Design a site to obtain nystatin substance from paste

Contents

INTRODUCTION

1. FEASIBILITY STUDY OF THE CHOSEN METHOD

2. CHARACTERISTICS OF FINISHED PRODUCT

3. CHARACTERISTICS OF RAW MATERIALS AND MATERIALS

4. PRODUCTION FLOW CHART

4.1. Process Description

5 Material calculations

5.1 Preliminary calculations

5.2 Calculation of material balance of nystatin paste drying stage

6 Calculation and selection of process equipment

6.1 Calculation and selection of main equipment

7 Thermal and energy calculations

7.1 Thermal calculations

7.1.1 Thermal calculation of treatment of water purified for nystatin paste washing

7.2 Energy Calculations

CONCLUSION

BIBLIOGRAPHIC LIST

Task

for a course project

in the discipline "Basis of design of biotechnological production"

Topic of work: "Design a section to obtain nystatin substance from paste"

Source Data

1. The production capacity of the finished product is 260000 billion. U/year.

2. Activity of culture fluid 85000 U/ml.

3. Introduction.

4. Feasibility study of the selected method.

5. Characteristics of the finished product.

6. Characteristics of raw materials and materials.

7. Production flow chart and process description.

8. Material calculations.

9. Calculation and selection of main process equipment.

10. Thermal and energy calculations..

11. Conclusion.

Introduction

The main goal of the course project is to calculate the area of ​ ​ obtaining nystatin substance from paste. The production capacity of the finished product is 260000 billion. U/year. Activity of culture fluid 85000 U/ml.

In this course project, it is necessary to make material, thermal and energy calculations, as well as design a hardware diagram.

OJSC Biosynthesis, which produces nystatin, is one of the leading manufacturers of medicines and substances in Russia.

More than 43% of the drugs produced by Biosynthesis OJSC are included in the "List of Vital and Important Medicines" of the Ministry of Health of the Russian Federation. Annually, the range of products is increased by 1015 items.

Feasibility study of the selected method

The term "antibiotic" was proposed in 1942 by S. A. Waxman to refer to substances formed by microorganisms and having antimicrobial effects. Subsequently, many researchers proposed their formulations, sometimes investing too limited content in them or overextending this concept.

Currently, antibiotics mean chemotherapeutic substances obtained from microorganisms or other natural sources, as well as their semi-synthetic analogues and derivatives, which have the ability to selectively suppress the pathogens of diseases in the patient's body and (or) delay the development of malignancies.

The most successful from a theoretical point of view and reflecting the current state of the question is the definition proposed by M. M. Shemyakin, A. S. Khokhlov and others: "Antibiotic substances (antibiotics) should be called all metabolic products of any organisms capable of selectively suppressing or killing microorganisms (bacteria, fungi, viruses, etc.)." A close wording is given by M. Gerold and others. Recently, the term "antitumor antibiotic" has been recognized, although it does not fit within the scope of this definition. [7]

Described more than 6 thousand natural antibiotics, many tens of thousands of semisynthetic derivatives. Of greatest practical importance are about 50 antibiotics produced in a variety of dosage forms.

Antibiotic substances are subject to the following basic requirements:

absence or low level of toxicity of the drug and products of its destruction in the body;

a pronounced antimicrobial effect at minimal concentrations;

slow development of resistance during the drug application;

good solubility in water, stability under normal storage conditions;

optimal suction, distribution and discharge conditions,

preservation of antimicrobial action in different conditions of physiological fluids and body tissues environment.

To ensure all quality indicators of the finished product, special conditions are created for the execution of process steps and operations. There are special requirements for the cleanliness of production premises, operation of process equipment, ventilation, the system for preparing basic and auxiliary materials, and certain requirements for personnel are also imposed. At different stages of the technology, the probability of contamination and contamination is different. [8]

Extraction from solid substances is used in production of nystatin at the stage of chemical purification. Dry mycelium is used as solid substances, 2% solution of calcium chloride in methanol is used as extractant.

Extraction from solids has found application in the pharmaceutical industry. In chemical technology, extraction from solid porous substances with water or aqueous solutions of acids and alkalis (leaching processes) is mainly used.

