Capturing the Significance of X-Ray Crystallography in Pharmaceutical Field

Total Page:16

File Type:pdf, Size:1020Kb

Capturing the Significance of X-Ray Crystallography in Pharmaceutical Field Capturing The Significance of X-Ray Crystallography in Pharmaceutical Field: The Application to Characterize New Salt, Co-Crystal and Co-Amorphous Etsuo Yonemochi Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, This document was presented at PPXRD - Pharmaceutical Powder X-ray Diffraction Symposium Sponsored by The International Centre for Diffraction Data This presentation is provided by the International Centre for Diffraction Data in cooperation with the authors and presenters of the PPXRD symposia for the express purpose of educating the scientific community. All copyrights for the presentation are retained by the original authors. The ICDD has received permission from the authors to post this material on our website and make the material available for viewing. Usage is restricted for the purposes of education and scientific research. PPXRD Website – www.icdd.com/ppxrd ICDD Website - www.icdd.com Acyclovir • Guanosine analogue antiviral drugs. • The treatment of herpes simplex virus infections. 2 Outline Screening and Characterization Screenig methods and used additives Selected cocrystals (PXRD、TG/DTA、DSC) Application for oral dosage form Intrinsic dissolution of selected cocrystal Crystal structure of selected cocrystal Mechanism for solubility enhansment Application for transdermal dosage form Transdermal adsorption propertiy of selected complex Solubility of amorphous comples Improvement of transdermal properties 2/3 Hydrate Commercially available Recrystalized from ethanol solution P21/n a 25.459(1)Å b 11.282(1)Å c 10.768(1)Å β 95.16(1)° Volume Column structure 3080.342Å3 Stacking purine moiety Z 12 R-factor 5.3% Dihydrate From ammonium solution P-1 a 6.8386(7)Å b 11.3679(14)Å c 14.942(2)Å α 82.845(4)° β 82.419(3)° γ 89.326(3)° Channel structure Volume 1142.5(2)Å3 Stacking purine moiety Z 4 R-factor 7.71% Anhydrate2 Dehydration of hydrates P21/c a 10.9399(6)Å b 11.1837(6)Å c 8.1164(4)Å Stacking purine β 108.6277(34)° Volume moiety 941.009Å3 Z 4 Anhydrate2 Crystallization by Vapor-Diffusion. Procedure. (DMF+Acetonitrile) P 212121 a 4.5387(10)Å b 15.0308(3)Å c 28.3320(6)Å Volume 1932.82Å3 Z 8 R-factor 9.88% Different stacking mode Dissolution properties for acyclovir polymorphs Intrinsic dissolution rate 1.5 ・area for disson:0.2 cm2) Similar dissolutin rate ・pH 6.8 Phosphate buffer 1.2 ・37℃ . ・50 rpm anhydrate1 c n o 2/3hydrate ) 0.9 C L r i m / v g o l μ c ( 0.6 Anhydrate2 y c 2hydrate A 0.3 polymorphs 0 0 1 2 3 4 5 Time (min) Transformation of anhydrate to hydrate was quick. Anhydrates were useless Hydration mechanisum? Hydration properties for acyclovir anhydrate2 Reversible Anhydrate 2 Dihydrate 2/3 hydrate Hydration properties for acyclovir anhydrate1 25℃ RH95% 1week Anhydrate 1 2/3 hydrate Dihydrate Irreversible Anhydrate 2 Comparison between transition behavior and stacking mode antiparallel parallel parallel 2/3 Hydrate Anhyd. 1 Anhyd. 