Factory-produced medical solutions. Intensification of the dissolution process. Cleaning methods.
TABLE OF CONTENTS

INTRODUCTION

Liquid dosage forms (LDF) from pharmacies account for more than 60% of the total number of all drugs prepared in pharmacies.

The widespread use of LDF is due to a number of advantages over other dosage forms:

Thanks to the use of certain technological methods (dissolution, peptization, suspension or emulsification), a medicinal substance in any state of aggregation can be brought to the optimal degree of particle dispersion, dissolved or evenly distributed in a solvent, which is of great importance for providing a therapeutic effect of the medicinal substance on body and confirmed by biopharmaceutical research;
liquid dosage forms are distinguished by a wide variety of composition and methods of use;
as part of the LLF, it is possible to reduce the irritating effect of certain medicinal substances (bromides, iodides, etc.);
these dosage forms are simple and convenient to use;
in WLF it is possible to mask the unpleasant taste and smell of medicinal substances, which is especially important in pediatric practice;
when taken orally, they are absorbed and act faster than solid dosage forms (powders, tablets, etc.), the effect of which manifests itself after they are dissolved in the body;
the emollient and enveloping effect of a number of medicinal substances is most fully manifested in the form of liquid medicines.

However, liquid medications have a number of disadvantages:

they are less stable during storage, since the substances are more reactive in dissolved form;
solutions are more quickly subject to microbiological deterioration, and accordingly they have a limited shelf life of no more than 3 days;
YLF require quite a lot of time and special utensils for preparation, and are inconvenient for transportation;
Liquid medicines are inferior in dosing accuracy to other dosage forms, as they are dosed in spoons and drops.

Thus, YLF is a widely used dosage form today. Due to their advantages, liquid medicines have great prospects in the future for the creation of new medicines, so studying this topic is very advisable.

In addition, such a disadvantage of LDF as instability during storage does not allow reducing the number of extemporaneous drugs and increasing the number of finished liquid drugs, so the study of LDF technology remains very relevant.

The purpose and objectives of this work is to study a factory-produced medical solution.

Chapter 1 GENERAL CHARACTERISTICS OF MEDICAL SOLUTIONS

1.1 Characteristics and classification of solutions

Solutions are liquid homogeneous systems consisting of a solvent and one or more components distributed in it in the form of ions or molecules 1 .

Medical solutions are distinguished by a wide variety of properties, composition, methods of preparation and purpose. Separate solutions, the production of which involves chemical reactions, are obtained at chemical and pharmaceutical plants.

Solutions have a number of advantages over other dosage forms, since they are absorbed much faster in the gastrointestinal tract. The disadvantage of solutions is their large volume, possible hydrolytic and microbiological processes that cause rapid destruction of the finished product.

Knowledge of solution technology is also important in the manufacture of almost all other dosage forms, where solutions are intermediates or auxiliary components in the manufacture of a specific dosage form.

Solutions occupy an intermediate position between chemical compounds and mechanical mixtures. Solutions differ from chemical compounds in their variable composition, and from mechanical mixtures in their homogeneity. That is why solutions are called single-phase systems of variable composition, formed by at least two independent components. The most important feature of the dissolution process is its spontaneity. A simple contact of the solute with the solvent is sufficient to form a homogeneous system solution after some time.

Solvents can be polar or non-polar substances. The first include liquids that combine a large dielectric constant, a large dipole moment with the presence of functional groups that ensure the formation of coordination (mostly hydrogen) bonds: water, acids, lower alcohols and glycols, amines, etc. Non-polar solvents are liquids with a small dipole moment that do not have active functional groups, for example hydrocarbons, haloalkyls, etc.

When choosing a solvent, one must use primarily empirical rules, since the proposed theories of solubility cannot always explain the usually complex relationships between the composition and properties of solutions.

Most often they follow the old rule: “Like dissolves in like” (“Similia similibus solventur”). In practice, this means that the most suitable solvents for dissolving a substance are those that are structurally similar and, therefore, have similar or similar chemical properties 2 .

The solubility of liquids in liquids varies widely. Liquids are known that dissolve indefinitely in each other (alcohol and water), that is, liquids similar in the type of intermolecular action. There are liquids that are sparingly soluble in each other (ether and water), and, finally, liquids that are practically insoluble in each other (benzene and water).

Limited solubility is observed in mixtures of a number of polar and non-polar liquids, the polarizability of the molecules of which, and consequently the energy of intermolecular dispersion interactions, differ sharply. In the absence of chemical interactions, solubility is maximum in those solvents whose intermolecular field intensity is close to the molecular field of the solute. For polar liquid substances, the particle field intensity is proportional to the dielectric constant.

The dielectric constant of water is 80.4 (at 20 °C). Consequently, substances with high dielectric constants will be more or less soluble in water. For example, glycerin (dielectric constant 56.2), ethyl alcohol (26), etc. mixes well with water. On the contrary, petroleum ether (1.8), carbon tetrachloride (2.24), etc. are insoluble in water. However, this rule is not always valid, especially when applied to organic compounds. In these cases, the solubility of substances is influenced by various competing functional groups, their number, relative molecular weight, size and shape of the molecule, and other factors. For example, dichloroethane, whose dielectric constant is 10.4, is practically insoluble in water, while diethyl ether, which has a dielectric constant of 4.3, is soluble in water at 20 ° C in an amount of 6.6%. Apparently, the explanation for this must be sought in the ability of the ethereal oxygen atom to form unstable complexes such as oxonium compounds with water molecules 3 .

With increasing temperature, the mutual solubility of sparingly soluble liquids in most cases increases and often when a certain temperature for each pair of liquids, called critical, is reached, the liquids completely mix with each other (phenol and water at a critical temperature of 68.8 ° C and higher dissolve each other in each other in any proportions). When pressure changes, mutual solubility changes slightly.

