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10CHEMICAL SCIENCES
THE MATHEMATICAL PLANNING OF SAMPLE PREPARATION FOR DOSAGE FORM
"DETRALEX®" TABLETS
Voronin A.,
Doctor of Pharmacy, Chief of the Department of Chemistry, Faculty of Pharmacy
Samara State Medical University Karpov A.
Postgraduate of the Department of Chemistry, Faculty of Pharmacy
Samara State Medical University
Abstract
To obtain high-quality analysis results, it is necessary to choose the suitable analytical methods and evaluate the factors influencing the analysis' procedure (individual stages of analysis' procedure). Mathematical planning for analysis' stages using statistical soft allows to plan an experiment, select the optimal parameters for the extraction of diosmin from dosage forms. The research of extraction factors is necessary to optimize the parameters of sample preparation.
Keywords: diosmin, sample preparation, mathematical planning, metrological characteristics.
The choice of adequate and objective methods for quality control of drugs from the pharmaceutical substance diosmin is an important practical problem of pharmaceutical analysis.
In most dosage forms, diosmin is contained in the form of micronized flavonoid fraction. It's resulting in low recovery by solid-liquid extraction of diosmin [2].
The purpose of this research is testing of mathematical planning algorithm of sample preparation for "Detralex®" tablets 1000 mg.
Materials and methods. The study of the recovery of diosmin was made to the scheme of three-factor experimental planning using the 5/1/81 plan (5 factors, 1 block, 81 runs).
To formulate a mathematical model of sample preparation, two iteration of the plan were implemented
after its randomization [1]. This version of mathematical modeling is a multivariate method for selecting the optimal values of the sample preparation factors, and as statistical processing of the experimental data with subsequent search optimization.
The optimization parameter is diosmin recovery from dosage form. The main factors influencing the optimization parameter: sodium hydroxide concentration (extractant), mol/L; acetonitrile concentration^ (solvent for the decomposition of micelles of dimosmin); extraction time, min; centrifugation time, min; ammonium sulfate concentration^ (salting out reagent).
The experimental factors levels for sample preparation of "Detralex®" tablets are presented in Table 1.
Table 1
The experimental factors levels of diosmin extraction from "Detralex®" tablets
Factor Level
-1 0 +1
Xi - sodium hydroxide concentration, mol/L 0,1 0,05 0,02
X2 - acetonitrile concentration, % (to the volume of water phase) 50,0 25,0 -
X3 - extraction time, min 5,0 10,0 20,0
X4 - centrifugation time, min 5,0 10,0 20,0
X5 - ammonium sulfate concentration^ 10,0 5,0 -
Main part. The characteristics of experimental data sampling on the study of diosmin recovery are presented in Table 2.
Table 2
The metrological characteristics of experimental data sampling of diosmin recovery from
"Detralex®" tablets
m f xm S2 S P t(P, f) Ax Ô
1 2 3 4 5 6 7 8 9 10
Sample 1
100 60 66,39 178,91 13,37 95 2,00 ±26,74 5,15% 66,4%
Sample 2
100 60 66,28 234,63 15,31 95 2,00 ±30,64 5,91% 66,3%
The mathematical model of the main optimization parameter from the values of the sample preparation factors is described by the function ra-f(Xi, X2, X3, X4, X5). To determine what part of the variation in the effective indicator (ra) is due to the variation in factor indicators, a determination coefficient (r2) is required.
It has values from 0 to 1. The closer determination coefficient is to 1, the stronger the functional dependence, and for r2> 0,5 the model can be considered acceptable. In our research, the determination coefficient is 0.8803, which is interpreted as a good fitting of the mathematical model to the experimental data and indicates a high level accuracy of the approximation.
The statistical reliability of multiple regression was assessed using the Fisher test (F-test), which tests the hypothesis (H0) to the statistical insignificance of the parameters of the regression equations. For this, the
actual values of the F-criterion were compared with the tabular (Ftabl) [1] for a given significance level (a -0,05-5%) and the degrees of freedom. In our research, Ftabl value (dfi= 5, df2 - 60) is 2,37.
In regression analysis for diosmin F > Ftabl, this means that with the hypothesis that the experimental data is not random and formed under the influence of significant factors is accepted (a probability of more than 95%). The statistical significance of the regression equations and their parameters for diosmin is recognized.
For a visualization of all effects, interactions of factors and further assessment of the significance of influencing factors, Pareto Charts were obtained for standardized effects (L - linear effects, Q - quadratic effects).
Pareto Chart of Standardized Effects; Variable: Проба 1 63-levelfactors, 1 Blocks, 61 Rins; MS Pure Error=6,913054 DV: Проба 1
(1 )Var1 (L) ■-32,9879
1-5,16563 14,67252 И 2406
1Lby5L 3Lby5 L
13,647076 13,442228 I 2 34195
(4)Var4(L)
1^2,14595 12,039598 11,985026
VarS(Q)
2Lby3 L
11,761968
2Lby5L 1-1,4489 I.9749358 L9580727 I 700899
(2)Var2(L) 3Lby4L
1,3408327 1-282072 1,1673943
(3)Var3(L)
p=,05
Standardized Effect Estimate (Absolute Value)
Figure 1 - Pareto Chart of standardized effects for diosmin
From the analysis of Pareto Chart (figure 1), it follows that a change of sodium hydroxide concentration in the extractant (factor Xi) leads to a significant effect on diosmin recovery. The rest of the effects do not have a significant effect.