2 Di hydrate antiparallel antiparallel Similarity of stacking The phase transition mechanism is complicated. X-ray DSC Anhydrate Form 2 Anhydrate Form 4 Anhydrate Form 2 Anhydrate Form 4 Anhydrate Form 3 2/3 hydrate 12 XRPD patterns of acyclovir using HT capillary sample holder 2.5e+004 2.0e+004 Intensity(cps) 1.5e+004 Anhydrate Form 2 (RT) 1.0e+004 Anhydrate Form 4 (210℃) 5.0e+003 2/3 hydrate (RT) 20 40 60 80 2-theta (deg) 13 Comparison from the view of stacking structure antiparallel 2/3 hydrate Anhydrate Form 4 Anhydrate Form 2 antiparallel parallel parallel 14 Anhydrate Form 1 Phase Transition of Acyclovir polymorphs Anhydrate 3 120oC o RH95% 170 C 2/3 hydrate Anhydrate 1 at 25oC Anhydrate 4 RH0% RH20% o at 25oC 170 C at 25oC Dihydrate Anhydrate 2 Conclusion • There are two packing manners for purine moiety. Anhydrate 1, anhydrate 2, 2/3 hydrate and ACV dihydrate were packed in parallel, antiparallel, mixture of parallel—anti-parallel and parallel manners, respectively. • Based on the packing manner of ACV, it can be seen why the phase transformation occurs with readily or with difficulty. 16 Outline Characterization Screenig methods and used additives Selected cocrystals (PXRD、TG/DTA、DSC) Application for oral dosage form Intrinsic dissolution of selected cocrystal Crystal structure of selected cocrystal Mechanism for solubility enhansment Application for transdermal dosage form Transdermal adsorption propertiy of selected complex Solubility of amorphous comples Improvement of transdermal properties dissolution properties O N HN N Sprangly soluble in water O H2N N OH Dissolution rate and solubility for water Activity related to the solubility in base Oral dosage form Transdermal Bioavailability:low Transdermal Absorption :low D. Patel, et al. Drug. Dev. Ind. Pharm. 33:1318 (2007). D. J. Freeman, et al. Antimicrob. Agents Chemother. 29:730 (1986). Improvement of solubility Improvement of the physicoshemical properties methods polymorphs Salt formation Package gringing Solvate Cocrystal Solid dispersion amorphous O N HN N O H2N N OH Applicaton for oral dosage form Cocrystal→Improvement of dissolution properties Application for transdermal dosage form Amorphization→Increase the solubility in base→ Increase the absorption Cocrystal・・・ polymorph hydrate/solvate pure API salt of API of pure API of API ・単位格子中に固体分子 種以上含有 Multicomponent crystal2 Neutral API ・水素結合等で分子が結合 ・多Hydrogen成分結晶 bonding, Neutral Water/solvent Charged API 単Multicomponent一分子から構成される crystal結晶では得られない Counter ion pharmaceutical に期待 Hydrogen物性・機 bonding,能の発 Neutral現 Cocrystal former cocrystals ACV has many functional groups, O N Capable to make hydrogen bonding HN N O Cocrystal formation H2N N OH Generally recognized as safe compound :Hydrogen bond donor or acceptor sites Amorphization of Acyclovir Melt O Decomposion N HN Solvent evaporation N O Unstable H2N N OH Spray dry Addition of polymer Freeze dry High Cost Decrease the diffusion rate in base Comventional methods isn’t suitable for the amorphization Preparation of Amorphous complex with additives Outline Characterization Screenig methods and used additives Selected cocrystals (PXRD、TG/DTA、DSC) Application for oral dosage form Intrinsic dissolution of selected cocrystal Crystal structure of selected cocrystal Mechanism for solubility enhansment Application for transdermal dosage form Transdermal adsorption propertiy of selected complex Solubility of amorphous comples Improvement of transdermal properties Screening methods Acyclovir anhydrous Excipient Screening by form 2 Solvent, Grinding Solvent method