The solubility of gases in liquids is usually expressed by the absorption coefficient, which indicates how many volumes of a given gas, reduced to normal conditions (temperature 0 ° C, pressure 1 atm), dissolve in one volume of liquid at a given temperature and partial gas pressure of 1 atm. The solubility of gas in liquids depends on the nature of the liquids and gas, pressure and temperature. The dependence of gas solubility on pressure is expressed by Henry's law, according to which the solubility of a gas in a liquid is directly proportional to its pressure above the solution at a constant temperature, however, at high pressures, especially for gases that chemically interact with the solvent, a deviation from Henry's law is observed. With increasing temperature, the solubility of gas in liquid decreases.

Any liquid has limited dissolving ability. This means that a given amount of solvent can dissolve the drug substance in quantities not exceeding a certain limit. Solubility of a substance is its ability to form solutions with other substances. Information on the solubility of medicinal substances is given in pharmacopoeial monographs. For convenience, SP XI indicates the number of parts of solvent required to dissolve 1 part of the drug at 20 °C. Substances are classified according to their degree of solubility 4 :

1. Very easily soluble, requiring no more than 1 part of solvent for dissolution.

2. Easily soluble from 1 to 10 parts of solvent.

3. Soluble 10 to 20 parts solvent.

4. Sparingly soluble from 30 to 100 parts of solvent.

5. Slightly soluble from 100 to 1000 parts of solvent.

6. Very slightly soluble (almost insoluble) from 1000 to 10,000 parts of solvent.

7. Practically insoluble more than 10,000 parts of solvent.

The solubility of a given drug in water (and other solvents) depends on temperature. For the vast majority of solids, their solubility increases with increasing temperature. However, there are exceptions (for example, calcium salts).

Some drugs may dissolve slowly (although they dissolve in significant concentrations). In order to accelerate the dissolution of such substances, they resort to heating, preliminary grinding of the dissolved substance, and stirring the mixture.

Solutions used in pharmacy are very diverse. Depending on the solvent used, the entire variety of solutions can be divided into the following groups 5 .

Water . Solutions aquosae seu Liquores.

Alcohol. Solutions spirituosae.

Glycerin. Solutions glycerinatae.

Oil . Solutiones oleosae seu olea medicata.

According to the state of aggregation of medicinal substances soluble in them:

Solutions of solids.

Solutions of liquid substances.

Solutions with gaseous drugs.

1.2 Intensification of the dissolution process

To speed up the dissolution process, you can use heating or increasing the contact surface of the solute and the solvent, which is achieved by preliminary grinding of the solute, as well as shaking the solution. Typically, the higher the temperature of the solvent, the greater the solubility of the solid, but sometimes the solubility of the solid decreases as the temperature increases (for example, calcium glycerophosphate and citrate, cellulose ethers). The increase in the dissolution rate is due to the fact that when heated, the strength of the crystal lattice decreases, the diffusion rate increases, and the viscosity of solvents decreases. In this case, the diffusion force acts positively, especially in non-polar solvents, where diffusion forces are of primary importance (in this case, no solvates are formed). It should be noted that with increasing temperature, the solubility of certain substances in water increases sharply (boric acid, phenacetin, quinine sulfate), while others increase slightly (ammonium chloride, sodium barbital). The maximum degree of heating is largely determined by the properties of the dissolved substances: some tolerate heating in liquid up to 100 ° C without changes, while others decompose already at a slightly elevated temperature (for example, aqueous solutions of some antibiotics, vitamins, etc.). We must also not forget that an increase in temperature can cause loss of volatile substances (menthol, camphor, etc.). As already mentioned, the solubility of a solid also increases as the contact surface between the solute and the solvent increases. In most cases, increasing the contact surface is achieved by grinding the solid (for example, tartaric acid crystals are more difficult to dissolve than powder). In addition, to increase the contact surface of a solid with a solvent, shaking is often used in pharmacy practice. Stirring facilitates access of the solvent to the substance, helps to change the concentration of the solution at its surface, and creates favorable conditions for dissolution 6 .

1.3 Cleaning methods

Filtration is the process of separating heterogeneous systems with a solid dispersed phase using a porous partition that allows liquid to pass through (filtrate) and retains suspended solids (sediment). This process is carried out not only due to the retention of particles larger than the diameter of the capillaries of the partition, but also due to the adsorption of particles by the porous partition, and due to the layer of sediment formed (slurry type of filtration).

The movement of liquid through the porous filter membrane is mainly laminar. If we assume that the capillaries of the partition have a circular cross-section and the same length, then the dependence of the filtrate volume on various factors obeys Poiselle’s law 7 :

Q = F · z · π · r ·Δ P · τ /8·ŋ· l · α ,where

F - filter surface, m²;

z - number of capillaries per 1 m²;

r - average radius of capillaries, m;

ΔP - pressure difference on both sides of the filter partition (or pressure difference at the ends of the capillaries), n/m²;

τ - filtering duration, sec;

ŋ is the absolute viscosity of the liquid phase in N/s m²;

l -average length of capillaries, m²;

α - correction factor for capillary curvature;

Q - volume of filtrate, m³.

Otherwise, the volume of filtered liquid is directly proportional to the filter surface ( F), porosity (r, z ), pressure drop (ΔР), filtration duration (τ) and is inversely proportional to the viscosity of the liquid, the thickness of the filter partition and the curvature of the capillaries. From the Poiselle equation, the filtration rate equation is derived ( V ), which is determined by the amount of liquid passing through a unit of surface per unit of time.

V = Q / F τ

After transforming the Poiselle equation, it takes the form:

V = Δ P / R sediment + R partition

where R resistance to fluid movement. From this equation follows a number of practical recommendations for the rational conduct of the filtration process. Namely, to increase the pressure difference above and below the partition, either increased pressure is created above the filter partition, or a vacuum is created below it.

Separating solids from liquids using a filter baffle is a complex process. For such separation there is no need to use a partition with pores whose average size is less than the average size of solid particles.

