CC BY
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Section 5. Materials Science
Section 5. Materials Science
Dishluk Lubov Sergeevna, Kemerovo Technological Institute of Food Industry, postgraduate student, the Faculty of Bionanotechnology E-mail: [email protected]
Defining Compositions of vegetative analogs for pharmaceutical gelatin for obtaining soft capsules
Abstract: This work describes methods ofpreparing pharmaceutical compositions intended for oral administration, and for manufacturing soft capsules in particular, which are shell containers for pre-dosed powdered, granular, pastelike, liquid or micro capsulated drugs. Soft capsules were obtained from vegetative analogs of pharmaceutical gelatin that feature long shelf life, are simple in manufacturing with standard equipment and ensure rapid therapeutic effect when administered orally. Compositions for obtaining encapsulated drugs from vegetative analogues ofpharmaceutical gelatin were analyzed. The optimal composition has been established for obtaining medical purpose soft capsules ensuring most efficient technical result.
Key words: Starch, gelomil, carrageenan capsules.
Compositions are known for manufacturing a medication capsule [1-6]. The known composition contains type A ammonium methacrylate copolymer (Eudragit RL), at least one filler that modifies dissolution, being a mixture of hydroxypropyl cellulose polymers, each having a different molecular weight and, optionally, a second filler, dissolution modifier selected from a group that consists of a swelling solid substance, disintegrating agent, a water-soluble filler and a nonreducing sugar [7-9]. Besides, the composition contains an optional lubricant, a surfactant and/or a plasticizer and/or a substance that improves technological properties. The disadvantage of the known composition is low consumer properties of capsules obtained on its base. A composition is known for obtaining rigid capsules, as well. The composition for obtaining rigid capsules contains hydroxypropylmethicellulose containing 27.0-30.0%
(wt./wt.) of methoxy groups, 4.0-7.5% (wt./wt.) of hydroxypropoxy groups and water [10]. However, the use of hydroxypropylmethicellulose is not entirely appropriate, as the capsules obtained feature low plasticity and process durability. The technical problem solved by the invention developed is broadening the component base used for manufacturing soft capsules.
Technical result obtained by implementation of the invention developed is obtaining soft capsules of vegetative analogues of pharmaceutical gelatin,
featuring long shelf life, being simple in manufacturing on standard equipment and ensuring rapid therapeutic effect when administered orally.
In order to achieve this technical result it is proposed to use a composition containing (wt.%):
Kappa — carageenan 2.7-3.3 Iota — carageenan 0.45-0.55 Gelamil 308 18.0-22.0 Glycerin 10.0-14.0 Water the rest.
Also, the composition may contain potassium chloride in the amount up to 0.25 wt.%, Amylase corn starch — up to 20 wt.%, Propylparahydroxibenzoate as preservative in the amount up to 0.004 wt.%, methyl parahydroxybenzoate as preservative in the amount up to 0.015 wt.%, and aromatizers and/or sweeteners in pharmacologically acceptable amountsThe capsules may be simultaneously molded and filed using conventional methods and equipment. Capsules made of pharmaceutical gelatin vegetative analogs are molded to the desired shape and size to make swallowing convenient, usually washed down with water. A capsule thus obtained is soluble in water and gastric juice. Glycerin and water act as moisturizers by establishing equilibrium between moisture in the contents and shell of the soft capsule. Thus, water and glycerin prevent soft capsules from becoming rigid, fragile and prone to damage and leakage.
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Defining Compositions of vegetative analogs for pharmaceutical gelatin for obtaining soft capsules
Experimental compositions of capsule content according to this invention are shown in Example 1.
Example 1. Obtaining soft capsules from a mixture of kappa-carageenan, iota-carageenan, gelamil 308, glycerin, and water in the ratio, wt.% kappa-carageenan, 3.0; iota-carageenan (iota) 0.5; gelamil 308 20.0; glycerin 10.0; water 66.5.
A composition ofcapsule shell has been obtained with composition shown in Table. 1 The components were thoroughly mixed and put into soft molds. Capsule shell materials were compatible with conventional process for making soft gelatin capsules, such as described in [5] (closest analog).
Table 1. - Capsules Composition according to Example 1.
Ingredients [5] Amount, wt.% Ingredients (proposed composition) Amount, wt.%
Lysinchlonyxinate 22.3 Kappa — carageenan 3
Polyethyleneglycol 400 61.4 Iota — carageenan 0.5
Anhydrous glycerin 6.3 Gelamil 308 20
Water 10 Glycerin 10
Water 66.5
Viscosity of mixture prepared according to Example 1 was 700cPs at 800 °C. Capsules wall thickness ranged between 0.1 and 0.3 mm. Visual inspection showed that capsules made of the developed composition feature have greater plasticity compared to capsules made of the nearest analog composition. However, attempts have been made
Table 2. - Capsules Compo
to increase plasticity of the mixture of vegetative analogs of pharmaceutical gelatin for obtaining soft capsules and ensuring process durability of capsules obtained.