Grinding method Solvent Liquid assisted grinding Neat grinding (Solvent drop method) Hot suspension of drug and cocrystal former Liquid assisted grindig Filtration Solvent Ground manually at room temperature Ground manually at room temperature Saturated solution of 14additives drug and cocrystal former Slow evaporation 9 solvent or Cooling Crystallized complex or Amorphous complex Evaluated by PXRD, Themal Analysis PXRD, TG/DTA Generally recognized as safe compounds used O OH OH O O OH O O O HO OH O OH HO H N OH HO OH O 2 OH O OH OH NH2 Citric acid Tartaric acid Malic acid Glycine Alanine O NH O O HO OH H N N OH 2 H OH O NH2 NH2 Stearic acid Aspartic acid Arginine O OH O O O Palmitic acid NH NH2 H N NH S 2 2 O O N O OH Urea Nicotinamide Saccharin Docosanoic acid O OH Lauric acid Existence of the records as Oral or Trandermal application PXRD patterns of samples Anhydrate1 5 10 15 20 25 Anhydrate2 5 10 15 20 25 2/3 hydrate 5 10 15 20 25 2hydrate Relative intensityRelative 5 10 15 20 25 Citric acid 5 10 15 20 25 Cocrystal 5 10 15 Halo2 0pattern 25 Amorphous complex 5 10 15 20 25 2θ/ degree TG/DTA curve of samples 0 0 169℃ Citric acid Anydrate1 Weight loss DTA curve 100 100 0 exo.→ 0 25 80 135 190 245 300 T 25 80 135 190 245 300 Δ Weight loss (%) loss Weight Anhydrate2 157℃ Cocrystal 100 100 → exo.→ 0 25 80 135 190 245 300 T 25 80 135 190 245 300 Δ Weight loss (%) loss Weight 2/3hydrate 100 0 25 80 135 190 245 300 Clear difference in curves 2hydrate No possibility of the 250℃ formation of solvate 100 25 80 135 190 245 300 DSCcurves of amorphous complex Tg ) mW 40 50 60 70 80 90 Tg Heat flow( ↑ Endo 68℃ -40 -20 0 20 40 60 80 100 Temperature (ºC) Glass transition temperature Tg was higher than the room temperature. Confirmation of the physical stability of amorphous complex Outline Characterization Screenig methods and used additives Selected cocrystals (PXRD、TG/DTA、DSC) Application for oral dosage form Intrinsic dissolution of selected cocrystal Crystal structure of selected cocrystal Mechanism for solubility enhansment Application for transdermal dosage form Transdermal adsorption propertiy of selected complex Solubility of amorphous comples Improvement of transdermal properties Crystal structure of Acyclovir‐Citric acid Cocrystal Single crystals weren’t obtained Crystal structure analysis using powder diffraction data obtained by synchrotron radiation Stoichiometry of Acyclovir : Citric acid was 1:1 Comparison of stacking structure of Acyclovir and its cocrystal Anhydrare2 Acv-Citric acid Cocrystal Cocrystal Stacking structure of Purine frame Citric acid Un-stabilize the stacking structure by intercalation of citric acid Enhancement of the solubility Distance in the purine frame in the crystals 14 ) Å 12 10 8 No difference 6 4 stacking distance stacking( distance π π - 2 π 0 Anhyd.1 Anhyd.2 2/3hydrate Dihydrate Cocrystal Change in the crystal strucuture by cocrystal Improvement of dissolution property Saturated Solubility of Cocrystal in various solvents 10.00 Enhancement of solubilty : Distilled water 8.00 : Phosphate buffer pH 6.8 : Ethanol 6.00 4.00 2.00 Saturated solubility (mg/mL) 0.00 1 2 3 4 5 6 7 8 9 Acyclovir anhydrous form 2 ACV-TA-PM ACV-TA cocrystal Physical mixture showed the similar solubility compare to the Cocrystal ACV and Citric acid was interacted, even in the solution.
