SIMULATION OF VINPOCETINE RELEASE PROCESS FROM MICROCAPSULES WITH HYDROPHOBIC SHELL

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ɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in PharmacyɍȾКʺОʪʫЛʰˀОʦʤʻʰʫʿˀОˉʫˁˁʤʦˏˁʦОʥОʮʪʫʻʰЯʺʰКˀОКʤʿˁ˄ЛОʥОЛОЧКОʱПолкоɜникоɜɚȽлɭшкоМиɯɚйлоɜɫкɚяКɚɪиɟɜɚɎɟɞɟɪɚльноɟɝоɫɭɞɚɪɫɬɜɟнноɟɛюɞжɟɬноɟоɛɪɚзоɜɚɬɟльноɟɭчɪɟжɞɟниɟоɛɪɚзоɜɚнияȼоɪонɟжɫкийɝоɫɭɞɚɪɫɬɜɟнныйɭниɜɟɪɫиɬɟɬɊоɫɫияȼоɪонɟжɋɬɭɞɟнчɟɫкɚямɟɞикоɮɚɪмɚцɟɜɬичɟɫкийинɫɬиɬɭɬɎȽȻОɍȼолɝȽМɍМинзɞɪɚɜɚɊоɫɫииɊоɫɫия, 11. E-mail: alexander.glushko@lcmmp.ruɌɚшкɟнɬɫкийɮɚɪмɚцɟɜɬичɟɫкийɭниɜɟɪɫиɬɟɬɍзɛɟкиɫɬɚнɌɚшкɟнɬȺйɛɟкɚМикɪокɚпɫɭлынɚɫɬоящɟɟɜɪɟмяɪɚзличныɯМикɪокɚпɫɭлыɜиɬɚминɚмиэɮиɪнымимɚɫлɚмиɜɯоɞяɬɫоɫɬɚɜɪɚзличныɯкоɫмɟɬичɟɫкиɯɫɪɟɞɫɬɜкɪɟмоɜɝɟлɟйɫыɜоɪоɬок). Микɪокɚпɫɭлиɪоɜɚнныɟпɪоɛиоɬикииɫпользɭюɬɫякоɪмɚɯкоɪмоɜыɯɞоɛɚɜкɚɯɜɟɬɟɪинɚɪиилɚɫɬьмикɪокɚпɫɭлиɪоɜɚнияɮɚɪмɚции ? ɫоɜмɟщɟниɟоɛщɟйɞозиɪоɜкɟлɟкɚɪɫɬɜɟнныɯɜɟщɟɫɬɜнɟɫоɜмɟɫɬимыɯɫɜоɛоɞномɜиɞɟЦɟльɪɚɛоɬы ? ɫɪɚɜниɬɟльныйɬɟɪмоɞинɚмичɟɫкиɯɪɚкɬɟɪиɫɬикɜыɫɜоɛожɞɜинпоцɟɬинɚɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚо 3:2 ɪɚɫɬɜоɪкиɫлоɯлоɪиɫɬоɜоɞоɪоɞной 0,01 ɫпиɪɬэɬилоɜыйМɚɬɟɪиɚлымɟɬоɞымоɞɟлиɪоɜɚнияпɪоцɟɫɫɚɜыɫɜоɛожɞɟнияɜинпоцɟɬинɚɫплɚɜɚɪɚзличныɯɫɪɟɞɚɯмоɞɟликомпонɟнɬоɜиɫɫлɟɞɭɟмыɯɫиɫɬɟмɜычиɫлɟнызɚɪяɞыɚɬомоɜкɜɚнɬоɜоɯимичɟɫкиммɟɬоɞоммоɞɟликомпонɟнɬоɜиɫпользоɜɚниɟм Hyper Chem 8.01. кɚчɟɫɬɜɟнɚчɚльноɝоɫоɫɬоянияɪɚɫчɟɬɚмоɞинɚмичɟɫкиɯɯɚɪɚкɬɟɪиɫɬикɜыɫɜоɛожɞɜинпоцɟɬинɚɫплɚɜɚɛылɚиɫпользоɜɚнɚконɮоɪмɚцияɫɬɟмыɫплɚɜɜинпоцɟɬинпоɫлɟɬɟɪмоɞинɚмичɟɫкоɝоɭɪɚɜноɜɟшиɜɚниямɟɬоɞоммолɟкɭляɪнойȻиоэɜɪикɚɬɟчɟниɟ 5 ɜыɞɟлɟнныɯɫиɫɬɟмпɪоɜоɞилɫяколɟɛɚɬɟльныйиɫпользоɜɚнинɟоɝɪɚничɟнноɝомɟɬоɞɚɏɚɪɬɪиɎокɚɛɚзиɫɟ STO-3G Orca 4.0. Ɋɟзɭльɬɚɬыоɛɫɭжɞɟниɟȼыɫɜоɛожɞɜинпоцɟɬинɚɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚо 3:2 ɪɚзличныɯ pH эɬɚнолɪɚɫɬɜоɪимоɫɬиэɬиɯɫɪɟɞɚɯɬɚкɪɚɫɬɜоɪимоɫɬиɫплɚɜɚЗɚключɟниɟПɪоɜɟɞɟнныɟиɫɫлɟɞоɜɚниямоɞɟлиɪоɜɚниямолɟкɭляɪнойɜыɫɜоɛожɞɜинпоцɟɬинɚɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚо 3:2 покɚзыɜɚɟɬɜозможноɫɬьɜыɫɜоɛожɞɜинпоцɟɬинɚ pH 2,0 эɬɚнолПолɭчɟнныɟɪɟзɭльɬɚɬыпозɜоляюɬпɪɟɞположиɬьɛолɟɟɜыɫɜоɛожɞɜинпоцɟɬинɚɫплɚɜɚэɬɚнолɪɚɫɬɜоɪомкиɫлоɬыɯлоɪиɫɬоɜоɞоɪоɞнойКлючɟɜыɟɫлоɜɚмикɪокɚпɫɭлыоɛолочкɚɜинпоцɟɬинɜоɫкмɚɫлокɚкɚокɜɚнɬоɜоɯимичɟɫкийɪɚɫчɟɬɜыɫɜоɛожɞSIMULATION OF VINPOCETINE RELEASE PROCESS FROM MICROCAPSULES WITH HYDROPHOBIC SHELLYu.A. Polkovnikova, A.A. Glushko, I.Yu. Mikhailovskaya, Yo.S. Karieva?Voronezh State University?, 3, Student str., Voronezh, Russia, 394036Pyatigorsk Medical and Pharmaceutical Institute ? branch of Volgograd State Medical University, 11, Kalinin ave., Pyatigorsk, Russia,357532 E-mail: alexander.glushko@lcmmp.ruTashkentskiy Pharmaceutical University, 45, Aybeka Str., Tashkent, Uzbekistan,100015циɬиɪоɜɚнияПолкоɜникоɜɚȽлɭшкоМиɯɚйлоɜɫкɚяКɚɪиɟɜɚМОȾȿЛИɊОȼȺНИȿПɊОЦȿɋɋȺȼЫɋȼОȻОЖȾȿНИЯМИКɊОКȺПɋɍЛȽИȾɊОɎОȻНОЙОȻОЛОЧКОЙɎɚɪмɚцияɮɚɪмɚколоɝияПолкоɜникоɜɚȽлɭшкоМиɯɚйлоɜɫкɚяКɚɪиɟɜɚFor citation:Polkovnikova Yu.A., Glushko A.A., Mikhailovskaya I.Yu., Karieva Yo.S. SIMULATION OF VINPOCETINE RELEASE Pharmacy & Pharmacology V. 5 N 4, 2017Nowadays microcapsules are widely spread in different industries. Microcapsules with vitamins, etheric and fatty oils are included into different cosmetics (creams, gels, serums). Microencapsulated probiotics are used in foods and fodder additives in veterinary. An important eld of application of microencapsulation in pharmacy is the combination in the total dosage of drugs that are incompatible when mixed in free form. of thermodynamic characteristics of vinpocetine release from the melt of beeswax and cacao butter 3:2 into water, solution of hydrochloric acid 0.01 M and ethanol. For simulation of the process of vinpocetine release from the melt into different environments models component models of the studied systems were built and their atom charges were calculated by quantum-chemical method. Spatial models of the components were built in Hyper Chem 8.01. As an initial state for the thermodynamic characteristics of the calculation of vinpocetine release from the ics simulation in Bioeurica program for 5 ns. For isolated systems a vibrational analysis was performed with the use of unrestricted Hartree-Fock method in STO-3G basis set in Orca 4.0 program. Vinpocetine release from the melt of beeswax and cacao butter 3:2 into water with different pH values and to ethanol depends on its solubility in these environments, and also on solubility of the melt. release from the melt of beeswax and cacao butter 3:2 by molecular dynamics simulation demonstrates the opportunity of vinpocetine release into water with pH=2 and into ethanol. The obtained results make it possible to assume a lower degree of vinpocetine release from the melt into ethanol compared with the solution of hydrochloric acid 0,01 M. microcapsule, shell, vinpocetine, beeswax, cacao butter, quantum chemistry, molecular dynamics simulation, degree of releaseȼɜɟɞɟниɟИнкɚпɫɭлиɪоɜɚниɟэɬопɪоцɟɫɫкоɬоɪоммɟльчɚйшиɟжиɞкоɝоɬɜɟɪɞоɝоɝɚзоɜоɝоɚкɬиɜноɝоинɝɪɟɞиɟнɬɚɭпɚкоɜɚныɜɬоɪоймɚɬɟɪиɚлɟɝоɜозɞɟйɫɬɜийокɪɭжɚюɫɪɟɞы [ 1, 2]. Ƚиɞɪоɮоɛнɭюоɛолочкɭмɚɬɪицɭмикɪокɚпɫɭлɜыɛиɪɚюɬоɫноɜɚниинɟоɛɯоɞимыɯɫɜойɫɬɜмикɪокɚпɫɭлынɚпɪимɟɪоɫноɜɚниизнɚчɟниямикɪокɚпɫɭлɬɟмпɟɪɚɬɭɪы2]. Пɪɟɞпочɬиɬɟльнɚяоɛолочкɚмɚɬɪиɞолжнɚоɛлɚɞɚɬьɬɟмпɟɪɚɬɭɪойплɚɜлɟния 45?ɬɚкчɬоɛыможнокомнɚɬнойɬɟмпɟɪɚɬɭɪɟможноиɫпользоɜɚɬьлюɛоɟɝиɞɪоɮоɛноɟɜɟщɟɫɬɜоɟɫлимикɪокɚпɫɭлыɬɟмпɟɪɚɬɭɪɟɬɟмпɟɪɚɬɭɪыɝиɞɪоɮоɛноɝоɜɟщɟɫɬɜ 45?ȽиɞɪоɮоɛнɚяоɛолочкɚмɚɬɪицɚможɟɬɝɪɭппыɜключɚюмɚɫлɚɜоɫкиɫмолыэмɭльɝɚɬоɪыɫмɟɫиПɪɟɞпочɬиɬɟльнɚяоɛолочкɚɬɪицɚɜыɛиɪɚɟɬɫяɝɪɭппыɜключɚющɟйжиɜоɬныɟмɚɫлɚполноɫɬьюɝиɞɪиɪоɜɚнныɟжиɜоɬмɚɫлɚɝиɞɪиɪоɜɚнныɟполноɫɬьюɝиɞɪиɪоɜɚнныɟɫɜоɛоɞныɟкиɫлоɬыɞɪɭɝиɟэмɭльɝɚɬоɪыжиɜоɬныɟɜоɫкиɜоɫкиминɟɪɚльныɟɜоɫкиɫинɬɟɬичɟɫкиɟɜоɫкипɪиɪоɞныɟɫинɬɟɬичɟɫкиɟɫмолыЖиɜоɬныɟɜоɫкипɪɟɞɫɬɚɜляюɬɜоɫклɚнолинɜоɫкɜоɫккиɬɚйɫкоɝоɜоɫкоɜоɝочɟɪɜɟцɚПɟɪɫпɟкɬиɜнымлɟкɚɪɫɬɜɟннымɜɟщɟɫɬɜомɫозɞɚниямикɪокɚпɫɭлиɪоɜɚннойɮоɪмыяɜляɟɬɫя [5, 6]. плоɯоɪɚɫɬɜоɪяɟɬɫяɜоɞɟпɪоɜɟɞɟнияпɪɟɞɜɚɪиɬɟльныɯиɫɫлɟɞоɜɚнийɫноɜɚниюɫоɫɬɚɜɚмикɪокɚпɫɭлопɪɟɞɟлɟниюполɭчɟнияиɫɫлɟɞоɜɚкɚчɟɫɬɜɟɫɪɟɞыɜоɞойочищɟннойɪɚɫɬɜоɪомкиɫлоɬыɯлоɪиɫɬоɜоɞоɪоɞнойможɟɬиɫпользоɜɚнɫпиɪɬчɬопозɜолиɬɛолɟɟопɪɟɞɟлиɬьɜлияниɟɜɫпомоɝɚɬɟльныɯɜɟщɟɫɬɜɬɟɯнолоɝичɟɫкиɯɮɚкɬ [5, 6]. Микɪокɚпɫɭлыоɛолочкойполɭчɟнымɟɬоɞомɜɚния [8]. нɚкозɚчɚɫɬɭюɫложноɫɬьɚппɚɪɚɬɭɪноɝооɮоɪмлɟпɪоцɟɫɫɚнизкɚяэɮɮɟкɬиɜноɫɬьɞɟлɚюɬпоɞмɟɬоɞикимикɪокɚпɫɭлиɪоɜɚнияɞоɪоɝоɫɬоящимиɫɫлɟɞоɜɚниɟмМоɞɟлиɪоɜɚниɟмолɟкɭляɪнойɪɚɫɬɜоɪоɜизɭчɟниипɪоцɟɫɫɚɜыɫɜоɛожɞɟниялɟкɚɪɫɬɜɟнныɯɜɟщɟɫɬɜмикɪокɚпɫɭлпозɜоляɟɬпоɞоɛɪɚɬьопɬимɚльныйплɟнкооɛɪɚзоɜɚɬɟльɜоɞоɪоɞныйпокɚзɚɬɟльɫɪɟɞɭɜыɫɜоɛожɞɟнияɞɪɭɝиɟɮɚкɬоɪыɜɚжныɟɭɫпɟшноɝопɪоɜɟɞɟнияпɪоцɟɫɫɚмикɪокɚпɫɭлиɪоɜɚэɬомнɟоɛɯоɞимоɫɬьпɪоɜɟɞɟнияɪɟɚльноɝоэкɫпɟɪимɟнɬɚɫɜоɞиɬɫянимɭмɭ [8]. Цɟль иɫɫлɟɞоɜɚнияɚнɚлизɬɟɪмоɞинɚмичɟɫкиɯɯɚɪɚкɬɟɪиɫɬикɜыɫɜоɛожɞɟнияɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚо 3:2 ɜоɞɭɪɚɫɬɜоɪкиɫлоɬыɯлоɪиɫɬоɜоɞоɪоɞɫпиɪɬМɚɬɟɪиɚлымɟɬоɞымоɞɟлиɪоɜɚнияцɟɫɫɚɜыɫɜоɛожɞɟнияɫплɚɜɚɫɪɟɞɚɯпɪɟɞɜɚɪиɬɟльнопоɫɬɪоɟныкомпонɟнɬоɜиɫɫлɟɞɭɟмыɯɬɚккомпонɟнɬыɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚоɚɬомоɜкɜɚнɬоɜомичɟɫкиммɟɬоɞоммолɟкɭлыɭчиɬыɜɚлɚɫьзɚɜиɫимоɫɬиɜɟличины pH ɫɪɟɞыɜоɫпɪоизɜɟɞɟнияɟɝопоɜɟɞɟнияɪɚɫɬɜоɪиɬɟлɟɍчиɬыɜɚяпокɚзɚɬɟльконɫɬɚнɬы (pKоɞɟ 7.1 [10] пользɭяȽɟнɞɟɪɫонɚɫɟльɛɚɯɚ [11], можноɫɞɟлɚɬьɜыɜоɞɬомчɬо pH пɪɚкɬичɟɫкиполноɫɬьюионизиɪоɜɚн pH ɞоляионизиɪоɜɚнныɯмолɟкɭлɫɬɚɜляɟɬɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in PharmacyɝɞɟоɬноɫиɬɟльноɟɫоɞɟɪжɚниɟоɫноɜɚниякɚɬионɚɪɚɫɬɜоɪɟɫооɬɜɟɬɫɬɜɟнноɊиɫɭнокОɬноɫиɬɟльноɟɫоɞɟɪжɚниɟɜинпоцɟɬинɚоɫноɜɚнияɜинпоцɟɬинɚкɚɬионɚɪɚɫɬɜоɪɟɫооɬɜɟɬɫɬɜииɭɪɚɜнɟниɟмȽɟнɞɟɪɫонɚɏɚɫɫɟльɛɚɯɚкɚɬионоɫноɜɚниɟэɬомɪɚɫɬɜоɪимоɫɬьɬɪɚльнойɜоɞнойɫɪɟɞɟлиɬɟɪɚɬɭɪы [ 12] низкɚя (1,89?10чɬоɝоɜоɪиɬнɟзнɚчиɬɟльконцɟнɬɪɚцииɜоɞнойɫɪɟɞɟкɚккɚɬионɚɬɚкоɫноɜɚнияИнɬɟɪɟɫнымɞɚнномиɫɫлɟɞоɜɚниипɪɟɞɫɬɚɜляɟɬɫямоɞɟлиɪоɜɚниɟɜыɫɜоɛожɞɟниякɚккɚɬионɚɬɚкоɫноɜɚɫɪɟɞɭɪɚɫɬɜоɪиɬɟляэɬоɜозможноɫɬьоɛъяɫниɬьэɮɮɟкɬиɜноɫɬиɜыɫɜоɛожɞɟнияɞɚнноɝоɜɟщɟɫɬɜɚɪɚɫɬɜоɪиɬɟль pH ɬочкиɫɬɪоɟниямолɟкɭлэɬомпɟɪɟɯоɞмолɟкɭлыɫплɚɜɚɪɚɫɬɜоɪиɬɟльможɟɬɫопɪоɜожɞɚɬьɫязɚɜиɫимоɫɬиɜɟличиныɜоɞоɪоɞноɝопокɚзɚɬɟляɪɚɫɬɜоɪиɬɟляможɟɬпɪоиɫɯоɞиɬьɯожɞɟниимолɟкɭлыɜɟɪɯноɫɬиконɬɚкɬɟɪɚɫɬɜоɪиɬɟлɟмоɫɭщɟɫɬɜлɟномоɞɟлиɪоɜɚниɟэɬоɝочɟɫкоɝоэɬɚпɚпɪоцɟɫɫɚɜыɫɜоɛожɞɟния ? пɪɟоɞомолɟкɭлойɪɚзɞɟлɚɪɚɫɬɜоɪиɬɟлькɚчɟɫɬɜɟпоɞоɛноɝоиɫɫлɟɞоɜɚнияможнопɪиɜɟɫɬиɪɚɛоɬɭ Hui-dong Zheng [13].