Recent advances in pharmaceutical cocrystals of theophylline

doi:10.1007/s13659-024-00470-y

Natural Products and Bioprospecting ›› 2024, Vol. 14 ›› Issue (6): 53-53.DOI: 10.1007/s13659-024-00470-y

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Recent advances in pharmaceutical cocrystals of theophylline

Yanxiao Jia¹, Dezhi Yang¹, Wenwen Wang¹, Kun Hu¹, Min Yan², Li Zhang^1,2, Li Gao², Yang Lu¹

1. Beijing City Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing 100050, People's Republic of China;
2. Prescription Laboratory of Xinjiang Traditional Uyghur Medicine, Xinjiang Institute of Traditional Uyghur Medicine, Urumqi 830000, People's Republic of China

Received:2024-06-26 Online:2024-12-13 Published:2024-12-24
Contact: Li Zhang,E-mail:gaoli_535@163.com;Li Gao,E-mail:gaoli_535@163.com;Yang Lu,E-mail:luy@imm.ac.cn
Supported by:
The authors are thankful to Xinjiang Uygur Autonomous Region Innovation Environment Construction Special Fund and Technology Innovation Base Construction Key Laboratory Open Project (Grant No. 2022D04016), the Key R&D Program of Shan Dong Province (Grant No. 2021ZDSYS26), CAMS Innovation Fund for Medical Sciences (Grant No. 2022-I2M-1-015), Chinese Pharmacopoeia Commission Drug Standard Promoting Fund (Grant No. 2023Y11), Independent Innovation and Achievement Transformation Plan Project of Zaozhuang City (Grant No. 2022GH15), and 2023 Xinjiang Uygur Autonomous Region Innovation Tianchi Talent Introduction Program for financial support.

Recent advances in pharmaceutical cocrystals of theophylline

Yanxiao Jia¹, Dezhi Yang¹, Wenwen Wang¹, Kun Hu¹, Min Yan², Li Zhang^1,2, Li Gao², Yang Lu¹

1. Beijing City Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing 100050, People's Republic of China;
2. Prescription Laboratory of Xinjiang Traditional Uyghur Medicine, Xinjiang Institute of Traditional Uyghur Medicine, Urumqi 830000, People's Republic of China

通讯作者: Li Zhang,E-mail:gaoli_535@163.com;Li Gao,E-mail:gaoli_535@163.com;Yang Lu,E-mail:luy@imm.ac.cn
基金资助:
The authors are thankful to Xinjiang Uygur Autonomous Region Innovation Environment Construction Special Fund and Technology Innovation Base Construction Key Laboratory Open Project (Grant No. 2022D04016), the Key R&D Program of Shan Dong Province (Grant No. 2021ZDSYS26), CAMS Innovation Fund for Medical Sciences (Grant No. 2022-I2M-1-015), Chinese Pharmacopoeia Commission Drug Standard Promoting Fund (Grant No. 2023Y11), Independent Innovation and Achievement Transformation Plan Project of Zaozhuang City (Grant No. 2022GH15), and 2023 Xinjiang Uygur Autonomous Region Innovation Tianchi Talent Introduction Program for financial support.

Abstract

Abstract: Currently, cocrystallization is a promising strategy for tailoring the physicochemical properties of active pharmaceutical ingredients. Theophylline, an alkaloid and the most primary metabolite of caffeine, is a readily available compound found in tea and coffee. It functions primarily as a bronchodilator and respiratory stimulant, making it a mainstay treatment for lung diseases like asthma. Theophylline’s additional potential benefits, including anti-inflammatory and anticancer properties, and its possible role in neurological disorders, have garnered significant research interest. Cocrystal formation presents a viable approach to improve the physicochemical properties of theophylline and potentially mitigate its toxic effects. This review comprehensively explores several successful studies that utilized cocrystallization to favorably alter the physicochemical properties of theophylline or its CCF. Notably, cocrystals can not only enhance the solubility and bioavailability of theophylline but also exhibit synergistic effects with other APIs. The review further delves into the hydrogen bonding sites within the theophylline structure and the hydrogen bonding networks observed in cocrystal structures.

