Kinetics (in vivo) release of active pharmaceutical ingredients from the drug under the conditional name AMO-sol

Keywords: drug; kinetic process, pharmacokinetic model, aerosol, ofloxacin, miramistin. benzocaine.

Abstract

Introduction. Pharmacokinetics plays a significant role in pharmacy. Studies of the dependence of the reaction rate on various factors make it possible to intensify the technological processes for the manufacture of drugs. Pharmacokinetic studies related to the study of the rate of absorption and withdrawal of drugs from the body allow us to interpret the mechanisms of their physiological action. The final process begins with the release of the active pharmaceutical ingredients from the pharmaceutical system (aerosol), then the absorption and diffusion of the active substances to the absorption surface - the wound surface. The absorption process itself is also diffusion and depends on many factors: the amount, properties and physical state of the active substance, the total composition and properties of the aerosol, as well as technological factors and the physiological state of the absorption surface (the first stage of the wound process).

The purpose is to conduct in vivo pharmacokinetic studies to isolate and detect benzocaine and miramistin in the blood of rats using a single-chamber pharmacokinetic model.

Materials and methods. During experimental studies, the materials were active pharmaceutical ingredients – ofloxacin, benzocaine, miramistin, as well as auxiliary substances – sodium carboxymethyl cellulose, methylcellulose, polyvinyl alcohol, polyvinyl pyrolidone, propylene glycol, glycerol, polyethylene oxide-400, ethyl alcohol, citric acid monohydrate, chladon-134a. In vitro methods established the order of the kinetic reaction to select a model for determining pharmacokinetic parameters by the in vivo method. The pharmacokinetic parameters of AMO sol were examined in the blood of white Wistar rats after its disposable application to a model wound. The isolation of active pharmaceutical ingredients (benzocaine, miramistin) was carried out using the Agilent chromato-mass spectrometer 6850/5973N manufactured by Agilent Technologies, a quartz capillary column NR-5MS 0.25 mm x 30 m. Temperature: injector – 250 0С, mass spectrometer interface (Transfer line) – 280 0С, ion sources – 230 0С, quadruplets – 150 0С. Ionization mode – electron shock, electron energy – 70 eV, electric multiplier voltage – 106 V more than at Autotune. Scan range 40 – 550 a.o.m. Thermostat temperature programming mode: 90 0С – 2 min. Then it rises to 300 0С at a rate of 20 0С /xv, and holds at this temperature 10 min. Carrier gas speed (helium) – 1,0 ml/min. Sample input mode – 2 mcL without flow separation.

Results. A single-chamber pharmacokinetic model was used to perform in vivo pharmacokinetic studies to isolate and detect benzocaine and miramistine in the blood of rats. The calculated values of the ke and ka constants showed that the application of drugs to the tissues of test rats is an example of a flip flop phenomenon, since the elimination rate constant is greater than (0,022 1/min) the absorption rate constant (0,007 1/min), and changes its position with respect to the time tmax, which corresponds to the equality of the parameters of the elimination and absorption rates. It was determined that when LS containing 12,5 μg/x benzocaine and 1,25 μg/x miramistin were administered, the maximum blood concentration (0,052 μg/ml) was observed for benzocaine after 30 minutes and 0,072 μg/ml after 240 minutes for miramistin. The clearance for benzocaine is calculated to be 0,00011 ml/( khvg) and for miramistin to be 0,000112 ml/( min g), respectively. In clinical settings, clearance serves to calculate the dose necessary to maintain an equilibrium concentration of drugs in the blood, that is, a maintenance dose. The volume of distribution is determined, which serves to calculate the loading dose of the preparation, which is necessary to achieve its desired concentration in the blood. For this model, the volume of drug distribution in the body for both benzocaine and miramistin is 0,005 ml/h, respectively. The final stage of in vivo studies using a single-chamber pharmacokinetic model was the determination of the half-life. In one period, 50 % of drugs is excreted from the body, in two – 75 %, in three – 90 %. Thus, the half-life of benzocaine at the elimination rate is 30,904 minutes, and at the suction rate – 98,18 minutes. The half-life of miramistin at the elimination rate is 30.942 minutes, and at the suction rate – 92,821 minutes. Therefore, in pharmacokinetic studies, the above parameters are used to evaluate changes in the concentration of drugs over time in a specific chamber where the desired therapeutic effect of the drug is obtained.

