In vitro dissolution profile study of mucolytic drug ambroxol hydrochloride from solid oral dosage form by UHPLC-MS/MS

Main Article Content

Maja M. Vujović
Milan Jokanović
Goran M. Nikolić

Abstract

In this paper, a simplified dissolution test was performed for the release of ambroxol from tablets according to the European Pharmacopoeia. In vitro, three different dissolution media; 0.1 M HCl pH 1.2, acetate buffer (ABS) pH 4.5 and phosphate buffer (PBS) pH 6.8 were used for the simulation of the gastrointestinal conditions at temperature of 37.0±0.5 °C. The drug release was evaluated by a new ultra-high performance liquid chromato­graphy (UHPLC)-tandem mass spectrometry (MS/MS) method. The method was validated to meet requirements as per ICH guidelines which include linearity, specificity, precision, accuracy and robustness. The corresponding dissolution profiles showed more than 80% drug release within 30 min without significant differences. Further, the developed and vali­dated UHPLC-MS/MS method could find a useful application in the process of production, quality control and bioavailability/bioequivalence studies of new pharmaceutical formul­ations of drugs in order to achieve a safe therapeutic efficacy.

Downloads

Download data is not yet available.

Article Details

How to Cite
Vujović, M. M., Jokanović, M., & Nikolić, G. M. (2017). In vitro dissolution profile study of mucolytic drug ambroxol hydrochloride from solid oral dosage form by UHPLC-MS/MS. HEMIJSKA INDUSTRIJA (Chemical Industry), 71(1), 75–83. https://doi.org/10.2298/HEMIND160315020V
Section
General

References

Material Safety Data Sheet Ambroxol Hydrochloride MSD, http://www.sciencelab.com/msds.php?msdsId= =9922869 (accessed 7 March 2016).

S. Budavari, The Merck Index: An Encyclopedia of Chemicals, Drugs and Biologicals. 13th ed., Merck Research Laboratories Division of Merck and Co., Inc., Whitehouse Station, NJ, 2001, pp. 67–68.

M. Malerba, B. Ragnoli, Ambroxol in the 21st century: pharmacological and clinical update, Expert Opin. Drug Metab. Toxicol. 4 (2008) 1119–1129.

T. Weiser, Ambroxol: A CNS Drug?, CNS Neurosci. Ther. 14 (2008) 17–24.

S. Püschmann, R. Engelhorn, Pharmacological study on the bromhexine metabolit ambroxol. Arzneimittel-forschung. 28 (1978) 889–898.

K.F. Klier, U. Papendick, The local anaesthetic effect of eye drops containing NA 872. Die lokalanaesthetische Wirkung von NA–872–haltigen Augentropfen, Med. Monatsschr. 31 (1977) 575.

V. Štětinová, V. Herout, J. Květina, In vitro and in vivo antioxidant activity of ambroxol, Clin. Exp. Med. 4 (2004) 152–158.

D. Nowak, G. Pierscinski, J. Drzewoski, Ambroxol inhibits doxorubicin-induced lipid peroxidation in heart of mice. Free Radic. Biol. Med. 19 (1995) 659–663.

B.F. Gibbs, W. Schmutzler, I.B. Vollrath, P. Brosthardt, U. Braam, H.H. Wolff, G. Zwadlo-Klarwasser, Ambroxol inhibits the release of histamine, leukotrienes and cyto-kines from human leukocytes and mast cells, Inflamm. Res. 48 (1999) 86–93.

T. Weiser, Comparison of the effects of four Na+ chan-nel analgesics on TTX-resistant Na+ currents in rat sen-sory neurons and recombinant Nav1.2 channels, Neuro-sci. Lett. 395 (2006) 179–184.

M. Hafez, M. Aboulwafa, M. Yassien, N. Hassouna, Acti-vity of some mucolytics against bacterial adherenceto mammalian cells. Appl. Biochem. Biotechnol. 158 (2009) 97–112.

F. Li, J. Yu, H. Yang, Z. Wan, D. Bai, Effects of ambroxol on alginate of mature Pseudomonas aeruginosa Bio-films, Curr. Microbiol. 57 (2008) 1–7.

B. Yang, D. F. Yao, M. Ohuchi, M. Ide, M. Yano, Y. Oku-mura, H. Kido, Ambroxol suppresses influenza–virus proliferation in the mouse airway by increasing antiviral factor levels, Eur. Respir. J. 19 (2002) 952–958.