It has been found that solid particles are successfully retained by pores larger than the average particle size retained. Solid particles carried by the fluid flow to the filter baffle are exposed to various conditions.

The simplest case is when a particle is retained on the surface of the partition, having a size larger than the initial cross section of the pores. If the particle size is smaller than the capillary size at its narrowest cross section, then 8 :

the particle can pass through the partition along with the filtrate;
the particle can be retained inside the partition as a result of adsorption on the pore walls;
the particle can be retained due to mechanical braking at the site of the pore convolution.

The turbidity of the filter at the beginning of filtration is explained by the penetration of solid particles through the pores of the filter membrane. The filtrate becomes transparent when the partition acquires sufficient retention capacity.

Thus, filtering occurs by two mechanisms:

due to the formation of sediment, since solid particles almost do not penetrate into the pores and remain on the surface of the partition (slurry type of filtration);
due to clogging of pores (clogging type of filtration); in this case, almost no sediment is formed, since the particles are retained inside the pores.

In practice, these two types of filtering are combined (mixed type of filtering).

Factors influencing the filtrate volume and, therefore, the filtration rate are divided into 9 :

Hydrodynamic;

Physico-chemical.

Hydrodynamic factors are the porosity of the filter partition, its surface area, the pressure difference on both sides of the partition and other factors taken into account in the Poiselle equation.

Physico-chemical factors this is the degree of coagulation or peptization of suspended particles; content of resinous, colloidal impurities in the solid phase; the influence of the double electrical layer that appears at the boundary of the solid and liquid phases; the presence of a solvation shell around solid particles, etc. The influence of physicochemical factors, closely related to surface phenomena at the interface, becomes noticeable at small sizes of solid particles, which is precisely what is observed in pharmaceutical solutions subject to filtration.

Depending on the size of the particles to be removed and the purpose of filtration, the following filtration methods are distinguished:

1. Coarse filtration to separate particles 50 microns in size or more;

2. Fine filtration ensures removal of particles sized
1-50 microns.

3. Sterile filtration (microfiltration) is used to remove particles and microbes measuring 5-0.05 microns. In this variety, ultrafiltration is sometimes used to remove pyrogens and other particles with a size of 0.1-0.001 microns. Sterile filtration will be discussed in the topic: “Injectable dosage forms.”

All filtering devices in industry are called filters; their main working part is filter partitions.

Filters operating under vacuum Nutsch filters.

Nutsch filters are convenient in cases where it is necessary to obtain clean, washed sediments. It is not advisable to use these filters for liquids with mucous sediments, ether and alcohol extracts and solutions, since ether and ethanol evaporate faster under vacuum, are sucked into the vacuum line and enter the atmosphere.

Filters operating under excess pressure druk filters. The pressure drop is much greater than in suction filters and can range from 2 to 12 atm. These filters are simple in design, highly efficient, and allow you to filter viscous, highly volatile and highly resistive liquid sediments. However, to unload the sediment, it is necessary to remove the top part of the filter and collect it manually.

Frame filter press consists of a series of alternating hollow frames and plates, which have corrugations and grooves on both sides. Each frame and plate are separated by filter fabric. The number of frames and slabs is selected based on productivity, quantity and purpose of sludge, within 10-60 pieces. Filtration is carried out under a pressure of 12 atm. Filter presses have high productivity, they produce well-washed sediments and clarified filtrate, and have all the advantages of druk filters. However, very durable materials should be used for filtering.

The “Mushroom” filter can operate both under vacuum and at excess pressure. The filter unit consists of a container for the filtered liquid; “Mushroom” filter in the form of a funnel onto which filter fabric (cotton wool, gauze, paper, belting, etc.) is attached; receiver, filtrate collector, vacuum pump.

Thus, filtration is an important process in a technological sense. It is used either independently or can be an integral part of the production scheme for such pharmaceutical products as solutions, extraction preparations, purified sediments, etc. The quality of these products depends on correctly selected filtering devices, filter materials, filtration speed, ratio of solid and liquid phases, structure solid phase and its surface properties.

Chapter 2 EXPERIMENTAL PART

2.1 Quality control of a solution of sodium bromide 6.0, magnesium sulfate 6.0, glucose 25.0, purified water up to 100.0 ml

Features of chemical control. Qualitative and quantitative analyzes are carried out without preliminary separation of ingredients.

The most rapid method for determining glucose in liquid dosage forms is the refractometry method.

Organoleptic control. Colorless transparent liquid, odorless.

Determination of authenticity

Sodium bromide

1. To 0.5 ml of the dosage form add 0.1 ml of diluted hydrochloric acid, 0.2 ml of chloramine solution, 1 ml of chloroform, and shake. The chloroform layer turns yellow (bromide ion).

2. Place 0.1 ml of solution in a porcelain cup and evaporate in a water bath. To the dry residue add 0.1 ml of copper sulfate solution and 0.1 ml of concentrated sulfuric acid. A black color appears, which disappears when 0.2 ml of water (bromide ion) is added.

2NaBr + CuSO4 → CuBr2↓ + Na2SO4

3. Part of the solution on a graphite stick is introduced into a colorless flame. The flame turns yellow (sodium).

4. Add 0.1 ml of picric acid solution to 0.1 ml of the dosage form on a glass slide and evaporate to dryness. Yellow crystals of a specific shape are examined under a microscope (sodium).

Magnesium sulfate

1. To 0.5 ml of the dosage form add 0.3 ml of ammonium chloride solution, sodium phosphate and 0.2 ml of ammonia solution. A white crystalline precipitate is formed, soluble in diluted acetic acid (magnesium).

2. To 0.5 ml of the dosage form add 0.3 ml of barium chloride solution. A white precipitate is formed, insoluble in dilute mineral acids (sulfates).

Glucose. To 0.5 ml of the dosage form add 1-2 ml of Fehling's reagent and heat to a boil. A brick-red precipitate forms.

Quantification.