Extraction is broadly referred to as the recovery of one or more components from solutions or solids using selective solvents (extractants). When reacting with the extractant, only the extractable components dissolve well in it and the remaining components of the starting mixture are significantly weaker or practically not dissolved.

Dissolution of solid particles in liquids is one of the widely used main processes of chemical technology (production of organic semi-products and dyes, mineral fertilizers and many others). Dissolution is a prerequisite for accelerating various chemical and technological processes, since in a dissolved and largely dissociated state, the mobility and chemical activity of solute molecules increases.

In industry, the dissolution of almost pure solids is used, the transfer of which allows accelerating subsequent chemical reactions or diffusion of solutes, as well as the dissolution resulting from chemical

interaction of solid particles and liquid.

Dissolution processes, which are the diffusion recovery by a solvent of a component (or components) from a porous solid material, are called solid-liquid extraction, or leaching.

In some cases, dissolution occurs as a result of a heterogeneous reaction at the interface, the formation of which is accompanied by the formation of not only soluble, but also insoluble (or partially soluble) solids, as well as gaseous reaction products. The release of solid and gaseous products may result in the formation of a porous film or the settling of gas bubbles on the surface of the solid material. The solid phase can also form and settle on the surface of the starting solid material due to crystallization by supersaturation of the solution. All these phenomena can significantly reduce the surface of the material available for interaction with the solvent, and accordingly - reduce the speed of the process.

Crystallization is the process of separating a solid solute from its solution. Such crystallization is used in the production of nystatin.

Crystallization from solutions is based on limited solubility of solids. A solution containing the maximum amount of solute in a given amount of solvent at a certain temperature is called saturated. After the crystals were isolated, the solution became saturated. This saturated solution obtained by crystal separation is called mother liquor or mother liquor. [2]

The solubility is equal to the concentration of the saturated solution and depends on the temperature, as well as the properties of the solute and solvent. For most solids, solubility increases with increasing temperature, but for some substances, it decreases with increasing temperature or has a maximum value at a certain temperature.

To carry out the crystallization process in the production of nystatin, the following method of creating a supersaturated solution is used: the precipitation of nystatin from the methanol extract occurs when water is added to it, while the calcium complex of nystatin is destroyed and water-insoluble nystatin precipitates .

The crystallization process consists of two stages - the formation of crystal nuclei and crystal growth. By changing the factors affecting the rate of nucleation and the rate of growth thereof, crystal sizes can be controlled. Rapid cooling, mixing of the solution, high temperature and low molecular weight of crystals contribute to nucleation and production of fine crystals. On the contrary, slow cooling, immobility of the solution, low temperature and high molecular weight contribute to the growth process and the production of large crystals.

Crystallization can be accelerated by the introduction of seed - small particles of crystallizing substance, which are the embryos of crystals. In this case, crystallization occurs mainly due to the growth of seed crystals introduced into the solution. To produce large crystals, the number of seed crystals must be small.

After crystallization, the slurry is separated from the mother liquor by filtration on a filter press. After repeated cleaning, the paste is sent to the stage of drying and screening of nystatin.

Characteristics of the finished product

Nystatin (Nystatinum) is allowed for release for use in medical practice by order of the Minister of Health of the USSR No. 228, paragraph 183 of 1964.

Number of registration certificate P N001707/01.

The quality of the preparation shall meet the requirements of P N001707/01 031008 (FSP42312708).

The main purpose of the drug is the substance used for the manufacture of dosage forms.

Activity. The preparation must contain at least 4500 U/mg in terms of dry substance at the time of release. One unit of action (Unit) corresponds to the unit of action of the International Nystatin Standard.

Description. Light yellow powder with a specific smell, bitter taste. Hygroscopic. Unstable to light, air oxygen and heating.

Solubility. Practically insoluble in water, ether, chloroform, very little soluble in 95% alcohol, soluble in dimethyl sulfoxide.

Authenticity. The preparation must meet the requirements of P N001707/01 031008 (FSP 42312708 ).

Specific absorption rate. E1% 1 cm at wavelength (305 ± 2) nm not less than 640 in terms of dry matter. pH 5.5 to 8.0.

