Crystal Transition and Drug-excipient Compatibility of Clarithromycin in Sustained Release Tablets

Author(s): Yu Li*, Xiangwen Kong, Fan Hu

Journal Name: Current Pharmaceutical Analysis

Volume 16 , Issue 7 , 2020

DOI : 10.2174/1573412915666190328234326

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Graphical Abstract:


Abstract:

Background: Clarithromycin is widely used for infections of helicobacter pylori. Clarithromycin belongs to polymorphic drug. Crystalline state changes of clarithromycin in sustained release tablets were found.

Objective: The aim of this study was to find the influential factor of the crystal transition of clarithromycin in preparation process of sustained-release tablets and to investigate the possible interactions between the clarithromycin and pharmaceutical excipients.

Methods and Results: The crystal transition of active pharmaceuticals ingredients from form II to form I in portion in clarithromycin sustained release tablets were confirmed by x-ray powder diffraction. The techniques including differential scanning calorimetry and infrared spectroscopy, x-ray powder diffraction were used for assessing the compatibility between clarithromycin and several excipients as magnesium stearate, lactose, sodium carboxymethyl cellulose, polyvinyl-pyrrolidone K-30 and microcrystalline cellulose. All of these methods showed compatibilities between clarithromycin and the selected excipients. Alcohol prescription simulation was also done, which showed incompatibility between clarithromycin and concentration alcohol.

Conclusion: It was confirmed that the reason for the incompatibility of clarithromycin with high concentration of alcohol was crystal transition.

Keywords: Clarithromycin, compatibility, differential scanning calorimetry, x-ray powder diffraction, infrared spectroscopy.

