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VETERINARY SCIENCES / «€®LL®qU]UM~J®UTMaL» 2022
Veterinary sciences
Sachuk R.M., Velesik T.A.,
Rivne State University for the Humanities, Rivne, Ukraine Gutyj B. V., Katsaraba O.A., Vasiv R.O., Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies Lviv, Ukraine
Tesarivska V.I., Kurilas L. V., Ponomareva S.A.
State Scientific Research Control Institute of Veterinary Medicinal Products and Feed Additives,
Lviv, Ukraine
DOI: 10.24412/2520-6990-2022-21144-4-6 DEVELOPMENT OF SPECIFICATIONS AND TECHNOLOGICAL INSTRUCTIONS FOR ANTIBACTERIAL AGENT BASED ON COLYSTINE SULPHATE
Abstract.
The aim of the study is to create a preparation based on colistin sulfate of appropriate quality and justify the process of its production in order to constantly produce products with specified functional characteristics. The objects of the study were experimental samples of the veterinary medicinal product «Kolidev 8M» (powder for oral use) (TU 21.2-40781800-034: 2022) which includes colistin sulfate, as well as excipients: glucose and citric acid. Taking into account modern pharmacopoeial requirements, obtained pharmaco-technological and physico-chemical characteristics, a specification for a veterinary medicinal product has been developed and substantiated, which includes the following quality indicators: composition, identification, packaging, storage, shelf life. Developed technological instructions for the production of «Kolidev 8M», which is responsible for the technological process and provides for the following operations: preparation for production, preparation of the drug, packaging, sterilization, labeling and packaging of antibacterial drugs, labor protection requirements, industrial sanitation and fire safety.
Keywords: Kolidev 8M, powder for oral use, veterinary drug.
Introduction. To substantiate the target quality profile of a veterinary medicinal product, first of all, it is necessary to have a certain list of quality criteria for the developed formulation. Based on these criteria, potential critical quality indicators in the manufacture of a medicinal product can be further identified [1-3]. The general list of quality criteria includes standardized pharmacological and physicochemical parameters. According to the current edition of the State Pharmacopoeia of Ukraine, the developed drug must meet the requirements of the general article «Powder for oral use». Standardized quality indicators for veterinary medicinal products, in the form of powder for oral use, are given in the relevant articles of the State Pharmacopoeia of Ukraine, as well as in TU 21.2-40781800-034: 2022 [4, 5]. Taking into account the requirements of the current edition of the State Pharmacopoeia of Ukraine, Order № 133 of the State Committee of Veterinary Medicine of Ukraine of 14.07.2008 and regulations, the main quality indicators and eligibility criteria are included in the specification for quality control of oral powder colistin sulfate, namely: description, identification, packaging, storage, shelf life. To characterize and determine the quality of the drug, in addition to physical and chemical tests, the technological process and its control remain important.
The aim of the study is to create a preparation based on colistin sulfate of appropriate quality and justify the process of its production in order to constantly produce products with specified functional characteristics.
Materials and methods. The objects of the study were experimental samples of the veterinary medicinal product «Kolidev 8M» (powder for oral use) (TU 21.2-
40781800-034: 2022) which includes colistin sulfate, as well as excipients: glucose and citric acid.
Main equipment: mixer for bulk materials; electronic weight VLE-1000 and dispenser DV 150L. Auxiliary equipment: enameled and plastic utensils; laboratory scales.
Raw materials: colistin sulfate of imported production, in the presence of a certificate of origin, and in the presence of a certificate of conformity; glucose according to DSTU 4464: 2005 and citric acid according to GOST 908-2004.
When developing the specification and technology of powder for oral use based on colistin sulfate, the pharmaco-technological characteristics of the masses for the manufactured powder were studied according to the generally accepted methods given in the State Pharmacopoeia of Ukraine [4-6].
The main results. Description. Veterinary drug «Kolidev 8M» - hygroscopic powder from white to light yellow.
Ingredients per 1 g of the drug: colistin sulfate -8,000,000 IU; glucose, citric acid up to 1 g
The active substance of the drug is Colistin N- (4-amino-1- (1- (4-amino-1-oxo-1- (3,12,23-tris) (2-ami-noethyl) - 20- (1-hydroxyethyl) - 6,9-diisobutyl-2,5,8,11,14,19,22-heptaoxo-1,4,7,10,13,18-hexaazacy-clotricosan-15-ylamino) butane-2-ylamino) -3-hy-droxybutane -2-ylamino) -1-oxobutan-2-yl-N, 5-dime-thylheptanamide.
Packaging of the drug. The preparation «Kolidev 8M» is packed in plastic bags of 500 and 1000 g. Permissible deviation in the weight of the package ± 3%.
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Storage. Store the drug in the manufacturer's packaging, in dry, dark, ventilated warehouses at a temperature of 8 to 15°C.
Shelf life - 24 months.
The basis for the development of the block of stages of the technological process of production of the selected drug is the technology of this dosage form, which consists of the following operations.
Production preparation. The premises of the section for the production of veterinary drugs for oral use LLC «DEVIE» are equipped with local and general supply and exhaust ventilation in accordance with GOST 12.4.021 and SNiP 2.04.05, which ensures the clean air of the working area. Production equipment is airtight and meets the requirements of GOST 12.2.003.
There is no dust formation and dust release during operation. The air quality of the working zone corresponds to GOST 12.1.005, the maximum allowable concentration of dust of ingredients in the air of the working zone is 1 mg / m3. Employees are provided with overalls in accordance with GOST 12.4.099, GOST 12.4.100, GOST 20010 and individual means of protection in accordance with current standard standards. Workers follow the rules of personal hygiene. Production facilities are provided with drinking water in accordance with GOST 2874. It is forbidden to smoke, eat or drink while working.