Recommended publications
  • Mechanochemical Synthesis of a Cocrystal of Two Supramolecular
    crystals Article Mechanochemical Synthesis of a Cocrystal of Two Supramolecular Hydrogen-Bonded Aggregates of 1,3,6,8-Tetraazatricyclo[4.3.1.13,8]undecane (TATU) with 4-tert-Butylphenol Bearing Different Hydrogen Bonding Interactions Augusto Rivera 1,*, Jicli José Rojas 1, Jaime Ríos-Motta 1 and Michael Bolte 2 ID 1 Departamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia, Sede Bogotá, Carrera 30 No. 45-03, Bogotá,Código Postal 111321, Colombia; [email protected] (J.J.R.); [email protected] (J.R.-M.) 2 Institut für Anorganische Chemie, J. W. Goethe-Universität Frankfurt, Max-von Laue-Str., 7, 60438 Frankfurt/Main, Germany; [email protected] * Correspondence: [email protected]; Tel.: +57-1-316-5000 Received: 2 July 2018; Accepted: 20 July 2018; Published: 30 July 2018 Abstract: The synthesis and single crystal structure of a new cocrystal, which is composed of OHphenolic···OHphenolic···Naminalic supramolecular heterosynthons assembled from 4-tert-butylphenol and the macrocyclic aminal TATU, is presented. This cocrystal was prepared by solvent-free assisted grinding, which is a commonly used mechanochemical method. Crystal structure, supramolecular assembly through hydrogen bonding interactions as well as the physical and spectroscopic properties of the title cocrystal are presented in this paper. Keywords: supramolecular chemistry; crystal engineering; cocrystals; hydrogen bonds; noncovalent interactions; aminal structure 1. Introduction Noncovalent interactions, such as electrostatic forces, H-bonds, halogen bonds, CH–π, π–π stacking, cation–π, anion–π, lone pair–π associations and other weak forces, play significant roles in a variety of fields, including molecular recognition, host–guest chemistry, crystal engineering, supramolecular chemistry, biochemistry, pharmaceutical chemistry, and materials science [1,2].
    [Show full text]
  • Cocrystal Prediction Using Machine Learning Models and Descriptors
    applied sciences Article Cocrystal Prediction Using Machine Learning Models and Descriptors Medard Edmund Mswahili 1,† , Min-Jeong Lee 2,†, Gati Lother Martin 1, Junghyun Kim 3, Paul Kim 4, Guang J. Choi 2 and Young-Seob Jeong 1,* 1 Department of ICT Convergence, Soonchunhyang University, Asan-si 31538, Korea; [email protected] (M.E.M.); [email protected] (G.L.M.) 2 Department of Pharmaceutical Engineering, Soonchunhyang University, Asan-si 31538, Korea; [email protected] (M.-J.L.); [email protected] (G.J.C.) 3 Department of Future Convergence Technology, Soonchunhyang University, Asan-si 31538, Korea; [email protected] 4 Department of Medical Science, Soonchunhyang University, Asan-si 31538, Korea; [email protected] * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: Cocrystals are of much interest in industrial application as well as academic research, and screening of suitable coformers for active pharmaceutical ingredients is the most crucial and challeng- ing step in cocrystal development. Recently, machine learning techniques are attracting researchers in many fields including pharmaceutical research such as quantitative structure-activity/property relationship. In this paper, we develop machine learning models to predict cocrystal formation. We extract descriptor values from simplified molecular-input line-entry system (SMILES) of compounds and compare the machine learning models by experiments with our collected data of 1476 instances. As a result, we found that artificial neural network shows great potential as it has the best accuracy, sensitivity, and F1 score. We also found that the model achieved comparable performance with about Citation: Mswahili, M.E.; Lee, M.-J.; half of the descriptors chosen by feature selection algorithms.
    [Show full text]
  • Selection of Effective Cocrystals Former for Dissolution Rate Improvement Of
    Selection of effective cocrystals former for dissolution rate improvement of active pharmaceutical ingredients based on lipoaffinity index Piotr Cysewski, Maciej Przybylek To cite this version: Piotr Cysewski, Maciej Przybylek. Selection of effective cocrystals former for dissolution rate im- provement of active pharmaceutical ingredients based on lipoaffinity index. European Journal of Pharmaceutical Sciences, Elsevier, 2017, 107, pp.87-96. 10.1016/j.ejps.2017.07.004. hal-01773096 HAL Id: hal-01773096 https://hal.archives-ouvertes.fr/hal-01773096 Submitted on 29 Apr 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Accepted Manuscript Selection of effective cocrystals former for dissolution rate improvement of active pharmaceutical ingredients based on lipoaffinity index Piotr Cysewski, Maciej Przybyłek PII: S0928-0987(17)30403-7 DOI: doi: 10.1016/j.ejps.2017.07.004 Reference: PHASCI 4127 To appear in: European Journal of Pharmaceutical Sciences Received date: 11 April 2017 Revised date: 6 June 2017 Accepted date: 3 July 2017 Please cite this article as: Piotr Cysewski, Maciej Przybyłek , Selection of effective cocrystals former for dissolution rate improvement of active pharmaceutical ingredients based on lipoaffinity index, European Journal of Pharmaceutical Sciences (2017), doi: 10.1016/j.ejps.2017.07.004 This is a PDF file of an unedited manuscript that has been accepted for publication.