Пɪоɫɬɪɚнɫɬɜɟнныɟмоɞɟликомпонɟнɬоɜпоɫɬɪоɟныиɫпользоɜɚниɟм Hyper Chem ɮɚкɬоɪомкоɬоɪыйнɟоɛɯоɞимоɜɚɬьмоɞɟлиɪоɜɚниимолɟкɭляɪнойɬɟɪоɝɟнныɯяɜляɟɬɫяɪɚɫпɪɟɞɟлɟниɟɚɬомоɜэɬойɚɬомоɜкомпонɟнɬоɜмоɞɟлиɪɭɟмыɯмɟɬоɞомчɬопɪоɞикɬоɜɚнонɟɞоɫɬɚɬочнойɬочноɫɬьюполɭэмпиɪичɟɫкиɯмɟɬоɞоɜкɜɚнɬоɜомичɟɫкиɯмɟɬоɞоɜопɪɟɞɟлɟнияɚɬомоɜмолɟкɭлкомпонɟнɬоɜɫплɚɜɚɬоɞɏɚɪɬɪиɎокɚнɚɛоɪом 3-21G* ɝɟомɟɬɪиимɟɬоɞɮɭнкционɚплоɬноɫɬи UB3LYP нɚɛоɪом 6-31G*) ɫооɬɜɟɬɫɬɜииɪɟзɭльɬɚɬɚмииɫɫлɟɞоɜɚнияпɪиɜɟɞɟннымиɪɚɛоɬɟ [14]. Оɛоɫноɜɚнноɫɬьиɫпользоɜɚниямɟɬоɞоɜɪɚɫчɟɬɚɚɬомоɜмоɞɟлиɪоɜɚниимолɟкɭляɪнойɬɪɚнɫпоɪɬɚɜɟщɟɫɬɜчɟɪɟзпоɜɟɪɯноɫɬьɞɟмонɫɬɪиɪɭɟɬɫяɪɚɛоɬ[14]. Ƚɟомɟɬɪиякомпонɟнɬоɜɫплɚɜɚɪоɜɚнɚмɟɬоɞоммолɟкɭляɪноймɟɯɚники m m+ [16] иɫпользоɜɚниɟм Hyper Chem 8.09. ȾɚлɟɟпɪоɜɟɞɟнɚɝɟомɟɬɪиимолɟкɭлɬоɞоммɟɬоɞɏɚɪɬɪиɎокɚ 3-21G* [ 17]). ɬоɞоммɟɬоɞɮɭнкционɚлɚплоɬноɫɬиU B 3LYP [18], Pharmacy & Pharmacology V. 5 N 4, 2017Полɭчɟннɚяɫиɫɬɟмɚɞɚлɟɟɜɫɬɪɚиɜɚлɚɫьɬɜоɪиɬɟли ? ɜоɞɭэɬɚнолПоɫлɟэɬоɝопɪоɜоɞилоɫьɬɟɪмоɞинɚмичɟɫкоɟɭɪɚɜноɜɟшиɜɚниɟиɫпользоɜɚȻиоэɜɪикɚɚɜɬоɪɭшко ? (ɫилоɜоɟполɟ Am ber 94 [20], пɪямоɭɝольныɟɞичɟɫкиɟɬɟɪмоɫɬɚɬɟнɞɫɟнɚber 94 [20], К, ɜɪɟмя ɪɟлɚкɫɚцииɬɟɪмоɫɬɚɬɚ 100 моɞɟлиɪоɜɚнияɌɟɪмоɫɬɚɬиɪоɜɚниɟоɫɭщɟɫɬɜлялоɫьɫооɬɜɟɬɝɪɚɮикомпɪиɜɟɞɟннымɬɚɛлицɟ 1. ɌɟмпɟɪɚɬɭɪɚзɚɞɚɜɚɟмɚяɬɟɪмоɫɬɚɬомизмɟнялɚɫьмомɟнɬɚмиɝɪɚɮикɚɌɚɛлицɚȽɪɚɮикɪɚɛоɬыɬɟɪмоɫɬɚɬɚпɪоцɟɫɫɟмоɞɟлиɪоɜɚниямолɟкɭляɪнойɮɫɌɟмпɟɪɚɬɭɪɚ300000310ȾɚлɟɟпɪоизɜоɞилоɫьмоɞɟлиɪоɜɚниɟɜыɫɜоɛоɭчɚɫɬкɚɫплɚɜɚɪɚɫɬɜоɪиɬɟчɟниɟкɚчɟɫɬɜɟнɚчɚльноɝоɫоɫɬоянияɪɚɫчɟɬɚɬɟɪмоɞинɚмичɟɫкиɯɯɚɪɚкɬɟɪиɫɬикɜыɫɜоɛожɞɟнияɫплɚɜɚиɫпользоɜɚнɚконɮоɪмɚпоɫлɟɬɟɪмоɞинɚмичɟɫкоɝоɭɪɚɜноɜɟшиɜɚниямɟɬоɞоммолɟкɭляɪнойȻиоэɜɪикɚɬɟчɟниɟ 5 кɚчɟɫɬɜɟконɟчноɝоɫоɫɬоянияиɫпользоɜɚлɫямомɟнɬмоɞɟлиɪоɜɚниямолɟкɭляɪнойоɬɜɟɬɫɬɜɭющийполномɭɜыɯоɞɭмолɟкɭлыɫплɚɜɚɪɚɫɬɜоɪиɬɟлькɚчɟɫɬɜɟɜыɯоɞɚɪɚɫɬɜоɪиɬɟльиɫпользоɜɚлɫямоɞɭльȼɚɚльɫоɜɚɜзɚимоɞɟйɫɬɜиямолɟкɭлойɫплɚɜом (|E| мольɫоɫɬоянийпɪоɜоɞилɚɫьɝɟомɟɬɪии ɫилоɜомполɟ Amber 94 Ȼиоэɜɪикɚпɪоɜоɞилɫяколɟɛɚɬɟльɚнɚлиз [ 22] иɫпользоɜɚниɟмнɟоɝɪɚничɟнноɝомɟɬоɞɚɏɚɪɬɪиɎокɚɛɚзиɫɟ STO-3G ɫɜоɛоɞноɪɚɫпɪоɫɬɪɚняɟмой Orca 4.0 [17]. ɪɟзɭльɬɚɬɟполɭчɟныɬɟɪмоɞинɚмичɟɫкиɟɯɚɪɚкɬɟɪимоɞɟлиɪɭɟмыɯɮɪɚɝмɟнɬоɜэнɬɚльпияэнɬɪопияȾɚлɟɟпɪоизɜоɞилɫяɪɚɫчɟɬэнɬɚльпииэнɬɪопииɜыɫɜоɛожɞɟнияɫплɚɜɚɮоɪмɭлɚмиɫпользоɜɚниɟмполɭчɟнныɯэнɬɚльпийɬɪопийɪɚɫɫчиɬыɜɚлиɫьȽиɛɛɫɚɜыɫɜоɛожɞɟнияɫɪɟɞыɮоɪмɭɬɟмпɟɪɚɬɭɪыɝɞɟ T ? ɬɟмпɟɪɚɬɭɪɚɊɟзɭльɬɚɬыоɛɫɭжɞɟниɟкɚчɟɫɬɜɟкомпонɟнɬоɜиɫɫлɟɞɭɟмыɯиɫпользоɜɚнымоɞɟлимолɟкɭлыоɫноɜɚнияɬɚкжɟмоɞɟликомпонɟнɬоɜɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚоɊиɫɭнокɏимичɟɫкɚяɫɬɪɭкɬɭɪɚпɪоɫɬɪɚнɫɬɜɟнноɟɜинпоцɟɬинɚоɫноɜɚниɟкɚɬионɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in PharmacyЦɟɪоɬиноɜɚякиɫлоɬɚНɟоцɟɪоɬиноɜɚякиɫлоɬɚМɟлиɫɫиноɜɚякиɫлоɬɚМонɬɚниноɜɚякиɫлоɬɚМɟлиɫɫилпɚльмиɬɚɬМиɪицилпɚльмиɬɚɬɞиɫɬɟɚɪоолɟинпɚльмиɬоɞиолɟинPharmacy & Pharmacology V. 5 N 4, 2017ПɚльмиɬоɫɬɟɚɪоолɟинɊиɫɭнокɋɬɪɭкɬɭɪныɟɮоɪмɭлыпɪоɫɬɪɚнɫɬɜɟнноɟкомпонɟнɬоɜɫплɚɜɚпчɟлиноɝоɜоɫкɚкɚкɚоКоличɟɫɬɜɟнныйɫоɫɬɚɜɫплɚɜɚɜоɫкɚмɚɫлɚкɚоɪɚɫɫчиɬɚниɫɯоɞялиɬɟɪɚɬɭɪныɯɯимичɟɫкомɫоɫɬɚɜɟпчɟлиноɝоɜоɫкɚ [ 23] мɚɫлɚкɚо [24]. Ⱦɚлɟɟиɫɯоɞямолɟкɭляɪныɯмɚɫɫɪɚɫɫчиɬɚныколичɟɫɬɜɚмолɟкɭлоɫноɜныɯкомпонɟнɬоɜмоɞɟлиɪɭɟмойɍчиɬыɜɚяоɛъɟммоɞɟлиɪɭɟмоɝоɮɪɚɝмɟнɬɚɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚо 3:2, 125 моɞɟльɜключɟныкомпонɟнɬыколичɟɫɬɜомолɟкɭлкоɬоɪыɯиɫɯоɞяколичɟɫɬɜɟнноɝоɫоɫɬɚɜɚ 2-моɞɟлиɪɭɟоɛъɟмкɚчɟɫɬɜɟɫоɫɬɚɜɚɝокомпонɟнɬнойможнопɪиɜɟɫɬиɪɚɛоɬɭкоɬоɪойоɫɭщɟɫɬɜлялоɫьмоɞɟлиɪоɜɚниɟмɚɫлɚкɚкɚомɟɬоɞоммолɟкɭляɪнойэɬомɫоɫɬɚɜɫмɟɫиɜключɟныɬɪиɬɪиɝлицɟɪиɞоɜɜключɟныкиɫлоɬыɞɪɭɝиɟмноɝокомпонɟнɬымɚɫлɚ [25]. оɞнимɪɚɫпɪоɫɬɪɚнɟннымпɪимɟɪоммоɞɟлиɪоɜɚнияɫложныйɫоɫɬɚɜяɜляɟɬɫямоɞɟлиɪоɜɚниɟмолɟкɭляɪнойɮоɫɮолипиɞныɯ [26]. эɬомɫоɫɬɚɜɞɟлиɪоɜɚнииɜключɚюɬɫякомпонɟнɬыɫоɞɟɪжɚщиɟɫяɞоɫɬɚɬочноɛольшомколичɟɫɬɜɟМоɞɟлиɪоɜɚниɟмолɟкɭляɪнойнɚɫɬоящɟɟɞоɫɬɭпномɚɫшɬɚɛɟɞɟɫяɬкоɜнɚномɟɬɪоɜоɛъɟмɟкɭɛичɟɫкиɯнɚномɟɬɪ [27]. компонɟнɬыɜɟщɟɫɬɜпɪиɪоɞноɝопɪоиɫɯожɞɟнияимɟюɬнɚɫɬолькоконцɟнɬɪɚциичɬомолɟкɭлыпɪɟɞɫɬɚɜлɟныɟɞиничномэкзɟмпляɪɟоɛъɟмɚɯнɚмноɝокɭɛичɟɫкиɯнɚномɟɬɪоɜɍчиɬыɜɚяэɬонɚɫɬоящɟɟпɪɟɞɫɬɚɜляɟɬɫяɜозможнымкомпонɟнɬоɜɫмɟɫɟйпɪиɪоɞноɝопɪоиɫɯожɞɟниямоɞɟлиɪоɜɚниимолɟкɭляɪнойОɞнɚкоɬɟоɪɟɬичɟɫкиймɟɬоɞшиɪокоиɫпользɭɟɬɫяизɭчɟнияɯимичɟɫкиɯɫɜойɫɬɜ [27]. ȾɚлɟɟɭчиɬыɜɚямолɟкɭляɪныɟмɚɫɫыɫчиɬɚныколичɟɫɬɜɚмолɟкɭлоɫноɜныɯкомпонɟнɬоɜмоɞɟлиɪɭɟмойɬɚɛлоɫноɜɟɫɬɪɭкɬɭɪкомпонɟнɬоɜпоɫɬɪоɟнɚмоɞɟльɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚоɌɚɛлицɚКоличɟɫɬɜɟнныйɫоɫɬɚɜмоɞɟлиɪɭɟмоɝоɫплɚɜɚпчɟлиноɝоɜоɫкɚкɚкɚоȼɟщɟɫɬɜоМоляɪнɚямɚɫмольМɚɫɫоɜɚяɞоляɫплɚɜɟмолɟкɭлмоɞɟлиɫплɚɜɚɚɬомоɜмоɞɟлиЦɟɪоɬиноɜɚякиɫлоɬɚ396,77,28640Нɟоцɟɪоɬиноɜɚякиɫлоɬɚ382,67333231Мɟлиɫɫиноɜɚякиɫлоɬɚ452,8082,42184Монɬɚниноɜɚякиɫлоɬɚ438,7812,42178Мɟлиɫɫилпɚльмиɬɚɬ677,2433212940пɚльмиɬɚɬ691,2671271001ɞиɫɬɟɚɪоолɟин889,4857,94684пɚльмиɬоɞиолɟин803,3075,33453Пɚльмиɬоɫɬɟɚɪоолɟин805,32326,8142142ИɌОȽО:1008453мɚɫлɟкɚкɚопомимоɬɪиɝлицɟɪиɞоɜɫоɞɟɪжɚɬɫяɬɚкжɟɫɜоɛоɞныɟкиɫлоɬыконцɟнɬɪɚможноɫɭɞиɬьɜɟличинɟкиɫлоɬноɝоɫɭɞɚɪɫɬɜɟннɚяɮɚɪмɚкопɟя X [ 24] ɞопɭɫкɚɟɬкиɫлоɬноɟмɚɫлɚкɚкɚоɛолɟɟ 2,25 KOH 1 мɚɫлɚэɬоɝоɫлɟɞɭɟɬчɬоɫоɞɟɪжɚниɟкиɫлоɬмɚɫлɟкɚкɚоɫооɬɜɟɬɫɬɜɭющɟмɬɪɟɛоɜɚниямȽоɫɭɞɚɪɫɬɜɟннойɮɚɪмɚкопɟимольɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in Pharmacyɝɞɟкиɫлоɬɫоɞɟɪжɚниɟкиɫлоɬмɚɫлɚкɚкɚомольмɚɫɫɚ KOH, нɟоɛɯоɞимоɝоɬɪɚлизɚциикиɫлоɬɫоɞɟɪжɚщиɯɫямɚɫлɟкɚкɚо 1 мɚɫлɚкиɫлоɬноɟмоляɪнɚямɚɫɫɚмольɋɭммɚɪнɚямɚɫɫɚкомпонɟнɬоɜмɚɫлɚкɚкɚоɜключɚɟмыɯмолɟкɭляɪнɭюмоɞɟльɫоɫɬɚɜляɟɬɬɚɛлɌɚкимоɛɪɚзомколичɟɫɬɜокиɫлоɬмɚɫлɚкɚкɚомоɞɟлиɪɭɟмомоɛъɟмɟɞолжнопɪɟɜышɚɬьмольчɬоɫооɬɜɟɬɫɬɜɭɟɬмолɟкɭлкиɫлоɬɝɞɟ m ? мɚɫɫɚмɚɫлɚкɚкɚомоɞɟлиɪɭɟмойȺɜоɝɚɞɪомольмолɟкɭлкиɫлоɬмоɞɟлиɪɭɟПолɭчɟнныɟɪɟзɭльɬɚɬыɫооɬɜɟɬɫɬɜɭюɬɛлизиɬɟльно 1 молɟкɭлɟкиɫлоɬы 64 молɟкɭлкомпонɟнɬоɜɫплɚɜɚɬɚɛл. 2), коɬоɪыɯɫɪɚɜнимɚɪɚзмɟɪɚмкиɫлоɬɚмимɚɫлɚкɚкɚоɞɪɭɝɚяɬɪиɝзɚнимɚɟɬзнɚчиɬɟльноɛольшийоɛъɟмИɫɯоɞяэɬоɝомолɟкɭлыкиɫлоɬмɚɫлɚкɚкɚоɜключɟныɫоɫɬɚɜмоɞɟлиɪɭɟмойȾɚлɟɟиɫпользоɜɚниɟмȻиоэɜɪикɚпɪоизɜоɞилоɫьɬɟɪмоɞинɚмичɟɫкоɟɭɪɚɜноɜɟшиɜɚмоɞɟлиɫплɚɜɚмɟɬоɞоммолɟкɭляɪнойпоɫлɟчɟɝоɫиɫɬɟмɚɜɫɬɪɚиɜɚлɚɫьɪɚɫɬɜоɪи ? ɜоɞɭэɬɚнолПоɫлɟɬɟɪмоɞинɚмичɟɫкоɝоɭɪɚɜноɜɟшиɜɚниямɟɬоɞоммолɟкɭляɪнойɬɟчɟниɟ 5 пɪоизɜоɞилоɫьмоɞɟлиɪоɜɚниɟɜыɫɜоɛожɞɟнияɭчɚɫɬкɚɫплɚɜɚɪɚɫɬɜоɪиɬɟльɬɟчɟниɟ 20 ɬɚɛлицɟ 3 пɪиɜɟɞɟныизоɛɪɚжɟнияпɪоɫɬɪɚнɫɬɜɟнныɯɫɬɪɭкɬɭɪмоɞɟлиɪɭɟмыɯмомɟнɬыɌɚɛлицɚɋоɫɬояниямоɞɟлиɪɭɟмыɯɫиɫɬɟмɪɚзличныɟмомɟнɬыɜɪɟмɟниɜоɞɚкɚɬионɜоɞɚэɬɚнолɌɟɪмоɞинɚмичɟɫкоɟɭɪɚɜноɜɟшиɜɚниɟМоɞɟлиɪоɜɚниɟɜыɫɜоɛожɞɟнияPharmacy & Pharmacology V. 5 N 4, 2017Пɪоɞолжɟниɟɬɚɛлицыɪɟзɭльɬɚɬɟɬɟɪмоɞинɚмичɟɫкоɝоɭɪɚɜноɜɟшиɜɚнияɜоɞнойɫɪɟɞɟполɭчɟнɚɝɟɬɟɪоɝɟннɚяɫɬɟмɚчɟɬкоɜыɪɚжɟннойпоɜɟɪɯноɫɬьюɭпоɪяɞочɟннымиɫɬɪɭкɬɭɪɚмиɫплɚɜɟɫɪɟɞɟэɬɚнолɚпɪоизошлочɚɫɬичноɟɫмɟшиɜɚниɟɫплɚɜɚɪɚɫɬɜоɪиɬɟлɟмɬɚɛлɪɟзɭльɬɚɬɚмɚнɚлизɚɜɚнɜɚɚльɫоɜɚɜинпоцɟɬиномɫплɚɜомопɪɟɞɟɞлиɬɟльноɫɬиɜыɫɜоɛожɞɟниямолɟкɭлыɪɚɫɬɜоɪиɬɟльэɬоɝоопɪɟɞɟлɟноɬɟчɟниɟкоɬоɪоɝомоɞɭльɜɚнɜɚɚльɫоɜɚɜзɚимоɞɟйɫɬɜиямолɟкɭлойиономɫплɚɜомɫɬɚноɜилɫя 0,1 мольɜɚнɜɚɚльɫоɜɚɜзɚимоɞɟйɫɬɜияпɪɟɞɜɚɪиɬɟльнопоɞɜɟɪɝɚлиɫьɫɝлɚжиɜɚниюмɟɬоɞомɫкользящɟɝоɫɪɟɞнɟɝоɭɫɪɟɞнɟнияɊиɫɭнокȾинɚмикɚɜɚнɜɚɚльɫоɜɚɜзɚимоɞɟйɫɬɜиямɟжɞɭмолɟкɭлойиономɜинпоцɟɬинɚɫплɚɜомпчɟлиноɝоɜоɫкɚкɚкɚоɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in PharmacyȺнɚлизɪɟзɭльɬɚɬоɜмоɞɟлиɪоɜɚнияпокɚзыɜɚɟɬчɬоɜыɫɜоɛожɞɟниɟкɚɬионɚɫплɚɜɚэɬɚнолпɪоиɫɯоɞиɬȼыɫɜоɛожɞɟниɟоɫноɜɚɫплɚɜɚɜоɞɭ pH 7,0 ɯоɞиɬɛолɟɟɜыɫокойɝиɞɪоɮоɛноɫɬиоɫноɜɚнияȼыɫɜоɛожɞɟниɟɜоɞɭ pH 2,0 иɫɯоɞиɬоɞнɚкомолɟкɭлɚоɫɬɚɟɬɫяɬɟльноɟɫɜязɚннойпоɜɟɪɯноɫɬьюɌɚɛлицɚȾлиɬɟльноɫɬьɜыɫɜоɛожɞɟнияɜинпоцɟɬинɚɪɚɫɬɜоɪиɬɟльɪɟзɭльɬɚɬɚммоɞɟлиɪоɜɚниямолɟкɭляɪнойɊɚɫɬɜоɪиɬɟльȾлиɬɟльноɫɬьконɬɚкɬɚɫплɚɜомȼоɞɚ (pH 7,0)ɞɚ20ȼоɞɚ (pH 2,0)ɞɚ20ЭɬɚнолПɪоɜɟɞɟнныɟиɫɫлɟɞоɜɚнияпокɚзɚличɬоɜоɞнойɫɪɟɞɟ pH 2,0 пчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚо 3:2 ɪɚɫɬɜоɪимчɬояɜляɟɬɫяɮɚкɬоɪомзɚмɟɞляющимɜыɫɜоɛожɞɟниɟɪɚɫɬɜоɪиɬɟльɫɪɟɞɟ (pH 2,0) кɚɬионɜыɫɜоɛожɞɚɟɬɫяɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚо 3:2 пɟɪɟɯоɞиɬɜоɞɭэɬомɟɫɬьпоɜɟɪɯноɫɬиɫплɚɜɚɜыɫɜоɛожɞɚɟɬɫяɫплɚɜɚноɝоɜоɫкɚмɚɫлɚкɚкɚо 3:2 эɬɚнолполноɫɬьюпɟɪɟɯоɞиɬɪɚɫɬɜоɪиɬɟльэɬомпɪоиɫɯоɞиɬɫɬичноɟɪɚɫɬɜоɪɟниɟɫплɚɜɚэɬɚнолɟкɜɚнɬоɜоɯимичɟɫкоɝоɪɚɫчɟɬɚɬɟɪмоɞинɚмичɟɫкиɯɯɚɪɚкɬɟɪиɫɬикиɫпользоɜɚɜшиɯɫямоɞɟлиɪоɜɚниимолɟкɭляɪнойɮɪɚɝмɟнɬынɚчɚльноɝоконɟчноɝоɫоɫɬоянийɪɚɫɬɜоɪиɬɟльɪɚɫɬɜоɪиɬɟльɊиɫɭнокȼыɫɜоɛожɞɟниɟɜинпоцɟɬинɚɫплɚɜɚPharmacy & Pharmacology V. 5 N 4, 2017Ɋиɫɭнокȼыɫɜоɛожɞɟниɟɜинпоцɟɬинɚɫплɚɜɚэɬɚнолзɭльɬɚɬыɬɟɪмоɞинɚмичɟɫкиɯɯɚɪɚкɬɟɪиɫɬикмоɞɟлиɪɭɟмыɯɮɪɚɝмɟнɬоɜпɪɟɞɫɬɚɜлɟныɬɚɛл. 5, 6. ɊиɫɭнокȼыɫɜоɛожɞɟниɟɜинпоцɟɬинɚɫплɚɜɚɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in PharmacyɌɚɛлицɚɊɟзɭльɬɚɬыкɜɚнɬоɜоɯимичɟɫкоɝоɪɚɫчɟɬɚɜыɫɜоɛожɞɟнияɜинпоцɟɬинɚɫплɚɜɚɪɚɫɬɜоɪиɬɟльɋиɫɬɟмɚЭнɬɚльпиямольЭнɬɚльпияɜыɫɜоɛожɞɟниямольɫплɚɜɟɊɚɫɬɜоɪиɬɟльɛɟзɪɚɫɬɜоɪиɬɟлɟ pH 2,0-10658071,42-9450228,56-7786164,35-12322871,38pH 7,0-9847693,09-7284608,01-6976933,10-10155553,84Эɬɚнол-14228766,63-8000056,02-11357749,23-10870588,77ЭнɬɪопиямольpH 2,02,33911,94081,97152,0721pH 7,02,22911,47591,85501,6409Эɬɚнол2,83141,96521,99451,7424ɌɚɛлицɚɊɟзɭльɬɚɬыкɜɚнɬоɜоɯимичɟɫкоɝоɪɚɫчɟɬɚȽиɛɛɫɚɜыɫɜоɛожɞɟнияɜинпоцɟɬинɚɫплɚɜɚɪɚɫɬɜоɪиɬɟльɋиɫɬɟмɚȽиɛɛɫɚмольȽиɛɛɫɚɜыɫɜоɛожɞɟниямольɫплɚɜɟɊɚɫɬɜоɪиɬɟльɛɟзɪɚɫɬɜоɪиɬɟлɟpH 2,0-10658796,55-9450830,21-7786775,523-12323513,74pH 7,0-9848384,12-7285065,55-6977508,17-10156062,51Эɬɚнол-14229644,37-8000665,24-11358367,54-10871128,92ȼыɫɜоɛожɞɟниɟɫплɚɜɚɜоɫкɚмɚɫлɚкɚкɚо 3:2 ɜоɞɭ pH эɬɚнолɟɝоɪɚɫɬɜоɪимоɫɬиɫɪɟɞɚɯɬɚкжɟɪɚɫɬɜоɪимоɫɬиɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚоɪɚɫɬɜоɪяɟɬɫяэɬɚнолɟчɬояɜляɟɬɫяɮɚкɬоɪомɭɫкоɪяющимɜыɫɜоɛожɞɟниɟɪɚɫɬɜооɫɬɚɟɬɫяɫплɚɜɚмоɞɟлиɪоɜɚнииɜоɞойчɬоɝоɜоɪиɬɬомчɬоɜыɫɜоɛожɞɟниɟɫплɚɜɚɜоɫкɚмɚɫлɚкɚкɚо 3:2 ɜоɞɭ pH 7,0 зɚɬɪɭɞЗɚключɟниɟȼыɫɜоɛожɞɟниɟɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚо 3:2 ɜоɞɭяɜляɟɬɫяэнɟɪɝɟɬичɟɫкиɜыɝоɞнымпɪоцɟɫɫомɬɚкжɟɫопɪоɜожɞɚɟɬɫяɭɜɟличɟниɟмэнɬɪопиичɬоɝоɜоɪиɬɛолɟɟɜыɫокойɬɟɪмоɞинɚмичɟɫкойɜɟɪояɬноɫɬиконɟчноɝоɫоɫɬоянияɪɚɫɬɜоɪɟȼыɫɜоɛожɞɟниɟɫплɚɜɚɜоɞɭэнɟɪɝɟɬичɟɫкиɜыɝоɞноɜыɫɜоɛожɞɟниɟмɜоɞɭȼыɫɜоɛожɞɟниɟэɬɚнолɫплɚɜɚэнɟɪɝɟɬичɟɫкиɜыɝоɞноɜыɫɜоɛожɞɟниɟмɜоɞɭоɬɫɭɬɫɬɜияɪɚɫɬɜоɫплɚɜɚэɬɚнолɟОɞнɚкоɪɟзɭльɬɚɬымоɞɟлиɪоɜɚниямолɟкɭляɪнойɫɜиɞɟɬɟльɫɬɜɭюɬɜозможноɫɬиɪɚɫɬɜоɪɟниякомпонɟнɬоɜɫплɚɜɚэɬɚнолɟЭɬояɜляɟɬɫяɮɚкɬоɪомэɮɮɟкɬиɜноɫɬьɜыɫɜоɛожɞɟнияПɪоɜɟɞɟнныɟиɫɫлɟɞоɜɚниямоɞɟлиɪоɜɚниямолɟкɭляɪнойɜыɫɜоɛожɞɟнияɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚо 3:2 покɚзыɜɚɟɬɜозможноɫɬьɜыɫɜоɛожɞɟнияɜоɞɭэɬɚнолПолɭчɟнныɟɪɟзɭльɬɚɬыпозɜоляюɬпɪɟɞположиɬьɛолɟɟнизкɭюɜыɫɜоɛожɞɟнияɫплɚɜɚэɬɚнолɬɜоɪомкиɫлоɬыɯлоɪиɫɬоɜоɞоɪоɞнойIntroduction. uid, solid or gaseous ac-preserving them against environment [ 1, 2]. The choice of storage, etc. [3]. Preferable hydrophobic shell-matrix perature of hydrophobic substan ce[4]. ers and their mixtures. Preferable ers, animal waxes, plant waxes, Pharmacy & Pharmacology V. 5 N 4, 2017resins and their mixtures. Animal waxes are beeswax, Vinpocetine is a perspective medicinal substance for development of a microencapsulated fo r m [5, 6]. Vinpocetine is poorly soluble in water, and, for ed water and hydrochloric acid, which uence of auxiliary substances and technological fac tors [7].prepared by dispersion m ethod [8]. But often the ciency make the choice of microencapsulation lm former, is min imized [9].from the melt of beeswax and cacao butter 3:2 into water, release process simulation from the melt into different charges were calculated by quantum-chemical method.Taking into account the vinpocetine ionization )in wa ter 7.1 [10] and using Henderson?Hasselbalch equation [11], it is possible to are a relative content of vinpocetine-base and vinpocetine-cation in the solution respectively.environment according to the literature data [ 12] is low cant concentration cation and in the form of base. The release simulation of to be interesting in this study, since it gives an opportuni-ty to explain the difference between release ef ciency of this substance into the solvent in different values of pH from the molecular structure point of view.ɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in Pharmacying on the value of solvent pH. Moreover, ionization can We performed the simulation of exactly this critical As an example of a similar study the work by Hui-dong Zheng [ 13] can be represented.tems is the atom charge distribution. For this purpose atom charges of the simulated sys- method, cient accuracy of semi-em-pirical methods. The choice of quantum-chemical meth-ods to detect the atom charges of melt component mo-al theory method UB3LYP with 6-31G* basis set) was made according to the results of the study, represented in the wor k [14]. The validity of methods used for atom charge calculation in molecular dynamics simula-demonstrated in the wo rk [15].by molecular mechanics mm+ met h od [16] in Hyper method (unrestricted Hartree-Fock method, basis set 3 -21G* [17]). The charges were calculated by method (density functional theory method U B3LYP [18], basis solvents ? water and ethanol. After that thermodynamic author is A.A. Glushko) [19] (force el d Amber94 [20], rectangular periodic boundary conditions, Berendsen integration step 1 fs).Thermostating was performed according to the graph in Table 1. The temperature, set by the thermostat, was Table 1 ? Graph of thermostat work in molecular dynamics simulation processTime, fsTemperature, K300000310tine release from the melt spot to the solvent was per- nal state, a moment of time of molecular dynamics simulation was used, corresponding to full release a module of Van-der-Waals energy interaction between mol). For both states geometry optimization in Amber94 eld was performed by Bioeurica program.[ 22] by unrestricted Hartree-Fock method in basis set STO-3G in free distributable program Orca 4.0 [17]. and entropy energies () of vinpocetine release into different where T istemperature, Pharmacy & Pharmacology V. 5 N 4, 2017(A ? base, B ? cation)Cerotinic acidMelissinic acidMontaninic acid BɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in PharmacyMelissilpalmitateMiricilpalmitate1,3-distearo-2-olein1-palmito-2,3-dioleinabout chemical composition of beeswax [ 2 3] and cacao butter [24]. Further, based on molecular masses quantities of molecules of the simulated system basic components were calculated. Accounting the volume of the simulated beeswax and cacao butter melt 3:2 a fragment, equal to 125 nm, the components which molecules? number according to the quantitative composition was more than 2 for the simulated volume, were included into the not include d [25].Pharmacy & Pharmacology V. 5 N 4, 2017dynamics simulation of phospholipid membran es [26].Hereby only the components contained in a fairly large thousands of cubic nanomet ers [27].Taking that into consideration, nowadays it does not for physical-chemical properties of mixtures st udy [28-Further, taking into consideration molecular masses, simulated system were calculated (Table 2).Table 2 ? Quantitative composition of the simulated beeswax and cacao butter melt 3:2Cerotinic acid396.77.28640Neocerotinic acid382.67333231Melissinic acid452.8082.42184Montaninic acid438.7812.42178Melissilpalmitate677.2433212940Miricilpalmitate691.26712710011,3-distearo-2-olein889.4857.946841-palmito-2,3-diolein803.3075.33453Palmitostearoolein805.32326.8142142TOTAL:1008453In cacao butter, besides triglycerides, free fatty acids are contained. Their concentration can be learnt by the Their concentration can be learnt by the acid value of cacao butter to be no more than 2.25 mg of KOH per 1 g of butter. Therefore, the content of fatty acids in cacao butter, meeting the requirements of State (fatty acids) is content of fatty acids in 1 g of cacao butter, mol/g;Total mass of cacao butter components, included in g (Table 2), therefore mol, which ? Avogadro number, molmolecule of fatty acid per 64 different molecules of the in volume with fatty acids of cacao butter, and another cantly larger volume. molecular dynamics method. After that the system was included into the solvents ? water and ethanol. After the systems for different moments of time are represented in Table 3.ɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in PharmacyTable 3 ? States of simulated systems at different moments of timeTime,water (pH=7)water (pH=2)Vinpocetine release simulationPharmacy & Pharmacology V. 5 N 4, 2017melt with water took place (Table3).According to the results Van-der-Waals interaction (Fig. 4).To do it, the time was detected,while the module of Van-der-Waals interaction energy between molecule kDj/mol. Time series of Van-der-Waals? interaction energy were preliminary smoothed by moving average Figure 4 ? Dynamics of Van-der-Waals? interaction energy between vinpocetine molecule (ion) The analysis of the obtained results shows, that the release of vinpocetine cation from the melt into ethanol goes during 15.5 ns. The release of vinpocetine base from the melt into water with pH = 7.0 doesn?t go, due to higher hydrophobicity of The release into water with pH = 2.0 goes, but vinpocetine Table 4 ? Durability of vinpocetine release into solvent according to the results of molecular dynamics simulationSolventDurability of vinpocetine contact with the melt, nsWater (pH = 7.0)�20Water (pH = 2.0)�20Ethanol15,5ɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in PharmacyThe performed study has shown, that the melt of beeswax and cacao butter 3:2 is not soluble in water environment which appears to be the factor, slowing ic environment (pH = 2.0) vinpocetine cation releases from the beeswax and cacao butter 3:2 and passes into water. Hereby vinpocetine adsorption tends to exists on Vinpocetine molecule releases from the beeswax For the quantum chemical calculation of thermodynamic characteristics of vinpocetine release from systems, used in the molecular dynamics simulation, fragments of initial and nal states were isolated (Fig. 5?7):Figure 5 ? Vinpocetine release from the melt into water in pH 2Figure 6 ? Vinpocetine release from the melt into water in pH 7Pharmacy & Pharmacology V. 5 N 4, 2017Th e results of thermodynamic characteristics calculation of the simulated system fragments are represented in Tables 5 and 6.Table 5 ? Results of quantum-chemical calculation of enthalpy and entropy SystemSystem enthalpy, kDj/molVinpocetine Vinpocetine pH=2-10658071.42-9450228.56-7786164.35-12322871.38-735.75pH=7-9847693.09-7284608.01-6976933.10-10155553.84-185.85Ethanol-14228766.63-8000056.02-11357749.23-10870588.77484.64System entropy, kDj/molpH=22.33911.94081.97152.0721-0.2363pH=72.22911.47591.85501.64090.0971Ethanol2.83141.96521.99451.7424-1.0597Table 6 ? Results of quantum-chemical calculation of the Gibbs energySystem Gibbs energy, kDj/molGibbs energy of VinpocetineVinpocetine in pH=2-10658796.55-9450830.21-7786775.523-12323513.74-662.50pH=7-9848384.12-7285065.55-6977508.17-10156062.51-121.02Ethanol-14229644.37-8000665.24-11358367.54-10871128.92813.15Figure 7 ? Vinpocetine release from the melt into ethanolVinpocetine release from the melt of beeswax and cacao butter 3:2 into water with different pH and into dissolves in ethanol, and that is the factor, speeding up Vinpocetine stays in the melt phase during simulation ɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in Pharmacy cult. Vinpocetine release from the melt pH = 2.0 is energetically advantageous process, and it is also accompanied by increase of entropy, which indicates nal state (vin-Vinpocetine release from the melt into water with pH = 7.0 is energetically less advantageous comparedwith Vinpocetine release into ethanol from the melt is en-ergetically less advantageous compared with the release ciency of vinpocetine re-into water with pH = 2.0 and into ethanol. The obtained ȻиɛлиоɝɪɚɮичɟɫкийПоɫɬɪɚшɏишоɜɚМИКɊОКȺПɋɍЛИɊОȼȺНИȿɎȺɊМȺЦИИ ? ɋОɋɌОПȿɊɋПȿКɌИȼЫȼɟɫɬникɮɚɪмɚцииПолкоɜникоɜɚɋɬɟпɚноɜɚȼОЗМОЖНОɋɌИɋОЗȾȺНИЯПɊОЛОНȽИɊОȼȺННЫɏɎОɊМȺɎОȻȺЗОЛȺНɚɭчныɟɜɟɞомоɫɬиȻɟлɝоɪоɞɫкоɝоɝоɫɭɞɚɪɫɬɜɟнноɝоɜɟɪɫиɬɟɬɚɋɟɪияМɟɞицинɚɎɚɪмɚция. 2011. 4(13). ȺɜɬинɚПиɫɚɪɟɜПɚнкɪɭшɟɜɚȼоɪонкоɜɚɊȺЗɊȺȻОɌКȺȾȿɌɋКОЙЛȿКȺɊɋɌȼȿННОЙɎОɊМЫОɋНОȼȿМИКɊОКȺПɋɍЛМȿɌɊОНИȾȺЗОЛОМ // НɚɭчныɟɜɟɞоȻɟлɝоɪоɞɫкоɝоɝоɫɭɞɚɪɫɬɜɟнноɝоɭниɜɟɪɫиɬɟɬɚɋɟɪияМɟɞицинɚɎɚɪмɚция. 2011. КойнȽɭɟнɏɚнɫɟнИɫɚкɌомɚɫɌɫɟМикɪокɚпɫɭлы // ПɚɬɊоɫɫия A61K9/56. N 2006108860/15; ЗɚяɜлОпɭɛлПолкоɜникоɜɚȽɚнзюкɊɚзɪɚɛоɬкɚпɪолонɝиɪоɜɚннойпɟɪоɪɚльнойлɟкɚɪɫɬɜɟннойɮоɪмыкомпозицииɪɟɬинолɚɚцɟɬɚɬомɮоɪмыɫоɜɟɪшɟнɫɬɜоɜɚнияɮɚɪмɚцɟɜɬичɟɫкоɝоɪɚзоɜɚнияɮизиолоɝичɟɫкиɚкɬиɜныɯɜɟщɟɫɬɜмɚɬɟɪиɚлы 4-ȼɫɟɪоɫɫийɫкойɪоɞнымнɚɭчномɟɬоɞичɟɫкойконɮɟɪɟнцииɎɚɪмоɛɪɚзоɜɚниɟɋɬɟпɚноɜɚПолкоɜникоɜɚȽɚнзюкȺɪльɬИɋɋЛȿȾОȼȺНИȿȼЛИЯНИЯɊȺɋɌȼОɋɍɋПȿНЗИИМИКɊОКȺПɋɍЛȾИНȺМИКɍОȻЪЁМНОЙɋКОɊОɋɌИМОЗȽОȼОȽОКɊОȼОɌОКȺЛȺȻОɊȺɌОɊНЫɏ // НɚɭчныɟɜɟɞомоɫɬиȻɟлɝоɪоɞɫкоɝоɝоɫɭɞɚɪɫɬɜɟнноɝоɭниɜɟɪɫиɬɟɬɚɋɟɪияМɟɞицинɚɎɚɪмɚция. 2011. ПолкоɜникоɜɚȼЫɋȼОȻОЖȾȿНИȿМИКɊОКȺПɋɍЛИɊОȼȺННОЙɎОɊМЫɏимикоɮɚɪмɚцɟɜɬичɟɫкийжɭɪнɚлШɟɜчɟнкоȻиɪюкоɜɚКɭɞɪяɜцɟɜȺппɚɪɚɬɞиɫпɟɪɝиɪоɜɚниямикɪокɚпɫɭлиɪоɜɚнияжиɞкоɫɬɟй // ПɚɬɊоɫɫия. B01F11/02. 2000100442/12; Зɚяɜл. 11.01.2000; Опɭɛл27.12.2000. URL: http://www.freepatent.ru.ȽлɭшкоɏɚлилоɜɚНоɜɚямɟɬоɞикɚмɚɬɟмɚɬичɟɫкоɝомоɞɟлиɪоɜɚнияпɪоцɟɫɫɚжиɞкоɫɬнойэкɫɬɪɚкцииоɫноɜɟмолɟкɭляɪной // ȻɟликоɜɫкиɟМɚɬɟɪиɚлы IV ȼɫɟɪоɫɫийɫкойнɚɭчпɪɚкɬичɟɫкойконɮɟɪɟнциинɚɭчПяɬиɝоɪɫкИзɞɚɬɟльɫɬɜоПМɎИ. 60?62. 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Current Opinion in Colloid & Vol. 5. 2000. P. 217-223. DOI: 10.1016/S1359-0294(00)00058-3Rapaport D.K. ISKUSSTVO MOLEKULYARNOY DINAMIKI [THE ART OF MOLECULAR DYNAMICS]. Izhevsk: IKI [Izhevsk: ICS], 2012. P. 632. (In Russ.)Miyamoto H., Rein D.M., Kazuyoshi U., Yamane C., Cohen Y. MOLECULAR DYNAMICS SIMULATION OF CELLULOSE-COATED OIL-IN-WATER EMULSIONS. Vol. 24. Is. 7. 2017. P. 2699?2711. Leo D., Maranon J. CONFINED WATER/OIL INTERFACE. MOLECULAR DYNAMICS STUDY. Vol. 672. 2004. P. 221?229. DOI: 10.1016/j.theochem.2003.11.032 Sedghi M., Piri M., Goual L. ATOMISTIC MOLECULAR DYNAMICS SIMULATIONS OF CRUDE OIL/BRINE DISPLACEMENT IN CALCITE MESOPORES. . 2016. Vol. 32. P. 3375?3384.DOI:acs.langmuir.5b04713. ict of interest ict of interest.Polkovnikova Yulia Alexandrovna Candidate of Educational Institution of Higher Education ?Voronezh State University?. Research interests: dosage forms, microcapsules, prolongation, biopharmaceutical research. E-mail: juli-polk@mail.ru Candidate of Sciences (Pharmacy), Lecturer of the Department of Inorganic, Physical and Colloidal Chemistry of branch of Volgograd State Medical University. Research interests: computer chemistry, software development dynamics, QSAR. E-mail: alexander.glushko@lcmmp.ruMikhailovskaya Irina Yurievna student of Educational Institution of Higher Education ?Voronezh State University?. Research interests: dosage forms, microencapsulation, prolongation. E-mail: Kariyeva Yoshut Saidkarimovna Doctor of Sciences (Pharmacy), associate professor, head. Department of Technology of Medicinal Forms of Tashkent Pharma-ceutical Institute. Research interests: soft dosage forms, КонɮликɬинɬɟɪɟɫоɜȺɜɬоɪызɚяɜляюɬоɬɫɭɬɫɬɜииконɮликɬɚинɬɟɪɟɫоɜȺɜɬоɪыПолкоɜникоɜɚȺлɟкɫɚнɞɪоɜнɚ ? кɚнɞиɞɚɬɮɚɪмɚцɟɜɬичɟɫкиɯнɚɭкɞоцɟнɬɎȽȻОɍнɟжɫкийɝоɫɭɞɚɪɫɬɜɟнныйɭниɜɟɪɫиɬɟɬОɛлɚɫɬьнɚɭчныɯинɬɟɪɟɫоɜлɟкɚɪɫɬɜɟнныɟɮоɪмыкɚпɫɭлыпɪолонɝиɪоɜɚниɟɛиоɮɚɪмɚцɟɜɬичɟɫкиɟиɫɫлɟɞоɜɚнияȽлɭшкоȺлɟкɫɚнɞɪȺлɟкɫɟɟɜич ? кɚнɞиɞɚɬмɚцɟɜɬичɟɫкиɯнɚɭкпɪɟпоɞɚɜɚɬɟльПяɬиɝоɪɫкоɝомɟɞикоɮɚɪмɚцɟɜɬичɟɫкоɝоинɫɬиɬɭɬɚ ? ɮилиɚлɚɎȽȻОɍȼолɝȽМɍМинзɞɪɚɜɚɊоɫɫииОɛлɚɫɬьнɚɭчныɯинɬɟɪɟɫоɜкомпьюɬɟɪнɚяɛоɬкɚоɛɟɫпɟчɟниямолɟкɭляɪноɝомоɞɟлиɪоɜɚниямолɟкɭляɪныймолɟкɭляɪнɚяɞинɚмикɚ, QSAR. E-mail: alexander.glushko@lcmmp.ruМиɯɚйлоɜɫкɚя ? ɫɬɭɞɟнɬкɚɮɚɪмɚцɟɜɬичɟɫкоɝоɮɚкɭльɬɟɬɚɎȽȻОɍɪонɟжɫкийɝоɫɭɞɚɪɫɬɜɟнныйɭниɜɟɪɫиɬɟɬлɚɫɬьнɚɭчныɯинɬɟɪɟɫоɜлɟкɚɪɫɬɜɟнныɟɮоɪмымикɪокɚпɫɭлиɪоɜɚниɟпɪолонɝиɪоɜɚниɟ E-mail: Кɚɪиɟɜɚɋɚиɞкɚɪимоɜнɚ ? ɞокɬоɪɮɚɪмɚцɟɜɬичɟɫкиɯнɚɭкɞоцɟнɬкɚɮɟɞɪойɬɟɯнолоɝиилɟкɚɪɫɬɜɟнныɯɮоɪмɌɚшкɟнɬɫкоɝоɮɚɪмɚцɟɜɬичɟɫкоɝоинɫɬиɬɭɬɚОɛлɚɫɬьнɚɭчныɯинɬɟɪɟɫоɜлɟкɚɪɫɬɜɟнныɟɮоɪмыɝɟлиɬɟлимɚɬɟмɚɬичɟɫкоɟплɚниɪоɜɚниɟэкɫпɟɪимɟнɬɚПоɫɬɭпилɚɪɟɞɚкциюОɬпɪɚɜлɟнɚɞоɪɚɛоɬкɭПɪиняɬɚпɟчɚɬиɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in