G.M. Hadad, A. El-Gindy, W.M.M. Mahmoud, HPLC and chemometrics–assisted UV spectroscopy methods for the simultaneous determination of ambroxol and doxy-cycline in capsule, Spectrochim. Acta, A-M 70 (2008) 655–663.

K.A. Shaikh, S.D. Patil, A.B. Devkhile, Development and validation of a reversed-phase HPLC method for simul-taneous estimation of ambroxol hydrochloride and azi-thromycin in tablet dosage form, J. Pharm. Biomed. Anal. 48 (2008) 1481–1484.

F.J. Flores-Murrieta, C. Hoyo-Vadillo, E. Hong, G. Casta-neda-Hernandez, Assay of ambroxol in human plasma by high-performance liquid chromatography with amp-ero¬metric detection, J. Chromatogr. Biomed. Appl. 490 (1989) 464–469.

L. Colombo, F. Marcucci, Determination of ambroxol in biological material by gas chromatography with elec-tron-capture detection. J. Chromatogr. Biomed. Appl. 530 (1990) 141–147.

E. Satana, H. Basan, N.G. Goger, Determination of amb-roxol hydrochloride in tablets using flow-injection UV spectrophotometry and HPLC, J. Anal. Chem. 63 (2008) 451–454.

T. Pérez-Ruiz, C. Martínez-Lozano, A. Sanz, E. Bravo, Determination of bromhexine and ambroxol in pharma-ceutical dosage forms, urine and blood serum. J. Chro-matogr., B 692 (1997) 199–205.

F.S. Felix, C.M.A. Brett, L. Angnes, Flow injection analysis using carbon film resistor electrodes for amperometric determination of ambroxol, Talanta 76 (2008) 128–133.

A. Levent, Y. Yardım, Z. Sentürk, Electrochemical per-form¬ance of boron-doped diamond electrode in surfact-ant-containing media for ambroxol determination, Sen-sors Actuators, B: Chem. 203 (2014) 517–526.

T. Hang, M. Zhang, M. Song, J. Shen, Y. Zhang, Simul-taneous determination and pharmacokinetic study of roxithromycin and ambroxol hydrochloride in human plasma by LC–MS/MS, Clin. Chim. Acta. 382 (2007) 20–

–24.

X. Dong, L. Ding, X. Cao, L. Jiang, S. Zhong, A sensitive LC–MS/MS method for the simultaneous determination of amoxicillin and ambroxol in human plasma with seg-mental monitoring, Biomed. Chromatogr. 27 (2013) 520–526.

W. Hu, Y. Xu, F. Liu, A. Liu, Q. Guo, Rapid and sensitive liquid chromatography tandem mass spectrometry method for the quantification of ambroxol in human plasma, Biomed. Chromatogr. 22 (2008) 1108–1114.

M.M. Vujović, M. Jokanović, G.M. Nikolić, Development of a new ultra-high performance liquid chromatography--tandem mass spectrometry method for determination of ambroxol hydrochloride in serum with pharmaco¬kinetic application, Hem. Ind. 70 (2016) 409–418.

H. Zhang, L. Yu, Dsissolution testing for solid oral drug products: Theoretical Cosiderations, Am. Pharm Rev. 7 (2005) 26–31.

United States Pharmacopeia (USP): <711> Dissolution Test USP 28, 2nd Supplement, 2009.

FDA/CDER, Guidance for Industry, Dissolution testing of immediate release solid oral dosage forms, 1997.

European Pharmacopoeia (Ph. Eur.): 6th ed. (official on January 2008), Dissolution Test (reference 01/2008: 20903).

Japanese Pharmacopoeia (JP): 6.10 Dissolution Test as it appears in Supplement I to the JP Fifteenth Edition (September 28, 2007), The Ministerial Notification No. 316.

British Pharmacopoeia (BP), 5th ed., 2007.

International Harmonized Tripartite Guideline (ICH)/ /World Health Organization (WHO), Validation of Ana-lytical Procedures: Text and Methodology, Q2(R1), cur-rent step 4 version, parent guidelines on methodology dated November 6, 1996, incorporated in November 2005.

Similar Articles

You may also start an advanced similarity search for this article.