Rational Pharmacotherapy in Cardiology

Advanced search

Assessment of in Vitro Comparative Dissolution Kinetics of Moxonidine Products as a Factor Potentially Determining Effectiveness of Antihypertensive Treatment

Full Text:


Aim. Investigation of comparative dissolution kinetics of generic medicinal products containing moxonidine versus reference drug. Material and methods. Objects of the research were film-coated tablets containing moxonidine (INN) in a dose 0.4 mg: a reference drug Physiotens® and 4 generic drugs. In vitro dissolution test of moxonidine from the study drugs was performed using comparative dissolution kinetics test (CDKT). The CDKT was performed in the media with the following pH: 1.2 (1:9 mixture of 0.1 M hydrochloric acid and water), 4.5 (acetate buffer solution, prepared as per State Pharmacopoeia, XIII), and 6.8 (phosphate buffer solution, prepared as per State Pharmacopoeia, XIII). The sampling for dissolved moxonidine was performed 5, 10, 15, 20, and 30 min after the test was started. An high performance liquid chromatography method with ultraviolet detection at 220 nm was used to assay. Results. Within 15 min more that 85% of moxonidine dissolved from the reference drug and all study drugs at pH 1.2; dissolution profiles were similar without calculation of similarity factor f2. Similarly, at pH 4.5 dissolution profiles of study drugs #2 and #3 were similar to that of the reference drug, and the similarity factor f2 was not calculated. However, in case of study drugs #1 and #4 significant differences were observed at a single time point (15 min), which suggests that their dissolution profiles are non-similar to that of the reference drug. Similarity factors f2 were calculated 17.52 and 35.30, respectively (less than 50). At pH 6.8 similarity factors f2 for all study generic drugs were also less than 50 (23.8, 49.8, 38.6, and 35.9), so their dissolution curves were non-similar to that of reference drug. Conclusion. In our study we observed difference in release in vitro of medicinal products containing moxonidines: none of the study drugs was fully similar to the reference drug in all media. The differences observed at pH 6.8 were noteworthy, where the samples had or faster kinetics (study drugs #2 and #3), or slower dissolution kinetics (test drugs #1 and #4). Observed differences in moxonidine release rate may impact absorption of active pharmaceutical ingredient into the blood following drug administration.

About the Authors

G. V. Ramenskaya
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation
D.Sc.Pharm., Prof., Head of Chair of Pharmaceutical and Toxicological Chemistry named after A.P. Arzamastsev

I. E. Shokhin
Center of Pharmaceutical Analytics
Russian Federation
D.Sc.Pharm., General Director

N. I. Gaponova
A.I. Evdokimov Moscow State University of Medicine and Dentistry
Russian Federation
MD, PhD, Professor, Chair of Emergency Medicine

V. R. Abdrakhmanov
A.I. Evdokimov Moscow State University of Medicine and Dentistry
Russian Federation
MD, PhD, Professor, Chair of Emergency Medicine


1. Foronzaufar M.H., Liu P., Roth G.A., et al. Global Burder of Hypertension and Systolic Blood Pressure of at Least 110 to mm Hg, 1990-2015. JAMA. 2017;317(2):165-82. doi:10.1001/jama. 2016.19043.

2. Chazova I.E., Zhernakova Yu.V., Oschepkova E.V. The prevalence of risk factors for cardiovascular diseases in the Russian population of patients with arterial hypertension. Kardiologiia. 2014;10:4-12 (In Russ.)

3. Williams B., Mancia G., Spiering W. et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39:3021-104. doi:10.1093/eurheartj/ehy339.

4. Ruksin V.V., Grishin O.V. Emergency care for high blood pressure, not life-threatening. Kardiologiia. 2011;2:45-51 (In Russ.)

5. Ruksin V.V., Grishin O.V., Onuchin M.V. Comparison of the efficacy of preparations containing moxonidine during emergency antihypertensive therapy. Systemic Hypertension. 2015;2:8-12 (In Russ.)

6. Tereshchenko S.N., Gaponova N.I., Abdrakhmanov V.R. A randomized, multicenter, controversial study of the efficacy of moConidine in patients with uncomplicated hypertensive crisis (ABEC, AVES). Arterial Hypertension. 2011;4:316-24 (In Russ.)

7. Tereshchenko S.N., Gaponova N.I., Abdrakhmanov V.R. et al. Evaluation of the antihypertensive efficacy and safety of moxonidine in the treatment of uncomplicated hypertensive crisis. Systemic Hypertension. 2013;1:41-7 (In Russ.)

8. Plavunov N.F., Gaponova N.I., Abdrakhmanov V.R. Ambulance for acute increase in blood pressure. IX All-Russian Forum "Issues of Urgent Cardiology 2016". November 23-25, 2016; Moscow (In Russ.)

9. Guidelines for the examination of medicines. Volume III. Moscow: POLYGRAFPLYUS; 2014 (In Russ.)

10. Rules for conducting bioequivalence studies of medicinal products within the framework of the Eurasian Economic Union. Approved by the Resolution of the Council of the Eurasian Economic Commission No 85 of Nov 3, 2016 [cited by Dec 10, 2018]. Available from: (In Russ.)

11. Sanjuliani A.E., Genelhu de Abreu V., Ueleres Braga J., Francischetti E.A. Effects of moxonidine on the sympathetic nervous system, blood pressure, plasma renin activity, plasma aldosterone, leptin and metabolic profile in obese hypertensive patients. J Clin Basic Cardial. 2004;7;19-25.

12. Shlyakhto E., Almazov V.A., Chazova I. Moxonidine improves glycaemic control in mildly hypertensive, overwueight patients: a comparison with metformin. Diabetes, Obesity and Metabolism. 2006;8:456-65. doi:10.1111/j.1463-1326.2006.00606.x.

13. Chazova I.E., Schlaich M.P. Improved Hypertension Control with the Imidazoline Agonist Moxonidine in a Multinational Metabolic Syndrome Population: Principal Results of the MERSY Study. Int J Hypertens. 2013;2013:541-689. doi:10.1155/2013/541689.

14. Instructions for use of the drug for medical use Physiotens® [cited by Dec 10, 2018]. Available from: (In Russ.)

15. Order of the Ministry of Health of the Russian Federation dated July 5, 2016 No. 470n “On approval of the standard of emergency medical care for hypertension” [cited by Dec 10, 2018]. Available from: (In Russ.)

For citation:

Ramenskaya G.V., Shokhin I.E., Gaponova N.I., Abdrakhmanov V.R. Assessment of in Vitro Comparative Dissolution Kinetics of Moxonidine Products as a Factor Potentially Determining Effectiveness of Antihypertensive Treatment. Rational Pharmacotherapy in Cardiology. 2018;14(6):951-957.

Views: 686

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)