PharmacyɍȾКʺОʪʫЛʰˀОʦʤʻʰʫʿˀОˉʫˁˁʤʦˏˁʦОʥОʮʪʫʻʰЯʺʰКˀОКʤʿˁ˄ЛОʥОЛОЧКОʱПолкоɜникоɜɚȽлɭшкоМиɯɚйлоɜɫкɚяКɚɪиɟɜɚɎɟɞɟɪɚльноɟɝоɫɭɞɚɪɫɬɜɟнноɟɛюɞжɟɬноɟоɛɪɚзоɜɚɬɟльноɟɭчɪɟжɞɟниɟоɛɪɚзоɜɚнияȼоɪонɟжɫкийɝоɫɭɞɚɪɫɬɜɟнныйɭниɜɟɪɫиɬɟɬɊоɫɫияȼоɪонɟжɋɬɭɞɟнчɟɫкɚямɟɞикоɮɚɪмɚцɟɜɬичɟɫкийинɫɬиɬɭɬɎȽȻОɍȼолɝȽМɍМинзɞɪɚɜɚɊоɫɫииɊоɫɫия, 11. E-mail: alexander.glushko@lcmmp.ruɌɚшкɟнɬɫкийɮɚɪмɚцɟɜɬичɟɫкийɭниɜɟɪɫиɬɟɬɍзɛɟкиɫɬɚнɌɚшкɟнɬȺйɛɟкɚМикɪокɚпɫɭлынɚɫɬоящɟɟɜɪɟмяɪɚзличныɯМикɪокɚпɫɭлыɜиɬɚминɚмиэɮиɪнымимɚɫлɚмиɜɯоɞяɬɫоɫɬɚɜɪɚзличныɯкоɫмɟɬичɟɫкиɯɫɪɟɞɫɬɜкɪɟмоɜɝɟлɟйɫыɜоɪоɬок). Микɪокɚпɫɭлиɪоɜɚнныɟпɪоɛиоɬикииɫпользɭюɬɫякоɪмɚɯкоɪмоɜыɯɞоɛɚɜкɚɯɜɟɬɟɪинɚɪиилɚɫɬьмикɪокɚпɫɭлиɪоɜɚнияɮɚɪмɚции ? ɫоɜмɟщɟниɟоɛщɟйɞозиɪоɜкɟлɟкɚɪɫɬɜɟнныɯɜɟщɟɫɬɜнɟɫоɜмɟɫɬимыɯɫɜоɛоɞномɜиɞɟЦɟльɪɚɛоɬы ? ɫɪɚɜниɬɟльныйɬɟɪмоɞинɚмичɟɫкиɯɪɚкɬɟɪиɫɬикɜыɫɜоɛожɞɜинпоцɟɬинɚɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚо 3:2 ɪɚɫɬɜоɪкиɫлоɯлоɪиɫɬоɜоɞоɪоɞной 0,01 ɫпиɪɬэɬилоɜыйМɚɬɟɪиɚлымɟɬоɞымоɞɟлиɪоɜɚнияпɪоцɟɫɫɚɜыɫɜоɛожɞɟнияɜинпоцɟɬинɚɫплɚɜɚɪɚзличныɯɫɪɟɞɚɯмоɞɟликомпонɟнɬоɜиɫɫлɟɞɭɟмыɯɫиɫɬɟмɜычиɫлɟнызɚɪяɞыɚɬомоɜкɜɚнɬоɜоɯимичɟɫкиммɟɬоɞоммоɞɟликомпонɟнɬоɜиɫпользоɜɚниɟм Hyper Chem 8.01. кɚчɟɫɬɜɟнɚчɚльноɝоɫоɫɬоянияɪɚɫчɟɬɚмоɞинɚмичɟɫкиɯɯɚɪɚкɬɟɪиɫɬикɜыɫɜоɛожɞɜинпоцɟɬинɚɫплɚɜɚɛылɚиɫпользоɜɚнɚконɮоɪмɚцияɫɬɟмыɫплɚɜɜинпоцɟɬинпоɫлɟɬɟɪмоɞинɚмичɟɫкоɝоɭɪɚɜноɜɟшиɜɚниямɟɬоɞоммолɟкɭляɪнойȻиоэɜɪикɚɬɟчɟниɟ 5 ɜыɞɟлɟнныɯɫиɫɬɟмпɪоɜоɞилɫяколɟɛɚɬɟльныйиɫпользоɜɚнинɟоɝɪɚничɟнноɝомɟɬоɞɚɏɚɪɬɪиɎокɚɛɚзиɫɟ STO-3G Orca 4.0. Ɋɟзɭльɬɚɬыоɛɫɭжɞɟниɟȼыɫɜоɛожɞɜинпоцɟɬинɚɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚо 3:2 ɪɚзличныɯ pH эɬɚнолɪɚɫɬɜоɪимоɫɬиэɬиɯɫɪɟɞɚɯɬɚкɪɚɫɬɜоɪимоɫɬиɫплɚɜɚЗɚключɟниɟПɪоɜɟɞɟнныɟиɫɫлɟɞоɜɚниямоɞɟлиɪоɜɚниямолɟкɭляɪнойɜыɫɜоɛожɞɜинпоцɟɬинɚɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚо 3:2 покɚзыɜɚɟɬɜозможноɫɬьɜыɫɜоɛожɞɜинпоцɟɬинɚ pH 2,0 эɬɚнолПолɭчɟнныɟɪɟзɭльɬɚɬыпозɜоляюɬпɪɟɞположиɬьɛолɟɟɜыɫɜоɛожɞɜинпоцɟɬинɚɫплɚɜɚэɬɚнолɪɚɫɬɜоɪомкиɫлоɬыɯлоɪиɫɬоɜоɞоɪоɞнойКлючɟɜыɟɫлоɜɚмикɪокɚпɫɭлыоɛолочкɚɜинпоцɟɬинɜоɫкмɚɫлокɚкɚокɜɚнɬоɜоɯимичɟɫкийɪɚɫчɟɬɜыɫɜоɛожɞSIMULATION OF VINPOCETINE RELEASE PROCESS FROM MICROCAPSULES WITH HYDROPHOBIC SHELLYu.A. Polkovnikova, A.A. Glushko, I.Yu. Mikhailovskaya, Yo.S. Karieva?Voronezh State University?, 3, Student str., Voronezh, Russia, 394036Pyatigorsk Medical and Pharmaceutical Institute ? branch of Volgograd State Medical University, 11, Kalinin ave., Pyatigorsk, Russia,357532 E-mail: alexander.glushko@lcmmp.ruTashkentskiy Pharmaceutical University, 45, Aybeka Str., Tashkent, Uzbekistan,100015циɬиɪоɜɚнияПолкоɜникоɜɚȽлɭшкоМиɯɚйлоɜɫкɚяКɚɪиɟɜɚМОȾȿЛИɊОȼȺНИȿПɊОЦȿɋɋȺȼЫɋȼОȻОЖȾȿНИЯМИКɊОКȺПɋɍЛȽИȾɊОɎОȻНОЙОȻОЛОЧКОЙɎɚɪмɚцияɮɚɪмɚколоɝияПолкоɜникоɜɚȽлɭшкоМиɯɚйлоɜɫкɚяКɚɪиɟɜɚFor citation:Polkovnikova Yu.A., Glushko A.A., Mikhailovskaya I.Yu., Karieva Yo.S. SIMULATION OF VINPOCETINE RELEASE Pharmacy & Pharmacology V. 5 N 4, 2017Nowadays microcapsules are widely spread in different industries. Microcapsules with vitamins, etheric and fatty oils are included into different cosmetics (creams, gels, serums). Microencapsulated probiotics are used in foods and fodder additives in veterinary. An important eld of application of microencapsulation in pharmacy is the combination in the total dosage of drugs that are incompatible when mixed in free form. of thermodynamic characteristics of vinpocetine release from the melt of beeswax and cacao butter 3:2 into water, solution of hydrochloric acid 0.01 M and ethanol. For simulation of the process of vinpocetine release from the melt into different environments models component models of the studied systems were built and their atom charges were calculated by quantum-chemical method. Spatial models of the components were built in Hyper Chem 8.01. As an initial state for the thermodynamic characteristics of the calculation of vinpocetine release from the ics simulation in Bioeurica program for 5 ns. For isolated systems a vibrational analysis was performed with the use of unrestricted Hartree-Fock method in STO-3G basis set in Orca 4.0 program. Vinpocetine release from the melt of beeswax and cacao butter 3:2 into water with different pH values and to ethanol depends on its solubility in these environments, and also on solubility of the melt. release from the melt of beeswax and cacao butter 3:2 by molecular dynamics simulation demonstrates the opportunity of vinpocetine release into water with pH=2 and into ethanol. The obtained results make it possible to assume a lower degree of vinpocetine release from the melt into ethanol compared with the solution of hydrochloric acid 0,01 M. microcapsule, shell, vinpocetine, beeswax, cacao butter, quantum chemistry, molecular dynamics simulation, degree of releaseȼɜɟɞɟниɟИнкɚпɫɭлиɪоɜɚниɟэɬопɪоцɟɫɫкоɬоɪоммɟльчɚйшиɟжиɞкоɝоɬɜɟɪɞоɝоɝɚзоɜоɝоɚкɬиɜноɝоинɝɪɟɞиɟнɬɚɭпɚкоɜɚныɜɬоɪоймɚɬɟɪиɚлɟɝоɜозɞɟйɫɬɜийокɪɭжɚюɫɪɟɞы [ 1, 2]. Ƚиɞɪоɮоɛнɭюоɛолочкɭмɚɬɪицɭмикɪокɚпɫɭлɜыɛиɪɚюɬоɫноɜɚниинɟоɛɯоɞимыɯɫɜойɫɬɜмикɪокɚпɫɭлынɚпɪимɟɪоɫноɜɚниизнɚчɟниямикɪокɚпɫɭлɬɟмпɟɪɚɬɭɪы2]. Пɪɟɞпочɬиɬɟльнɚяоɛолочкɚмɚɬɪиɞолжнɚоɛлɚɞɚɬьɬɟмпɟɪɚɬɭɪойплɚɜлɟния 45?ɬɚкчɬоɛыможнокомнɚɬнойɬɟмпɟɪɚɬɭɪɟможноиɫпользоɜɚɬьлюɛоɟɝиɞɪоɮоɛноɟɜɟщɟɫɬɜоɟɫлимикɪокɚпɫɭлыɬɟмпɟɪɚɬɭɪɟɬɟмпɟɪɚɬɭɪыɝиɞɪоɮоɛноɝоɜɟщɟɫɬɜ 45?ȽиɞɪоɮоɛнɚяоɛолочкɚмɚɬɪицɚможɟɬɝɪɭппыɜключɚюмɚɫлɚɜоɫкиɫмолыэмɭльɝɚɬоɪыɫмɟɫиПɪɟɞпочɬиɬɟльнɚяоɛолочкɚɬɪицɚɜыɛиɪɚɟɬɫяɝɪɭппыɜключɚющɟйжиɜоɬныɟмɚɫлɚполноɫɬьюɝиɞɪиɪоɜɚнныɟжиɜоɬмɚɫлɚɝиɞɪиɪоɜɚнныɟполноɫɬьюɝиɞɪиɪоɜɚнныɟɫɜоɛоɞныɟкиɫлоɬыɞɪɭɝиɟэмɭльɝɚɬоɪыжиɜоɬныɟɜоɫкиɜоɫкиминɟɪɚльныɟɜоɫкиɫинɬɟɬичɟɫкиɟɜоɫкипɪиɪоɞныɟɫинɬɟɬичɟɫкиɟɫмолыЖиɜоɬныɟɜоɫкипɪɟɞɫɬɚɜляюɬɜоɫклɚнолинɜоɫкɜоɫккиɬɚйɫкоɝоɜоɫкоɜоɝочɟɪɜɟцɚПɟɪɫпɟкɬиɜнымлɟкɚɪɫɬɜɟннымɜɟщɟɫɬɜомɫозɞɚниямикɪокɚпɫɭлиɪоɜɚннойɮоɪмыяɜляɟɬɫя [5, 6]. плоɯоɪɚɫɬɜоɪяɟɬɫяɜоɞɟпɪоɜɟɞɟнияпɪɟɞɜɚɪиɬɟльныɯиɫɫлɟɞоɜɚнийɫноɜɚниюɫоɫɬɚɜɚмикɪокɚпɫɭлопɪɟɞɟлɟниюполɭчɟнияиɫɫлɟɞоɜɚкɚчɟɫɬɜɟɫɪɟɞыɜоɞойочищɟннойɪɚɫɬɜоɪомкиɫлоɬыɯлоɪиɫɬоɜоɞоɪоɞнойможɟɬиɫпользоɜɚнɫпиɪɬчɬопозɜолиɬɛолɟɟопɪɟɞɟлиɬьɜлияниɟɜɫпомоɝɚɬɟльныɯɜɟщɟɫɬɜɬɟɯнолоɝичɟɫкиɯɮɚкɬ [5, 6]. Микɪокɚпɫɭлыоɛолочкойполɭчɟнымɟɬоɞомɜɚния [8]. нɚкозɚчɚɫɬɭюɫложноɫɬьɚппɚɪɚɬɭɪноɝооɮоɪмлɟпɪоцɟɫɫɚнизкɚяэɮɮɟкɬиɜноɫɬьɞɟлɚюɬпоɞмɟɬоɞикимикɪокɚпɫɭлиɪоɜɚнияɞоɪоɝоɫɬоящимиɫɫлɟɞоɜɚниɟмМоɞɟлиɪоɜɚниɟмолɟкɭляɪнойɪɚɫɬɜоɪоɜизɭчɟниипɪоцɟɫɫɚɜыɫɜоɛожɞɟниялɟкɚɪɫɬɜɟнныɯɜɟщɟɫɬɜмикɪокɚпɫɭлпозɜоляɟɬпоɞоɛɪɚɬьопɬимɚльныйплɟнкооɛɪɚзоɜɚɬɟльɜоɞоɪоɞныйпокɚзɚɬɟльɫɪɟɞɭɜыɫɜоɛожɞɟнияɞɪɭɝиɟɮɚкɬоɪыɜɚжныɟɭɫпɟшноɝопɪоɜɟɞɟнияпɪоцɟɫɫɚмикɪокɚпɫɭлиɪоɜɚэɬомнɟоɛɯоɞимоɫɬьпɪоɜɟɞɟнияɪɟɚльноɝоэкɫпɟɪимɟнɬɚɫɜоɞиɬɫянимɭмɭ [8]. Цɟль иɫɫлɟɞоɜɚнияɚнɚлизɬɟɪмоɞинɚмичɟɫкиɯɯɚɪɚкɬɟɪиɫɬикɜыɫɜоɛожɞɟнияɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚо 3:2 ɜоɞɭɪɚɫɬɜоɪкиɫлоɬыɯлоɪиɫɬоɜоɞоɪоɞɫпиɪɬМɚɬɟɪиɚлымɟɬоɞымоɞɟлиɪоɜɚнияцɟɫɫɚɜыɫɜоɛожɞɟнияɫплɚɜɚɫɪɟɞɚɯпɪɟɞɜɚɪиɬɟльнопоɫɬɪоɟныкомпонɟнɬоɜиɫɫлɟɞɭɟмыɯɬɚккомпонɟнɬыɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚоɚɬомоɜкɜɚнɬоɜомичɟɫкиммɟɬоɞоммолɟкɭлыɭчиɬыɜɚлɚɫьзɚɜиɫимоɫɬиɜɟличины pH ɫɪɟɞыɜоɫпɪоизɜɟɞɟнияɟɝопоɜɟɞɟнияɪɚɫɬɜоɪиɬɟлɟɍчиɬыɜɚяпокɚзɚɬɟльконɫɬɚнɬы (pKоɞɟ 7.1 [10] пользɭяȽɟнɞɟɪɫонɚɫɟльɛɚɯɚ [11], можноɫɞɟлɚɬьɜыɜоɞɬомчɬо pH пɪɚкɬичɟɫкиполноɫɬьюионизиɪоɜɚн pH ɞоляионизиɪоɜɚнныɯмолɟкɭлɫɬɚɜляɟɬɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in PharmacyɝɞɟоɬноɫиɬɟльноɟɫоɞɟɪжɚниɟоɫноɜɚниякɚɬионɚɪɚɫɬɜоɪɟɫооɬɜɟɬɫɬɜɟнноɊиɫɭнокОɬноɫиɬɟльноɟɫоɞɟɪжɚниɟɜинпоцɟɬинɚоɫноɜɚнияɜинпоцɟɬинɚкɚɬионɚɪɚɫɬɜоɪɟɫооɬɜɟɬɫɬɜииɭɪɚɜнɟниɟмȽɟнɞɟɪɫонɚɏɚɫɫɟльɛɚɯɚкɚɬионоɫноɜɚниɟэɬомɪɚɫɬɜоɪимоɫɬьɬɪɚльнойɜоɞнойɫɪɟɞɟлиɬɟɪɚɬɭɪы [ 12] низкɚя (1,89?10чɬоɝоɜоɪиɬнɟзнɚчиɬɟльконцɟнɬɪɚцииɜоɞнойɫɪɟɞɟкɚккɚɬионɚɬɚкоɫноɜɚнияИнɬɟɪɟɫнымɞɚнномиɫɫлɟɞоɜɚниипɪɟɞɫɬɚɜляɟɬɫямоɞɟлиɪоɜɚниɟɜыɫɜоɛожɞɟниякɚккɚɬионɚɬɚкоɫноɜɚɫɪɟɞɭɪɚɫɬɜоɪиɬɟляэɬоɜозможноɫɬьоɛъяɫниɬьэɮɮɟкɬиɜноɫɬиɜыɫɜоɛожɞɟнияɞɚнноɝоɜɟщɟɫɬɜɚɪɚɫɬɜоɪиɬɟль pH ɬочкиɫɬɪоɟниямолɟкɭлэɬомпɟɪɟɯоɞмолɟкɭлыɫплɚɜɚɪɚɫɬɜоɪиɬɟльможɟɬɫопɪоɜожɞɚɬьɫязɚɜиɫимоɫɬиɜɟличиныɜоɞоɪоɞноɝопокɚзɚɬɟляɪɚɫɬɜоɪиɬɟляможɟɬпɪоиɫɯоɞиɬьɯожɞɟниимолɟкɭлыɜɟɪɯноɫɬиконɬɚкɬɟɪɚɫɬɜоɪиɬɟлɟмоɫɭщɟɫɬɜлɟномоɞɟлиɪоɜɚниɟэɬоɝочɟɫкоɝоэɬɚпɚпɪоцɟɫɫɚɜыɫɜоɛожɞɟния ? пɪɟоɞомолɟкɭлойɪɚзɞɟлɚɪɚɫɬɜоɪиɬɟлькɚчɟɫɬɜɟпоɞоɛноɝоиɫɫлɟɞоɜɚнияможнопɪиɜɟɫɬиɪɚɛоɬɭ Hui-dong Zheng [13].