. To achieve a comprehensive understanding of solid-state transformations different analytical techniques are applied. In our studies the variable–temperature powder X-ray diffraction (VT–PXRD), differential scanning calorimetry (DSC), thermogravimetry (TGA), Fourier transformed infrared (FTIR), attenuated total reflectance (ATR) and Raman spectroscopy were used to investigate the correlation between the thermal behavior and structural transformations of polymorphic forms of erlotinib salts. VT-PXRD method has detected the temperature range of the existence of polymorphic transitions, spectroscopy methods have characterized intramolecular vibrations and thermal methods have provided information on the transition and melting temperature and relationships between polymorphic forms.

scholarly journals The investigation of polymorph transition of erlotinib salts

2016 ◽  
Author(s):  
Wioleta Maruszak ◽  
Marta Łaszcz ◽  
Kinga Trzcińska ◽  
Wojciech Łuniewski ◽  
Krzysztof Bańkowski ◽  
...  
Keyword(s):  
Solid State ◽  
Kinase Inhibitor ◽  
Drug Product ◽  
Variable Temperature ◽  
Drug Substance ◽  
Crystalline Solid ◽  
Scanning Calorimetry ◽  
Thermal Methods ◽  
Polymorphic Transitions ◽  
Polymorphic Forms

Erlotinib is a reversible tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor (EGFR) and is used to treat non-small cell lung cancer (NSCLC), pancreatic cancer and several other types of cancer [1]. It is known that erlotinib forms different salts which can exist in multiple crystalline solid forms. This important property known as a polymorphism may have an impact on physical and chemical stability of the drug substance (API), processability during manufacturing in the final drug product and bioavailability of the drug to the patient. Changes in the crystal structure of API can lead to the undesired changes in properties. Hence, the control of the polymorphic form is essential during the drug substance manufacture and requires a thorough understanding of solid-state changes that may occur in pharmaceutical materials. To achieve a comprehensive understanding of solid-state transformations different analytical techniques are applied. In our studies the variable–temperature powder X-ray diffraction (VT–PXRD), differential scanning calorimetry (DSC), thermogravimetry (TGA), Fourier transformed infrared (FTIR), attenuated total reflectance (ATR) and Raman spectroscopy were used to investigate the correlation between the thermal behavior and structural transformations of polymorphic forms of erlotinib salts. VT-PXRD method has detected the temperature range of the existence of polymorphic transitions, spectroscopy methods have characterized intramolecular vibrations and thermal methods have provided information on the transition and melting temperature and relationships between polymorphic forms.

scholarly journals Physicochemical characteristics of abiraterone acetate used for the treatment of prostate cancer

2016 ◽  
Author(s):  
Marta Łaszcz ◽  
Kinga Trzcińska ◽  
Elżbieta U. Stolarczyk
Keyword(s):  
Prostate Cancer ◽  
Solid State ◽  
Drug Product ◽  
Treatment Options ◽  
Polymorphic Form ◽  
Abiraterone Acetate ◽  
Crystalline Solid ◽  
Castration Resistant Prostate Cancer ◽  
Scanning Calorimetry ◽  
X Ray

Prostate cancer is the most common cancer among men and often has no early symptoms. The major treatment options that include surgical or medical castration cause ablation of the production of testosterone, dihydrotestosterone and related androgens by the testes. These procedures do not affect adrenal, prostate and other tissues androgen production, therefore they are combined with androgen receptor antagonists to block their action. Recent studies have established that in castration-resistant prostate cancer many androgen-regulated genes become re-expressed and tissue androgen levels increase despite low serum levels. Abiraterone acetate inhibits the key enzyme cytochrome P450 17α-hydroxy/17,20-lyase (CYP17) which catalyzes the biosynthesis of androgens and provides the effective treatment of prostate cancer patients. The aim of this work was abiraterone acetate polymorph diagnostics and physcicochemical characteristics of polymorphs. Polymorphism is the ability of a compound in the solid state to exist in different crystalline forms. Molecules, having the same chemical composition, exhibit different spatial arrangements and/or exist in different conformations. Substances that exist in a non-crystalline solid state are said to be amorphous. The term pseudopolymorphism is used to describe solvates (including hydrates). Different polymorphs of a solid compound exhibit distinct physical properties such as, e.g.: hygroscopicity, solubility, dissolution rate, melting point and stability. All of which play a very important role in the pharmaceutical industry. The undesirable polymorphic form with lower solubility and consequently with a lower absorption rate decreases the concentration of active substance in the blood. The Biopharmaceutics Classification System classifies drugs taking into account their solubility. Because a change in a polymorphic form may influence on a drug product affectivity and its toxic properties the regulations required by the ICH Q6A guideline according to the decision tree no 4 demand the control of solid state behavior. Therefore, the polymorphic behavior of abiraterone acetate has to be carefully investigated and all found polymorphs have to be fully characterized. Abiraterone acetate was characterized by following methods: X-ray powder diffraction, infrared and Raman spectroscopy, differential scanning calorimetry. Polymorph screening was performed and single crystals were obtained by a vapour diffusion crystallisation. The structure of abiraterone acetate was solved by the single crystal X-ray diffraction. Additionally the structure was confirmed by the direct sample injection method (DI).

