Hot-stage microscopy and ATR-FTIR in ramipril co-crystal screening

Excerpt:


J. Pharm. Pharmacogn. Res., vol. 11, no. 6, pp. 1137-1148, Nov-Dec 2023. DOI: https://doi.org/10.56499/jppres23.1723_11.6.1137 Original Article Utilizing hot-stage polarized microscopy and ATR-FTIR for ramipril co-crystal screening, supported by principal component analysis and cluster analysis [Utilización de microscopía polarizada en caliente y ATR-FTIR para el cribado de co-cristales de ramipril, con el apoyo del análisis de componentes … Continue reading Hot-stage microscopy and ATR-FTIR in ramipril co-crystal screening

J. Pharm. Pharmacogn. Res., vol. 11, no. 6, pp. 1137-1148, Nov-Dec 2023.

DOI: https://doi.org/10.56499/jppres23.1723_11.6.1137

Original Article

Utilizing hot-stage polarized microscopy and ATR-FTIR for ramipril co-crystal screening, supported by principal component analysis and cluster analysis

[Utilización de microscopía polarizada en caliente y ATR-FTIR para el cribado de co-cristales de ramipril, con el apoyo del análisis de componentes principales y el análisis de conglomerados]

Indra Indra1,4, Saleh Wikarsa2, Yuda Prasetya Nugraha2, Veinardi Suendo3, Hidehiro Uekusa5, Sundani Nurono Soewandhi2*

1Doctoral Program of Pharmacy, School of Pharmacy, Institut Teknologi Bandung, Jl. Ganesha No. 10, Bandung 40132, Indonesia.

2Department of Pharmaceutics, School of Pharmacy, Institut Teknologi Bandung, Jl. Ganesha No. 10, Bandung 40132, Indonesia.

3Division of Inorganic and Physical Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Bandung 40132, Indonesia.

4Faculty of Pharmacy, Universitas Bakti Tunas Husada, Tasikmalaya 46115, Indonesia.

5 Department of Chemistry, School of Science, Tokyo Institute of Technology, Tokyo 1528551, Japan.

*E-mail: sundani@itb.ac.id

Abstract

Context: Co-crystal formation, a method for enhancing the physicochemical properties of active pharmaceutical ingredients (APIs), has gained traction in pharmaceutical research. However, the current landscape lacks comprehensive and dependable co-crystal screening methods.

Aims: To implement and assess a comprehensive methodology for co-crystal screening. This methodology combines hot-stage polarized microscopy (HSPM) and attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy, along with principal component analysis (PCA) and cluster analysis (CA).

Methods: Three binary compounds containing ramipril, an API that had not previously been co-crystallized, and three pharmaceutical coformers were investigated. The Kofler mixed fusion method was initially employed for initial co-crystal system identification. Subsequently, potential co-crystals were produced in a solid state via a procedure involving the gradual evaporation of the solvent. PCA and CA were applied to ATR-FTIR spectral data to identify patterns indicative of co-crystal formation.

Results: Our analysis revealed characteristic ATR-FTIR bands indicative of the formation of hydrogen bonds between ramipril and its coformers, signifying the successful formation of co-crystals. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) measurements confirmed these findings. Experiments revealed two potential co-crystals, ramipril-vanillin, and ramipril-anthranilic acid. The study discusses the intricate HSPM images, spectra, thermogram of DSC, and X-ray diffraction properties of these systems in depth.

Conclusions: Our findings validate the proposed methodology as a prospective tool for co-crystal screening, as ramipril co-crystals were successfully identified and characterized. This integrated method simplifies co-crystal screening and has the potential to substantially advance pharmaceutical research.

Keywords: anthranilic acid; crystallization; isonicotinamide; multivariate analysis; vanillin; X-ray diffraction.

jppres_pdf_free

Resumen

Contexto: La formación de cocristales, un método para mejorar las propiedades fisicoquímicas de los principios activos farmacéuticos (API), ha ganado terreno en la investigación farmacéutica. Sin embargo, el panorama actual carece de métodos de cribado de cocristales completos y fiables.

Objetivos: Implementar y evaluar una metodología integral para el cribado de cocristales. Esta metodología combina la microscopía polarizada de fase caliente (HSPM) y la espectroscopia infrarroja de transformada de Fourier de reflexión total atenuada (ATR-FTIR), junto con el análisis de componentes principales (PCA) y el análisis de conglomerados (CA).

