THEOPHYLLINE–NA–SACHARRINE SINGLE CRYSTAL ISOLATION FOR ITS STRUCTURE DETERMINATION

Authors

  • Ilma Nugrahani School of Pharmacy ITB, Jl. Ganesha 10 Bandung Indonesia 40132
  • Evalianty Agiana Pertiwi School of Pharmacy ITB, Jl. Ganesha 10 Bandung Indonesia 40132
  • Okky Dwichandra Putra School of Pharmacy ITB, Jl. Ganesha 10 Bandung Indonesia 40132

Keywords:

Co-crystal, Single-crystal, Slow evaporation, Theophylline anhydrous, Sodium saccharin dihydrate

Abstract

Objective: Co-crystal is a crystal form which consists of two or more components in a specific stoichiometric ratio. Theophylline has been reported to form a co-crystal with sodium saccharin, but its single-crystal has not been isolated, so its structure also has not been known yet. This research aimed to isolate the theophylline-sodium saccharin co-crystal with several solvent, studied its single-crystal structure, and observed the stability of the co-crystal formed in a high humidity.

Methods: Theophylline anhydrous powder (TA), sodium saccharin dihydrate (NSD), and the physical mixtures of TA-NSD were characterized using a polarizing microscope, Fourier-Transform Infrared Spectroscopy (FTIR), Powder X-ray Diffractometer (PXRD), and Karl Fischer Titration (KFT); respectively. The single TA-NSD co-crystal formation was done by slow evaporation at ambient temperature (25 °C) and 12 °C, using four types of solvent mixtures, such as: water-isopropanol; water-acetone; ethanol-dichloromethane; and ethanol. The rate formations of co-crystals were observed and characterized using polarizing microscopy, FTIR, PXRD. The isolated co-crystal was analyzed using a Single-crystal X-Ray Diffractometer (SC-XRD). Finally; stability test was applied to TA-NSD co-crystal at an RH 95% chamber.

Results: Single-crystals at most formed in water-isopropanol (1:7), with the size of 0.6 to 1.2 cm (at ambient temperature) and 0.6 to 1 cm (at 12 °C) and solvent of water-acetone 1: 9 with a size of 0.5 to 1.1 cm (at ambient temperature/25 °C). Meanwhile from the other solvents, co-crystal just was produced in the crystalline form; and thin crystals with a size of ≤ 5 mm both in ambient temperature and 12 °C. Visual observations that were supported by polarizing microscope magnification showed TA-NSD co-crystal has rod-shaped and translucent color. FTIR spectra analysis results showed N-H stretching of the co-crystal shift from a wavenumber 3124.12 to 3129.7-3131.83 cm-1. The diffractogram from PXRD analysis indicated that TA-NSD co-crystal has sharp peaks on 2Ɵ = 5.58, 12.32, 17.48, 22.40, 26.86, 27.4, 28.84, and 34.1 °. The SC-XRD result showed the TA-NSD co-crystal has monoclinic crystal system, which has not been reported previously. The stability test in high humidity proved that the co-crystal shows unchanged shift N-H strain, which means that TA-NSD co-crystal is stable.

Conclusion: Based on all data, it is concluded that TA-NSD co-crystal has rod-shaped with translucent color, and has a monoclinic crystal system with volume 1583.9 (7) Å3. The single-crystals yielded from the water-isopropanol solvent system at ambient temperature and 12 °C; while from water-acetone 1: 9 was formed at 12 °C. The stability test in an RH 95% chamber showed that TA-NSD co-crystal is stable against the moisture.

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References

Trask AV, Motherwell WD, Sam W, Jones W. Physical stability enhancement of theophylline via co-crystallization. Int J Pharm 2006;320:114-23.

Ronco MPF, Kluge J, Mazzotti M. High-pressure homogenization as a novel approach for the preparation of co-crystals. Cryst Growth Des 2013;13:2013-24.

Amjad A. Theophylline co-crystals prepared by spray drying: physicochemical properties and aerosolization performance. AAPS Pharm Sci Tech 2013;41:265–76.

Banerjee R, Bhatt PM, Ravindra NV, Desiraju GR. Saccharin salts of active pharmaceutical ingredients their crystal structures and increased water solubilities. Cryst Growth Des 2005;5:2298-09.

Nugrahani I, Bahari MU. The dynamic study of co-crystal formation between anhydrous and monohydrate theophylline with sodium saccharine dihydrate by FTIR. J Chem Biochem 2014;2:117-37.

Syahbani MM, Nugrahani I. Determination stoichiometry of theophylline and sodium saccharine co-crystal and hygroscopicity test. Undergraduate Thesis. School of Pharmacy-ITB, Bandung; 2014.

Khanam J. Crystallization. Jadavpur University. Kolkatta; 2007. p. 8-11.

Trask AV, Jones W. Crystal engineering of organic co-crystal by the solid state grinding approach. Top Curr Chem 2005;254:41-70.

Salih AI. Effect of carbon wt % on the iron X-ray diffraction pattern and the volume of iron unit cell. Sci Studies 2010;6:155-65.

Zhishen MB, Hao Y, Dan-Ni Z. The degree of crystallinity of multicomponent Polymers by WAXD. Chin J Polym Sci 1994;12:296-301.

Chung FH, Scott RW. A new approach to the determination of crystallinity of polymers by X-ray diffraction. J Appl Cryst 1973;6:225-30.

Published

01-12-2015

How to Cite

Nugrahani, I., E. A. Pertiwi, and O. D. Putra. “THEOPHYLLINE–NA–SACHARRINE SINGLE CRYSTAL ISOLATION FOR ITS STRUCTURE DETERMINATION”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 12, Dec. 2015, pp. 15-24, https://mail.innovareacademics.in/journals/index.php/ijpps/article/view/7749.

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