Example 2. Obtaining soft gelatin capsules from a mixture of kappa-carageenan, iota-carageenan, amylase corn starch, glycerol, water in the ratio specified. on according to Example 2.
Ingredients [5] Amount, wt.% Ingredients (proposed composition) Amount, wt.%
Lysinchlonyxinate 22.3 Kappa — carageenan 3
Polyethyleneglycol 400 61.4 Iota — carageenan 0.5
Anhydrous glycerin 6.3 Amylase corn starch 15
Water 10 Glycerin 11.5
Water 70
Viscosity of mixture prepared according to Example 2 was 850 cPs at 800 °C.
Capsules wall thickness ranged between 0.2 and
0.5 mm. Visual inspection showed that capsules made of the developed composition feature have greater plasticity compared to capsules made of the nearest analog composition. However, attempts have been
Table 3. - Capsules Compc
made to increase plasticity of the mixture of vegetative analogs of pharmaceutical gelatin for obtaining soft capsules and ensuring process durability of capsules obtained.
Example 3. Obtaining soft gelatin capsules from a mixture of kappa-carageenan, iota-carageenan, amylase corn starch, glycerol, water in the ratio specified in Table. 3. on according to Example 3.
Ingredients [5] Amount, wt.% Ingredients (proposed composition) Amount, wt.%
Lysinchlonyxinate 22.3 Kappa — carageenan 2
Polyethyleneglycol 400 61.4 Iota — carageenan 0.33
Anhydrous glycerin 6.3 Amylase corn starch 20
Water 10 Glycerin 12
Water 65.67
Viscosity of mixture prepared according to Example 3 was 850 -900 cPs at 800 °C.
Capsules wall thickness ranged between 0.2 and
0.5 mm. Visual inspection showed that capsules made of the developed composition feature have greater plasticity compared to capsules made of the nearest analog composition. However, attempts have been
made to increase plasticity of the mixture of vegetative analogs of pharmaceutical gelatin for obtaining soft capsules and ensuring process durability of capsules obtained.
Example 4. Obtaining soft gelatin capsules from a mixture of kappa-carageenan, iota-carageenan, gelamil 308, glycerin, and water in the ratio shown in Table 4.
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Section 5. Materials Science
Table 4. - Capsules Composition according to Example 4.
Ingredients [5l Amount, wt.% Ingredients (proposed composition) Amount, wt.%
Lysinchlonyxinate 22.3 Kappa — carageenan 3
Polyethyleneglycol 400 61.4 Iota — carageenan 0.5
Anhydrous glycerin 6.3 Gelamil 308 30
Water 10 Glycerin 11.5
Water 55
Viscosity of mixture prepared according to Example 4 was 1700-1900 cPs at 800 °C.
Capsules wall thickness ranged between 0.8 and 1.0 mm. Visual inspection showed that capsules made of the developed composition feature have greater plasticity compared to capsules made of the nearest analog composition.
However, the mixture for obtaining capsules turned
out to be too viscous, which complicated the process
of capsules manufacturing from vegetative analogs of pharmaceutical gelatin. Ready capsules were too elastic, has too thick walls, which complicated their dissolution gastric juice and digestibility.
Further attempts were made to improve the formulation for preparing a mixture of pharmaceutical
Table 5. - Capsules Compo
gelatin vegetative analogs for obtaining soft capsules in order to ensure optimum mixture viscosity and plasticity for manufacturing capsules with wall thickness optimal for digesting.
Example 5. Obtaining soft gelatin capsules from a mixture of kappa-carageenan, iota-carageenan, gelamil 308, glycerin, and water with addition of potassium chloride, propylparahydroxibenzoate and methylparahydroxybenzoate in the ratio shown in Table 5.
Capsules wall thickness ranged between 0.7 and
0.8 mm. Visual inspection showed that capsules made of the developed composition feature have greater plasticity compared to capsules made of the nearest analog composition. on according to Example 5.
Ingredients [5] Amount, wt.% Ingredients (proposed composition) Amount, wt.%
Lysinchlonyxinate 22.3 Carageenan (kappa) 3
Polyethyleneglycol 400 61.4 Carageenan (iota) 0.5
Anhydrous glycerin 6.3 Gelamil 308 20
Water 10 Glycerin 11.463
Water 65
Potassium chloride 0.02
Propylp arahydroxibenzoate 0.0035
Methylparahydroxybenzoate 0.014
Studies ofcapsules solubility in gastric juice, and drug release rate showed that the formulation developed is optimal for manufacturing and storing capsules made of pharmaceutical gelatin vegetative analogues. Viscosity of mixture prepared according to Example 4 was 1300-1500cPsat 800°C.
