SOLID-STATE PROPERTIES AND SOLUBILITY STUDIES OF NOVEL PHARMACEUTICAL COCRYSTAL OF ITRACONAZOLE


Stevanus Hiendrawan, Bambang Veriansyah, Raymond R. Tjandrawinata

Abstract


Objective: Pharmaceutical cocrystal is a promising method to improve the solubility of active pharmaceutical ingredients (APIs). Itraconazole (ITZ) is a BCS class II antifungal drug with poor aqueous solubility, therefore an attempt was made to improve the solubility of ITZ using cocrystallization technique. In this work, six novel pharmaceutical cocrystals of ITZ with various coformers, including 4-hydroxybenzoic acid (4HBA), trans-cinnamic acid (TCA), suberic acid (SUB), sebacic acid (SBC), 1-hydroxy-2-naphthoic acid (1H2N), and benzamide (BZD) were prepared.

Methods: ITZ cocrystals was prepared by solvent evaporation process. The cocrystals produced were characterized using powder x-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and fourier transform infrared (FTIR) spectroscopy. Solubility analysis was performed to evaluate the cocrystals.

Results: PXRD and DSC analysis revealed that the pattern of all ITZ cocrystals was distinguishable from the individual compounds which indicates the formation of new phase. The solubility of ITZ and its cocrystals from highest to lowest after 24 h in 0.1 N HCl solution (pH 1.2) follows the order ITZ-TCA (1.97-fold), ITZ-SBC (1.09-fold), ITZ, ITZ-1H2N (0.58-fold) and ITZ-4HBA (0.46-fold).

Conclusion: This study demonstrates that the selection of coformers has pronounced an impact on the physicochemical properties of ITZ. Based on this study, it can be concluded that cocrystallization offers a valuable way to improve the solubility of ITZ.


Keywords


Crystal engineering; Cocrystal; Itraconazole; Solubility

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References


De Beule K. Itraconazole: pharmacology, clinical experience and future development. Int J Antimicrob Agents 1996;6:175-81.

Peeters J, Nesskens P, Tollenaere JP, Van Remoortere P, Brewster ME. Characterization of the interaction of 2-hydroxypropyl-β-cyclodextrin with itraconazole at pH 2, 4, and 7. J Pharm Sci 2002;91:1414-22.

Lee SY, Jung S, Kim JK, Lim GB, Ryu JH. Preparation of itraconazole/HP-β-CD inclusion complexes using supercritical aerosol solvent extraction system and their dissolution characteristics. J Supercrit Fluids 2008;44:400-8.

Janssens S, Roberts C, Smith EF, Van der Mooter G. Physical stability of ternary solid dispersions of itraconazole in polyethyleneglycol 6000/hydroxypropylmethylcellulose 2910 E5 blends. Int J Pharm 2008;355:100-7.

Hong JY, Kim JK, Song YK, Park JS, Kim CK. A new self-emulsifying formulation of itraconazole with improved dissolution and oral absorption. J Controlled Release 2006;110:332-8.

Mellaerts R, Mols R, Jammaer JAG, Aerts CA, Annaert P, Van Humbeeck J, et al. Increasing the oral bioavailability of the poorly water-soluble drug itraconazole with ordered mesoporous silica. Eur J Pharm Biopharm 2008;69:223-30.

Domingos S, Andre V, Quaresma S, Martins ICB, Piedade MFM, Duarte MT. New forms of old drugs: improving without changing. J Pharm Pharmacol 2015;67:830-46.

Zhang S, Lee TWY, Chow AHL. Crystallization of itraconazole polymorphs from melt. Cryst Growth Des 2016;16:3791-801.

Zhang S, Britten JF, Chow AHL, Lee TWY. Impact of crystal structure and polymer excipients on the melt crystallization kinetics of itraconazole polymorphs. Cryst Growth Des 2017;17:3433–42.

Serajuddin ATM. Salt formation to improve drug solubility. Adv Drug Delivery 2007;1285:603-16.

Mittapalli S, Mannava MKC, Kandavilli UBR, Allu S, Nangia A. Soluble salts and cocrystals of clotrimazole. Cryst Growth Des 2015;15:2493-504.

Srirambhatla VK, Kraft A, Watt S, Powell AV. Crystal design approaches for the synthesis of paracetamol co-crystals. Cryst Growth Des 2012;12:4870-9.

Bolla G, Sanphui P, Nangia A. Solubility advantage of tenoxicam phenolic cocrystals compared to salts. Cryst Growth Des 2013;13:1988-2003.

Stephenson GA, Aburub A, Woods TA. Physical stability of salts of weak bases in the solid-state. J Pharm Sci 2011;100:1607-17.

Aitipamula S, Banerjee R, Bansal AK, Biradha K, Cheney ML, Choudhury AR, et al. Polymorphs, salts, and cocrystals: what's in a name? Cryst Growth Des 2012;12:2147-52.

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;7:160-4.

Gao Y, Gao J, Liu Z, Kan H, Zu H, Sun W, et al. Coformer selection based on degradation pathway of drugs: a case study of adefovir dipivoxil-saccharin and adefovir dipivoxil-nicotinamide cocrystals. Int J Pharm 2012;438:327-35.

Wang ZZ, Chen JM, Lu TB. Enhancing the hygroscopic stability of S-Oxiracetam via pharmaceutical cocrystal. Cryst Growth Des 2012;12:4562-6.

Hiendrawan S, Veriansyah B, Widjojokusumo E, Soewandhi SN, Wikarsa S, Tjandrawinata RR. Simultaneous cocrystallization and micronization of paracetamol-dipicolinic acid cocrystal by supercritical antisolvent (SAS). Int J Pharm Pharm Sci 2016;8:89-98.