Métodos: Se investigaron tres compuestos binarios que contenían ramipril, un API que no se había co-cristalizado previamente, y tres coformadores farmacéuticos. Inicialmente se empleó el método de fusión mixta de Kofler para la identificación inicial del sistema de cocristales. Posteriormente, se produjeron posibles cocristales en estado sólido mediante un procedimiento que implicaba la evaporación gradual del disolvente. Se aplicaron PCA y CA a los datos espectrales ATR-FTIR para identificar patrones indicativos de la formación de cocristales.

Resultados: Nuestro análisis reveló bandas ATR-FTIR características indicativas de la formación de enlaces de hidrógeno entre el ramipril y sus coformadores, lo que significa la formación satisfactoria de cocristales. Las mediciones de calorimetría diferencial de barrido (DSC) y difracción de rayos X en polvo (PXRD) confirmaron estos hallazgos. Los experimentos revelaron dos posibles cocristales, ramipril-vanillina y ramipril-ácido antranílico. El estudio analiza en profundidad las intrincadas imágenes HSPM, los espectros, el termograma de DSC y las propiedades de difracción de rayos X de estos sistemas.

Conclusiones: Nuestros resultados validan la metodología propuesta como una herramienta prospectiva para el cribado de co-cristales, ya que los co-cristales de ramipril fueron identificados y caracterizados con éxito. Este método integrado simplifica el cribado de cocristales y tiene el potencial de hacer avanzar sustancialmente la investigación farmacéutica.

Palabras Clave: ácido antranílico; análisis multivariante; cristalización; difracción de rayos X; isonicotinamida; vainillina.

jppres_pdf_free
Citation Format: Indra I, Wikarsa S, Nugraha YP, Suendo V, Uekusa H, Soewandhi SN (2023) Utilizing hot-stage polarized microscopy and ATR-FTIR for ramipril co-crystal screening, supported by principal component analysis and cluster analysis. J Pharm Pharmacogn Res 11(6): 1137–1148. https://doi.org/10.56499/jppres23.1723_11.6.1137
References

Aitipamula S, Banerjee R, Bansal AK, Biradha K, Cheney ML, Choudhury AR, Desiraju GR, Dikundwar AG, Dubey R, Duggirala N, Ghogale PP, Ghosh S, Goswami PK, Goud NR, Jetti RRKR, Karpinski P, Kaushik P, Kumar D, Kumar V, Moulton B, Mukherjee A, Mukherjee G, Myerson AS, Puri V, Ramanan A, Rajamannar T, Reddy CM, Rodriguez-Hornedo N, Rogers RD, Guru Row TN, Sanphui P, Shan N, Shete G, Singh A, Sun CC, Swift JA, Thaimattam R, Thakur TS, Kumar Thaper R, Thomas SP, Tothadi S, Vangala VR, Variankaval N, Vishweshwar P, Weyna DR, Zaworotko MJ (2012) Polymorphs, salts, and cocrystals: What’s in a name? Cryst Growth Des 12(5): 2147–2152. https://doi.org/10.1021/cg3002948

Berry DJ, Seaton CC, Clegg W, Harrington RW, Coles SJ, Horton PN, Hursthouse MB, Storey R, Jones W, Friščić T, Blagden N (2008) Applying hot-stage microscopy to co-crystal screening: A study of nicotinamide with seven active pharmaceutical ingredients. Cryst Growth Des 8(5): 1697–1712. https://doi.org/10.1021/cg800035w

Budziak-Wieczorek I, Maciołek U (2021) Synthesis and characterization of a (-)-epicatechin and barbituric acid cocrystal: Single-crystal X-ray diffraction and vibrational spectroscopic studies. ACS Omega 6(12): 8199–8209. https://doi.org/10.1021/acsomega.0c06239

Caliandro R, Di Profio G, Nicolotti O (2013) Multivariate analysis of quaternary carbamazepine-saccharin mixtures by X-ray diffraction and infrared spectroscopy. J Pharm Biomed Anal 78–79: 269–279. https://doi.org/10.1016/j.jpba.2013.01.042

Castiñeiras A, Frontera A, García-Santos I, González-Pérez JM, Niclós-Gutiérrez J, Torres-Iglesias R (2022) Multicomponent solids of DL-2-hydroxy-2-phenylacetic acid and pyridinecarboxamides. Crystals 12(2): 142. https://doi.org/10.3390/cryst12020142

Center of Drug Evaluation and Research (2018) Regulatory classification of pharmaceutical co-crystals, guidance for industry. Food and Drug Administration, U.S. Department of Health and Human Services, February, pp. 1–4.