Sodium bromide. 1. Argentometric method. To 0.5 ml of the mixture add 10 ml of water, 0.1 ml of bromophenol blue, dropwise acetic acid diluted to a greenish-yellow color, and titrate with a 0.1 mol/l solution of silver nitrate to a violet color.

1 ml of 0.1 mol/l silver nitrate solution corresponds to 0.01029 g of sodium bromide.

Magnesium sulfate. Complexometric method. To 0.5 ml of the mixture add 20 ml of water, 5 ml of ammonia buffer solution, 0.05 g of an indicator mixture of special acid chromium black (or acid chromium dark blue) and titrate with 0.05 mol/l solution of Trilon B until the color turns blue.

1 ml of 0.05 mol/l solution of Trilon B corresponds to 0.01232 g of magnesium sulfate.

Glucose. The determination is carried out refractometrically.

Where:

n is the refractive index of the analyzed solution at 20 0 C; n 0 - refractive index of water at 20 0 C;

F NaBr - growth factor of the refractive index of 1% sodium bromide solution, equal to 0.00134;

C NaBr - concentration of sodium bromide in solution, found by argentometric or mercurimetric method, in%;

F MgSO4 7H2O - refractive index increase factor of a 2.5% magnesium sulfate solution, equal to 0.000953;

C MgSO4 7H2O - concentration of magnesium sulfate in solution, found by the trilonometric method, in%;

1.11 is the conversion factor for glucose containing 1 molecule of water of crystallization;

R WITHOUT.GLITCH. - factor of increase in the refractive index of anhydrous glucose solution, equal to 0.00142.

2.2 Quality control of novocaine solution (physiological) composition: Novocaine 0.5, hydrochloric acid solution 0.1 mol/l 0.4 ml, sodium chloride 0.81, water for injection up to 100.0 ml

Features of chemical control. Novocaine is a salt formed by a strong acid and a weak base, therefore it can undergo hydrolysis during sterilization. To prevent this process, hydrochloric acid is added to the dosage form.

When quantitatively determining hydrochloric acid by the neutralization method, methyl red is used as an indicator (in this case, only free hydrochloric acid is titrated and hydrochloric acid associated with novocaine is not titrated).

Organoleptic control. Colorless, transparent liquid, with a characteristic odor.

Determination of authenticity.

Novocaine. 1. To 0.3 ml of the dosage form add 0.3 ml of diluted hydrochloric acid 0.2 ml of 0.1 mol/l sodium nitrite solution and 0.1-0.3 ml of the resulting mixture is poured into 1-2 ml of a freshly prepared alkaline solution r-naphthol. An orange-red precipitate forms. When 1-2 ml of 96% ethanol is added, the precipitate dissolves and a cherry-red color appears.

2. Place 0.1 ml of the dosage form on a strip of newsprint and add 0.1 ml of diluted hydrochloric acid. An orange spot appears on the paper.

Sodium chloride. 1. Part of the solution on a graphite stick is introduced into a colorless flame. The flame turns yellow (sodium).

2. To 0.1 ml of solution add 0.2 ml of water, 0.1 ml of diluted nitric acid and 0.1 ml of silver nitrate solution. A white cheesy precipitate (chloride ion) is formed.

Hydrochloric acid. 1. To 1 ml of the dosage form add 0.1 ml of methyl red solution. The solution turns red.

2. Determination of the pH of the dosage form is carried out potentiometrically.

Quantification.

Novocaine. Nitritometric method. To 5 ml of the dosage form add 2-3 ml of water, 1 ml of diluted hydrochloric acid, 0.2 g of potassium bromide, 0.1 ml of tropeolin 00 solution, 0.1 ml of methylene blue solution and titrate dropwise at 18-20°C 0.1 mol/l sodium nitrite solution until the red-violet color changes to blue. At the same time, a control experiment is carried out.

1 ml of 0.1 mol/l sodium nitrite solution corresponds to 0.0272 g of novocaine.

Hydrochloric acid. Alkalimetric method. 10 ml of the dosage form is titrated with 0.02 mol/l sodium hydroxide solution until yellow (indicator - methyl red, 0.1 ml).

The number of milliliters of 0.1 mol/l hydrochloric acid is calculated using the formula:

Where

0.0007292 titer of 0.02 mol/l sodium hydroxide solution in hydrochloric acid;

0.3646 hydrogen chloride content (g) in 100 ml of 0.1 mol/l hydrochloric acid.

Novocaine, hydrochloric acid, sodium chloride.

Argentometry Faience method. To 1 ml of the dosage form add 0.1 ml of a solution of bromophenol blue, dropwise acetic acid diluted to a greenish-yellow color and titrate with a 0.1 mol/l solution of silver nitrate to a violet color. The number of milliliters of silver nitrate spent on interaction with sodium chloride is calculated from the difference in the volumes of silver nitrate and sodium nitrite.

1 ml of 0.1 mol/l silver nitrate solution corresponds to 0.005844 g of sodium chloride.

CONCLUSIONS

Dissolution is a spontaneous, spontaneous diffusion-kinetic process that occurs when a soluble substance comes into contact with a solvent.

In pharmaceutical practice, solutions are prepared from solid, powdery, liquid and gaseous substances. As a rule, obtaining solutions from liquid substances that are mutually soluble in each other or miscible with each other proceeds without any particular difficulties as a simple mixing of two liquids. The dissolution of solids, especially slowly and sparingly soluble ones, is a complex and time-consuming process. During dissolution, the following stages can be distinguished:

1. The surface of the solid is in contact with the solvent. The contact is accompanied by wetting, adsorption and penetration of the solvent into the micropores of solid particles.

2. Solvent molecules interact with layers of substance at the interface. In this case, solvation of molecules or ions occurs and their separation from the phase interface.

3. Solvated molecules or ions pass into the liquid phase.

4. Equalization of concentrations in all layers of the solvent.

The duration of the 1st and 4th stages depends mainly on

speed of diffusion processes. The 2nd and 3rd stages often occur instantly or quite quickly and are of a kinetic nature (mechanism of chemical reactions). It follows from this that the dissolution rate mainly depends on diffusion processes.