    [Show full text]
  • Investigation of Carbamazepine- Nicotinamide Cocrystal Solubility and Dissolution by a UV Imaging System
    Investigation of Carbamazepine- Nicotinamide cocrystal solubility and dissolution by a UV imaging system PhD Thesis Ning Qiao This thesis is submitted in partial fulfilment of the requirements of De Montfort University for the award of Doctor of Philosophy April 2014 Faculty of Health and Life Sciences De Montfort University Leicester CONTENTS CONTENTS CONTENTS ................................................................................................................................... I DECLARATION ........................................................................................................................... v ABSTRACT .................................................................................................................................. vi ACKNOWLEDGEMENTS ......................................................................................................... vii PUBLICATIONS ........................................................................................................................ viii LIST OF FIGURES ....................................................................................................................... x LIST OF TABLES ...................................................................................................................... xiii ABBREVIATIONS ..................................................................................................................... xv Chapter 1 Introduction .................................................................................................................
    [Show full text]
  • Cocrystal Prediction by Artificial Neural Networks
    Cocrystal prediction by artificial neural networks Jan-Joris Devogelaer, Hugo Meekes, Paul Tinnemans, Elias Vlieg, and René de Gelder* Radboud University, Institute for Molecules and Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands E-mail: [email protected] Abstract A significant amount of attention has been given to the design and synthesis of cocrys- tals by both industry and academia because of its potential to change a molecule’s physico- chemical properties. Yet, difficulties arise when searching for adequate combinations of molecules (or coformers) to form cocrystals, hampering the efficient exploration of the tar- get’s solid-state landscape. This paper reports on the application of a data-driven cocrystal prediction method, based on two types of artificial neural network models and cocrystal data present in the Cambridge Structural Database. The models accept pairs of coformers and predict whether a cocrystal is likely to form. By combining the output of multiple models of both types, our approach shows to have excellent performance on the proposed cocrystal training and validation sets, and has an estimated accuracy of 80% for molecules for which previous cocrystallization data is unavailable. 1 1 Introduction Molecular solids appear in many different ways, and the solid-state landscape of a molecule may cover various crystalline forms, ranging from polymorphs and hydrates to more complex multicomponent crystals [1, 2]. The latter have been promoted as excellent tools to modify the physico-chemical characteristics of a target compound, such as the (aqueous) solubility, bio- availability, density, and melting point [3–8]. Multicomponent crystals therefore play a pivotal role in the effective formulation of pharmaceuticals and will continue to be part of the solid form screening process in drug development.