Cerreia Vioglio P, Chierotti MR, Gobetto R (2017) Pharmaceutical aspects of salt and cocrystal forms of APIs and characterization challenges. Adv Drug Deliv Rev 117: 86–110. https://doi.org/10.1016/j.addr.2017.07.001

Chun NH, Lee MJ, Song GH, Chang KY, Kim CS, Choi GJ (2014) Combined anti-solvent and cooling method of manufacturing indomethacin-saccharin (IMC-SAC) co-crystal powders. J Crystal Growth 408: 112–118. https://doi.org/10.1016/j.jcrysgro.2014.07.057

Du Y, Fang HX, Zhang Q, Zhang HL, Hong Z (2016) Spectroscopic investigation on cocrystal formation between adenine and fumaric acid based on infrared and Raman techniques. Spectrochim Acta A Mol Biomol Spectrosc 153: 580–585. https://doi.org/10.1016/j.saa.2015.09.020

Fatoni A, Hariani PL, Hermansyah Lesbani A (2018) Synthesis and characterization of chitosan linked by methylene bridge and schiff base of 4,4-diaminodiphenyl ether-vanillin. Indonesian J Chem 18(1): 92–101. https://doi.org/10.22146/ijc.25866

FDA (2016) Regulatory Classification of Pharmaceutical Co-Crystals Guidance for Industry. U.S. Department of Health and Human Services Food and Drug Administration, August, pp. 1–5.

Garbacz P, Wesolowski M (2018) DSC, FTIR and raman spectroscopy coupled with multivariate analysis in a study of co-crystals of pharmaceutical interest. Molecules 23(9): 2136. https://doi.org/10.3390/molecules23092136

Gong W, Mondal PK, Ahmadi S, Wu Y, Rohani S (2021) Cocrystals, salts, and salt-solvates of olanzapine; selection of coformers and improved solubility. Int J Pharm 608: 121063. https://doi.org/10.1016/j.ijpharm.2021.121063

Indra I, Soewandhi SN, Wikarsa S, Prasetya Y (2020) Designing and characterization of ramipril spherical agglomerates. Int J Pharm Res 12(2): 3177–3183. https://doi.org/10.31838/ijpr/2020.12.02.426

Issa N, Barnett SA, Mohamed S, Braun DE, Copley RCB, Tocher DA, Price SL (2012) Screening for cocrystals of succinic acid and 4-aminobenzoic acid. CrystEngComm 14(7): 2454–2464. https://doi.org/10.1039/c2ce06325e

Karagianni A, Malamatari M, Kachrimanis K (2018) Pharmaceutical cocrystals: New solid phase modification approaches for the formulation of APIs. Pharmaceutics 10(1) 18. https://doi.org/10.3390/pharmaceutics10010018

Karimi-Jafari M, Padrela L, Walker GM, Croker DM (2018) Creating cocrystals: A review of pharmaceutical cocrystal preparation routes and applications. Crystal Growth Des 18(10) 6370–6387. https://doi.org/10.1021/acs.cgd.8b00933

Kelleher JF, Gilvary GC, Madi AM, Jones DS, Li S, Tian Y, Almajaan A, Senta-Loys Z, Andrews GP, Healy AM (2018) A comparative study between hot-melt extrusion and spray-drying for the manufacture of anti-hypertension compatible monolithic fixed-dose combination products. Int J Pharm 545(1–2): 183–196. https://doi.org/10.1016/j.ijpharm.2018.05.008

Kumar A, Singh P, Nanda A (2020) Hot stage microscopy and its applications in pharmaceutical characterization. Appl Microsc 50(1): 12. https://doi.org/10.1186/s42649-020-00032-9

Lee LC, Liong CY, Jemain AA (2017) A contemporary review on Data Preprocessing (DP) practice strategy in ATR-FTIR spectrum. Chemom Intell Lab Syst 163: 64–75. https://doi.org/10.1016/j.chemolab.2017.02.008

Levy DH, Florio GM, Longarte A, Zwier TS (2003) Electronic and infrared spectroscopy of anthranilic acid in a supersonic jet cathrine. J Phys Chem A 107(20): 4032–4040. https://doi.org/10.1021/jp027041x

Lin HL, Zhang GC, Hsu PC, Lin SY (2013) A portable fiber-optic Raman analyzer for fast real-time screening and identifying cocrystal formation of drug-coformer via grinding process. Microchem J 110: 15–20. https://doi.org/10.1016/j.microc.2013.01.004

Luu V, Jona J, Stanton MK, Peterson ML, Morrison HG, Nagapudi K, Tan H (2013) High-throughput 96-well solvent mediated sonic blending synthesis and on-plate solid/solution stability characterization of pharmaceutical cocrystals. Int J Pharm 441(1–2): 356–364. https://doi.org/10.1016/j.ijpharm.2012.11.020