LIST OF REFERENCES USED

GOST R 52249-2004. Rules for the production and quality control of medicines.
State Pharmacopoeia of the Russian Federation. 11th ed. M.: Medicine, 2008. Issue. 1. 336 pp.; issue 2. 400 p.
State Register of Medicines / Ministry of Health of the Russian Federation; edited by A. V. Katlinsky. M.: RLS, 2011. 1300 p.
Mashkovsky M. D. Medicines: in 2 volumes / M. D. Mashkovsky. 14th ed. M.: Novaya Volna, 2011. T. 1. 540 p.
Mashkovsky M. D. Medicines: in 2 volumes / M. D. Mashkovsky. 14th ed. M.: Novaya Volna, 2011. T. 2. 608 p.
Muravyov I. A. Technology of drugs: in 2 volumes / I. A. Muravyov. M.: Medicine, 2010. T. 1. 391 p.
OST 42-503-95. Control, analytical and microbiological laboratories of technical control departments of industrial enterprises producing medicines. Requirements and procedure for accreditation.
OST 42-504-96. Quality control of medicines at industrial enterprises and organizations. General provisions.
OST 64-02-003-2002. Products of the medical industry. Technological production regulations. Contents, procedure for development, coordination and approval.
OST 91500.05.001-00. Quality standards for medicines. Basic provisions.
Industrial technology of drugs: textbook. for universities: in 2 volumes / V.I. Chueshov [and others]. Kharkov: NFAU, 2012. T. 1. 560 p.
Technology of dosage forms: in 2 volumes / ed. L. A. Ivanova. M.: Medicine, 2011. T. 2. 544 p.
Technology of dosage forms: in 2 volumes / ed. T. S. Kondratieva. M.: Medicine, 2011. T. 1. 496 p.

2 Chueshov V.I. Industrial technology of drugs: textbook. for universities: in 2 volumes / V.I. Chueshov [and others]. Kharkov: NFAU, 2012. T. 2. 716 p.

3 Chueshov V.I. Industrial technology of drugs: textbook. for universities: in 2 volumes / V.I. Chueshov [and others]. Kharkov: NFAU, 2012. T. 2. 716 p.

4 Chueshov V.I. Industrial technology of drugs: textbook. for universities: in 2 volumes / V.I. Chueshov [and others]. Kharkov: NFAU, 2012. T. 2. 716 p.

5 Chueshov V.I. Industrial technology of drugs: textbook. for universities: in 2 volumes / V.I. Chueshov [and others]. Kharkov: NFAU, 2012. T. 2. 716 p.

6 Workshop on the technology of factory-produced dosage forms / T. A. Brezhneva [etc.]. Voronezh: Voronezh Publishing House. state Univ., 2010. 335 p.

7 Workshop on the technology of factory-produced dosage forms / T. A. Brezhneva [etc.]. Voronezh: Voronezh Publishing House. state Univ., 2010. 335 p.

8 Muravyov I. A. Technology of drugs: in 2 volumes / I. A. Muravyov. M.: Medicine, 2010. T. 2. 313 p.

9 Mashkovsky M. D. Medicines: in 2 volumes / M. D. Mashkovsky. 14th ed. M.: Novaya Volna, 2011. T. 2. 608

Definition. Classification. Characteristic.

Technological schemes for obtaining solutions for oral and external use. Technology for the production of aqueous and non-aqueous solutions.

Preparation of medicinal and auxiliary substances.

Solubility of drugs.

Dissolution, cleaning methods. Assessment of the quality of solutions for oral and external use. Nomenclature.

INFORMATION MATERIAL

Medical solutions are homogeneous systems containing at least two substances, one of which is a medicinal substance. Water, oils, and aqueous-alcohol solutions are used as solvents.

Other solvents and co-solvents are also used: glycerin, propylene glycol, isopropyl alcohol.

In a solution, one or more substances are evenly distributed in the environment of another. When a solid is dissolved in a liquid, the liquid component is considered the solvent; in liquid-liquid solutions, the component in excess is considered the solvent.

Solutions vary in composition. There are solutions of individual substances or compositions of medicinal substances.

In addition to medicinal substances, medicinal solutions may contain excipients: taste and odor flavoring agents, preservatives, dyes, stabilizers, buffer systems. Medical solutions for oral administration (syrups, aromatic waters, etc.), as a rule, are prepared using purified water; solutions for external

For special use (rinsing lotions, drops, etc.) are prepared using purified water and other solvents (ethyl alcohol, glycerin, fatty and mineral oils, DMSO, silicones, etc.).

Depending on the solvent, medical solutions are divided into:

Aqueous solutions;

Alcohol solutions;

Glycerin solutions;

Oil solutions;

Sugar solutions (syrups);

Fragrant waters.

Water as a solvent

Water of the “Purified Water” category (FS 42-2619-97) is used as a solvent for preparing medical solutions. Water is used as a solvent most often. Advantages of water as a solvent:

High bioavailability of aqueous solutions of medicinal substances;

Cheapness;

Easy to obtain.

Flaws:

Chemical instability of medicinal substances during storage (hydrolysis, oxidation);

Susceptibility to microbial contamination;

The need to use chemical-resistant glass packaging to prevent leaching.

Non-aqueous solvents

The quality of non-aqueous solutions, as well as the technological methods for their production, are largely determined by the physicochemical properties of the solvents. Non-aqueous solvents differ in chemical structure, dielectric constant, and, consequently, in their ability to dissolve drugs.

Classification of non-aqueous solvents. Solvents used to obtain non-aqueous solutions are divided into volatile and non-volatile.

To obtain medical solutions, volatile solvents are often used, which include: ethyl alcohol, medical ether.

For example, glycerin, fatty oils, vaseline oil, etc. are used as non-volatile solvents. p.