Determination of the content of components A1 nystatin and Ah nystatin. The maintenance of A1 component has to be not less than 85%, the total content of impurity Ah - no more than 15% (R N001707/01 031008 (FSP42312708).

Loss in weight during drying. Not more than 4%.

Residual solvent content. Gas-liquid chromatography method. The total solvent content (acetone, methylene chloride, methyl alcohol) should not exceed 0.25%, including the content of methyl alcohol should not exceed 0.15%, methylene chloride should not exceed 0.06% (P N001707/01 031008 (FSP42312708)).

Microbiological cleanliness test. In 1 g of the preparation, the presence of no more than 1000 bacteria and 100 yeast and mold fungi (total) is allowed. The presence of bacteria of the family Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus is not allowed.

Marking of transport containers in accordance with GOST 1419296.

Transportation. In accordance with GOST 1776890.

Storage. In a dry, light-protected place, at a temperature not higher than 5 0С.

Shelf life 2 years.

Antibiotic.

Process Description

Drying through nystatin consists of the following operations:

1. Preparation of equipment for operation

2. Drying of nystatin paste, sifting

Preparation of equipment for operation

12 according to the schedule 2 times a month wash drying installation of "SS" with the desalinated water from a hose via the top hatch of the dryer. Washing water is drained into sewer, drying unit chamber is treated with 3% hydrogen peroxide solution from hand sprayer. Filter material (capron pre-treated with 3% hydrogen peroxide solution) on quick-detachable bag filters is replaced.

Filters are loosened, inner surfaces are treated with stringy napkin wetted with 3% hydrogen peroxide solution with detergent, washed with hot demineralized water with temperature from 45 to 50 ° C. Filter material (capron) is treated with 3% hydrogen peroxide solution with detergent, rinsed in demineralized water with temperature from 45 to 50 ° C, dried, filters are filled. Filtration material is replaced 1 once a month.

Drying installation of "SS" 12 is dried a stream of hot nitrogen to lack of moisture. Mobile hopper is washed with hot water with temperature from 45 to 50 ° C 2 times a week, treated with 3% hydrogen peroxide solution after each operation.

Cleaning, washing of granulator and hammer mill is performed according to schedule. Inner surface, components of granulator and mills are washed with 3% hydrogen peroxide solution with detergent with lint-free cloth, then washed with hot demineralized water with temperature from 45 to 50 ° C. The nystatin paste washed with methylene chloride was charged into a granulator. The pellets are collected in a mobile hopper.

Drying of nystatin carry out on drying installation of "SS" of the 12th FG type (drying installation for antibiotics). Nystatin paste is loaded into drying string through loading hose by means of vacuum in amount of not more than 60 kg per one load. To maintain the temperature in the column, hot water with a temperature of 70 to 80 ° C is supplied to the jacket, which is heated in the collector. Hot water from collector is supplied by centrifugal pump into jacket of drying column.

The drying process is carried out in a nitrogen stream, which is supplied from the heat exchanger through filters (capron filter material) with a temperature of 55 to 65 ° C. Heated nitrogen is supplied through pulsator to gas distributor of drying column. The pulsator allows nitrogen to be supplied in portions, which creates an intermittent flow of nitrogen, a pulsating layer of material, provides the necessary mixing of the nystatin powder and its contact with the heating surface of the drying column, fast and high-quality drying for 15 to 20 hours.

After drying, the finished product is discharged into a stringy bag, weighed, and a sample is taken to determine moisture.

Dried nystatin granulate is milled in a hammer mill and sieved twice: through a silk fabric for sieve No. 26, then capron fabric for sieve No. 32.

The yield in the step is from 96 to 98%.

Average yield - 97.6%

The sieved powder is transferred to the packing stage.

Finished product - nystatin must meet the requirements of FS 42114098.

Shelf life 2 years.

Conclusion

In this course project, a site for obtaining nystatin substance from paste was designed. In the course of familiarization with the used raw materials and auxiliary materials, a process diagram was compiled according to the data of the enterprise, taking into account the projected changes in the technological process. And also a hardware scheme was designed, material, thermal and energy calculations were made .

The following process equipment was also calculated and selected:

Drying unit - 4 units;

Centrifuge - 1 unit.