scholarly journals Physicochemical characteristics of abiraterone acetate used for the treatment of prostate cancer

2016 ◽  
Author(s):  
Marta Łaszcz ◽  
Kinga Trzcińska ◽  
Elżbieta U. Stolarczyk
Keyword(s):  
Prostate Cancer ◽  
Solid State ◽  
Drug Product ◽  
Treatment Options ◽  
Polymorphic Form ◽  
Abiraterone Acetate ◽  
Crystalline Solid ◽  
Castration Resistant Prostate Cancer ◽  
Scanning Calorimetry ◽  
X Ray

Prostate cancer is the most common cancer among men and often has no early symptoms. The major treatment options that include surgical or medical castration cause ablation of the production of testosterone, dihydrotestosterone and related androgens by the testes. These procedures do not affect adrenal, prostate and other tissues androgen production, therefore they are combined with androgen receptor antagonists to block their action. Recent studies have established that in castration-resistant prostate cancer many androgen-regulated genes become re-expressed and tissue androgen levels increase despite low serum levels. Abiraterone acetate inhibits the key enzyme cytochrome P450 17α-hydroxy/17,20-lyase (CYP17) which catalyzes the biosynthesis of androgens and provides the effective treatment of prostate cancer patients. The aim of this work was abiraterone acetate polymorph diagnostics and physcicochemical characteristics of polymorphs. Polymorphism is the ability of a compound in the solid state to exist in different crystalline forms. Molecules, having the same chemical composition, exhibit different spatial arrangements and/or exist in different conformations. Substances that exist in a non-crystalline solid state are said to be amorphous. The term pseudopolymorphism is used to describe solvates (including hydrates). Different polymorphs of a solid compound exhibit distinct physical properties such as, e.g.: hygroscopicity, solubility, dissolution rate, melting point and stability. All of which play a very important role in the pharmaceutical industry. The undesirable polymorphic form with lower solubility and consequently with a lower absorption rate decreases the concentration of active substance in the blood. The Biopharmaceutics Classification System classifies drugs taking into account their solubility. Because a change in a polymorphic form may influence on a drug product affectivity and its toxic properties the regulations required by the ICH Q6A guideline according to the decision tree no 4 demand the control of solid state behavior. Therefore, the polymorphic behavior of abiraterone acetate has to be carefully investigated and all found polymorphs have to be fully characterized. Abiraterone acetate was characterized by following methods: X-ray powder diffraction, infrared and Raman spectroscopy, differential scanning calorimetry. Polymorph screening was performed and single crystals were obtained by a vapour diffusion crystallisation. The structure of abiraterone acetate was solved by the single crystal X-ray diffraction. Additionally the structure was confirmed by the direct sample injection method (DI).

scholarly journals Mesomorphic Behavior in Silver(I) N-(4-Pyridyl) Benzamide with Aromatic π–π Stacking Counterions

Materials ◽  
2018 ◽  
Vol 11 (9) ◽  
pp. 1666 ◽  
Author(s):  
Issac Torres ◽  
Mauro Ruiz ◽  
Hung Phan ◽  
Noemi Dominguez ◽  
Jacobo Garcia ◽  
...  
Keyword(s):  
Solid State ◽  
Organic Semiconductors ◽  
Flexible Electronics ◽  
Crystalline Solid ◽  
Naval Research ◽  
Scanning Calorimetry ◽  
New Family ◽  
Π Stacking ◽  
Capable Groups ◽  
New Generation