Key words: Pharmaceutical cocrystals, Theophylline, Physiochemical properties, Synergistic effect, Formation mechanism

摘要： Currently, cocrystallization is a promising strategy for tailoring the physicochemical properties of active pharmaceutical ingredients. Theophylline, an alkaloid and the most primary metabolite of caffeine, is a readily available compound found in tea and coffee. It functions primarily as a bronchodilator and respiratory stimulant, making it a mainstay treatment for lung diseases like asthma. Theophylline’s additional potential benefits, including anti-inflammatory and anticancer properties, and its possible role in neurological disorders, have garnered significant research interest. Cocrystal formation presents a viable approach to improve the physicochemical properties of theophylline and potentially mitigate its toxic effects. This review comprehensively explores several successful studies that utilized cocrystallization to favorably alter the physicochemical properties of theophylline or its CCF. Notably, cocrystals can not only enhance the solubility and bioavailability of theophylline but also exhibit synergistic effects with other APIs. The review further delves into the hydrogen bonding sites within the theophylline structure and the hydrogen bonding networks observed in cocrystal structures.

关键词: Pharmaceutical cocrystals, Theophylline, Physiochemical properties, Synergistic effect, Formation mechanism

Yanxiao Jia, Dezhi Yang, Wenwen Wang, Kun Hu, Min Yan, Li Zhang, Li Gao, Yang Lu. Recent advances in pharmaceutical cocrystals of theophylline[J]. Natural Products and Bioprospecting, 2024, 14(6): 53-53.

Yanxiao Jia, Dezhi Yang, Wenwen Wang, Kun Hu, Min Yan, Li Zhang, Li Gao, Yang Lu. Recent advances in pharmaceutical cocrystals of theophylline[J]. 应用天然产物, 2024, 14(6): 53-53.