Fire safety complies with GOST 1.004. In the event of a fire, the extinguishing agents are chemical foam fire extinguishers, finely divided water, sand, asbestos cloth, powder and gas fire extinguishers, and fire equipment.
The noise level in the premises must comply with GOST 12.1.003.
When performing tests on quality control of the drug in the laboratory for quality control, safety and registration of veterinary drugs and feed additives LLC «DEVIE» follow the rules of work in accordance with MLA 07.001 and DNAOP 2.2.00-1.01.
Incoming control of raw materials is carried out in accordance with GOST 24297.
The results of the control are recorded in the «Journal of incoming quality control of raw materials».
Preparation of the drug. One technological load: colistin sulfate - 42,0 kg; glucose - up to 36.0 kg and citric acid - 22,0 kg.
After weighing, the components are loaded into the mixing chamber of the mixer, they are mixed for 30 minutes
After completion of the technological process, the mixing chamber is subject to mechanical cleaning and washing with warm water. Losses at this stage are 3%.
Packing. Polymer packing bags are made of a suitable polymer sleeve by cutting and sealing one end. After loading the drug into the bag, it is sealed. Packing is carried out using a dispenser. Losses at this stage are 1%.
Sterilization of the drug is not required.
Labeling and packaging of the drug. Each unit of consumer packaging is marked with a label indicating: country, name of the manufacturer, its address and trademark, name of the drug, composition, method of use, the inscription «For veterinary medicine», batch
number, control number, weight of the drug in packaging, date of manufacture, expiration date, storage conditions, TU data designation, conformity mark in accordance with DSTU 2296, EAN bar code mark in accordance with DSTU 3147.
Marking on each unit of consumer packaging can be applied with paint that does not wash off.
On each unit of group packaging (box, box) stick a label of label or other paper or apply non-washable paint, the following symbols: country, name of the manufacturer, its address and trademark, name of the drug, composition, inscription «For veterinary medicine», its quantity in a box, box number, control number, date of manufacture, expiration date, storage conditions, data of TU data, mark of conformity according to DSTU 2296, bar code mark EAN according to DSTU 3147.
The text of the marking and packing list is performed in Ukrainian. When delivered for export, the labeling text shall be executed in the language specified in the contract.
Labels are made of label paper A or B in accordance with GOST 7625, or chalk paper grade C in accordance with GOST 21444, or offset paper №2 brands A, B, B in accordance with GOST 9094, or other paper whose quality is not lower specified.
Packaging sheet and card-insert for use must be printed on writing paper № 2 in accordance with GOST 18510 or offset paper № 1 or № 2 brands A, B, B in accordance with GOST 9094.
Marking of transport containers is carried out according to GOST 14192. Cargo is not dangerous and according to GOST 19433 is not classified.
Transport marking is applied in black paint on one side of each box on a stencil.
Transport marking contains:
- main inscriptions: name of the consignee, number of cargo places in the series;
- additional inscriptions: name of the consignee, name of the point of departure with indication of the railway station of departure;
- informational inscriptions: gross and net weight of cargo space in kilograms, name of the drug, inscription «For veterinary medicine», quantity of the drug in the box, date of manufacture, batch number, control number, expiration date, storage conditions, designation TU U.
Combining transport markings and markings that characterize packaged products on one side of the transport container is not allowed.
The drug is packaged in plastic bags of 500 and 1000 g. Permissible deviation in the weight of the package ± 2%.
The drug is packed in containers, the size system of which complies with GOST 21140, boxes of corrugated cardboard according to GOST 13841, according to OST 64-064, in cardboard boxes according to GOST 12301 from cardboard box according to GOST 7933 or plastic bags, which ensures safety. Boxes are pasted over with a tape with an adhesive layer according to GOST 18251 of the B or B brand or a tape like «Scotch tape». Instructions for use are placed in each box or
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VETERINARY SCIENCES / «<g®LL®(qU]UM~J®U®MaL» #2ffim)), 2022
package. Weight of one cargo place - no more than 10 kg.
Requirements for labor protection, industrial sanitation and fire safety. Persons who have reached the age of 18, have passed the annual medical examination and safety training are allowed to work.
Minors, pregnant women and nursing mothers are not allowed to work.
Production facilities consist of five zones:
1. Packaging material preparation area;
2. Area of control of input raw materials and weighing;
3. Mixing zone;
4. Packing area;
5. Zone of marking and quality control of the finished product.
Cleaning of work areas and cleaning is carried out once - at the end of the working day.
All rooms are equipped with powder fire extinguishers type VP-5 (3).
On the basis of the proposed technological approaches and specifications developed «Technological instructions for the production of the drug «Kolidev 8M»; TI № 009-21 dated 01.09.2021». This document was developed in the laboratory for quality control, safety and registration of veterinary drugs and feed additives LLC «DEVIE» and at the Department of Pharmacology and Toxicology of Lviv National University of Veterinary Medicine and Biotechnology S.Z. Gzhyt-sky. The technological instruction was tested at the pharmaceutical enterprise LLC «DEVIE» (Rivne).
Conclusions. Taking into account modern phar-macopoeial requirements, obtained pharmaco-techno-logical and physico-chemical characteristics, a specification for a veterinary medicinal product has been developed and substantiated, which includes the following quality indicators: composition, identification, packaging, storage, shelf life. Developed technological instructions for the production of «Kolidev 8M», which is responsible for the technological process and provides for the following operations: preparation
for production, preparation of the drug, packaging, sterilization, labeling and packaging of antibacterial drugs, labor protection requirements, industrial sanitation and fire safety.
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