Soft capsules obtained from pharmaceutical gelatin vegetative analogs, kappa-carageenan, iota-carageenan, gelamil 308 and, possibly, with addition of amylase corn starch feature greater plasticity, long shelf life and more rapid therapeutic effect when administered orally.
References:
1. Morris, V.J., A. Gromer, A. R. Kirby et al, 2011. Using AFM and force spectroscopy to determine pectin structure and (bio) functionality. Food hydrocolloids, 25: 230-327.
2. Murthy, S. N. and R. H. S. Shobha, 1998. Comparative pharmacokinetic and pharmacodynamic evaluation of oral vs. transdermal delivery of terbutaline sulphate. Indian Drugs, 35: 34-36.
3. Narayani, R. and K. P. Rao, 1995. Polymer-coated gelatin capsules as oral delivery devices and their gastrointestinal tract behavior in humans. Journal of Biomaterials Science, Polymer Edition, 7: 39-48.
4. Panchagnula, R., 1997. Transdermal delivery of drugs. Indian Journal of Pharmacology, 29: 140-156.
5. Parker, R. and S. G. Ring, 2001. Aspects of the Physical Chemistry of Starch. Journal of Cereal Science, 34: 1-17.
6. Prasad, Y. V., Y. S. Krishnaiah and S. Satyanarayana, 1998. In vitro evaluation of guar gum as a carrier for colon-specific drug delivery. Journal of Controlled Release, 51: 281-287.
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Improving the physical and chemical activity of the medium of binding agents hydration
7. Rangaiah, K. V., S. Madhusudhan and P. R. P. Verma, 1995. Sustained release of theophylline from HPMC and Eudragit tablet. Indian Drugs, 32: 543-547.
8. Rao, P. R. and P. V. Diwan, 1998. Formulation and in vitro evaluation of polymeric films of diltiazem hydrochloride and indomethacin for transdermal administration. Drug Development and Industrial Pharmacy, 24: 327-336.
9. Rasmussen, М. R., Т. Snabe and L. Н. Pedersen, 2003. Numerical modeling of insulin and amyloglucosidase release from swelling Ca-alginate beads. Journal of Controlled Release, 91: 395-405.
10. Smitsrod, О. And A. Haug, 1971. Estimation of the relative stiffness of the molecular chain in polyelectrolytes from measurements of viscosity at different ionic strengths. Biopolymers, 10: 1213-1227.
Zayakhanov Mikhail Egorovich, East-Siberian State University of Technologies and Management, Doctor of Technical Sciences, Professor, the Faculty of Construction
E-mail: [email protected]
Improving the physical and chemical activity of the medium of binding agents hydration
Abstract: The article deals with the possibility of increasing the reactivity of the hydration process of binding agents. It is shown that the electromagnetic activation leads to regulation of the hydration process.
Keywords: hydration, binding agents, activity, frequency, energy costs
Заяханов Михаил Егорович, Восточно-Сибирский государственный университет технологий и управления, д. т. н., профессор, строительный факультет
E-mail: [email protected]
Повышение физико-химической активности среды гидратации вяжущих веществ
Аннотация: В статье рассматривается возможность повышения реакционноспособности процесса гидратации вяжущих веществ. Показано, что электромагнитная активация приводит к регулированию процесса гидратации.
Ключевые слова: гидратация, вяжущие вещества, активность, частота, энергетические затраты
Повышение реакционноспособности, уменьшение энергии активации процесса гидратации вяжущих возможно при повышении физико-химической активности среды, приводящей к увеличению активной поверхности твердых компонентов вяжущих.
Для рассмотрения вопросов, связанных с процессами диссипации в качестве исходной предпосылки воспользуемся равновесием диссоциации некоторого электролита (воды) в произвольном растворителе:
ki + -
H2o ^ h + oh (1)
К.
где Ц и k2 — константы скоростей; H+ и OH- — соль-ватированные катион и анион. С точностью до гидродинамических флуктуаций сдвиг равновесия вправо увеличивает локальную плотность зарядов, влево — уменьшает. При фиксированной концентрации вещества средняя длина свободного пробега ионов H+ и OH- конечна. Согласно
общим положениям механики, любое одномерное конечное движение есть колебательное, имеющее предельные циклы с асимптотической устойчивостью. Для раскрытия физического содержания этих колебаний представляется оправданным сделать кинетический анализ равновесия диссоциации (1) произвольного электролита.
Система уравнений, характеризующий процесс равновесия (1) выглядит следующим образом:
v2
_ _d_ dt
de
dt
(C0 _C) = k(C0 _C)
k2C2
(2)
(3)
Здесь С0 — начальная концентрация электролита, С — концентрация диссоциированных молекул электролита. Очевидно, что С0-С=5 есть концентрация недиссоциированных молекул.
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