Study of Lercanidipine Drug Release from Medicine in Combination with Ramipril in vitro and in vivo

Introduction. Hypertension is the most common non-infectious disease in the world. New clinical recommendations for the diagnosis and management of patients with arterial hypertension are considering the issue of prescribing combination therapy and prefer fixed combinations of drugs in a single pill. The study of the pharmacokinetics of medicinal substances and the consideration of their pharmacokinetic parameters today is a necessary step in the complex of work, both in the creation of new original medicines and in the application of known generic drugs, and this is primarily due to obtaining objective characteristics of all processes occur in the body of the animal (human) with the drug. Pharmacokinetics is assessed in individual studies or as part of efficacy, safety, and tolerability studies.

Aim. The study of the release of lercanidipine from bilayer tablets containing two API (ramipril and lercanidipine) in the dissolution medium used for quality control in vitro and release in vivo, after oral administration of the drug to rabbits.

Materials and methods. Studies have been conducted on the release of lercanidipine from the combined drug in vitro and in vivo. As a test system were used laboratory rabbits Soviet chinchilla breed. Pharmacokinetic parameters were determined.

Results and discussion. A graph of the release of lercanidipine from the combined drug was constructed and the dependence of the concentration of this substance in the blood plasma of rabbits on time was revealed. Calculated pharmacokinetic parameters. An in vivo release study shows that the pharmacokinetics of lercanidipine are consistent with literature data.

Conclusion. The test drug has all the advantages of a rational fixed combination of antihypertensive drugs and simplifies therapy, meets the requirements of the latest clinical guidelines.

1. Ionov M. V., Zvartau N. E., Konradi A. O. First look at new 2018 join ESH/ESC Guidelines on diagnosis and management of hypertension. Arterial Hypertension. 2018; 24(3): 351–358 (In Russ.).

2. Smekhova I. E., Perova Ju. M., Kondrat’eva I. A. et al. The «dissolution» test and modern approaches to the evaluation of drug equivalence (review). Drug development & registration. 2013; 1(2): 50-61 (In Russ.).

3. Guidelines for the examination of medicines. V. I. – M.: Grifi K. 2013: 328 (In Russ.).

4. Shadrin A. A. Development of the technology of two-layer coated tablets, based on pharmaceutical substances – carboxylic acidand carboxylic acid ester // Book of Abstracts of the V AllRussian Scientific Conference of Students and Postgraduates with International Participation «Young Pharmacy – Potential of the Future», St. Petersburg, April 20-21, 2015 – St. Petersburg: Publishing House of SPCPA. 2015: 367–370 (In Russ.).

5. Shadrin A. A., Flisyuk E. V., Smekhova I. E. Dissolution profile studies for ramipril and lercanidipine fixed-dose combination. Drug Development & Registration. 2016; 3(16): 30–34 (In Russ.).

6. BCS electronic database. Available at: http://www.tsrlinc.net/search.cfm (accessed 20.01.2019) (In Russ.).

7. Guidelines for the laboratory animals and alternative models in biomedical technologies. Eedited by N. N. Karkishchenko and S. V. Grachev. M.: Profil-2S. 2010: 358 (In Russ.).

8. Guidelines for preclinical studies of drugs. Part one. M.: Grief and K., 2012: 944 (In Russ.).

9. Zhang Y., Huo M., Zhou J., Xie S. PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel. Comp Meth Prog Biomed. 2010; 99(3): 306.

10. Medication package insert of the drug Zanidip®-Recordati, Recordati Ireland Ltd., Ireland. State Register of Medicinal Products of the Russian Federation. Available at: http://grls.rosminzdrav.ru (accessed 20.01.2019) (In Russ.).

11. Preobrazhenskij D. V., Stecenko T. M., Vyshinskaja I. D. Fixed and random combinations of antihypertensive drugs: which are more preferable for long-term therapy? Consilium Medicum. 2009; 5: 33– 37 (In Russ.).