    [Show full text]
  • Synthesis, Crystal Structure, and Solubility Analysis of a Famotidine Cocrystal
    crystals Article Synthesis, Crystal Structure, and Solubility Analysis of a Famotidine Cocrystal Yan Zhang 1,2,* , Zhao Yang 2, Shuaihua Zhang 3 and Xingtong Zhou 2 1 School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China 2 Qingdao Institute for Food and Drug Control, Qingdao 266071, China 3 School of Pharmacy, Qingdao University, Qingdao 266071, China * Correspondence: [email protected]; Tel.: +86-532-5875-9178 Received: 15 May 2019; Accepted: 10 July 2019; Published: 15 July 2019 Abstract: A novel cocrystal of the potent H2 receptor antagonist famotidine (FMT) was synthesized with malonic acid (MAL) to enhance its solubility. The cocrystal structure was characterized by X-ray single crystal diffraction, and the asymmetry unit contains one FMT and one MAL connected via intermolecular hydrogen bonds. The crystal structure is monoclinic with a P21/n space group and unit cell parameters a = 7.0748 (3) Å, b = 26.6502 (9) Å, c = 9.9823 (4) Å, α = 90, β = 104.2228 (12), γ = 90,V = 1824.42 (12) Å3, and Z = 4. The cocrystal had unique thermal, spectroscopic, and powder X-ray diffraction (PXRD) properties that differed from FMT. The solubility of the famotidine-malonic acid cocrystal (FMT-MAL) was 4.2-fold higher than FMT; the FAM-MAL had no change in FMT stability at high temperature, high humidity, or with illumination. Keywords: cocrystal; famotidine; malonic acid; crystal structure; solubility 1. Introduction Drugs with low water solubility usually show dissolution-limited absorption and low bioavailability [1]. Recent estimates suggest that approximately 40% of currently marketed drugs and up to 75% of compounds currently under development are poorly water soluble; thus, enhancing the aqueous solubility of poorly water-soluble active pharmaceutical ingredients (APIs) is a key challenge for pharmaceutical scientists [2].
    [Show full text]
  • Non-Covalent Derivatives: Cocrystals and Eutectics
    Molecules 2015, 20, 14833-14848; doi:10.3390/molecules200814833 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review Non-Covalent Derivatives: Cocrystals and Eutectics Emily Stoler † and John C. Warner †,* The Warner Babcock Institute for Green Chemistry, 100 Research Drive, Wilmington, MA 01887, USA; E-Mail: [email protected] † These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +1-978-229-5420; Fax: +1-978-229-5401. Academic Editor: Kei Saito Received: 9 June 2015 / Accepted: 5 August 2015 / Published: 14 August 2015 Abstract: Non-covalent derivatives (NCDs) are formed by incorporating one (or more) coformer molecule(s) into the matrix of a parent molecule via non-covalent forces. These forces can include ionic forces, Van der Waals forces, hydrogen bonding, lipophilic-lipophilic interactions and pi-pi interactions. NCDs, in both cocrystal and eutectic forms, possess properties that are unique to their supramolecular matrix. These properties include critical product performance factors such as solubility, stability and bioavailability. NCDs have been used to tailor materials for a variety of applications and have the potential to be used in an even broader range of materials and processes. NCDs can be prepared using little or no solvent and none of the reagents typical to synthetic modifications. Thus, NCDs represent a powerfully versatile, environmentally-friendly and cost-effective opportunity. Keywords: non-covalent derivative; cocrystals; eutectics; green chemistry 1. Introduction A non-covalent derivative (NCD) [1] is formed when one (or more) coformer molecule(s) is incorporated into the matrix of the target molecule by way of non-covalent forces [2–4].
    [Show full text]
  • Cocrystal Construction Between Rosuvastatin Calcium and L- Asparagine with Enhanced Solubility and Dissolution Rate
    Original Article DOI: 10.4274/tjps.galenos.2021.62333 Cocrystal Construction Between Rosuvastatin Calcium and L- asparagine with Enhanced Solubility and Dissolution Rate Venkata Deepthi Vemuri1*, Srinivas Lankalapalli 2 1Maharajah’s College of Pharmacy, Phool Baugh, Vizianagaram-535002, India 2GITAM Institute of Pharmacy, GITAM (Deemed to be University), Visakhapatnam, Andhra Pradesh, INDIA Corresponding author: Corresponding author: Venkata Deepthi Vemuri* Mailing address: Maharajah’s College of Pharmacy, Phool Baugh, Vizianagaram-535002, Andhra Pradesh, India Mobile phone: +91-9032292387 E-mail: [email protected] https://orcid.org/0000-0003-3243-4340 20.12.2020 03.04.2021 Abstract Background: Rosuvastatin calcium, a synthetic BCS class-II drug with low solubility and high permeability utilized in hyperlipidaemia management. In the present investigation, an attempt was made towards the modification of the physicochemical properties of rosuvastatin calcium by applying crystalproof engineering to prepare a cocrystal form. Cocrystals of rosuvastatin calcium with GRAS status co-former L-Asparagine were prepared by utilizing solvent evaporation method. Result: The Obtained cocrystals was evaluated by Fourier transform infrared spectroscopy, powder X-ray diffraction, FT-Nuclear magnetic resonance spectroscopy, Scanning electron microscopy, and differential scanning calorimetry. Powder X-ray diffraction studies revealed the presence of unique crystalline peaks, which provides the interaction details of API and the co-former. The changes in the thermal behaviour of cocrystals were confirmed by differential scanning calorimetry studies. Alteration in the chemical shift values of FT-NMR at OH group confirms the hydrogen bond interaction between drug and co-former. Comparative studies on the solubility and dissolution rate were conducted and exhibited an almost 2-fold higher than the parent drug.