For a visualization of the combination of extraction parameters for diosmin, which corresponds to the surface area that takes the maximum value, a graphic image was obtained in the form of contour diagrams and fitted surfaces (figure 2).
ill p-pa NaOti
Figure 2 - Fitted surface and contour diagram for dependence of diosmin recovery to factors Xi and X5
The contour diagram shows that the main effect is tor Xi) and as its value approaches 0,02 mol/L, the di-the sodium hydroxide concentration of extractant (fac- osmin recovery increases. The addition of the salting-
out agent ammonium sulfate (factor X5) has no effect.
Conclusion. It was found that the most significant factor determining the recovery diosmin from "De-tralex®" tablets is the sodium hydroxide concentration. Other extraction factors (acetonitrile concentration, extraction time, centrifugation time, addition of ammonium sulfate) did not have a significant effect. The optimal concentration of sodium hydroxide in the extract-ant is 0,02 mol/L.
REFERENCES:
1. Halafyan, A.A. Statisticheskij analiz dannyh. Statistica 6.0.: Uchebnoe posobie / A.A. Halafyan. Krasnodar: KubGU; 2005.(In Russ.)
2. Srilatha, D. Development and Validation of UV Spectrophotometric Method for Simultaneous Estimation of Hesperidin and Diosmin in the Pharmaceutical Dosage Form / D. Srilatha, M. Nasare, B. Na-gasandhya [et al.] // ISRN Spectroscopy. - 2013.: Hindawi Publishing Corporation. - Access: https://dx.doi.org/10.1155/2013/534830.
NEW EMULSIFIER AND ANTIDEGRADANT BASED ON CASTORIC ACID
Havriushenko K.,
Postgraduate Student, Department of Technology of Fats and Fermentation Products National Technical
University «Kharkiv Polytechnic Institute», Kharkiv, Ukraine
Gladkiy F.,
Doctor of Technical Sciences, Professor, Department of Technology of Fats and fermentation Products, National Technical University «Kharkiv Polytechnic Institute», Kharkiv, Ukraine
Skliar V.
Undergraduate Student, Department of Technology of Fats and Fermentation Products National Technical
University «Kharkiv Polytechnic Institute», Kharkiv, Ukraine
НОВИЙ ЕМУЛЬГАТОР I КОНСЕРВАНТ НА ОСНОВ1 РИЦИНОВО1 КИСЛОТИ
Гаврюшенко К.О.,
AcnipaHm, Кафедра технологи жирiв та npodyKmie бродiння, Нацюнальний техтчний yuieepcumem
«Хартвський полiтехнiчний iHcmumym», XapKie, Украша
Гладкий Ф.Ф.,
Доктор технiчних наук, професор, Кафедра технологи жирiв та npodyKmie бродтня, Нацюнальний mехнiчний утверситет «Хартвський noлimехнiчний iнсmиmym», Хартв, Украша
C^rap В.В.
Магктрант, Кафедра технологи жиpiв та npoдyкmiв бродтня, Нацioнальний mехнiчний утверситет «Хартвський noлimехнiчний iнсmиmym», Хартв, Украша
Abstract
The article is devoted to the determination of rational conditions for amonolysis of castor oil and sodium salt of glycine with the use of a heterogeneous catalyst - zeolites of the Na-X type. A mathematical description of the dependence of the degree of transformation on the main parameters of the process, namely: temperature and duration of interaction. Ways of using the sodium salt of ricinoylglycine as an effective solubilizer against glaze substances and a component that inhibits the appearance of mold and has bactericidal properties in the composition of cosmetic and food products are proposed.
Анотащя
Стаття присвячена визначенню рацюнальних умов амонолiзу рициново! оли та raipieBoi солi глщину i3 застосуванням гетерогенного каталзатору - цеолтв типу Na-X. Отримано математичний опис залеж-носп ступеню перетворення вщ основних паpаметpiв процесу, а саме: температури та тривалосп взаемоди. Запропоновано шляхи використання налево! солi рициношглщину, як ефективного солюбшзатора вщ-носно поляних речевин та компонента, що пригшчуе появу плюняви та проявляе бактерицидш властиво-сп, у склащ косметичних та харчових продукпв.
Keywords: surfactants, amino acids, heterogeneous catalyst, zeolites, amonolysis, castor oil, acyl aminoac-ids, bactericidal properties, solubilizer, rotatable central composition plan.
K^40Bi слова: поверхнево-активш речовини, амшокислоти, гетерогенний каталiзатоp, цеолгги, амо-нолiз, рицинова олiя, ациамшокислоти, бактеpициднi властивостi, солюбiлiзатоp, рототабельний центрально -композицшний план.
Вступ. В багатьох кранах свггу зростае штерес тва амiнокислотних ПАР зумовлений ïx багатофун-до використання поверхнево-активних речовин кцюнальшстю, низькою токсичнiстю, вщновлюва-(ПАР) на основi амiнокислот. Розвиток виробниц- льними джерелами сировини, та повним бюрозкла-