Conclusions. In vivo studies were conducted using a single-chamber pharmacokinetic model to isolate and detect benzocaine and miramistin in the blood of rats. It is proved that the developed drugs show predominantly local action, since at this moment the flow of release of active substances from the aerosol is greater than the flow of penetration through the natural biological barriers of the body. Qualitative evaluation of pharmacokinetic process with establishment of 15 pharmacokinetic parameters was carried out.

Author Biographies

O. P. Shmatenko, Ukrainian Military Medical Academy

Col. MS, DPSc, Professor, Head of the Department of Military Pharmacy, Ukrainian Military Medical Academy

L. L. Davtyan, Shupyk National Healthcare University of Ukraine

DPSc, Professor, Head of the Department of pharmaceutical technology and biopharmacy, Shupyk National Healthcare University of Ukraine

V. O. Tarasenko, Ukrainian Military Medical Academy

PhD, Associate Professor, senior lecturer of Military Pharmacy Department, Ukrainian Military Medical Academy

R. L. Prytula, National Military Medical Clinical Center "Main Military Clinical Hospital"

PhD, Associate Professor, Head of Medical Supply - Head of Pharmaceutical Center, National Military Medical Clinical Center "Main Military Clinical Hospital"

D. V. Voronenko, Ukrainian Military Medical Academy

PhD, Associate Professor, of Military Pharmacy Department, Ukrainian Military Medical Academy

D. V. Drozdov, Ukrainian Military Medical Academy

PhD, Associate Professor of Military Pharmacy Department, Ukrainian Military Medical Academy

Ya. R. Andriychuk, Shupyk National Healthcare University of Ukraine

PhD, Associate Professor, Associate Professor of the Department of pharmaceutical technology and biopharmacy, Shupyk National Healthcare University of Ukraine

N. A. Kozyko, National Medical University named after A.A. Bogomolets

PhD, Associate Professor, Associate Professor of the department of pharmacy and industrial technology of drugs, National Medical University named after A.A. Bogomolets

References

Davtyan, L. L. (2006). Naukovo-praktichne obgruntuvannya tekhnologії m’yakih lіkars'kih form dlya stomatologії [Scientific and practical justification of the technology of soft dosage forms for dentistry]. аvtoref. dis. dokt. farm. nauk. Kiїv : [in Ukrainian].

Drozdova, A. O. (2012). Doslіdzhennya farmakokіnetiki dіyuchih rechovin u skladі aerozolyu metodom in vitro [Investigation of pharmacokinetics of active substances in aerosol by in vitro method]. Farmacevtichnij chasopis. 4 : 155-158 [in Ukrainian].

Ivannikova, E. V., ZHerdev, V. P., Bojko, S. S. (2013). Issledovanie farmakokinetiki i biodostupnosti v sozdanii novyhoriginal'nyh lekarstvennyh sredstv peptidnoj struktury i ih optimal'nyh lekarstvennyh form [Issledovanie farmakokinetiki i biodostupnosti v sozdanii novyhoriginal'nyh lekarstvennyh sredstv peptidnoj struktury i ih optimal'nyh lekarstvennyh form]. Farmakokinetika i farmakodinamika, 2, 1-17 [in Ukrainian].

Karkishchenko, N. N., Horon'ko, V. V., Sergeeva, S. A. (2001). Farmakokіnetika [Farmakokіnetiks]. Rostov-na-Donu : Fenіks. [In Russian].

Tarasenko, V. A., Kuchmіstova, O. F., Solomennij, A. M., Pіdlіsnij, O. V. (2019). Strukturizacіya osoblivostej ta naslіdkіv bojovoї travmi u vіjs'kovosluzhbovcіv [Structuring of features and consequences of combat trauma in military personnel]. Vіjs'kova medicina Ukraїni, 19(4), 111-117 [in Ukrainian].

