• Iyan Sopyan Departement of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran
  • Intan Mutiara Sari Departement of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran
  • Insan Sunan K. Departement of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran


Objective: Interactions of active pharmaceutical ingredients (API) as well as pharmaceutical excipients don’t occur in a pharmaceutical dosage form. Base on structures of paracetamol (PCT) and chlorphenamine maleate (CTM), its combination is possible to give a physical interaction in the solid state. This study was conducted to investigate the physical interaction of PCT and CTM in the solid state.

Methods: Characterization used the polarization microscope, solubility test, powder x-ray diffraction (PXRD) to observe peak shifting in 2ÆŸ angle, and fourier transform infrared spectroscopy (FT-IR) to examine wavenumber shifting.

Results: Results of solubility exhibited an increased solubility percentage with increasing concentration. Polarization microscope analysis presented a combination of crystal morphology after the two substances were mixed in an equimolar ratio. The result of melting point determination of each pure substance was 172 °C for PCT, 132 °C for CTM, and 170 °C for the mixture of the two substances in various ratios. Diffractogram showed the shifting at angle 2Ɵ: 20.715, 19.355-23.500 and 21.840, 26.455-20.330 for concentration ratio of PCT: CTM in (132:0.5) and (330:1) respectively and any change in the functional group was observed from infrared spectrum.

Conclusion: All evaluation of PCT and CTM in the solid state has exhibited the interaction in solid condition.

Keywords: Paracetamol, Chlorphenamine maleate, Polarization microscope, X-Ray diffraction, FT-IR


1. Zaini E. Identification of physical interaction between trimethoprim and sulfamethoxazole by contact method kofler and crystallization reaction. Indones J Pharm 2016;21:31–7.
2. Airaksinen S, Karjalainen M, Kivikero N, Westermarck S, Shevchenko A, Rantanen J, et al. Excipient selection can significantly affect solid-state phase transformation in formulation during wet granulation. AAPS PharmSciTech 2005;6:11–22.
3. Löbmann K, Strachan C, Grohganz H, Rades T, Korhonen O, Laitinen R. Co-amorphous simvastatin and glipizide combinations show improved physical stability without evidence of intermolecular interactions. Eur J Pharm Biopharm 2012;81:159–69.
4. Hiendrawan S, Hartanti AW, Veriansyah B, Widjojokusumo E, Tjandrawinata RR. Solubility enhancement of ketoconazole via salt and cocrystal formation. Int J Pharm Pharm Sci 2015;21:160–4.
5. Nugrahani I, Asyarie S, Soewandhi SN, Ibrahim S. Solid state interaction between amoxicillin trihydrate and potassium Clavulanate. Malays J Pharm Sci 2007;5:45–57.
6. Putra OD, Nugrahani I, Ibrahim S, Uekusa H. Pembentukan padatan semi kristalin dan ko-kristal parasetamol. J Mat Sains 2013;17:83–8.
7. Maeno Y, Fukami T, Kawahata M, Yamaguchi K, Tagami T, Ozeki T, et al. Novel pharmaceutical cocrystal consisting of paracetamol and trimethylglycine, a new promising cocrystal former. Int J Pharm 2014;473:179–86.
8. Sopyan I, Fudholi A, Muchtaridi M, Puspitasari I. A simple effort to enhance solubility and dissolution rate of simvastatin using co-crystallization. Int J Pharm Pharm Sci 2016;8:342–6.
9. S MB, Dengale SJ, Shenoy GG, Bhat K. Preparation, solid-state characterisation of paclitaxel and naringen cocrystals with improved solubility. Int J Appl Pharm 2016;8:32–7.
10. Nugrahani I, Ibrahim S, Puspita DD. Kristal biru2, 3 dimetil-N-fenilalanin (DNF) hasil interaksi kimia padatan asam mefenamat dengan asam oksalat. J Mat Sains 2013;17:98–104.
11. Departemen Kesehatan RI. Farmakope Indonesia Edisi IV. IV. Jakarta: Depertementkesehatan RI; 1995. p. 63,210,649.
12. Naid T, Kasim S, Pakaya M. Penetapan kadar parasetamoldalam tablet kombinasi parasetamoldengan kofein secaraspektofotometri ultraviolet sinar tampak. Univ Hasanudin Makasar 2011;15:77–82.
13. Sopyan I, Fudhloli A, Muchtaridi M, Sari IP, Permatasari D. A novel of derivative spectrophotometry as rapid and accurate method in application of simvastatin co-crystal assay. Int J Res Pharm Sci 2017;20:301–6.
14. Sopyan I, Fudholi A, Muchtaridi M, Sari IP. Simvastatin-nicotinamide co-crystal: design, preparation and preliminary characterization. Trop J Pharm Res 2017;16:297-302.
15. Lin HL, Zhang GC, Lin SY. Real-time co-crystal screening and formation between indomethacin and saccharin via DSC analytical technique or DSC–FTIR microspectroscopy. J Therm Anal Calorim 2014;120:679–87.
16. Zaini E, Halim A, Sundani NS, Setyawan D. Peningkatan laju pelarutan trimetropim melalui metode ko-kristalisasidengan nikotinamida. J Farm Indones 2011;5:205–12.
17. Good DJ, Rodríguez-Hornedo N. Solubility advantage of pharmaceutical cocrystals. Cryst Growth Des 2009;9:2252–64.
18. Delori A, Galek PTA, Pidcock E, Patni M, Jones W. Knowledge-based hydrogen bond prediction and the synthesis of salts and cocrystals of the anti-malarial drug pyrimethamine with various drug and GRAS molecules. Cryst Eng Comm 2013; 15:2916–28.
19. Karpińska J. Derivative spectrophotometry—recent applications and directions of developments. Talanta 2004;64:801–22.
20. Chadha R, Saini A, Arora P, Jain DS, Dasgupta A, Row TNG. Multicomponent solids of lamotrigine with some selected coformers and their characterization by thermoanalytical, spectroscopic and X-ray diffraction methods. Cryst Eng Comm 2011;13:6271–84.
21. Caira MR, Nassimbeni LR, Van Oudtshoorn B. X-ray structural characterization of anhydrous metronidazole benzoate and metronidazole benzoate monohydrate. J Pharm Sci 1993; 82:1006–9.
22. Alam MS, Lee DU. Spectral (FT-IR, FT-Raman, UV, and fluorescence), DFT, and solidstate interaction analyses of (E)-4-(3,4-dimethoxybenzylideneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one. J Mol Struct 2017;1128:174–85.
23. Brittain HG. Vibrational spectroscopic studies of co-crystals and salts. 3. cocrystal products formed by benzene carboxylic acids and their sodium salts. Cryst Growth Des 2010;10:373-90.
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How to Cite
Sopyan, I., Sari, I. M., & K., I. S. (2018). SOLID STATE CHARACTERIZATION OF A NOVEL PHYSICAL INTERACTION (PARACETAMOL-CHLORPHENIRAMINE MALEATE). International Journal of Applied Pharmaceutics, 10(1), 21-25.
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