A Study Of The Properties Of Organosiloxane Sorbents With Hydrogel Of Methylsilicic Acid
A STUDY OF THE PROPERTIES OF ORGANOSILOXANE SORBENTS WITH HYDROGEL OF METHYLsilicic acid
AS A FORMING AGENT FOR PREPARATION
OF IMMOBILIZED medicineS
E. N. Gritsenko, Yu. N. Shevchenko, V. E. Butskaya
The Kiev Medical Academy of Postgraduate Education
named P.L.Shupic Ministry of Health, Ukraine
Ukrainian Internationaly Academy of Original Ideas, Киев, Ukraine
Closed Stock Company "Ecologoprotective firm "КRЕОМА-PHARM", Kiev, Ukraine
Experimentally discovered forming properties of methylsilicic acid hydrogel (MSAHG) as a gel-like organosiloxane sorbent, possessing porous globular matrix and known as enterosorbent Enterosgel (EG) (PA 42U-67-62-96), have opened the prospects for preparation of large series of medicines with the sorption-detoxicational effects in the form of sorbent-immobilized drug. MSAHG is gel-like porous sorbent with the formula (СН3SiО1,5·nН2О)¥, where n is between 39 and 50 depending on the porous structure. The main framework is formed from the sol-solution (globule size of 17-37 nm) due to sewing together globules with inter-globular ºSi-О-Siº siloxane linkages resulting in formation of pores with the average radius r » 100 nm and the pore volume V » 1.1 cm3/g.
In this work, the rheological properties of MSAHG, its aqueous suspension with the ratio of 1:1 (hydrogel-paste, HGP), and mixtures with Eleutherococcus extract (HGP-E), glycerin (HGP-G), dimexide (HGP-D) were studied. To determine the rheological characteristics, structural-mechanical analysis of MSAHG was made using methods of physicochemical mechanics of dispersed systems. The results of analysis of MSAHG as a dispersed system characterize such factors as dispersivity, number of particles per a volume unit, particle shape, surface properties of particles, their contacts with dispersion media (aqueous or organic) determining character of contacts between particles, the nature of dispersion medium and its impact on dispersion phase resulting in disintegration or aggregation of the last depending on the
hydrophilic-lipophilic balance (HLB) and the phase ratio, and temperature of the system. For evaluation of physicochemical stability of the systems, which is linked with biological accessibility and therapeutic efficiency, structural-mechanical analysis of the parameters of plasto-elasto-viscous dispersed systems was performed using the physicochemical mechanics methods. Commercial substance MSAHG-enterosorbent EG was used as a model. Microscopic investigations of the EG structure show that chosen forming agent possesses optically isotropic small-scale honeycomb structure. Its particles with hydrophobic patches can provide easy decomposition of the breakable EG structure due to outbreak of their solvate shells, which result in detachment of immobilized medicines and provide their biological accessibility. The last is an indicator of physicochemical stability of the systems and their biopharmaceutical evaluation.
The structural-mechanical characteristics of EG were explored using a Weiler-Rebinder apparatus to measure the strain parameter versus time and load. The plots of the deformation allow us to evaluate degree of evolution of fast and slow elastic and plastic strains per 900 s at a given load. Mathematical treatment of the experimental data with the structural-mechanical parameters allows one to conclude that EG possesses pronounced plasto-elasto-viscous characteristics, namely elasticity l = 0.55, plasticity = 1.6 s-1, plastic viscosity h1´10-5 = 630 Pa×s, and relaxation time Q1 = 7700 s.
Three series of the experiments performed to study the plasto-elasto-viscous properties of EG under standard conditions showed that all the samples studied can be assigned to the first structural-mechanical type of dispersed systems according to the classification of physicochemical mechanics of dispersed systems. Practical stability of the obtained experimental results for the structural-mechanical characteristics could be explained by the stability of conditions of the investigations and invariability of the EG composition. The stated parameters of structural-mechanical analysis can be monitoring ones to determine the property on production and the physicochemical stability and durability on storage of the products. It should be noted that embedding of effective and adjuvant matters into EG results in changes in the structural-mechanical characteristics. An important property of EG is its ability to be easy suspended in water and miscible with water in any ratio. In this case, finely divided system promotes an increase in the detoxication effect of the sorbent due to enhancement of the surface area of contacts between tiny EG particles and mucous membranes.
The investigation results obtained with a ‘Rheotest’ apparatus showed that a model mixture of EG with water (HGP) has low initial magnitudes of effective viscosity (15 MPa). Rheograms of the flow of the mixture as the whole characterize such a blend as a pseudo-plastic system with marked hysteresis loops. The gel-like model systems with a lower content of liquids possess greater viscous properties and their initial viscosity is below 100 MPa s, then its sharp diminution is observed, which corresponds to the structural destruction of the system. Sometimes a dilatative enhancement arises in the effective viscosity, which indicates that three-dimensional structures form. The structural-mechanical properties of HGP-E, HGP-G, and HGP-D suggest that a significant progress in elastic deformation occurs in the studied gel-like structures, which is feature of the first and second structural-mechanical types (Table 1) of the systems close to each other in the rheological properties.
Table 1. Rheological Characteristics of Gel-like Medicine Systems
System
Structural-mechanical
constants
Structural-mechanical
characteristics
Tentatively momentary modulus of elasticity, Е1´10-3, Pa
Elastic modulus, Е2´10-3, Pa
Static boundary of flowing, Рk1, Pa
Plastic viscosity h1´10-5 ,
Pa ×s
Slow elasticity,
l
Static plasticity,
, s-1
True relaxation time, Q1, s
Structural-mechanical type
EG
(MSAHG)
18.0
15.0
100
630
0.55
1.6
7700
I
HGP-E
5.0
7.0
20.0
79
0.42
2.5
2700
0
HGP-G
4.5
6.0
23.0
72
0.43
3.2
2600
0
HGP-D
4.9
6.8
20.0
78
0.42
2.6
2700
0
Structural-mechanical analysis allows one to determine quantitatively the main criterial magnitudes of the structural-mechanical characteristics, which specify the gel stability parameters, namely elasticity l = 0.4-0.6, plasticity = 1-3 s-1, and true relaxation time Q1= 2000-8000 s, which are monitoring property indicators on production and storage of the medicines. For all the parameters, these systems meet the criterial magnitudes of demands of the technological process and conditions of facilities operation regarding to the extrusion and elasticity distribution.
Obtained data lay at the heart of development of actual medicine compositions on the basis of MSAHG, namely Adaptogel composed of MSAHG + glycerin + Eleutherococcus extract, Bathoxidine (MSAHG + dioxidine + glycerin), Chlodixane (MSAHG + dioxidine + glycerin + dimexide), and other enteral and application medicines.
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