Shmatenko, O. P., Tarasenko, V. O., Davtyan, L. L., Drozdova, A. O., Shmatenko, V. V. (2012). Doslіdzhennya vplivu farmacevtichnih faktorіv na tekhnologіyu kremu [Research of influence of pharmaceutical factors on cream technology]. Vіjs'kova medicina Ukraїni. 12, 123-126 [in Ukrainian].

Tarasenko, V. O. (2020). Doslіdzhennya kіnetiki vivіl'nennya aktivnih farmacevtichnih іngredієntіv z plіvkoutvoryuyuchogo aerozolyu metodom in vitro [Study of kinetics of release of active pharmaceutical ingredients from film-forming aerosol by in vitro method]. Socіal'na farmacіya v ohoronі zdorov’ya. 6(1), 16-22 [in Ukrainian].

Shmatenko, O. P., Davtyan, L. L., Tarasenko, V. O., Drozdova, A. O. ta іn. (2018). Bіofarmacevtichnі doslіdzhennya yak osnova konstruyuvannya m’yakih lіkars'kih zasobіv pri lіkuvannі ranovogo procesu u poranenih vіjs'kovosluzhbovcіv [Biopharmaceutical studies as the basis for the design of soft medicines in the treatment of the wound process in wounded soldiers]. Vіjs'kova medicina Ukraїni. 18(4), 93-97 [in Ukrainian].

Tarasenko, V. O., Davtyan, L. L. (2008). Viznachennya farmakokіnetiki parametrіv gelyu na osnovі ceftriaksonu ta nіmesulіdu metodom in vitro. Zaporozhskij med. Zhurnal [Determination of pharmacokinetics of gel parameters based on ceftriaxone and nimesulide by in vitro method]. Zaporozhskij med. Zhurnal. 5, 139-141 [in Ukrainian].

Mincer, О. P., Voronenko, Y. V. & Vlasov, V. V. (2003). Obroblennya klinichnykh i eksperymental'nykh danykh u medytsyni [Treatment of clinical and experimental data in medicine]. Vishha shkola, Кyiv [in Ukrainian].

Nastanova 42-7.1:2005. (2005). Nastanovi z klіnіchnih doslіdzhen'. Lіkars'kі zasobi. Doslіdzhennya bіodostupnostі ta bіoekvіvalentnostі [Nastanovi z klіnіchnih doslіdzhen'. Lіkars'kі zasobi. Doslіdzhennya bіodostupnostі ta bіoekvіvalentnostі]. Ofіcіjne vidannya. Kiїv : MOZ Ukraїni [in Ukrainian].

Tarasenko, V. O., Shmatenko, V. V., Kuchmistov, V. O., Koziko, N. О. et al. (2017). Pharmaceutical development of complex wound-healing ointment for the military medicine needs. Regulatory Mechanisms in Biosystem. 8(4), 662-672.

Tarasenko, V., Pidlisnyy, А., Koval, А., Solomennyy, А. et al. (2020). Technological and biopharmaceutical aspects of developingthe basics of soft medicinal local action. Archives of Pharmacy Practice. 11(1), 92-99.

Tarasenko, V., Solomennyy, A., Pidlisnyy, A., Koval, A. et al. (2020). Theoretical Basis of Creation of Soft Medicinal Products of Local Application. Arch Pharma Pract. 11(2), 130-136.

Published
2021-12-30
How to Cite
Shmatenko, O. P., Davtyan, L. L., Tarasenko, V. O., Prytula, R. L., Voronenko, D. V., Drozdov, D. V., Andriychuk, Y. R., & Kozyko, N. A. (2021). Kinetics (in vivo) release of active pharmaceutical ingredients from the drug under the conditional name AMO-sol. Ukrainian Journal of Military Medicine, 2(4), 130-139. https://doi.org/10.46847/ujmm.2021.4(2)-130

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