This classification is important from a technological, pharmacological, consumer point of view and for proper compliance with industrial safety regulations.

Some medicinal substances do not dissolve in specific solvents to obtain a solution of the required concentration. To dissolve such substances, combined solvents (solvent mixtures) are used. Examples include mixtures of ethanol with glycerin, glycerin with dimexide, etc.

The use of combined solvents also makes it possible to combine several medicinal substances with different solubilities in an aqueous dosage form.

Cosolvents are substances used in complex solvents to increase the solubility of some difficultly soluble drugs. These include benzyl benzoate, which is used to increase solubility in oils, as well as ethanol, glycerol propylene glycol, which are used to increase the solubility of the drug in water.

Technology for obtaining solutions

Most medicinal solutions are prepared by dissolving medicinal substances in an appropriate solvent. Some aqueous solutions are prepared using chemical interactions.

Dissolution is carried out in reactors. The reactor is a steel or cast iron container, which is coated inside with enamel to protect against corrosion. In small industries, glass reactors can be used. The body of the apparatus is usually cylindrical with a spherical bottom. A steam jacket is used to heat the apparatus. The top of the apparatus is hermetically sealed with a lid on which an electric motor connected to a stirrer is installed. Various mixers are used in the production of medical solutions. The most commonly used types of mixers are shown in Fig. 4.1.

The reactor lid contains an inspection window and a hatch for loading solution components. The solvent enters the reactor by gravity or is forced by vacuum. The finished solution is compressed

It is released from the reactor using compressed air or leaves by gravity through the lower fitting. The reactor structure is shown in Fig. 4.2.

Dissolution in viscous liquids (glycerin, fatty oil, liquid paraffin) is often carried out at elevated temperatures to reduce viscosity and accelerate diffusion (solutions of boric acid, borax in glycerin, camphor in oil, etc.).

Alcohol solutions are prepared without heating in strict compliance with safety, labor protection and fire protection regulations.

Solutions are purified by settling and filtering. Filters are used that operate at atmospheric pressure due to a hydrostatic column of liquid, at excess pressure (druk filters) and under vacuum (nutsch filters). For large production volumes, it is rational to use a druk filter due to its higher filtration speed. Thus, filters operating due to the hydrostatic column of liquid can give a maximum pressure drop across the filter material on average up to 0.5-1 ATA, nutsch filters - up to 0.8 ATA, and druk filters - up to 12 ATA. The operation of the druk filter is shown in Fig. 4.3.

where 0.99703 is the density of water at 20°C (g/cm3) taking into account the density of air; 0.0012 - air density at 20°C and barometric pressure 760 mm Hg.

Of the various disinfectants, the most commonly used are chlorine-containing compounds, the antimicrobial properties of which are associated with the action of hypochlorous acid, released when chlorine and its compounds are dissolved in water.

The bleach solution is prepared according to certain rules. 1 kg of dry bleach is stirred in 10 liters of water, obtaining the so-called bleach-lime milk, and left in a tightly closed glass sun-protective container for 24 hours until clearing. In the future, for wet cleaning, a 0.5% clarified bleach solution is usually used, for which 9.5 liters of water and 0.5 liters of a 10% bleach solution are taken per 10 liters of solution. To prepare a 3% bleach solution, take 3 liters of a 10% clarified bleach solution with the addition of 7 liters of water.

A chloramine solution is most often used in the form of a 0.2-3% solution, in which the required amount of chloramine is first added to a small amount of water, stirred, and then the remaining volume of water is added to obtain the desired concentration of the chloramine solution.

To prepare a 1% chloramine solution, take 100 g of chloramine per 10 liters of water (10 g per 1 liter of water);

2% chloramine solution - 200 g of chloramine per 10 liters of water (20 g per 1 liter).

Solutions for general and current treatment

Soap-soda solution - dilute 50 g of soap in 10 liters of hot water, add 10 g of soda and 50 g of ammonia.

Chlorine-soap-soda solution: add 50 g of soap and 10 g of soda ash to 10 liters of 1% (0.5%) chloramine solution.

Currently, disinfectants “Samarovka”, “Clindamizin”, “Amiksan” are widely used for general and routine treatment.

It should be remembered that when treating vertical surfaces and ceilings from a hydraulic console, a 0.5% chloramine solution should be used.

Construction of the reception and diagnostic department

The reception and diagnostic department consists of a lobby-waiting room, reception and examination boxes, a sanitary checkpoint, and a room for storing clothes of admitted patients. In large multidisciplinary hospitals, the admission and diagnostic department has doctor’s offices, a diagnostic room, a dressing room, an emergency laboratory, a room for medical personnel, and sanitary rooms. It is possible to separate the therapeutic and surgical admission and diagnostic departments.

Main functions of the reception and diagnostic department:

■ organizing the reception and hospitalization of patients, in which a preliminary clinical diagnosis is established and the validity of hospitalization is assessed;

■ consultations with patients referred by local doctors and those who came “by gravity”;

■ provision of emergency medical care if necessary;

■ prevention of the introduction of infections into the hospital - isolation of an infectious patient and organization of specialized medical care for him;

■ sanitary treatment of the patient;

■ transporting the patient to the department;

■ reference and information service;

■ recording the movement of patients in the hospital.

Documentation of the reception and diagnostic department:

● log of admitted patients and refusals of hospitalization (form No. 001/u);

● alphabetical log of admitted patients;

● consultation log;

● a log of examinations for head lice;

● register of available beds in the hospital;

● medical record of an inpatient (form No. 003/у).

Large medical institutions employ a special staff of medical workers. In small medical institutions, patients are received by staff on duty. Patients are received in a strict sequence: registration, medical examination, necessary medical care, sanitary and hygienic treatment, transportation of the patient to the appropriate department.

