THEOPHYLLINE ASCORBIC ACID COCRYSTALS BY SONOCRYSTALLIZATION METHOD: FORMULATION AND CHARACTERIZATION STUDIES
DOI:
https://doi.org/10.22159/ajpcr.2024v17i8.51253Keywords:
Cocrystals, Sonocrystallization, Theophylline, Ascorbic acid, Drug–drug cocrystalAbstract
Objective: The objective of the current research work was to develop Theophylline Ascorbic acid cocrystals by sonocrystallization method. The approach is a coadministrative approach to provide drug:drug cocrystals in Chronic Obstructive Pulmonary Disorder.
Methods:The cocrystals were formulated in 3 stoichiometric ratios of 1:1, 1:2 and 2:1 using Sonocrystallization induced evaporation method. Methanol was used as solvent. The cocrystals were evaluated for visual morphology, melting point, FTIR studies, saturation solubility in water and Simulated Lung fluid pH 7.4, in vitro drug release in Simulated Lung Fluid pH 7.4, Differential scanning calorimetry studies, X-Ray Diffraction studies, Scanning Electron Microscopy studies and Raman spectroscopy.
Result:Cocrystals were successfully developed in all 3 stoichiometric ratios by sonocrystallization method. The cocrystal of Theophylline with Ascorbic acid in ratio of 1:1 was found to be most optimized with 10 fold increase in saturation solubility in water and 11.5 fold increase in solubility in simulated lung fluid pH 7.4 and two-fold increase in in vitro drug release in SLF pH 7.4. The cocrystal was found to show a lowered melting point as confirmed by DSC studies thus confirming formation of new crystalline phase. X Ray Diffraction studies. SEM and Raman spectroscopy studies were found to confirm the change in crystalline characteristics of the cocrystals by indicating formation of new crystalline phase.
Conclusion: Cocrystals were successfully developed by sonocrystallization method. Sonocrystallization method can be used as a preferred method for formation of drug-drug cocrystals for coadministrative approach of drug delivery.
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Qiao N, Li M, Schlindwein W, Malek N, Davies A, Trappitt G. Pharmaceutical cocrystals: An overview. Int J Pharm. 2011;419(1-2):1- 11. doi: 10.1016/j.ijpharm.2011.07.037, PMID: 21827842
Duggirala NK, Perry ML, Almarsson Ö, Zaworotko MJ. Pharmaceutical cocrystals: Along the path to improved medicines. Chem Commun (Camb). 2016;52(4):640-55. doi: 10.1039/c5cc08216a, PMID: 26565650
Shan N, Zaworotko MJ. The role of cocrystals in pharmaceutical science. Drug Discov Today. 2008;13(9-10):440-6. doi: 10.1016/j. drudis.2008.03.004, PMID: 18468562
Manin AN, Surov AO, Churakov AV, Perlovich GL. Crystal structures, thermal analysis, and dissolution behavior of new solid forms of the antiviral drug arbidol with dicarboxylic acids. Crystals. 2015;5(4):650- 69. doi: 10.3390/cryst5040650
Vishweshwar, P, McMahon JA, Bis JA, Zaworotko MJ. Pharmaceutical co-crystals. J Pharm Sci. 2006;95(3):499-516. doi: 10.1002/jps.20578, PMID: 16444755
Childs SL, Hardcastle KI. Cocrystals of piroxicam with carboxylic acids. Cryst Growth Des. 2007;7(7):1291-304. doi: 10.1021/cg060742p
Suzuki E, Shimomura K, Sekiguchi K. Thermochemical study of theophyline and its hydrate. Chem Pharm Bull. 1989;37(2):493-7. doi: 10.1248/cpb.37.493
Phadnis NV, Suryanarayanan R. Polymorphism in anhydrous theophylline--implications on the dissolution rate of theophylline tablets. J Pharm Sci. 1997;86(11):1256-63. doi: 10.1021/js9701418, PMID: 9383736
Seton L, Khamar D, Bradshaw IJ, Hutcheon GA. Solid state forms of theophylline: Presenting a new anhydrous polymorph. Cryst Growth Des. 2010;10(9):3879-86. doi: 10.1021/cg100165t
Huang Y, Zhou L, Yang W, Li Y, Yang Y, Zhang Z, et al. Preparation of theophylline-benzoic acid cocrystal and on-line monitoring of Cocrystallization process in solution by Raman spectroscopy. Crystals. 2019;9(7):329. doi: 10.3390/cryst9070329
McTague H, Rasmuson ÅC. Nucleation of the theophylline: Salicylic acid 1:1 cocrystal. Cryst Growth Des. 2021;21(5):2711-9. doi: 10.1021/ acs.cgd.0c01594, PMID: 35140547