References

[1] Patole T, Deshpande A, Nmims S, et al. Co-crystallization—a technique for solubility enhancement. Int J Pharm Sci Res. 2014;5(9):3566.
[2] Aitipamula S, Banerjee R, Bansal AK, et al. Polymorphs, salts, and cocrystals: what’s in a name? Cryst Growth Des. 2012;12(5):2147-52.
[3] Barnes PJ. Theophylline. Am J Respir Crit Care Med. 2013;188(8):901-6.
[4] Wang D, Hong SP, Row KH. Solid extraction of caffeine and theophylline from green tea by molecular imprinted polymers. Korean J Chem Eng. 2004;21(4):853-7.
[5] Yousaf M, Zahoor AF, Faiz S, et al. Recent synthetic approaches towards biologically potent derivatives/analogues of theophylline. J Heterocycl Chem. 2018;55(11):2447-79.
[6] Andel AEV, Reisner C, Menjoge SS, et al. Analysis of inhaled corticosteroid and oral theophylline use among patients with stable COPD from 1987 to 1995. Chest. 1999;115(3):703-7.
[7] Wang L, Li S, Xu X, et al. Drug-drug cocrystals of theophylline with quercetin. J Drug Deliv Sci Technol. 2022;70: 103228.
[8] Seton L, Khamar D, Bradshaw IJ, et al. Solid state forms of theophylline: presenting a new anhydrous polymorph. Cryst Growth Des. 2010;10(9):3879-86.
[9] Roy C, Vegagonzalez A, Subrapaternault P. Theophylline formulation by supercritical antisolvents. Int J Pharm. 2007;343(1-2):79-89.
[10] Yang D, Wang L, Yuan P, et al. Cocrystal virtual screening based on the XGBoost machine learning model. Chin Chem Lett. 2023;34(8): 107964.
[11] Xu J, Shi Q, Wang Y, et al. Recent advances in pharmaceutical cocrystals: a focused review of flavonoid cocrystals. Molecules. 2023;28(2):613.
[12] Guo M, Sun X, Chen J, et al. Pharmaceutical cocrystals: a review of preparations, physicochemical properties and applications. Acta Pharm Sin B. 2021;11(8):2537-64.
[13] Darwish S, Zeglinski J, Krishna GR, et al. A New 1:1 Drug-Drug Cocrystal of Theophylline and Aspirin: Discovery, Characterization, and Construction of Ternary Phase Diagrams. Cryst Growth Des. 2018;18(12):7526-32.
[14] Shaikh R, Walker GM, Croker DM. Continuous, simultaneous cocrystallization and formulation of theophylline and 4-aminobenzoic acid pharmaceutical cocrystals using twin screw melt granulation. Eur J Pharm Sci. 2019;137: 104981.
[15] Schultheiss N, Roe M, Boerrigter SXM. Cocrystals of nutraceutical p-coumaric acid with caffeine and theophylline: polymorphism and solid-state stability explored in detail using their crystal graphs. CrystEngComm. 2011;13(2):611-9.
[16] Cheney ML, Weyna DR, Shan N, et al. Coformer selection in pharmaceutical cocrystal development: a case study of a meloxicam aspirin cocrystal that exhibits enhanced solubility and pharmacokinetics. J Pharm Sci. 2011;100(6):2172-81.
[17] Aitipamula S, Wong ABH, Chow PS, et al. Cocrystallization with flufenamic acid: comparison of physicochemical properties of two pharmaceutical cocrystals. CrystEngComm. 2014;16(26):5793.
[18] Trask A, Motherwell W, Jones W. Physical stability enhancement of theophylline via cocrystallization. Int J Pharm. 2006;320(1-2):114-23.
[19] Hawkins BA, Du JJ, Lai F, et al. An experimental and theoretical charge density study of theophylline and malonic acid cocrystallization. R Soc Chem Adv. 2022;12(25):15670-84.
[20] Srivastava D, Fatima Z, Kaur CD. Multicomponent pharmaceutical cocrystals: a novel approach for combination therapy. Mini Rev Med Chem. 2018;18(14):1160-7.
[21] Thipparaboina R, Kumar D, Chavan RB, et al. Multidrug co-crystals: towards the development of effective therapeutic hybrids. Drug Discov Today. 2016;21(3):481-90.
[22] Sanphui P, Kumar SS, Nangia A. Pharmaceutical cocrystals of niclosamide. Cryst Growth Des. 2012;12(9):4588-99.
[23] Ervasti T, Aaltonen J, Ketolainen J. Theophylline-nicotinamide cocrystal formation in physical mixture during storage. Int J Pharm. 2015;486(1-2):121-30.
[24] Guinet Y, Paccou L, Hédoux A. Analysis of co-crystallization mechanism of theophylline and citric acid from Raman investigations in pseudo polymorphic forms obtained by different synthesis methods. Molecules. 2023;28(4):1605.
[25] Zhang S, Rasmuson ÅC. Thermodynamics and crystallization of the theophylline-glutaric acid cocrystal. Cryst Growth Des. 2013;13(3):1153-61.