Functional responsibilities of a nurse in the reception and diagnostic department:

♦ fills out the title page of the inpatient medical record (medical history): passport part, date and time of admission, diagnosis of the referring institution;

♦ fills out the register of admitted patients and the alphabet book for the information service;

♦ performs thermometry of the patient;

♦ carries out anthropometric measurements;

♦ examines the patient’s skin and pharynx to exclude an infectious disease;

♦ examines the patient for lice and scabies;

♦ fills out a statistical form for an admitted patient;

♦ carries out sanitary treatment of a hospitalized patient and transports him to the medical department.

When providing first aid use time sheets And henchmen means.

By means of personnelFirst aid includes dressings (bandages, medical dressing bags, large and small sterile dressings and napkins, cotton wool), a hemostatic tourniquet (tape and tubular), and for immobilization - special splints (plywood, ladder, mesh).

When providing first aid, medications are used - alcoholic iodine solution, brilliant green, validol in tablets, valerian tincture, ammonia in ampoules, sodium bicarbonate (baking soda) in tablets or powder, petroleum jelly, etc. For personal prevention of injuries from radioactive, toxic substances and individual first aid kit AI-2 can be used with bacterial agents in the affected areas.

Medical equipment is provided to sanitary groups and sanitary posts. First aid kits are stocked at construction and production sites, in workshops, on farms and in teams, in educational institutions and institutions, and in places of organized recreation for the population. Vehicles used to transport people, including personal cars, must be equipped with first aid kits.

As improvised means when applying first aid, a clean sheet, shirt, fabric (preferably non-colored) can be used when applying bandages; to stop bleeding - instead of a tourniquet, a trouser belt or belt, a twist made of fabric; for fractures, instead of tires - strips of hard cardboard or plywood, boards, sticks, etc.

P. 12.8. POT RO-13153-TsL-923-02. Enterprises must have first aid kits or first aid bags equipped with medicines and dressings, as well as first aid instructions, in designated places.

All workers must know the location of first aid kits and be able to provide first aid to the victim.

Cars are equipped with first aid medical equipment.

The first aid bag kit does not include a rubber ice pack, a glass, a teaspoon, boric acid, and baking soda. The remaining funds are completed in the amount of 50% of those indicated in the list.

Medicines and medical supplies	Purpose	Quantity
1. Dressing bag	Applying bandages	5 pcs.
2. Sterile bandage	Same	5 pcs.
3. Absorbent cotton wool, clinical, surgical	Same	5 packs of 50 g.
4. Tourniquet	Stop bleeding	1 piece
5. Tires	Strengthening limbs during fractures and dislocations	3-4 pcs.
6. Rubber bladder (warmer) for ice	Cooling the damaged area for bruises, fractures and dislocations	1 piece
7. Glass	Taking medication	1 piece
8. Teaspoon	Preparation of solutions	1 piece
9. Iodine (5% alcohol solution)	Lubricating tissue around wounds, fresh abrasions, scratches on the skin	1 bottle (50 ml)
10. Ammonia (10% ammonia solution)	Use for fainting conditions	1 bottle (50 ml)
11. Boric acid	For the preparation of solutions for washing eyes and skin, rinsing the mouth for burns with alkali, for lotions on the eyes for burns from a voltaic arc	1 packet (25 g)
12. Baking soda (sodium bicarbonate, or sodium bicarbonate)	Preparation of solutions for washing eyes and skin, rinsing mouth for acid burns	1 packet (25 g)
13. Hydrogen peroxide solution (3%)	Stops nosebleeds, minor wounds and scratches	1 bottle (50 ml)
14. Valerian tincture	Calming the nervous system	1 bottle (50 ml)
15. Bitters (Epsom salt)	Ingestion for food and other poisoning	50 g
16. Activated carbon (powder)	Same	50 g
17. Potassium permanganate (crystals)	Same	10 g
18. Validol or nitroglycerin	Oral administration for severe pain in the heart area	1 tube
19. Amidopyrine, analgin (tablets)	Taken orally as an antipyretic and analgesic	2 packs

In the summer, insect stings are possible in places of work; first aid kits (first aid bags) should contain diphenhydramine (one package) and cordiamine (one bottle).

On the inside of the medicine cabinet door, it should be clearly indicated which medications should be used for various injuries (for example, for nosebleeds - 3% hydrogen peroxide solution, etc.).

In order for first aid to be timely and effective, the places where personnel are constantly on duty must have:

first aid kits with a set of necessary medications and medical supplies (see table);

posters posted in prominent places depicting first aid techniques for victims of accidents, performing artificial respiration and external cardiac massage;

Directions and signs to make it easier to find first aid kits and health centers.

The result of disinfection measures directly depends on how disinfectants for treating health care facilities, instruments and objects of the hospital environment are prepared and stored.

Persons who have undergone special training are allowed to work with working solutions.

The main thing in the article

Disinfection in health care facilities is the responsibility of middle and junior medical personnel, and control of the effectiveness of these measures lies with the head nurse and senior nurses of the hospital departments.

Permission to work with disinfectants

Specialists who work with medical disinfectants must be familiar with the provisions of the instructional and methodological documentation for the preparation and storage of working solutions, as well as know the safety precautions and precautions when working with them.

Samples and special collections of standard operating procedures for nurses that can be downloaded.

In addition, medical personnel undergo:

professional training and certification (including on work safety issues and provision of first aid in case of chemical poisoning);
preliminary and periodic preventive medical examinations.

Minors, people with allergic and dermatological diseases, as well as people sensitive to the effects of fumes of chemical compounds are not allowed to work with disinfectants.

All admitted employees must be provided with special clothing, footwear, personal protective equipment and a first aid kit.

Methods for preparing working solutions of disinfectants

There are two ways dilution of disinfectants:

Centralized.
Decentralized.

With the centralized method, solutions are prepared in a separate well-ventilated room equipped with supply and exhaust ventilation.

It is prohibited to store food and personal belongings of staff, eat or smoke here. Persons not authorized to work with disinfectants are not allowed to be in this room.