Ervasti T, Aaltonen J, Ketolainen J. Theophylline-nicotinamide cocrystal formation in physical mixture during storage. Int J Pharm. 2015;486(1-2):121-30. doi: 10.1016/j.ijpharm.2015.03.012, PMID: 25800677
Singh M, Barua H, Jyothi VG, Dhondale MR, Nambiar AG, Agrawal AK, et al. Cocrystals by design: A rational coformer selection approach for tackling the API problems. Pharmaceutics. 2023 Apr 6;15(4):1161. doi: 10.3390/pharmaceutics15041161, PMID: 37111646
Park HJ, Byun MK, Kim HJ, Kim JY, Kim YI, Yoo KH, et al. Dietary Vitamin C intake protects against COPD: The Korea National Health and Nutrition Examination Survey in 2012. Int J Chron Obstruct Pulmon Dis. 2016;11:2721-8. doi: 10.2147/COPD.S119448, PMID: 27843308
Zhang S, Rasmuson ÅC. The theophylline-oxalic acid Co-crystal system: Solid phases, thermodynamics and crystallisation. CrystEngComm. 2012;14(14):4644-55. doi: 10.1039/c2ce25299f
Garbacz P, Wesolowski M. Benzodiazepines co-crystals screening using FTIR and Raman spectroscopy supported by differential scanning calorimetry. Spectrochim Acta A Mol Biomol Spectrosc. 2020;234:118242. doi: 10.1016/j.saa.2020.118242, PMID: 32179462
Liu Y, Yang F, Zhao X, Wang S, Yang Q, Zhang X. Crystal structure, solubility, and pharmacokinetic study on a hesperetin cocrystal with piperine as coformer. Pharmaceutics. 2022 Jan 1;14(1):94. doi: 10.3390/pharmaceutics14010094, PMID: 35056990
Kataoka M, Minami K, Takagi T, Amidon GE, Yamashita S. In vitro-in vivo correlation in cocrystal dissolution: Consideration of drug release profiles based on coformer dissolution and absorption behavior. Mol Pharm. 2021 Nov 1;18(11):4122-30. doi: 10.1021/acs. molpharmaceut.1c00537, PMID: 34618448
Wu N, Zhang Y, Ren J, Zeng A, Liu J. Preparation of quercetin-nicotinamide cocrystals and their evaluation under in vivo and in vitro conditions. RSC Adv. 2020 Jun 9;10(37):21852-9. doi: 10.1039/ d0ra03324c, PMID: 35516602
Gohel SK, Palanisamy V, Sanphui P, Prakash M, Singh GP, Chernyshev V. Isostructural cocrystals of metaxalone with improved dissolution characteristics. RSC Adv. 2021 Sep 15;11(49):30689-700. doi: 10.1039/d1ra05959a, PMID: 35479860
Dhibar M, Chakraborty S, Basak S, Pattanayak P, Chatterjee T, Ghosh B, et al. Critical analysis and optimization of stoichiometric ratio of drug-coformer on cocrystal design: Molecular docking, in vitro and in vivo assessment. Pharmaceuticals (Basel). 2023 Feb 13;16(2):284. doi: 10.3390/ph16020284, PMID: 37259428
Wallace CS, Davis MP, Korter TM. Low-frequency Raman spectroscopy of pure and cocrystallized mycophenolic acid. Pharmaceutics. 2023 Jul 11;15(7):1924. doi: 10.3390/pharmaceutics15071924, PMID: 37514110
Lei T, Lu T, Yu H, Su X, Zhang C, Zhu L, et al. Efficacy of Vitamin C supplementation on Chronic Obstructive Pulmonary Disease (COPD): A systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2022 Sep 10;17:2201-16. doi: 10.2147/COPD.S368645, PMID: 36118282
Srinivasan P, Almutairi M, Dumpa N, Sarabu S, Bandari S, Zhang F, et al. Theophylline-nicotinamide pharmaceutical co-crystals generated using hot melt extrusion technology: Impact of polymeric carriers on processability. J Drug Deliv Sci Technol. 2021 Feb;61:102128. doi: 10.1016/j.jddst.2020.102128, PMID: 33717231
Palanisamy V, Sanphui P, Palanisamy K, Prakash M, Bansal AK. Design of ascorbic acid eutectic mixtures with sugars to inhibit oxidative degradation. Front Chem. 2022 9;10:754269. doi: 10.3389/ fchem.2022.754269, PMID: 35615307
Panzade P, Shendarkar G. Superior solubility and dissolution of zaltoprofen via pharmaceutical cocrystals. Turk J Pharm Sci. 2019;16(3):310-6. doi: 10.4274/tjps.galenos.2018.15013, PMID: 32454729
Bo Y, Fang J, Zhang Z, Xue J, Liu J, Hong Z, et al. Terahertz and Raman spectroscopic investigation of monohydrate cocrystal of antitubercular isoniazid with protocatechuic acid. Pharmaceutics. 2021 Aug 20;13(8):1303. doi: 10.3390/pharmaceutics13081303, PMID: 34452267
Haskins MM, Lusi M, Zaworotko MJ. Supramolecular synthon promiscuity in phosphoric acid-dihydrogen phosphate ionic cocrystals. Cryst Growth Des. 2022;22(5):3333-42. doi: 10.1021/acs.cgd.2c00150, PMID: 35529065
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