[26] Das B, Baruah JB. Water bridged assembly and dimer formation in co-crystals of caffeine or theophylline with polycarboxylic acids. Cryst Growth Des. 2011;11(1):278-86.
[27] Dyulgerov V, Nikolova RP, Dimova LT, et al. 3-Carboxyphenylboronic acid-theophylline (1/1). Acta Crystallogr Sect E: Struct Rep Online. 2012;68(8):o2320-o2320.
[28] Abourahma H, Urban JM, Morozowich N, et al. Examining the robustness of a theophylline cocrystal during grinding with additives. CrystEngComm. 2012;14(19):6163.
[29] Heiden S, Tröbs L, Wenzel KJ, et al. Mechanochemical synthesis and structural characterisation of a theophylline-benzoic acid cocrystal (1:1). CrystEngComm. 2012;14(16):5128.
[30] Bučar DK, Henry RF, Zhang GGZ, et al. synthon hierarchies in crystal forms composed of theophylline and hydroxybenzoic acids: cocrystal screening via solution-mediated phase transformation. Cryst Growth Des. 2014;14(10):5318-28.
[31] TalwelkarShimpi M, Öberg S, Giri L, et al. Experimental and theoretical studies of molecular complexes of theophylline with some phenylboronic acids. R Soc Chem Adv. 2016;6(49):43060-8.
[32] Eddleston MD, Arhangelskis M, Fábián L, et al. Investigation of an amide-pseudo amide hydrogen bonding motif within a series of theophylline: amide cocrystals. Cryst Growth Des. 2016;16(1):51-8.
[33] Zhu B, Zhang Q, Wang J-R, et al. Cocrystals of Baicalein with higher solubility and enhanced bioavailability. Cryst Growth Des. 2017;17(4):1893-901.
[34] Sun J, Wang Y, Tang W, et al. Enantioselectivity of chiral dihydromyricetin in multicomponent solid solutions regulated by subtle structural mutation. Int Union Crystallogr J. 2023;10(2):164-76.
[35] Venkatesan P, Flores-Manuel F, Bernès S, et al. Structural and quantitative analysis of intermolecular solid-state interactions in cocrystals obtained from nucleobases and methylxanthines with gallic acid. J Mol Struct. 2023;1280: 135074.
[36] Aitipamula S, Chow PS, Tan RBH. Theophylline-gentisic acid (1/1). Acta Crystallogr Sect E: Struct Rep Online. 2009;65(9):o2126-7.
[37] Lu J, Rohani S. Preparation and characterization of theophylline-nicotinamide cocrystal. Org Process Res Dev. 2009;13(6):1269-75.
[38] Liu H, Chan HCS, Yu X, et al. Two polymorphic cocrystals of theophylline with ferulic acid. Cryst Growth Des. 2023;23(6):4448-59.
[39] Lu J, Cruz-Cabeza AJ, Rohani S, et al. A 2:1 sulfamethazine-theophylline cocrystal exhibiting two tautomers of sulfamethazine. Acta Crystallogr C. 2011;67(8):o306-9.
[40] Jafari MT, Rezaei B, Javaheri M. A new method based on electrospray ionisation ion mobility spectrometry (ESI-IMS) for simultaneous determination of caffeine and theophylline. Food Chem. 2011;126(4):1964-70.
[41] Jacobs A, Amombo Noa FM. Co-Crystals and co-crystal hydrates of vanillic acid. CrystEngComm. 2015;17(1):98-106.
[42] Goyal P, Rani D, Chadha R. Crystal engineering: a remedy to tailor the biopharmaceutical aspects of glibenclamide. Cryst Growth Des. 2018;18(1):105-18.
[43] Bommaka MK, Mannava MKC, Suresh K, et al. Entacapone: improving aqueous solubility, diffusion permeability, and cocrystal stability with theophylline. Cryst Growth Des. 2018;18(10):6061-9.
[44] Yeh KL, Lee T. Intensified crystallization processes for 1:1 drug-drug cocrystals of sulfathiazole-theophylline, and sulfathiazole-sulfanilamide. Cryst Growth Des. 2018;18(3):1339-49.
[45] Delori A, Galek PTA, Pidcock E, et al. Knowledge-based hydrogen bond prediction and the synthesis of salts and cocrystals of the anti-malarial drug pyrimethamine with various drug and GRAS molecules. CrystEngComm. 2013;15(15):2916.
[46] Deka P, Gogoi D, Althubeiti K, et al. Mechanosynthesis, characterization, and physicochemical property investigation of a favipiravir cocrystal with theophylline and GRAS coformers. Cryst Growth Des. 2021;21(8):4417-25.
[47] Surov AO, Voronin AP, Manin AN, et al. Pharmaceutical cocrystals of diflunisal and diclofenac with theophylline. Mol Pharm. 2014;11(10):3707-15.
[48] Mukaida M, Sato H, Sugano K, et al. Stability orders of acetaminophen and theophylline co-crystals determined by co-crystal former exchange reactions and their correlation within silico and thermal parameters. J Pharm Sci. 2017;106(1):258-63.