    [Show full text]
  • Preparation and Characterization of Carbamazepine Cocrystal in Polymer Solution
    pharmaceutics Article Preparation and Characterization of Carbamazepine Cocrystal in Polymer Solution Hao Zhang 1, Ying Zhu 1, Ning Qiao 1,2,* ID , Yang Chen 1,2 and Linghuan Gao 3 1 College of Materials Science and Engineering, North China University of Science and Technology, Tangshan 063210, China; [email protected] (H.Z.); [email protected] (Y.Z.); [email protected] (Y.C.) 2 Hebei Provincial Key Lab of Inorganic Nonmetallic Materials, College of Materials Science and Engineering, North China University of Science and Technology, Tangshan 063210, China 3 College of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063210, China; [email protected] * Correspondence: [email protected]; Tel.: +86-315-880-5620 Received: 1 October 2017; Accepted: 29 November 2017; Published: 1 December 2017 Abstract: In this study, we attempted to prepare carbamazepine (CBZ) cocrystal through the solution method in ethanol-water solvent mixture (volume ratio 1:1) and polyvinyl pyrrolidone (PVP) solution. Nicotinamide (NIC) and saccharin (SAC) were selected as cocrystal coformers. Cocrystal screening products were characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Powder X-ray Diffraction (PXRD) techniques. Characterization results show that in ethanol-water solvent mixture, pure CBZ-NIC cocrystal can be prepared, while CBZ-SAC cocrystal cannot be obtained. The addition of PVP can inhibit CBZ-NIC cocrystal formation and facilitate CBZ-SAC cocrystal formation. Keywords: cocrystal preparation; polyvinyl pyrrolidone; carbamazepine; nicotinamide; saccharin 1. Introduction Pharmaceutical cocrystal is a crystalline material with two components present in definite stoichimetric amounts [1]. One of the pharmaceutical cocrystal components is an active pharmaceutical ingredient (API), and the other component is a cocrystal coformer (CCF).
    [Show full text]
  • Improved Solubility and Dissolution Rates in Novel Multicomponent Crystals of Piperine with Succinic Acid
    Scientia Pharmaceutica Article Improved Solubility and Dissolution Rates in Novel Multicomponent Crystals of Piperine with Succinic Acid Erizal Zaini 1,* , Afriyani 1, Lili Fitriani 1 , Friardi Ismed 2, Ayano Horikawa 3 and Hidehiro Uekusa 3 1 Department of Pharmaceutics, Faculty of Pharmacy, Andalas University, Padang 25163, Indonesia; [email protected] (A.); lilifi[email protected] (L.F.) 2 Laboratory of Biota Sumatera and Faculty of Pharmacy, Andalas University, Padang 25163, Indonesia; [email protected] 3 Department of Chemistry, School of Science, Tokyo Institute of Technology, Tokyo 1528551, Japan; [email protected] (A.H.); [email protected] (H.U.) * Correspondence: [email protected] Received: 18 March 2020; Accepted: 9 April 2020; Published: 13 April 2020 Abstract: The objectives of this study were to prepare and characterize a novel piperine–succinic acid multicomponent crystal phase and to evaluate the improvement in the solubility and dissolution rate of piperine when prepared in the multicomponent crystal formation. The solid-state characterization of the novel multicomponent crystal was performed by powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform-infrared (FT-IR) spectroscopy. Solubility and dissolution rate profiles were evaluated in distilled water. The physical stability was evaluated under high relative humidity (75% and 100% RH). The determination of the single crystal X-ray diffraction structure revealed that this novel multicomponent crystal was a cocrystalline phase of piperine–succinic acid (2:1 molar ratio). The differential scanning calorimetry thermogram of the cocrystal showed a single and sharp endothermic peak at 110.49 ◦C.