Organic semiconductor materials composed of π–π stacking aromatic compounds have been under intense investigation for their potential uses in flexible electronics and other advanced technologies. Herein we report a new family of seven π–π stacking compounds of silver(I) bis-N-(4-pyridyl) benzamide with varying counterions, namely [Ag(NPBA)2]X, where NPBA is N-(4-pyridyl) benzamine, X = NO3− (1), ClO4− (2), CF3SO3− (3), PF6− (4), BF4− (5), CH3PhSO3− (6), and PhSO3− (7), which form extended π−π stacking networks in one-dimensional (1D), 2D and 3D directions in the crystalline solid-state via the phenyl moiety, with average inter-ring distances of 3.823 Å. Interestingly, the counterions that contain π–π stacking-capable groups, such as in 6 and 7, can induce the formation of mesomorphic phases at 130 °C in dimethylformamide (DMF), and can generate highly branched networks at the mesoscale. Atomic force microscopy studies showed that 2D interconnected fibers form right after nucleation, and they extend from ~30 nm in diameter grow to reach the micron scale, which suggests that it may be possible to stop the process in order to obtain nanofibers. Differential scanning calorimetry studies showed no remarkable thermal behavior in the complexes in the solid state, which suggests that the mesomorphic phases originate from the mechanisms that occur in the DMF solution at high temperatures. An all-electron level simulation of the band gaps using NRLMOL (Naval Research Laboratory Molecular Research Library) on the crystals gave 3.25 eV for (1), 3.68 eV for (2), 1.48 eV for (3), 5.08 eV for (4), 1.53 eV for (5), and 3.55 eV for (6). Mesomorphic behavior in materials containing π–π stacking aromatic interactions that also exhibit low-band gap properties may pave the way to a new generation of highly branched organic semiconductors.

Tautomeric polymorphism of the neuroactive inhibitor kynurenic acid

2019 ◽  
Vol 75 (6) ◽  
pp. 793-805
Author(s):  
Dorota Pogoda ◽  
Jan Janczak ◽  
Sylwia Pawlak ◽  
Michael Zaworotko ◽  
Veneta Videnova-Adrabinska
Keyword(s):  
Solid State ◽  
Kynurenic Acid ◽  
Variable Temperature ◽  
Neurological Diseases ◽  
Crystal Form ◽  
Phase Behaviour ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray

Kynurenic acid (KYN; systematic name: 4-hydroxyquinoline-2-carboxylic acid, C10H7NO3) displays a therapeutic effect in the treatment of some neurological diseases and is used as a broad-spectrum neuroprotective agent. However, it is understudied with respect to its solid-state chemistry and only one crystal form (α-KYN·H2O) has been reported up to now. Therefore, an attempt to synthesize alternative solid-state forms of KYN was undertaken and six new species were obtained: five solvates and one salt. One of them is a new polymorph, β-KYN·H2O, of the already known KYN monohydrate. All crystal species were further studied by single-crystal and powder X-ray diffraction, thermal and spectroscopic methods. In addition to the above methods, differential scanning calorimetry (DSC), in-situ variable-temperature powder X-ray diffraction and Raman microscopy were applied to characterize the phase behaviour of the new forms. All the compounds display a zwitterionic form of KYN and two different enol–keto tautomers are observed depending on the crystallization solvent used.

scholarly journals Systematic Investigation of Co-Crystallization Properties in Binary and Ternary Mixtures of Triacylglycerols Containing Palmitic and Oleic Acids in Relation with Palm Oil Dry Fractionation

Foods ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1891
Author(s):  
Veronique Gibon ◽  
Sabine Danthine
Keyword(s):  
Palm Oil ◽  
Unsaturated Fatty Acids ◽  
Variable Temperature ◽  
Ternary Mixtures ◽  
Effective Control ◽  
Dry Fractionation ◽  
Scanning Calorimetry ◽  
Fractionation Process ◽  
Polymorphic Transitions ◽  
Crystallization Properties