[49] Shefter E. Structural studies on complexes IV: crystal structure of a 1:1 5-chlorosalicylic acid and theophylline complex. J Pharm Sci. 1969;58(6):710-4.
[50] Shefter E, Sackman P. Structural studies on molecular complexes V: crystal structures of sulfathiazole—sulfanilamide and sulfathiazole—theophylline complexes. J Pharm Sci. 1971;60(2):282-6.
[51] Lu J, Rohani S. Synthesis and preliminary characterization of sulfamethazine-theophylline co-crystal. J Pharm Sci. 2010;99(9):4042-7.
[52] Abuhijleh AL, Ali HA, Emwas AH. Synthesis, spectral and structural characterization of dinuclear rhodium (II) complexes of the anticonvulsant drug valproate with theophylline and caffeine. J Organomet Chem. 2009;694(22):3590-6.
[53] Nakao S, Fujii S, Sakaki T, et al. The crystal and molecular structure of the 2:1 molecular complex of theophylline with phenobarbital. Acta Crystallogr Sect B: Struct Crystallogr Cryst Chem. 1977;33(5):1373-8.
[54] Neuvonen P, Kivisto K. The effects of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations. Br J Clin Pharmacol. 1991;32(2):215-20.
[55] Salas JM, Sanchez MP, Colacio E, et al. 8-Thiatheophylline nitrato silver (I): spectroscopic characterization and crystal structure. J Crystallogr Spectrosc Res. 1990;20(2):133-8.
[56] Giuseppetti G, Mazzi F, Tadini C, et al. Ambroxol theophylline-7-acetate salt monohydrate. Acta Crystallogr C. 1998;54(3):407-10.
[57] Biagini Cingi M, Manotti Lanfredi AM, Tiripicchio A. An anhydrous theophylline-copper (I) chloride compound, [Cu(C₇H₈N₄O₂)₂Cl₂]. Acta Crystallogr C. 1983;39(11):1523-5.
[58] Lou B, He F. Coordination polymers as potential solid forms of drugs: three zinc (II) coordination polymers of theophylline with biocompatible organic acids. New J Chem. 2013;37(2):309-16.
[59] Horn E, Botello AF, Salas JM, et al. Crystal structure of hexaaquocobalt (II) theophylline-7-acetate tetrahydrate, [Co(OH₂)₆][C₉H₉N₄O₄]₂·4H₂O. Zeitschrift Kristallogr New Crystal Struct. 2000;215(3):441-2.
[60] Bujdošová Z, Győryová K, Růžička A, et al. Crystal structures of two aromatic zinc (II) carboxylates: [Zn(4-Chlorosalicylato)₂(H₂O)₄]·2theophylline·(H₂O)₂ and Unique [Zn(5-Chlorosalicylato)₂ (Isonicotinamide)₂(H₂O)]. J Chem Crystallogr. 2011;41(7):1077-84.
[61] Hao XM, Zhao S, Wang H, et al. In vitro release of theophylline and cytotoxicity of two new metal-drug complexes. Polyhedron. 2018;142:38-42.
[62] Aoki K, Hoshino M, Okada T, et al. Interligand interactions affecting specific metal bonding to nucleic acid bases: X-ray crystal structure of tetrakis-μ-acetamidatobis (Theophylline) Rhodium (II)-Rhodium (III) Nitrate Monohydrate. J Chem Soc Chem Commun. 1986(4):314-316.
[63] Colacio E, Cuesta R, Ghazi M, et al. Metal-purine interactions: homo- and heterodinuclear platinum (II) and/or palladium (II) complexes of 8-thiotheophylline crystal structures of [Pt(μ-TT)(Dppm)]2·2DMSO and [(Dppm)Pt(μ-TT)2 Pd(Dppm)]·7H2O. Inorgan Chem. 1997;36(8):1652-6.
[64] Majodina S, Ndima L, Abosede OO, et al. Physical stability enhancement and antimicrobial properties of a sodium ionic cocrystal with theophylline. CrystEngComm. 2021;23(2):335-52.
[65] Griffitn E, Amma E. Reaction of PtCl₂- with theophylline:X-Ray crystal structures of bis (theophyllinium) tetrachloroplatinate (II) and theophyllinium trichlorotheophyllineplatinate (II). J Chem Soc, Chem Commun. 1979;7:322-4.
[66] Gardner MJ, Smith RX, Shefter E. Zn (II)-theophylline-ethylenediamine: structure and pH stability. J Pharm Sci. 1983;72(4):348-50.
[67] Yang D, Wang H, Liu Q, et al. Structural landscape on a series of Rhein: Berberine cocrystal salt solvates: the formation, dissolution elucidation from experimental and theoretical investigations. Chin Chem Lett. 2022;33(6):3207-11.
[68] Smit JP, Hagen EJ. Polymorphism in caffeine citric acid cocrystals. J Chem Crystallogr. 2015;45(3):128-33.
[69] Sarma B, Saikia B. Hydrogen bond synthon competition in the stabilization of theophylline cocrystals. CrystEngComm. 2014;16(22):4753-65.