Пɪоɫɬɪɚнɫɬɜɟнныɟмоɞɟликомпонɟнɬоɜпоɫɬɪоɟныиɫпользоɜɚниɟм Hyper Chem ɮɚкɬоɪомкоɬоɪыйнɟоɛɯоɞимоɜɚɬьмоɞɟлиɪоɜɚниимолɟкɭляɪнойɬɟɪоɝɟнныɯяɜляɟɬɫяɪɚɫпɪɟɞɟлɟниɟɚɬомоɜэɬойɚɬомоɜкомпонɟнɬоɜмоɞɟлиɪɭɟмыɯмɟɬоɞомчɬопɪоɞикɬоɜɚнонɟɞоɫɬɚɬочнойɬочноɫɬьюполɭэмпиɪичɟɫкиɯмɟɬоɞоɜкɜɚнɬоɜомичɟɫкиɯмɟɬоɞоɜопɪɟɞɟлɟнияɚɬомоɜмолɟкɭлкомпонɟнɬоɜɫплɚɜɚɬоɞɏɚɪɬɪиɎокɚнɚɛоɪом 3-21G* ɝɟомɟɬɪиимɟɬоɞɮɭнкционɚплоɬноɫɬи UB3LYP нɚɛоɪом 6-31G*) ɫооɬɜɟɬɫɬɜииɪɟзɭльɬɚɬɚмииɫɫлɟɞоɜɚнияпɪиɜɟɞɟннымиɪɚɛоɬɟ [14]. Оɛоɫноɜɚнноɫɬьиɫпользоɜɚниямɟɬоɞоɜɪɚɫчɟɬɚɚɬомоɜмоɞɟлиɪоɜɚниимолɟкɭляɪнойɬɪɚнɫпоɪɬɚɜɟщɟɫɬɜчɟɪɟзпоɜɟɪɯноɫɬьɞɟмонɫɬɪиɪɭɟɬɫяɪɚɛоɬ[14]. Ƚɟомɟɬɪиякомпонɟнɬоɜɫплɚɜɚɪоɜɚнɚмɟɬоɞоммолɟкɭляɪноймɟɯɚники m m+ [16] иɫпользоɜɚниɟм Hyper Chem 8.09. ȾɚлɟɟпɪоɜɟɞɟнɚɝɟомɟɬɪиимолɟкɭлɬоɞоммɟɬоɞɏɚɪɬɪиɎокɚ 3-21G* [ 17]). ɬоɞоммɟɬоɞɮɭнкционɚлɚплоɬноɫɬиU B 3LYP [18], Pharmacy & Pharmacology V. 5 N 4, 2017Полɭчɟннɚяɫиɫɬɟмɚɞɚлɟɟɜɫɬɪɚиɜɚлɚɫьɬɜоɪиɬɟли ? ɜоɞɭэɬɚнолПоɫлɟэɬоɝопɪоɜоɞилоɫьɬɟɪмоɞинɚмичɟɫкоɟɭɪɚɜноɜɟшиɜɚниɟиɫпользоɜɚȻиоэɜɪикɚɚɜɬоɪɭшко ? (ɫилоɜоɟполɟ Am ber 94 [20], пɪямоɭɝольныɟɞичɟɫкиɟɬɟɪмоɫɬɚɬɟнɞɫɟнɚber 94 [20], К, ɜɪɟмя ɪɟлɚкɫɚцииɬɟɪмоɫɬɚɬɚ 100 моɞɟлиɪоɜɚнияɌɟɪмоɫɬɚɬиɪоɜɚниɟоɫɭщɟɫɬɜлялоɫьɫооɬɜɟɬɝɪɚɮикомпɪиɜɟɞɟннымɬɚɛлицɟ 1. ɌɟмпɟɪɚɬɭɪɚзɚɞɚɜɚɟмɚяɬɟɪмоɫɬɚɬомизмɟнялɚɫьмомɟнɬɚмиɝɪɚɮикɚɌɚɛлицɚȽɪɚɮикɪɚɛоɬыɬɟɪмоɫɬɚɬɚпɪоцɟɫɫɟмоɞɟлиɪоɜɚниямолɟкɭляɪнойɮɫɌɟмпɟɪɚɬɭɪɚ300000310ȾɚлɟɟпɪоизɜоɞилоɫьмоɞɟлиɪоɜɚниɟɜыɫɜоɛоɭчɚɫɬкɚɫплɚɜɚɪɚɫɬɜоɪиɬɟчɟниɟкɚчɟɫɬɜɟнɚчɚльноɝоɫоɫɬоянияɪɚɫчɟɬɚɬɟɪмоɞинɚмичɟɫкиɯɯɚɪɚкɬɟɪиɫɬикɜыɫɜоɛожɞɟнияɫплɚɜɚиɫпользоɜɚнɚконɮоɪмɚпоɫлɟɬɟɪмоɞинɚмичɟɫкоɝоɭɪɚɜноɜɟшиɜɚниямɟɬоɞоммолɟкɭляɪнойȻиоэɜɪикɚɬɟчɟниɟ 5 кɚчɟɫɬɜɟконɟчноɝоɫоɫɬоянияиɫпользоɜɚлɫямомɟнɬмоɞɟлиɪоɜɚниямолɟкɭляɪнойоɬɜɟɬɫɬɜɭющийполномɭɜыɯоɞɭмолɟкɭлыɫплɚɜɚɪɚɫɬɜоɪиɬɟлькɚчɟɫɬɜɟɜыɯоɞɚɪɚɫɬɜоɪиɬɟльиɫпользоɜɚлɫямоɞɭльȼɚɚльɫоɜɚɜзɚимоɞɟйɫɬɜиямолɟкɭлойɫплɚɜом (|E| мольɫоɫɬоянийпɪоɜоɞилɚɫьɝɟомɟɬɪии ɫилоɜомполɟ Amber 94 Ȼиоэɜɪикɚпɪоɜоɞилɫяколɟɛɚɬɟльɚнɚлиз [ 22] иɫпользоɜɚниɟмнɟоɝɪɚничɟнноɝомɟɬоɞɚɏɚɪɬɪиɎокɚɛɚзиɫɟ STO-3G ɫɜоɛоɞноɪɚɫпɪоɫɬɪɚняɟмой Orca 4.0 [17]. ɪɟзɭльɬɚɬɟполɭчɟныɬɟɪмоɞинɚмичɟɫкиɟɯɚɪɚкɬɟɪимоɞɟлиɪɭɟмыɯɮɪɚɝмɟнɬоɜэнɬɚльпияэнɬɪопияȾɚлɟɟпɪоизɜоɞилɫяɪɚɫчɟɬэнɬɚльпииэнɬɪопииɜыɫɜоɛожɞɟнияɫплɚɜɚɮоɪмɭлɚмиɫпользоɜɚниɟмполɭчɟнныɯэнɬɚльпийɬɪопийɪɚɫɫчиɬыɜɚлиɫьȽиɛɛɫɚɜыɫɜоɛожɞɟнияɫɪɟɞыɮоɪмɭɬɟмпɟɪɚɬɭɪыɝɞɟ T ? ɬɟмпɟɪɚɬɭɪɚɊɟзɭльɬɚɬыоɛɫɭжɞɟниɟкɚчɟɫɬɜɟкомпонɟнɬоɜиɫɫлɟɞɭɟмыɯиɫпользоɜɚнымоɞɟлимолɟкɭлыоɫноɜɚнияɬɚкжɟмоɞɟликомпонɟнɬоɜɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚоɊиɫɭнокɏимичɟɫкɚяɫɬɪɭкɬɭɪɚпɪоɫɬɪɚнɫɬɜɟнноɟɜинпоцɟɬинɚоɫноɜɚниɟкɚɬионɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in PharmacyЦɟɪоɬиноɜɚякиɫлоɬɚНɟоцɟɪоɬиноɜɚякиɫлоɬɚМɟлиɫɫиноɜɚякиɫлоɬɚМонɬɚниноɜɚякиɫлоɬɚМɟлиɫɫилпɚльмиɬɚɬМиɪицилпɚльмиɬɚɬɞиɫɬɟɚɪоолɟинпɚльмиɬоɞиолɟинPharmacy & Pharmacology V. 5 N 4, 2017ПɚльмиɬоɫɬɟɚɪоолɟинɊиɫɭнокɋɬɪɭкɬɭɪныɟɮоɪмɭлыпɪоɫɬɪɚнɫɬɜɟнноɟкомпонɟнɬоɜɫплɚɜɚпчɟлиноɝоɜоɫкɚкɚкɚоКоличɟɫɬɜɟнныйɫоɫɬɚɜɫплɚɜɚɜоɫкɚмɚɫлɚкɚоɪɚɫɫчиɬɚниɫɯоɞялиɬɟɪɚɬɭɪныɯɯимичɟɫкомɫоɫɬɚɜɟпчɟлиноɝоɜоɫкɚ [ 23] мɚɫлɚкɚо [24]. Ⱦɚлɟɟиɫɯоɞямолɟкɭляɪныɯмɚɫɫɪɚɫɫчиɬɚныколичɟɫɬɜɚмолɟкɭлоɫноɜныɯкомпонɟнɬоɜмоɞɟлиɪɭɟмойɍчиɬыɜɚяоɛъɟммоɞɟлиɪɭɟмоɝоɮɪɚɝмɟнɬɚɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚо 3:2, 125 моɞɟльɜключɟныкомпонɟнɬыколичɟɫɬɜомолɟкɭлкоɬоɪыɯиɫɯоɞяколичɟɫɬɜɟнноɝоɫоɫɬɚɜɚ 2-моɞɟлиɪɭɟоɛъɟмкɚчɟɫɬɜɟɫоɫɬɚɜɚɝокомпонɟнɬнойможнопɪиɜɟɫɬиɪɚɛоɬɭкоɬоɪойоɫɭщɟɫɬɜлялоɫьмоɞɟлиɪоɜɚниɟмɚɫлɚкɚкɚомɟɬоɞоммолɟкɭляɪнойэɬомɫоɫɬɚɜɫмɟɫиɜключɟныɬɪиɬɪиɝлицɟɪиɞоɜɜключɟныкиɫлоɬыɞɪɭɝиɟмноɝокомпонɟнɬымɚɫлɚ [25]. оɞнимɪɚɫпɪоɫɬɪɚнɟннымпɪимɟɪоммоɞɟлиɪоɜɚнияɫложныйɫоɫɬɚɜяɜляɟɬɫямоɞɟлиɪоɜɚниɟмолɟкɭляɪнойɮоɫɮолипиɞныɯ [26]. эɬомɫоɫɬɚɜɞɟлиɪоɜɚнииɜключɚюɬɫякомпонɟнɬыɫоɞɟɪжɚщиɟɫяɞоɫɬɚɬочноɛольшомколичɟɫɬɜɟМоɞɟлиɪоɜɚниɟмолɟкɭляɪнойнɚɫɬоящɟɟɞоɫɬɭпномɚɫшɬɚɛɟɞɟɫяɬкоɜнɚномɟɬɪоɜоɛъɟмɟкɭɛичɟɫкиɯнɚномɟɬɪ [27]. компонɟнɬыɜɟщɟɫɬɜпɪиɪоɞноɝопɪоиɫɯожɞɟнияимɟюɬнɚɫɬолькоконцɟнɬɪɚциичɬомолɟкɭлыпɪɟɞɫɬɚɜлɟныɟɞиничномэкзɟмпляɪɟоɛъɟмɚɯнɚмноɝокɭɛичɟɫкиɯнɚномɟɬɪоɜɍчиɬыɜɚяэɬонɚɫɬоящɟɟпɪɟɞɫɬɚɜляɟɬɫяɜозможнымкомпонɟнɬоɜɫмɟɫɟйпɪиɪоɞноɝопɪоиɫɯожɞɟниямоɞɟлиɪоɜɚниимолɟкɭляɪнойОɞнɚкоɬɟоɪɟɬичɟɫкиймɟɬоɞшиɪокоиɫпользɭɟɬɫяизɭчɟнияɯимичɟɫкиɯɫɜойɫɬɜ [27]. ȾɚлɟɟɭчиɬыɜɚямолɟкɭляɪныɟмɚɫɫыɫчиɬɚныколичɟɫɬɜɚмолɟкɭлоɫноɜныɯкомпонɟнɬоɜмоɞɟлиɪɭɟмойɬɚɛлоɫноɜɟɫɬɪɭкɬɭɪкомпонɟнɬоɜпоɫɬɪоɟнɚмоɞɟльɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚоɌɚɛлицɚКоличɟɫɬɜɟнныйɫоɫɬɚɜмоɞɟлиɪɭɟмоɝоɫплɚɜɚпчɟлиноɝоɜоɫкɚкɚкɚоȼɟщɟɫɬɜоМоляɪнɚямɚɫмольМɚɫɫоɜɚяɞоляɫплɚɜɟмолɟкɭлмоɞɟлиɫплɚɜɚɚɬомоɜмоɞɟлиЦɟɪоɬиноɜɚякиɫлоɬɚ396,77,28640Нɟоцɟɪоɬиноɜɚякиɫлоɬɚ382,67333231Мɟлиɫɫиноɜɚякиɫлоɬɚ452,8082,42184Монɬɚниноɜɚякиɫлоɬɚ438,7812,42178Мɟлиɫɫилпɚльмиɬɚɬ677,2433212940пɚльмиɬɚɬ691,2671271001ɞиɫɬɟɚɪоолɟин889,4857,94684пɚльмиɬоɞиолɟин803,3075,33453Пɚльмиɬоɫɬɟɚɪоолɟин805,32326,8142142ИɌОȽО:1008453мɚɫлɟкɚкɚопомимоɬɪиɝлицɟɪиɞоɜɫоɞɟɪжɚɬɫяɬɚкжɟɫɜоɛоɞныɟкиɫлоɬыконцɟнɬɪɚможноɫɭɞиɬьɜɟличинɟкиɫлоɬноɝоɫɭɞɚɪɫɬɜɟннɚяɮɚɪмɚкопɟя X [ 24] ɞопɭɫкɚɟɬкиɫлоɬноɟмɚɫлɚкɚкɚоɛолɟɟ 2,25 KOH 1 мɚɫлɚэɬоɝоɫлɟɞɭɟɬчɬоɫоɞɟɪжɚниɟкиɫлоɬмɚɫлɟкɚкɚоɫооɬɜɟɬɫɬɜɭющɟмɬɪɟɛоɜɚниямȽоɫɭɞɚɪɫɬɜɟннойɮɚɪмɚкопɟимольɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in Pharmacyɝɞɟкиɫлоɬɫоɞɟɪжɚниɟкиɫлоɬмɚɫлɚкɚкɚомольмɚɫɫɚ KOH, нɟоɛɯоɞимоɝоɬɪɚлизɚциикиɫлоɬɫоɞɟɪжɚщиɯɫямɚɫлɟкɚкɚо 1 мɚɫлɚкиɫлоɬноɟмоляɪнɚямɚɫɫɚмольɋɭммɚɪнɚямɚɫɫɚкомпонɟнɬоɜмɚɫлɚкɚкɚоɜключɚɟмыɯмолɟкɭляɪнɭюмоɞɟльɫоɫɬɚɜляɟɬɬɚɛлɌɚкимоɛɪɚзомколичɟɫɬɜокиɫлоɬмɚɫлɚкɚкɚомоɞɟлиɪɭɟмомоɛъɟмɟɞолжнопɪɟɜышɚɬьмольчɬоɫооɬɜɟɬɫɬɜɭɟɬмолɟкɭлкиɫлоɬɝɞɟ m ? мɚɫɫɚмɚɫлɚкɚкɚомоɞɟлиɪɭɟмойȺɜоɝɚɞɪомольмолɟкɭлкиɫлоɬмоɞɟлиɪɭɟПолɭчɟнныɟɪɟзɭльɬɚɬыɫооɬɜɟɬɫɬɜɭюɬɛлизиɬɟльно 1 молɟкɭлɟкиɫлоɬы 64 молɟкɭлкомпонɟнɬоɜɫплɚɜɚɬɚɛл. 2), коɬоɪыɯɫɪɚɜнимɚɪɚзмɟɪɚмкиɫлоɬɚмимɚɫлɚкɚкɚоɞɪɭɝɚяɬɪиɝзɚнимɚɟɬзнɚчиɬɟльноɛольшийоɛъɟмИɫɯоɞяэɬоɝомолɟкɭлыкиɫлоɬмɚɫлɚкɚкɚоɜключɟныɫоɫɬɚɜмоɞɟлиɪɭɟмойȾɚлɟɟиɫпользоɜɚниɟмȻиоэɜɪикɚпɪоизɜоɞилоɫьɬɟɪмоɞинɚмичɟɫкоɟɭɪɚɜноɜɟшиɜɚмоɞɟлиɫплɚɜɚмɟɬоɞоммолɟкɭляɪнойпоɫлɟчɟɝоɫиɫɬɟмɚɜɫɬɪɚиɜɚлɚɫьɪɚɫɬɜоɪи ? ɜоɞɭэɬɚнолПоɫлɟɬɟɪмоɞинɚмичɟɫкоɝоɭɪɚɜноɜɟшиɜɚниямɟɬоɞоммолɟкɭляɪнойɬɟчɟниɟ 5 пɪоизɜоɞилоɫьмоɞɟлиɪоɜɚниɟɜыɫɜоɛожɞɟнияɭчɚɫɬкɚɫплɚɜɚɪɚɫɬɜоɪиɬɟльɬɟчɟниɟ 20 ɬɚɛлицɟ 3 пɪиɜɟɞɟныизоɛɪɚжɟнияпɪоɫɬɪɚнɫɬɜɟнныɯɫɬɪɭкɬɭɪмоɞɟлиɪɭɟмыɯмомɟнɬыɌɚɛлицɚɋоɫɬояниямоɞɟлиɪɭɟмыɯɫиɫɬɟмɪɚзличныɟмомɟнɬыɜɪɟмɟниɜоɞɚкɚɬионɜоɞɚэɬɚнолɌɟɪмоɞинɚмичɟɫкоɟɭɪɚɜноɜɟшиɜɚниɟМоɞɟлиɪоɜɚниɟɜыɫɜоɛожɞɟнияPharmacy & Pharmacology V. 5 N 4, 2017Пɪоɞолжɟниɟɬɚɛлицыɪɟзɭльɬɚɬɟɬɟɪмоɞинɚмичɟɫкоɝоɭɪɚɜноɜɟшиɜɚнияɜоɞнойɫɪɟɞɟполɭчɟнɚɝɟɬɟɪоɝɟннɚяɫɬɟмɚчɟɬкоɜыɪɚжɟннойпоɜɟɪɯноɫɬьюɭпоɪяɞочɟннымиɫɬɪɭкɬɭɪɚмиɫплɚɜɟɫɪɟɞɟэɬɚнолɚпɪоизошлочɚɫɬичноɟɫмɟшиɜɚниɟɫплɚɜɚɪɚɫɬɜоɪиɬɟлɟмɬɚɛлɪɟзɭльɬɚɬɚмɚнɚлизɚɜɚнɜɚɚльɫоɜɚɜинпоцɟɬиномɫплɚɜомопɪɟɞɟɞлиɬɟльноɫɬиɜыɫɜоɛожɞɟниямолɟкɭлыɪɚɫɬɜоɪиɬɟльэɬоɝоопɪɟɞɟлɟноɬɟчɟниɟкоɬоɪоɝомоɞɭльɜɚнɜɚɚльɫоɜɚɜзɚимоɞɟйɫɬɜиямолɟкɭлойиономɫплɚɜомɫɬɚноɜилɫя 0,1 мольɜɚнɜɚɚльɫоɜɚɜзɚимоɞɟйɫɬɜияпɪɟɞɜɚɪиɬɟльнопоɞɜɟɪɝɚлиɫьɫɝлɚжиɜɚниюмɟɬоɞомɫкользящɟɝоɫɪɟɞнɟɝоɭɫɪɟɞнɟнияɊиɫɭнокȾинɚмикɚɜɚнɜɚɚльɫоɜɚɜзɚимоɞɟйɫɬɜиямɟжɞɭмолɟкɭлойиономɜинпоцɟɬинɚɫплɚɜомпчɟлиноɝоɜоɫкɚкɚкɚоɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in PharmacyȺнɚлизɪɟзɭльɬɚɬоɜмоɞɟлиɪоɜɚнияпокɚзыɜɚɟɬчɬоɜыɫɜоɛожɞɟниɟкɚɬионɚɫплɚɜɚэɬɚнолпɪоиɫɯоɞиɬȼыɫɜоɛожɞɟниɟоɫноɜɚɫплɚɜɚɜоɞɭ pH 7,0 ɯоɞиɬɛолɟɟɜыɫокойɝиɞɪоɮоɛноɫɬиоɫноɜɚнияȼыɫɜоɛожɞɟниɟɜоɞɭ pH 2,0 иɫɯоɞиɬоɞнɚкомолɟкɭлɚоɫɬɚɟɬɫяɬɟльноɟɫɜязɚннойпоɜɟɪɯноɫɬьюɌɚɛлицɚȾлиɬɟльноɫɬьɜыɫɜоɛожɞɟнияɜинпоцɟɬинɚɪɚɫɬɜоɪиɬɟльɪɟзɭльɬɚɬɚммоɞɟлиɪоɜɚниямолɟкɭляɪнойɊɚɫɬɜоɪиɬɟльȾлиɬɟльноɫɬьконɬɚкɬɚɫплɚɜомȼоɞɚ (pH 7,0)ɞɚ20ȼоɞɚ (pH 2,0)ɞɚ20ЭɬɚнолПɪоɜɟɞɟнныɟиɫɫлɟɞоɜɚнияпокɚзɚличɬоɜоɞнойɫɪɟɞɟ pH 2,0 пчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚо 3:2 ɪɚɫɬɜоɪимчɬояɜляɟɬɫяɮɚкɬоɪомзɚмɟɞляющимɜыɫɜоɛожɞɟниɟɪɚɫɬɜоɪиɬɟльɫɪɟɞɟ (pH 2,0) кɚɬионɜыɫɜоɛожɞɚɟɬɫяɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚо 3:2 пɟɪɟɯоɞиɬɜоɞɭэɬомɟɫɬьпоɜɟɪɯноɫɬиɫплɚɜɚɜыɫɜоɛожɞɚɟɬɫяɫплɚɜɚноɝоɜоɫкɚмɚɫлɚкɚкɚо 3:2 эɬɚнолполноɫɬьюпɟɪɟɯоɞиɬɪɚɫɬɜоɪиɬɟльэɬомпɪоиɫɯоɞиɬɫɬичноɟɪɚɫɬɜоɪɟниɟɫплɚɜɚэɬɚнолɟкɜɚнɬоɜоɯимичɟɫкоɝоɪɚɫчɟɬɚɬɟɪмоɞинɚмичɟɫкиɯɯɚɪɚкɬɟɪиɫɬикиɫпользоɜɚɜшиɯɫямоɞɟлиɪоɜɚниимолɟкɭляɪнойɮɪɚɝмɟнɬынɚчɚльноɝоконɟчноɝоɫоɫɬоянийɪɚɫɬɜоɪиɬɟльɪɚɫɬɜоɪиɬɟльɊиɫɭнокȼыɫɜоɛожɞɟниɟɜинпоцɟɬинɚɫплɚɜɚPharmacy & Pharmacology V. 5 N 4, 2017Ɋиɫɭнокȼыɫɜоɛожɞɟниɟɜинпоцɟɬинɚɫплɚɜɚэɬɚнолзɭльɬɚɬыɬɟɪмоɞинɚмичɟɫкиɯɯɚɪɚкɬɟɪиɫɬикмоɞɟлиɪɭɟмыɯɮɪɚɝмɟнɬоɜпɪɟɞɫɬɚɜлɟныɬɚɛл. 5, 6. ɊиɫɭнокȼыɫɜоɛожɞɟниɟɜинпоцɟɬинɚɫплɚɜɚɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in PharmacyɌɚɛлицɚɊɟзɭльɬɚɬыкɜɚнɬоɜоɯимичɟɫкоɝоɪɚɫчɟɬɚɜыɫɜоɛожɞɟнияɜинпоцɟɬинɚɫплɚɜɚɪɚɫɬɜоɪиɬɟльɋиɫɬɟмɚЭнɬɚльпиямольЭнɬɚльпияɜыɫɜоɛожɞɟниямольɫплɚɜɟɊɚɫɬɜоɪиɬɟльɛɟзɪɚɫɬɜоɪиɬɟлɟ pH 2,0-10658071,42-9450228,56-7786164,35-12322871,38pH 7,0-9847693,09-7284608,01-6976933,10-10155553,84Эɬɚнол-14228766,63-8000056,02-11357749,23-10870588,77ЭнɬɪопиямольpH 2,02,33911,94081,97152,0721pH 7,02,22911,47591,85501,6409Эɬɚнол2,83141,96521,99451,7424ɌɚɛлицɚɊɟзɭльɬɚɬыкɜɚнɬоɜоɯимичɟɫкоɝоɪɚɫчɟɬɚȽиɛɛɫɚɜыɫɜоɛожɞɟнияɜинпоцɟɬинɚɫплɚɜɚɪɚɫɬɜоɪиɬɟльɋиɫɬɟмɚȽиɛɛɫɚмольȽиɛɛɫɚɜыɫɜоɛожɞɟниямольɫплɚɜɟɊɚɫɬɜоɪиɬɟльɛɟзɪɚɫɬɜоɪиɬɟлɟpH 2,0-10658796,55-9450830,21-7786775,523-12323513,74pH 7,0-9848384,12-7285065,55-6977508,17-10156062,51Эɬɚнол-14229644,37-8000665,24-11358367,54-10871128,92ȼыɫɜоɛожɞɟниɟɫплɚɜɚɜоɫкɚмɚɫлɚкɚкɚо 3:2 ɜоɞɭ pH эɬɚнолɟɝоɪɚɫɬɜоɪимоɫɬиɫɪɟɞɚɯɬɚкжɟɪɚɫɬɜоɪимоɫɬиɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚоɪɚɫɬɜоɪяɟɬɫяэɬɚнолɟчɬояɜляɟɬɫяɮɚкɬоɪомɭɫкоɪяющимɜыɫɜоɛожɞɟниɟɪɚɫɬɜооɫɬɚɟɬɫяɫплɚɜɚмоɞɟлиɪоɜɚнииɜоɞойчɬоɝоɜоɪиɬɬомчɬоɜыɫɜоɛожɞɟниɟɫплɚɜɚɜоɫкɚмɚɫлɚкɚкɚо 3:2 ɜоɞɭ pH 7,0 зɚɬɪɭɞЗɚключɟниɟȼыɫɜоɛожɞɟниɟɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚо 3:2 ɜоɞɭяɜляɟɬɫяэнɟɪɝɟɬичɟɫкиɜыɝоɞнымпɪоцɟɫɫомɬɚкжɟɫопɪоɜожɞɚɟɬɫяɭɜɟличɟниɟмэнɬɪопиичɬоɝоɜоɪиɬɛолɟɟɜыɫокойɬɟɪмоɞинɚмичɟɫкойɜɟɪояɬноɫɬиконɟчноɝоɫоɫɬоянияɪɚɫɬɜоɪɟȼыɫɜоɛожɞɟниɟɫплɚɜɚɜоɞɭэнɟɪɝɟɬичɟɫкиɜыɝоɞноɜыɫɜоɛожɞɟниɟмɜоɞɭȼыɫɜоɛожɞɟниɟэɬɚнолɫплɚɜɚэнɟɪɝɟɬичɟɫкиɜыɝоɞноɜыɫɜоɛожɞɟниɟмɜоɞɭоɬɫɭɬɫɬɜияɪɚɫɬɜоɫплɚɜɚэɬɚнолɟОɞнɚкоɪɟзɭльɬɚɬымоɞɟлиɪоɜɚниямолɟкɭляɪнойɫɜиɞɟɬɟльɫɬɜɭюɬɜозможноɫɬиɪɚɫɬɜоɪɟниякомпонɟнɬоɜɫплɚɜɚэɬɚнолɟЭɬояɜляɟɬɫяɮɚкɬоɪомэɮɮɟкɬиɜноɫɬьɜыɫɜоɛожɞɟнияПɪоɜɟɞɟнныɟиɫɫлɟɞоɜɚниямоɞɟлиɪоɜɚниямолɟкɭляɪнойɜыɫɜоɛожɞɟнияɫплɚɜɚпчɟлиноɝоɜоɫкɚмɚɫлɚкɚкɚо 3:2 покɚзыɜɚɟɬɜозможноɫɬьɜыɫɜоɛожɞɟнияɜоɞɭэɬɚнолПолɭчɟнныɟɪɟзɭльɬɚɬыпозɜоляюɬпɪɟɞположиɬьɛолɟɟнизкɭюɜыɫɜоɛожɞɟнияɫплɚɜɚэɬɚнолɬɜоɪомкиɫлоɬыɯлоɪиɫɬоɜоɞоɪоɞнойIntroduction. uid, solid or gaseous ac-preserving them against environment [ 1, 2]. The choice of storage, etc. [3]. Preferable hydrophobic shell-matrix perature of hydrophobic substan ce[4]. ers and their mixtures. Preferable ers, animal waxes, plant waxes, Pharmacy & Pharmacology V. 5 N 4, 2017resins and their mixtures. Animal waxes are beeswax, Vinpocetine is a perspective medicinal substance for development of a microencapsulated fo r m [5, 6]. Vinpocetine is poorly soluble in water, and, for ed water and hydrochloric acid, which uence of auxiliary substances and technological fac tors [7].prepared by dispersion m ethod [8]. But often the ciency make the choice of microencapsulation lm former, is min imized [9].from the melt of beeswax and cacao butter 3:2 into water, release process simulation from the melt into different charges were calculated by quantum-chemical method.Taking into account the vinpocetine ionization )in wa ter 7.1 [10] and using Henderson?Hasselbalch equation [11], it is possible to are a relative content of vinpocetine-base and vinpocetine-cation in the solution respectively.environment according to the literature data [ 12] is low cant concentration cation and in the form of base. The release simulation of to be interesting in this study, since it gives an opportuni-ty to explain the difference between release ef ciency of this substance into the solvent in different values of pH from the molecular structure point of view.ɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in Pharmacying on the value of solvent pH. Moreover, ionization can We performed the simulation of exactly this critical As an example of a similar study the work by Hui-dong Zheng [ 13] can be represented.tems is the atom charge distribution. For this purpose atom charges of the simulated sys- method, cient accuracy of semi-em-pirical methods. The choice of quantum-chemical meth-ods to detect the atom charges of melt component mo-al theory method UB3LYP with 6-31G* basis set) was made according to the results of the study, represented in the wor k [14]. The validity of methods used for atom charge calculation in molecular dynamics simula-demonstrated in the wo rk [15].by molecular mechanics mm+ met h od [16] in Hyper method (unrestricted Hartree-Fock method, basis set 3 -21G* [17]). The charges were calculated by method (density functional theory method U B3LYP [18], basis solvents ? water and ethanol. After that thermodynamic author is A.A. Glushko) [19] (force el d Amber94 [20], rectangular periodic boundary conditions, Berendsen integration step 1 fs).Thermostating was performed according to the graph in Table 1. The temperature, set by the thermostat, was Table 1 ? Graph of thermostat work in molecular dynamics simulation processTime, fsTemperature, K300000310tine release from the melt spot to the solvent was per- nal state, a moment of time of molecular dynamics simulation was used, corresponding to full release a module of Van-der-Waals energy interaction between mol). For both states geometry optimization in Amber94 eld was performed by Bioeurica program.[ 22] by unrestricted Hartree-Fock method in basis set STO-3G in free distributable program Orca 4.0 [17]. and entropy energies () of vinpocetine release into different where T istemperature, Pharmacy & Pharmacology V. 5 N 4, 2017(A ? base, B ? cation)Cerotinic acidMelissinic acidMontaninic acid BɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in PharmacyMelissilpalmitateMiricilpalmitate1,3-distearo-2-olein1-palmito-2,3-dioleinabout chemical composition of beeswax [ 2 3] and cacao butter [24]. Further, based on molecular masses quantities of molecules of the simulated system basic components were calculated. Accounting the volume of the simulated beeswax and cacao butter melt 3:2 a fragment, equal to 125 nm, the components which molecules? number according to the quantitative composition was more than 2 for the simulated volume, were included into the not include d [25].Pharmacy & Pharmacology V. 5 N 4, 2017dynamics simulation of phospholipid membran es [26].Hereby only the components contained in a fairly large thousands of cubic nanomet ers [27].Taking that into consideration, nowadays it does not for physical-chemical properties of mixtures st udy [28-Further, taking into consideration molecular masses, simulated system were calculated (Table 2).Table 2 ? Quantitative composition of the simulated beeswax and cacao butter melt 3:2Cerotinic acid396.77.28640Neocerotinic acid382.67333231Melissinic acid452.8082.42184Montaninic acid438.7812.42178Melissilpalmitate677.2433212940Miricilpalmitate691.26712710011,3-distearo-2-olein889.4857.946841-palmito-2,3-diolein803.3075.33453Palmitostearoolein805.32326.8142142TOTAL:1008453In cacao butter, besides triglycerides, free fatty acids are contained. Their concentration can be learnt by the Their concentration can be learnt by the acid value of cacao butter to be no more than 2.25 mg of KOH per 1 g of butter. Therefore, the content of fatty acids in cacao butter, meeting the requirements of State (fatty acids) is content of fatty acids in 1 g of cacao butter, mol/g;Total mass of cacao butter components, included in g (Table 2), therefore mol, which ? Avogadro number, molmolecule of fatty acid per 64 different molecules of the in volume with fatty acids of cacao butter, and another cantly larger volume. molecular dynamics method. After that the system was included into the solvents ? water and ethanol. After the systems for different moments of time are represented in Table 3.ɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in PharmacyTable 3 ? States of simulated systems at different moments of timeTime,water (pH=7)water (pH=2)Vinpocetine release simulationPharmacy & Pharmacology V. 5 N 4, 2017melt with water took place (Table3).According to the results Van-der-Waals interaction (Fig. 4).To do it, the time was detected,while the module of Van-der-Waals interaction energy between molecule kDj/mol. Time series of Van-der-Waals? interaction energy were preliminary smoothed by moving average Figure 4 ? Dynamics of Van-der-Waals? interaction energy between vinpocetine molecule (ion) The analysis of the obtained results shows, that the release of vinpocetine cation from the melt into ethanol goes during 15.5 ns. The release of vinpocetine base from the melt into water with pH = 7.0 doesn?t go, due to higher hydrophobicity of The release into water with pH = 2.0 goes, but vinpocetine Table 4 ? Durability of vinpocetine release into solvent according to the results of molecular dynamics simulationSolventDurability of vinpocetine contact with the melt, nsWater (pH = 7.0)�20Water (pH = 2.0)�20Ethanol15,5ɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in PharmacyThe performed study has shown, that the melt of beeswax and cacao butter 3:2 is not soluble in water environment which appears to be the factor, slowing ic environment (pH = 2.0) vinpocetine cation releases from the beeswax and cacao butter 3:2 and passes into water. Hereby vinpocetine adsorption tends to exists on Vinpocetine molecule releases from the beeswax For the quantum chemical calculation of thermodynamic characteristics of vinpocetine release from systems, used in the molecular dynamics simulation, fragments of initial and nal states were isolated (Fig. 5?7):Figure 5 ? Vinpocetine release from the melt into water in pH 2Figure 6 ? Vinpocetine release from the melt into water in pH 7Pharmacy & Pharmacology V. 5 N 4, 2017Th e results of thermodynamic characteristics calculation of the simulated system fragments are represented in Tables 5 and 6.Table 5 ? Results of quantum-chemical calculation of enthalpy and entropy SystemSystem enthalpy, kDj/molVinpocetine Vinpocetine pH=2-10658071.42-9450228.56-7786164.35-12322871.38-735.75pH=7-9847693.09-7284608.01-6976933.10-10155553.84-185.85Ethanol-14228766.63-8000056.02-11357749.23-10870588.77484.64System entropy, kDj/molpH=22.33911.94081.97152.0721-0.2363pH=72.22911.47591.85501.64090.0971Ethanol2.83141.96521.99451.7424-1.0597Table 6 ? Results of quantum-chemical calculation of the Gibbs energySystem Gibbs energy, kDj/molGibbs energy of VinpocetineVinpocetine in pH=2-10658796.55-9450830.21-7786775.523-12323513.74-662.50pH=7-9848384.12-7285065.55-6977508.17-10156062.51-121.02Ethanol-14229644.37-8000665.24-11358367.54-10871128.92813.15Figure 7 ? Vinpocetine release from the melt into ethanolVinpocetine release from the melt of beeswax and cacao butter 3:2 into water with different pH and into dissolves in ethanol, and that is the factor, speeding up Vinpocetine stays in the melt phase during simulation ɎɚɪмɚцияɮɚɪмɚколоɝияИнɮоɪмɚционныɟɬɟɯнолоɝииɮɚɪмɚцииInformational Technologies in Pharmacy cult. Vinpocetine release from the melt pH = 2.0 is energetically advantageous process, and it is also accompanied by increase of entropy, which indicates nal state (vin-Vinpocetine release from the melt into water with pH = 7.0 is energetically less advantageous comparedwith Vinpocetine release into ethanol from the melt is en-ergetically less advantageous compared with the release ciency of vinpocetine re-into water with pH = 2.0 and into ethanol. The obtained ȻиɛлиоɝɪɚɮичɟɫкийПоɫɬɪɚшɏишоɜɚМИКɊОКȺПɋɍЛИɊОȼȺНИȿɎȺɊМȺЦИИ ? ɋОɋɌОПȿɊɋПȿКɌИȼЫȼɟɫɬникɮɚɪмɚцииПолкоɜникоɜɚɋɬɟпɚноɜɚȼОЗМОЖНОɋɌИɋОЗȾȺНИЯПɊОЛОНȽИɊОȼȺННЫɏɎОɊМȺɎОȻȺЗОЛȺНɚɭчныɟɜɟɞомоɫɬиȻɟлɝоɪоɞɫкоɝоɝоɫɭɞɚɪɫɬɜɟнноɝоɜɟɪɫиɬɟɬɚɋɟɪияМɟɞицинɚɎɚɪмɚция. 2011. 4(13). ȺɜɬинɚПиɫɚɪɟɜПɚнкɪɭшɟɜɚȼоɪонкоɜɚɊȺЗɊȺȻОɌКȺȾȿɌɋКОЙЛȿКȺɊɋɌȼȿННОЙɎОɊМЫОɋНОȼȿМИКɊОКȺПɋɍЛМȿɌɊОНИȾȺЗОЛОМ // НɚɭчныɟɜɟɞоȻɟлɝоɪоɞɫкоɝоɝоɫɭɞɚɪɫɬɜɟнноɝоɭниɜɟɪɫиɬɟɬɚɋɟɪияМɟɞицинɚɎɚɪмɚция. 2011. КойнȽɭɟнɏɚнɫɟнИɫɚкɌомɚɫɌɫɟМикɪокɚпɫɭлы // ПɚɬɊоɫɫия A61K9/56. N 2006108860/15; ЗɚяɜлОпɭɛлПолкоɜникоɜɚȽɚнзюкɊɚзɪɚɛоɬкɚпɪолонɝиɪоɜɚннойпɟɪоɪɚльнойлɟкɚɪɫɬɜɟннойɮоɪмыкомпозицииɪɟɬинолɚɚцɟɬɚɬомɮоɪмыɫоɜɟɪшɟнɫɬɜоɜɚнияɮɚɪмɚцɟɜɬичɟɫкоɝоɪɚзоɜɚнияɮизиолоɝичɟɫкиɚкɬиɜныɯɜɟщɟɫɬɜмɚɬɟɪиɚлы 4-ȼɫɟɪоɫɫийɫкойɪоɞнымнɚɭчномɟɬоɞичɟɫкойконɮɟɪɟнцииɎɚɪмоɛɪɚзоɜɚниɟɋɬɟпɚноɜɚПолкоɜникоɜɚȽɚнзюкȺɪльɬИɋɋЛȿȾОȼȺНИȿȼЛИЯНИЯɊȺɋɌȼОɋɍɋПȿНЗИИМИКɊОКȺПɋɍЛȾИНȺМИКɍОȻЪЁМНОЙɋКОɊОɋɌИМОЗȽОȼОȽОКɊОȼОɌОКȺЛȺȻОɊȺɌОɊНЫɏ // НɚɭчныɟɜɟɞомоɫɬиȻɟлɝоɪоɞɫкоɝоɝоɫɭɞɚɪɫɬɜɟнноɝоɭниɜɟɪɫиɬɟɬɚɋɟɪияМɟɞицинɚɎɚɪмɚция. 2011. ПолкоɜникоɜɚȼЫɋȼОȻОЖȾȿНИȿМИКɊОКȺПɋɍЛИɊОȼȺННОЙɎОɊМЫɏимикоɮɚɪмɚцɟɜɬичɟɫкийжɭɪнɚлШɟɜчɟнкоȻиɪюкоɜɚКɭɞɪяɜцɟɜȺппɚɪɚɬɞиɫпɟɪɝиɪоɜɚниямикɪокɚпɫɭлиɪоɜɚнияжиɞкоɫɬɟй // ПɚɬɊоɫɫия. B01F11/02. 2000100442/12; Зɚяɜл. 11.01.2000; Опɭɛл27.12.2000. URL: http://www.freepatent.ru.ȽлɭшкоɏɚлилоɜɚНоɜɚямɟɬоɞикɚмɚɬɟмɚɬичɟɫкоɝомоɞɟлиɪоɜɚнияпɪоцɟɫɫɚжиɞкоɫɬнойэкɫɬɪɚкцииоɫноɜɟмолɟкɭляɪной // ȻɟликоɜɫкиɟМɚɬɟɪиɚлы IV ȼɫɟɪоɫɫийɫкойнɚɭчпɪɚкɬичɟɫкойконɮɟɪɟнциинɚɭчПяɬиɝоɪɫкИзɞɚɬɟльɫɬɜоПМɎИ. 60?62. 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Current Opinion in Colloid & Vol. 5. 2000. P. 217-223. DOI: 10.1016/S1359-0294(00)00058-3Rapaport D.K. ISKUSSTVO MOLEKULYARNOY DINAMIKI [THE ART OF MOLECULAR DYNAMICS]. Izhevsk: IKI [Izhevsk: ICS], 2012. P. 632. (In Russ.)Miyamoto H., Rein D.M., Kazuyoshi U., Yamane C., Cohen Y. MOLECULAR DYNAMICS SIMULATION OF CELLULOSE-COATED OIL-IN-WATER EMULSIONS. Vol. 24. Is. 7. 2017. P. 2699?2711. Leo D., Maranon J. CONFINED WATER/OIL INTERFACE. MOLECULAR DYNAMICS STUDY. Vol. 672. 2004. P. 221?229. DOI: 10.1016/j.theochem.2003.11.032 Sedghi M., Piri M., Goual L. ATOMISTIC MOLECULAR DYNAMICS SIMULATIONS OF CRUDE OIL/BRINE DISPLACEMENT IN CALCITE MESOPORES. . 2016. Vol. 32. P. 3375?3384.DOI:acs.langmuir.5b04713. ict of interest ict of interest.Polkovnikova Yulia Alexandrovna Candidate of Educational Institution of Higher Education ?Voronezh State University?. Research interests: dosage forms, microcapsules, prolongation, biopharmaceutical research. E-mail: juli-polk@mail.ru Candidate of Sciences (Pharmacy), Lecturer of the Department of Inorganic, Physical and Colloidal Chemistry of branch of Volgograd State Medical University. Research interests: computer chemistry, software development dynamics, QSAR. E-mail: alexander.glushko@lcmmp.ruMikhailovskaya Irina Yurievna student of Educational Institution of Higher Education ?Voronezh State University?. Research interests: dosage forms, microencapsulation, prolongation. E-mail: Kariyeva Yoshut Saidkarimovna Doctor of Sciences (Pharmacy), associate professor, head. Department of Technology of Medicinal Forms of Tashkent Pharma-ceutical Institute. Research interests: soft dosage forms, КонɮликɬинɬɟɪɟɫоɜȺɜɬоɪызɚяɜляюɬоɬɫɭɬɫɬɜииконɮликɬɚинɬɟɪɟɫоɜȺɜɬоɪыПолкоɜникоɜɚȺлɟкɫɚнɞɪоɜнɚ ? кɚнɞиɞɚɬɮɚɪмɚцɟɜɬичɟɫкиɯнɚɭкɞоцɟнɬɎȽȻОɍнɟжɫкийɝоɫɭɞɚɪɫɬɜɟнныйɭниɜɟɪɫиɬɟɬОɛлɚɫɬьнɚɭчныɯинɬɟɪɟɫоɜлɟкɚɪɫɬɜɟнныɟɮоɪмыкɚпɫɭлыпɪолонɝиɪоɜɚниɟɛиоɮɚɪмɚцɟɜɬичɟɫкиɟиɫɫлɟɞоɜɚнияȽлɭшкоȺлɟкɫɚнɞɪȺлɟкɫɟɟɜич ? кɚнɞиɞɚɬмɚцɟɜɬичɟɫкиɯнɚɭкпɪɟпоɞɚɜɚɬɟльПяɬиɝоɪɫкоɝомɟɞикоɮɚɪмɚцɟɜɬичɟɫкоɝоинɫɬиɬɭɬɚ ? ɮилиɚлɚɎȽȻОɍȼолɝȽМɍМинзɞɪɚɜɚɊоɫɫииОɛлɚɫɬьнɚɭчныɯинɬɟɪɟɫоɜкомпьюɬɟɪнɚяɛоɬкɚоɛɟɫпɟчɟниямолɟкɭляɪноɝомоɞɟлиɪоɜɚниямолɟкɭляɪныймолɟкɭляɪнɚяɞинɚмикɚ, QSAR. E-mail: alexander.glushko@lcmmp.ruМиɯɚйлоɜɫкɚя ? ɫɬɭɞɟнɬкɚɮɚɪмɚцɟɜɬичɟɫкоɝоɮɚкɭльɬɟɬɚɎȽȻОɍɪонɟжɫкийɝоɫɭɞɚɪɫɬɜɟнныйɭниɜɟɪɫиɬɟɬлɚɫɬьнɚɭчныɯинɬɟɪɟɫоɜлɟкɚɪɫɬɜɟнныɟɮоɪмымикɪокɚпɫɭлиɪоɜɚниɟпɪолонɝиɪоɜɚниɟ E-mail: Кɚɪиɟɜɚɋɚиɞкɚɪимоɜнɚ ? ɞокɬоɪɮɚɪмɚцɟɜɬичɟɫкиɯнɚɭкɞоцɟнɬкɚɮɟɞɪойɬɟɯнолоɝиилɟкɚɪɫɬɜɟнныɯɮоɪмɌɚшкɟнɬɫкоɝоɮɚɪмɚцɟɜɬичɟɫкоɝоинɫɬиɬɭɬɚОɛлɚɫɬьнɚɭчныɯинɬɟɪɟɫоɜлɟкɚɪɫɬɜɟнныɟɮоɪмыɝɟлиɬɟлимɚɬɟмɚɬичɟɫкоɟплɚниɪоɜɚниɟэкɫпɟɪимɟнɬɚПоɫɬɭпилɚɪɟɞɚкциюОɬпɪɚɜлɟнɚɞоɪɚɛоɬкɭПɪиняɬɚпɟчɚɬи

About the authors

Yu. A. Polkovnikova

Federal State Budget Educational Institution of Higher Education “Voronezh State University”

Email: juli-polk@mail.ru

A. A. Glushko

Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State

Email: alexander.glushko@lcmmp.ru

I. Yu. Mikhailovskaya

Federal State Budget Educational Institution of Higher Education “Voronezh State University”

Email: fake@neicon.ru

Yo. S. Karieva

Tashkentskiy Pharmaceutical University

Email: yosk@mail.ru

References

Supplementary files