The decentralized method involves the preparation of working solutions in diagnostic and treatment rooms. In this case, the place in which the solution is prepared must be equipped with an exhaust system.

The choice of method for preparing a disinfectant depends on the size of the organization and the volume and types of services provided to it.

Instructions, criteria for choosing disinfectants, what documents are attached to them, how often it is necessary to change disinfectants, find out in the Chief Nurse System.

widespread resistance of microorganisms to used disinfectants;

formed microbiological background;

an increase in the number of cases of healthcare-associated infections (HAIs).

Rules for breeding disinfectants: precautions, algorithm

Disinfectant solutions are toxic and irritate the mucous membranes, skin and organs of vision, so taking precautions when diluting and working with them is necessary to avoid serious health problems.

Dilution of disinfectants: It is strictly prohibited to add a new disinfectant to an old solution, or to mix old and new solutions.

Dilution of disinfectants must be done in a cap, gown, safety glasses and a respirator. The skin should be protected with rubber gloves.

Avoid contact of the chemical with the skin, mucous membranes, eyes and stomach. First aid measures in case of accidental poisoning or exposure are specified in the instructions for use of a specific disinfectant.

The negative effects of medical disinfectant solutions can be prevented by observing the following rules:

personnel must undergo regular training in working with disinfectant solutions;
responsible persons must regularly monitor strict adherence to the instructions for use of a specific disinfectant when preparing the working solution;
There should be a stand in a visible place with information about the procedure for use and precautions when working with disinfectants, about the rules for preparing working solutions, about periodic visual and express control.

The rules for working with disinfectants and their use must be controlled by the employee appointed responsible for carrying out disinfection measures in health care facilities.

Shelf life and service life of the working solution

A working solution of a disinfectant, like any chemical compound, can change its initial properties during storage and operation. This is influenced by external factors such as temperature, light, and foreign impurities. In this case, the shelf life of the solution is reduced.

Distinguish maximum and maximum shelf life of the working solution. The first shelf life is usually understood as the period of maintaining the original concentration of the active substance, acid-base balance, and bactericidal activity before its use.

The expiration date is set by the manufacturer and is indicated in the instructions for use. The shelf life of the working solution is calculated from the moment of its preparation.

The disinfectant solution cannot be used before the deadline for use if the activity of the working solutions has not been monitored using test strips.

The maximum shelf life of a solution is the period during which the antimicrobial activity stated in the instructions is maintained, and the concentration does not fall below the required level.

It is impossible to say how much the antimicrobial activity of a medical disinfectant will decrease after it has undergone several treatments. For this reason, the expiration date is set based on the results of chemical and visual control.

In this case, the countdown begins from the moment the instruments or products are first immersed in the solution.

Storage of working solutions

Reusable disinfectant solutions are prepared for future use and stored in closed containers in a separate room or specially designated place for 24 hours or more.

It is prohibited to use adapted containers (for example, food cans) as containers for disinfectants.

All containers containing working solutions must be labeled. They must have a tight-fitting lid and be used strictly for processing one specific object.

The name of the disinfectant solution, its concentration, preparation date and expiration date are applied to the container with an indelible marker. You can attach an adhesive label to it with the same data.

The calculator will help you calculate how much disinfectant you will need for disinfection of patient care items, cleaning equipment, laboratory glassware and toys.

Monitoring the activity of the working solution

Working solutions whose toxicity and effectiveness do not correspond to the declared values cannot be used for disinfection of health care facilities, equipment and instruments.

In some cases, control methods are specified in the instructions for use of disinfectants.

The activity of disinfectant solutions is checked using the following methods:

visual - assessment of the appearance of the solution, its transparency, color, presence of foreign impurities;
chemical - using means of quantitative control of the content of the active substance (carried out upon acceptance of each incoming batch, in case of unsatisfactory results of chemical control of the concentration of working solutions, and also once every six months - as part of production control);
express control - using test strips, carried out for the purpose of quickly checking the activity of the active substance in a disinfectant at least once every 7 days, at least one sample of each type (express control of the active substance in working solutions used for disinfection of endoscopic equipment and accessories for it, is carried out strictly once per shift).

To account for results express control in health care facilities, a separate log is opened. Its form is not regulated by law, so it can be approved by the head of the medical institution.

Testing using test strips allows you to monitor the consistency of the concentration of the medical disinfectant solution immediately after preparation and during operation.

If the concentration in the solution is below the standard specified by the manufacturer, it is considered unsuitable and must be replaced.

In order to assess the effectiveness of disinfection measures, bacteriological control is carried out in health care facilities every six months, which consists of taking swabs from surfaces as part of production control.

How often should I carry out express testing of working solutions?

The frequency of quality control of disinfectant solutions depends on the active substance.

For example, it is possible to store solutions of some products based on quaternary ammonium compounds for up to 30 days. In this case, it is advisable to carry out control each time before use.

If the working solution of the disinfectant must be used during a work shift, then its control can be carried out immediately after preparation. Another option is not to conduct the test at all, if the regulatory and methodological documentation allows this.

Violation of sanitary rules and regulations

Supervisory authorities, during scheduled and unannounced inspections, often identify the following violations of sanitary rules in medical institutions:

there are no results of monitoring the concentration of working solutions of medical disinfectants;
non-compliance of the disinfectant with the areas of application, preparation and storage specified by the manufacturer.

For these violations, the management of the health care facility and officials may be punished in accordance with Article 6.3. Code of Administrative Offenses of the Russian Federation.

Methods for monitoring the activity of working solutions, its frequency and criteria for assessing the results obtained must be enshrined in the Production Control Program, which is approved by the chief physician. The administration is responsible for its implementation.

It is recommended to reuse working solutions of medical disinfectants only during one work shift, despite their expiration date, since with longer use they may contain microorganisms that have resistance properties.

In this case, the solution becomes dangerous from the point of view of the spread of infection, since microorganisms develop mechanisms of resistance to disinfecting solutions.