[70] Friščić T, Fábián L, Burley JC, et al. Exploring cocrystal-cocrystal reactivity via liquid-assisted grinding: the assembling of racemic and dismantling of enantiomeric cocrystals. Chem Commun. 2006;48:5009-11.
[71] Xia M, Jiang Y, Cheng Y, et al. Rucaparib cocrystal: improved solubility and bioavailability over camsylate. Int J Pharm. 2023;631: 122461.
[72] Hopkins ME, MacKenzie-Ross RV. Case report: the risks associated with chronic theophylline therapy and measures designed to improve monitoring and management. BMC Pharmacol Toxicol. 2016;17(1):13.
[73] Kacirova I, Grundmann M. TDM of theophylline and digoxin as an indicator of the quality of medical care: results of the 7-years monitoring. Clin Ther. 2017;39(8):e83-4.
[74] Bhatt PM, Ravindra NV, Banerjee R, et al. Saccharin as a salt former enhanced solubilities of saccharinates of active pharmaceutical ingredients. Chem Commun. 2005;8:1073-5.
[75] Haeria ANN, Ismail I. Characterization and dissolution test of aspirin-nicotinamide cocrystal. SubStance. 2015;4(5):8-12.
[76] Liu H, Chan HCS, Zhang L, et al. The molecular mechanisms of plasticity in crystal forms of theophylline. Chin Chem Lett. 2023;34(8): 108057.
[77] Wang H, Yang D, Zhang W, et al. An innovative Rhein-Matrine cocrystal: synthesis, characterization, formation mechanism and pharmacokinetic study. Chin Chem Lett. 2023;34(2): 107258.
[78] Srinivas K, King JW, Howard LR, et al. Solubility and solution thermodynamic properties of quercetin and quercetin dihydrate in subcritical water. J Food Eng. 2010;100(2):208-18.
[79] Li W, Pi J, Zhang Y, et al. A strategy to improve the oral availability of Baicalein: the Baicalein-theophylline cocrystal. Fitoterapia. 2018;129:85-93.
[80] Hino T, Ford JL, Powell MW. Assessment of nicotinamide polymorphs by differential scanning calorimetry. Thermochim Acta. 2001;374(1):85-92.
[81] Shiraki K, Daikoku T. Favipiravir, an anti-influenza drug against life-threatening RNA virus infections. Pharmacol Ther. 2020;209: 107512.
[82] Tomita K, Takano T. Interaction of flufenamic acid on ethanol metabolism in rat. Ind Health. 1992;30(2):85-95.
[83] Song MK. The role of PARP inhibitors in ovarian cancer: therapeutic mechanisms and clinical data. Eur J Gynaecol Oncol. 2021;42(2):199.
[84] Syed YY. Rucaparib: first global approval. Drugs. 2017;77(5):585-92.
[85] Newman AW, Childs SL, Cowans BA. Salt and cocrystal form selection. preclinical development handbook: ADME and biopharmaceutical properties. 2008:455-481.
[86] Stanton SA, Du JJ, Lai F, et al. Understanding hygroscopicity of theophylline via a novel cocrystal polymorph: a charge density study. J Phys Chem A. 2021;125(45):9736-56.
[87] Otsuka M, Kaneniwa N, Kawakami K, et al. Effect of surface characteristics of theophylline anhydrate powder on hygroscopic stability. J Pharm Pharmacol. 2011;42(9):606-10.
[88] Huang S, Xue Q, Xu J, et al. Simultaneously improving the physicochemical properties, dissolution performance, and bioavailability of apigenin and daidzein by co-crystallization with theophylline. J Pharm Sci. 2019;108(9):2982-93.
[89] Wilson RH, Evans TJ, Middleton MR, et al. A phase I study of intravenous and oral rucaparib in combination with chemotherapy in patients with advanced solid tumours. Br J Cancer. 2017;116(7):884-92.
[90] Shapiro GI, Kristeleit RS, Burris HA, et al. Pharmacokinetic study of rucaparib in patients with advanced solid tumors. Clin Pharmacol Drug Dev. 2019;8(1):107-18.
[91] Li-Weber M. New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat Rev. 2009;35(1):57-68.
[92] Sato D, Kondo S, Yazawa K, et al. The potential anticancer activity of extracts derived from the roots of scutellaria baicalensis on human oral squamous cell carcinoma cells. Mol Clin Oncol. 2013;1(1):105-11.
[93] Abosede OO, Gordon AT, Dembaremba TO, et al. Trimesic acid-theophylline and isopthalic acid-caffeine cocrystals: synthesis, characterization, solubility, molecular docking, and antimicrobial activity. Cryst Growth Des. 2020;20(5):3510-22.

Recent advances in pharmaceutical cocrystals of theophylline

Recent advances in pharmaceutical cocrystals of theophylline

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