This work investigates the molecular interactions within the main triacylglycerols constitutive of palm oil, all having a key role in the multi-step dry fractionation process. Identification of these interactions is possible thanks to the establishment of binary and ternary phase diagrams, using differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD) at variable temperature. The following systems were selected: PPP-POP, PPP-OPP, PPP-POO, POP-OPP, POP-POO, OPP-POO, PPP-POP-POO and PPP-OPP-POO (P: palmitic acid and O: oleic acid), and analyzed in direct mode (heating at 5 °C/min., after melting and quenching at −60 °C), and after tempering for three months at 20 °C (tempered mode). DSC makes it possible to bring out crystallization and melting phenomena associated to polymorphic transitions, which are further characterized (crystalline forms) by XRD. The results show that unsaturated are poorly soluble in fully saturated triacylglycerols, that the intersolubility decreases in proportion to the number of unsaturated fatty acids, that positional isomerism (POP/OPP) has a major impact, that OPP may induce formation of molecular compounds and that co-crystallization properties are highly modified by tempering depending on the polymorphic properties of the systems. This provides a better understanding and allows for effective control of the palm oil dry fractionation process.

scholarly journals Polymorphism in Commercial Sources of Fusidic Acid: A Comparative Study of the In Vitro Release Characteristics of Forms I and III from a Marketed Pharmaceutical Cream

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Jonathan Byrne ◽  
Robert Reinhardt ◽  
Trinidad Velasco-Torrijos
Keyword(s):  
Fusidic Acid ◽  
Drug Product ◽  
In Vitro Release ◽  
Inert Atmosphere ◽  
Drug Substance ◽  
Intrinsic Dissolution ◽  
Polymorphic Forms ◽  
Commercial Sources ◽  
The Stability

A comparison of the polymorphic forms of 3 commercial sources of fusidic acid using FTIR and XRPD techniques has been performed in this study. It has been demonstrated that polymorphic Forms I and III are currently available on the commercial market. The influence of the observed polymorphism on the stability of the drug substance in bulk form has been investigated through stability and stress testing according to current ICH guidelines. Significant differences were detected between commercial sources with regard to the stability of the bulk substance under photolytic and humidity stress conditions. When properly packaged in an inert atmosphere, fusidic acid from all 3 manufacturers showed a comparable stability. The effects of the observed polymorphic differences on the intrinsic dissolution rate of the drug substance and its in vitro release from the marketed drug product Fusicutan® plus Betamethasone cream have been investigated. Results indicated that the release rate of the drug substance is similar for polymorphic Forms I and III, allowing both forms to be used during manufacture without affecting the safety or efficacy of the drug product.

scholarly journals Thorough investigation on the high-temperature polymorphism of dipentyl-perylenediimide: thermal expansion vs polymorphic transition.

2021 ◽  
Author(s):  
Francesco Marin ◽  
Serena Tombolesi ◽  
Tommaso Salzillo ◽  
Omer Yaffe ◽  
Lucia Maini
Keyword(s):  
Thermal Expansion ◽  
High Temperature ◽  
Solid State ◽  
Thermal Behaviour ◽  
Variable Temperature ◽  
Negative Thermal Expansion ◽  
Thermal Characterization ◽  
Polymorphic Transition ◽  
State Transitions ◽  
Scanning Calorimetry

N,N’-dipentyl-3,4,9,10-perylendiimide (PDI-C5) is an organic semiconducting material which has been extensively investigated as model compound for its optoelectronic properties. It is known to be highly thermally stable, that it exhibits solid-state transitions with temperature and that thermal treatments lead to an improvement in its performance in devices. Here we report a full thermal characterization of PDI-C5 by combination of differential scanning calorimetry, variable temperature X-ray diffraction, hot stage microscopy, and variable temperature Raman spectroscopy. We identified two high temperature polymorphs, form II and form III, which form respectively at 112 °C and at 221 °C and we determined their crystal structure from powder data. Form II is completely reversible upon cooling with low hysteresis, while form III revealed a different thermal behaviour upon cooling depending on the technique and crystal size. The crystal structure’s features of the different polymorphs are discussed and compared, and we looked into the role of the perylene core and alkyl chains during solid-state transitions. The thermal expansion principal axis of PDI-C5 crystal forms is reported showing that all the reported forms possess negative thermal expansion (X1) and large positive thermal expansion (X3) which are correlated to thermal behaviour observed.

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