Manin AN, Drozd KV, Churakov AV, Perlovich GL (2018) Hydrogen bond donor/acceptor ratios of the coformers: Do they really matter for the prediction of molecular packing in cocrystals? the case of benzamide derivatives with dicarboxylic acids. Crystal Growth Des 18(9): 5254–5269. https://doi.org/10.1021/acs.cgd.8b00711

Ouiyangkul P, Tantishaiyakul V, Hirun N (2020) Exploring potential coformers for oxyresveratrol using principal component analysis. Int J Pharm 587: 119630. https://doi.org/10.1016/j.ijpharm.2020.119630

Ouyang J, Xing X, Zhou L, Zhang C, Heng JYY (2022) Cocrystal design of vanillin with amide drugs: Crystal structure determination, solubility enhancement, DFT calculation. Cheml Eng Res Des 183: 170–180. https://doi.org/10.1016/j.cherd.2022.05.009

Rahman Z, Agarabi C, Zidan AS, Khan SR, Khan MA (2011) Physico-mechanical and stability evaluation of carbamazepine cocrystal with nicotinamide. AAPS PharmSciTech 12(2): 693–704. https://doi.org/10.1208/s12249-011-9603-4

Rinnan Å, Berg F van den, Engelsen SB (2009) Review of the most common pre-processing techniques for near-infrared spectra. Trends Anal Chem 28(10): 1201–1222. https://doi.org/10.1016/j.trac.2009.07.007

Saganowska P, Wesolowski M (2017) Principal component and cluster analyses as supporting tools for co-crystals detection. J Therm Anal Calorim 130(1) 45–55. https://doi.org/10.1007/s10973-017-6436-8

Sarraguça MC, Paisana M, Pinto J, Lopes JA (2016) Real-time monitoring of cocrystallization processes by solvent evaporation: A near infrared study. Eur J Pharm Sci 90: 76–84. https://doi.org/10.1016/j.ejps.2015.12.025

Wisudyaningsih B, Jember U, Setyawan D, Siswodihardjo S (2019) Co-crystallization of quercetin and isonicotinamide using using solvent evaporation method. Trop J Pharm Res 18(4): 697–702. http://dx.doi.org/10.4314/tjpr.v18i4.3

Wu TK, Lin SY, Lin HL, Huang YT (2011) Simultaneous DSC-FTIR microspectroscopy used to screen and detect the co-crystal formation in real time. Bioorg Med Chem Lett 21(10): 3148–3151. https://doi.org/10.1016/j.bmcl.2011.03.001

© 2023 Journal of Pharmacy & Pharmacognosy Research

Ageratum conyzoides and eggshell membrane hydrolysates in chronic inflammation
J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 972-993, Sep-Oct 2024. DOI: https://doi.org/10.56499/jppres24.1956_12.5.972 Original Article Anti-inflammatory effect of the mixture of Ageratum conyzoides L. extract and eggshell membrane hydrolysates and in silico active compound predictions [Efecto antiinflamatorio de la mezcla de extracto de Ageratum conyzoides L. e hidrolizados de membrana de cáscara de huevo, … Continue reading Ageratum conyzoides and eggshell membrane hydrolysates in chronic inflammation
SS-31 for diabetic nephropathy
J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 956-971, Sep-Oct 2024. DOI: https://doi.org/10.56499/jppres23.1904_12.5.956 Review SS-31 protects diabetic nephropathy progression: A systematic review of in vivo and in vitro studies [El SS-31 protege la progresión de la nefropatía diabética: Una revisión sistemática de estudios in vivo e in vitro] Jonathan Christianto Sutadji1#, Dian Anggraini Permatasari … Continue reading SS-31 for diabetic nephropathy
Hypertension knowledge and its associated factors in primary care
J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 943-955, Sep-Oct 2024. DOI: https://doi.org/10.56499/jppres24.1955_12.5.943 Original Article Hypertension knowledge and its associated factors among hypertensive patients in primary care settings in Central Vietnam: A cross-sectional study [Conocimiento de la hipertensión y sus factores asociados entre pacientes hipertensos en entornos de atención primaria en el centro de … Continue reading Hypertension knowledge and its associated factors in primary care

© 2013-2020 by the authors; licensee JPPRes, Antofagasta, Chile. This journal is an open-access journal distributed under the terms and conditions of the Creative Commons Attribution license-Non Commercial 4.0 international. The content on this site is intended for health professionals. If you are not a health professional, please talk to your doctor about any doubts or concerns regarding your health

Made with ♥ by AVAGAX Studio