Cheney ML, Shan N, Healey ER, Hanna M, Wojtas L, Zaworotko MJ, et al. Effects of crystal form on solubility and pharmacokinetics: a crystal engineering case study of lamotrigine. Cryst Growth Des 2010;10:394-405.

Trask AV. An overview of pharmaceutical cocrystals as intellectual property. Mol Pharm 2007;4:301-9.

Remenar JF, Morissette SL, Peterson ML, Moulton B, MacPhee JM, Guzmán HR, et al. Crystal engineering of novel cocrystals of a triazole drug with 1,4-dicarboxylic acids. J Am Chem Soc 2003;125:8456-7.

Tarsa PB, Towler CS, Woollam G, Berghausen J. The influence of aqueous content in small-scale salt screening—improving hit rate for weakly basic, low solubility drugs. Eur J Pharm Sci 2010;41:23-30.

Kumar N, Shishu, Bansal G, Kumar S, Jana AK. Ditosylate salt of itraconazole and dissolution enhancement using cyclodextrins. AAPS PharmSciTech 2012;13:863-74.

Shevchenko S, Miroshnyk I, Pietila LO, Haarala J, Salmia J, Sinervo K, et al. Diversity in itraconazole cocrystals with aliphatic dicarboxylic acids of varying chain length. Cryst Growth Des 2013;13:4877-84.

Munde AV, Kumar FN, Radheshyam BK. Co-crystallization: an alternative approach for solid modification. J Drug Ther 2013;3:166-72.

Cruz-Cabeza AJ. Acid-base crystalline complexes and the pKa rule. Cryst Eng Comm 2012;14:6362-5.

Hiendrawan S, Veriansyah B, Widjojokusumo E, Soewandhi SN, Wikarsa S, Tjandrawinata RR. Physicochemical and mechanical properties of paracetamol cocrystal with 5-nitroisophthalic acid. Int J Pharm 2016;497:106-13.

Huang Y, Zhang B, Gao Y, Zhang J, Shi L. Baicalein–nicotinamide cocrystal with enhanced solubility, dissolution, and oral bioavailability. J Pharm Sci 2014;103:2330-7.

Mulye SP, Jamadar SA, Karekar PS, Pore YV, Dhawale SC. Improvement in physicochemical properties of ezetimibe using a crystal engineering technique. Powder Technol 2012;222:131-8.

Perlovich GL. Thermodynamic characteristics of cocrystal formation and melting points for rational design of pharmaceutical two-component systems. Cryst Eng Comm 2015;17:7019-28.

Stanton MK, Bak A. Physicochemical properties of pharmaceutical co-crystals: a case study of ten AMG 517 co-crystals. Cryst Growth Des 2008;8:3856-62.

Jenniffer IAG, Dea HR, Rojas HM, Hopfl H. Interrelation of the dissolution behavior and solid-state features of acetazolamide cocrystals. Eur J Pharm Sci 2017;96:299-308.

Chadha R, Saini, Jain ADS, Venugopalan P. Preparation and solid-state characterization of three novel multicomponent solid forms of oxcarbazepine: improvement in solubility through saccharin cocrystal. Cryst Growth Des 2012;12:4211-24.

Demiana IN. Formulation and evaluation of itraconazole via liquid crystal for topical delivery system. J Pharm Biomed Anal 2001;26:387-99.

Brittain HG. Vibrational spectroscopic studies of cocrystals and salts.3. cocrystal products formed by benzenecarboxylic acids and their sodium salts. Cryst Growth Des 2010;10:1990-2003.

Luo YH, Sun BW. Pharmaceutical co-crystals of pyrazinecarboxamide (PZA) with various carboxylic acids: crystallography, hirshfeld surfaces, and dissolution study. Cryst Growth Des 2013;13:2098-106.

Chow SF, Shi L, Ng WW, Leung KHY, Nagapudi K, Sun CC, et al. Kinetic entrapment of a hidden curcumin cocrystal with phloroglucinol. Cryst Growth Des 2014;14:5079-89.

Goud NR, Gangavaram S, Suresh K, Pal S, Manjunatha SG, Nambiar S, et al. Novel furosemide cocrystals and selection of high solubility drug forms. J Pharm Sci 2012;101:664-80.

Maddileti D, Jayabun SK, Nangia A. Soluble cocrystals of the xanthine oxidase inhibitor febuxostat. Cryst Growth Des 2013;13:3188-96.




About this article

Title

SOLID-STATE PROPERTIES AND SOLUBILITY STUDIES OF NOVEL PHARMACEUTICAL COCRYSTAL OF ITRACONAZOLE

Keywords

Crystal engineering; Cocrystal; Itraconazole; Solubility

DOI

10.22159/ijap.2018v10i5.26663

Date

08-09-2018

Additional Links

Manuscript Submission

Journal

International Journal of Applied Pharmaceutics
Vol 10, Issue 5 (Sep-Oct), 2018 Page: 97-104

Online ISSN

0975-7058

Authors & Affiliations

Stevanus Hiendrawan
Dexa Laboratories of Biomolecular Sciences, Cikarang 17550, West Java, Indonesia
Indonesia

Bambang Veriansyah
Dexa Laboratories of Biomolecular Sciences, Cikarang 17550, West Java, Indonesia
Indonesia

Raymond R. Tjandrawinata
Dexa Laboratories of Biomolecular Sciences, Cikarang 17550, West Java, Indonesia
Indonesia


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