[1]
Sherman, D.; Xiong, L.; Mankin, A.S.; Melman, A. Synthesis and biological investigation of new 4′'-malonyl tethered derivatives of erythromycin and clarithromycin. Bioorg. Med. Chem. Lett., 2006, 16(6), 1506-1509.
[http://dx.doi.org/10.1016/j.bmcl.2005.12.033] [PMID: 16387493]
[2]
Inukai, K.; Takiyama, K.; Noguchi, S.; Iwao, Y.; Itai, S. Effect of gel formation on the dissolution behavior of clarithromycin tablets. Int. J. Pharm., 2017, 521(1-2), 33-39.
[http://dx.doi.org/10.1016/j.ijpharm.2017.01.065] [PMID: 28196716]
[3]
Spanton, S.G.; Henry, R.F.; Riley, D.A.; Liu, J.H. crystal form 0 of clarithromycin. u.s. patent 5,945,405, august 31, 1999.
[4]
Liu, J.H.; Riley, D.A.; Spanton, S.G. crystal form i of clarithromycin. u.s. patent 5,858,986, 1999. january 12.
[5]
Liu, J.H.; Rlley, D.A. preparation of crystal form ii of clarithromycin. u.s. patent 5,844,105, 1996.july 29,
[6]
Liu, J.H.; Henry, R.F.; Spanton, S.G. 6-o-methylerythromy-cin a crystal form iii. u.s. patent 6,627,743 b1,, december 31999.
[7]
Avrutov, I.; Lifshitz, I.; Borochovitz, R.; Masarwa, B.; Schwartz, E. processes for preparing clarithromycin polymorphs and novel polymorph iv. u.s. patent 6,599,884 b2, 2000. december 15
[8]
Gruss, M. polymorph of clarithromycin (form v). wo patent 2008/119543 a1, 2008.october 9,
[9]
Parvez, M.; Arayne, M.S.; Sabri, R.; Sultana, N. Clarithromycin hydrochloride 3.5-hydrate. Acta Crystallogr. C, 2000, 56(9), e398-e399.
[http://dx.doi.org/10.1107/S0108270100010490]
[10]
Iwasaki, H.; Sugawara, Y.; Adachi, T.; Morimoto, S.; Watanabe, Y. Structure of 6-O-methylerythromycin A (clarithromycin). Acta Crystallogr. C, 1993, C49, 1227-1230.
[http://dx.doi.org/10.1107/S0108270193000186]
[11]
Tozuka, Y.; Ito, A.; Seki, H.; Oguchi, T.; Yamamoto, K. Characterization and quantitation of clarithromycin polymorphs by powder X-ray diffractometry and solid-state NMR spectroscopy. Chem. Pharm. Bull. (Tokyo), 2002, 50(8), 1128-1130.
[http://dx.doi.org/10.1248/cpb.50.1128] [PMID: 12192153]
[12]
Jackson, K.; Young, D.; Pant, S. Drug-excipient interactions and their affect on absorption. Pharm. Sci. Technol. Today, 2000, 3(10), 336-345.
[http://dx.doi.org/10.1016/S1461-5347(00)00301-1] [PMID: 11050458]
[13]
Tiţa, B.; Fuliaş, A.; Bandur, G.; Marian, E.; Tiţa, D. Compatibility study between ketoprofen and pharmaceutical excipients used in solid dosage forms. J. Pharm. Biomed. Anal., 2011, 56(2), 221-227.
[http://dx.doi.org/10.1016/j.jpba.2011.05.017] [PMID: 21665404]
[14]
Chadha, R.; Bhandari, S. Drug-excipient compatibility screening--role of thermoanalytical and spectroscopic techniques. J. Pharm. Biomed. Anal., 2014, 87, 82-97.
[http://dx.doi.org/10.1016/j.jpba.2013.06.016] [PMID: 23845418]
[15]
Bruni, G.; Amici, L.; Berbenni, V.; Marini, A.; Orlandi, A. Drugexcipient compatibility studies: Search of interaction indicators. J. Therm. Anal. Calorim., 2002, 68(2), 561-573.
[http://dx.doi.org/10.1023/A:1016052121973]
[16]
Marini, A.; Berbenni, V.; Moioli, S.; Bruni, G.; Cofrancesco, P.; Margheritis, C.; Villa, M. Drug excipient compatibility studies by phsico-chemical techniques: The case of indomethacin. J. Therm. Anal. Calorim., 2003, 73, 529-545.
[http://dx.doi.org/10.1023/A:1025426012578]
[17]
Marini, A.; Berbenni, V.; Pegoretti, M.; Bruni, G.; Cofrancesco, P.; Sinistri, C.; Villa, M. Drug excipient compatibility studies by phsico chemical techniques: The case of atenolo. J. Therm. Anal. Calorim., 2003, 73(2), 547-561.
[http://dx.doi.org/10.1023/A:1025478129417]
[18]
Gao, R.; Jin, Y.; Yang, Q.Y.; Sun, B.W.; Lin, J. Study of stability and drug-excipient compatibility of estradiol and pharmaceutical excipients. J. Therm. Anal. Calorim., 2014, 120(1), 839-845.
[http://dx.doi.org/10.1007/s10973-014-4234-0]
[19]
Ding, T.; Chen, L.; Zhai, L.H.; Fu, Y.; Sun, B.W. Compatibility study of rivaroxaban and its pharmaceutical excipients. J. Therm. Anal. Calorim., 2017, 130(3), 1569-1573.
[http://dx.doi.org/10.1007/s10973-017-6412-3]
[20]
Manniello, M.D.; Del Gaudio, P.; Aquino, R.P.; Russo, P. Clarithromycin and N-acetylcysteine co-spray-dried powders for pulmonary drug delivery: A focus on drug solubility. Int. J. Pharm., 2017, 533(2), 463-469.
[http://dx.doi.org/10.1016/j.ijpharm.2017.03.079] [PMID: 28377314]


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Article Details

VOLUME: 16
ISSUE: 7
Year: 2020
Published on: 17 August, 2020
Page: [950 - 959]
Pages: 10
DOI: 10.2174/1573412915666190328234326
Price: $65

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