    [Show full text]
  • Cocrystals of Spironolactone and Griseofulvin Based on an in Silico Screening Method
    This is a repository copy of Cocrystals of spironolactone and griseofulvin based on an in silico screening method. White Rose Research Online URL for this paper: http://eprints.whiterose.ac.uk/119702/ Version: Accepted Version Article: Grecu, T., Prohens, R., McCabe, J.F. et al. (4 more authors) (2017) Cocrystals of spironolactone and griseofulvin based on an in silico screening method. CrystEngComm, 19 (26). pp. 3592-3599. ISSN 1466-8033 https://doi.org/10.1039/c7ce00891k Reuse Items deposited in White Rose Research Online are protected by copyright, with all rights reserved unless indicated otherwise. They may be downloaded and/or printed for private study, or other acts as permitted by national copyright laws. The publisher or other rights holders may allow further reproduction and re-use of the full text version. This is indicated by the licence information on the White Rose Research Online record for the item. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. [email protected] https://eprints.whiterose.ac.uk/ Please do not adjust margins Journal Name ARTICLE Cocrystals of Spironolactone and Griseofulvin Based on an in Silico Screening Method Received 00th January 20xx, Accepted 00th January 20xx DOI: 10.1039/x0xx00000x a b c a d d www.rsc.org/ Tudor Grecu, Rafel Prohens, James F. McCabe, Elliot J. Carrington, James S. Wright, Lee Brammer,d and Christopher A. Hunter*e Cocrystal formation is considered as one of the most effective solid-state methods to alter the physicochemical properties of active pharmaceutical ingredients (APIs).
    [Show full text]
  • X-Ray Crystallography and Its Role in Understanding The…
    J. Indian Inst. Sci. A Multidisciplinary Reviews Journal ISSN: 0970-4140 Coden-JIISAD © The Author(s) 2017. X‑Ray Crystallography and its Role in Understanding the Physicochemical Properties of Pharmaceutical Cocrystals Srinivasulu Aitipamula1* and Venu R. Vangala2* REVIEW ARTICLE Abstract | Properties of a matter are intrinsically dependent on the inter‑ nal arrangement of molecules in the solid state. Therefore, knowledge of three-dimensional structure of the matter is a prerequisite for struc‑ ture–property correlations and design of functional materials. Over the past century, X-ray crystallography has evolved as a method of choice for accurate determination of molecular structure at atomic resolution. The structural information obtained from crystallographic analysis paved the way for rapid development in electronic devices, mineralogy, geo‑ sciences, materials science, pharmaceuticals, etc. Knowledge of the structural information of active pharmaceutical ingredients (APIs) is a prerequisite for rational drug design and synthesis of new chemical entities for development as new medicines. Over the past two decades, X-ray crystallography has played a key role in the design of pharmaceu‑ tical cocrystals—crystalline solids containing an API and one or more of pharmaceutically acceptable coformers. These materials have proved X-ray crystallography: An analytical technique used for promising for fne-tuning several important properties of APIs. This short determining the atomic and molecular structure of a crys- review highlights the history of crystallography, early breakthroughs, and tal, in which the crystalline at- the role of crystallography in understanding the physicochemical proper‑ oms cause a beam of incident X-rays to diffract into many ties of pharmaceutical cocrystals. specifc directions.
    [Show full text]