Discussion On The Key Points Of Quality Control In Tablet Production

In the process of tablet production, there are many factors that affect the quality of drugs, so it is necessary to supervise and control all aspects of drug production. Starting from the production process of tablets, this paper analyzes various quality control points in the production process in order to provide a reference for tablet production of pharmaceutical companies.

Tablets are one of the common dosage forms in pharmaceutical production, and the quality control of tablets is the basic requirement of their production, and it is also an important responsibility of pharmaceutical companies. The following will introduce the key quality control points from the production process of tablets and discuss how to develop effective control measures.

1 Ensure The Hygiene Of The Process And The Environment

Before production, during production, and after the completion of the clearance at the end of production, it should be carefully checked whether the process hygiene and environmental hygiene meet the requirements. It should be ensured that the temperature, humidity and pressure difference between the operations meet the requirements of the production process; The equipment and tools used must be cleaned to avoid the use of fragile, easy to desquamation, easy to grow mold; The inner packaging materials used must also comply with hygienic standards.

Generally speaking, the cleanliness level of the environmental health production operation room is D level, and the environmental health must meet the requirements, specifically, the dust capture facilities in the operation room should be in good condition; Before production, it should be ensured that there is no previous batch of residual materials, doors and windows, ceilings, walls, floors, lampshades should be kept clean and dust-free, smooth and bright; The exhaust outlet should be clean and stain-free, and environmental maintenance should be paid attention to in peacetime to ensure the clean production of drugs.

2 Preparation Before Production

In the preparation stage before production, each process should receive batch production records, carefully read the product name, specifications, batch number, batch size and other contents; Check whether the room is hung with the “cleaned” logo, and whether the production date of the class is within the cleaning validity period; At the same time, check the cleaning status of each equipment and containers in turn to ensure that they are within the cleaning validity period. The operator shall check and confirm each item according to the “pre-production confirmation” column in the batch production record, and only after the reviewer has reviewed and passed the approval of QA (Quality Assurance Engineer) can production start; At this point, the “Cleaned” status label on the room should also be replaced with “In Production”.
Before picking, make sure the balance and scale have been calibrated before use. When picking materials, the post personnel should print the picking list according to the batch production records and production instructions and hand it to the warehouse personnel; After the warehouse material manager prepares the material according to the picking list, it is sent to the dismantling room of the workshop by the relevant personnel; After the material is sent to the designated area, the picking post personnel should check whether the material name, code, batch number, quantity and other information are correct according to the batch production record and the picking list; After confirmation, the picker should clean and disinfect the outer surface of the material packaging and then transfer it to the material staging area.

3 Points Of Attention In The Batching Process

Before batching, check whether the temperature, humidity and pressure difference of the room are within the specified range; Check whether the measuring instrument used is within the validity period of the calibration; Check the cleaning status of the containers used to ensure that they are within the validity period of the cleaning; The operator should check the label information of the material according to the production instruction list, including the material name, material code, material batch number and expiration date. During the weighing and feeding process, it should also be reviewed by two people.

When batching, the auxiliary materials should be prepared first, and then the main ingredients should be prepared. The prepared material should be packed in a clean container and labeled – write down the name, weight, batch number, date and name of the formulator of the material, so as to avoid the mixing and pollution of the container; In addition, the batching room, the ingredient equipment, and the preparation container should also be cleaned according to the regulations, and the cleaning and placement expiration date should be affixed.

4 Points Of Attention During Crushing And Sieving

Before crushing the screen, the appropriate screen should be selected according to the process requirements to ensure that the screen does not cause contamination to the product. At the beginning of the crushing and after the crushing, it is necessary to check the integrity and model of the screen to avoid the broken screen falling into the product. The process of crushing the sieved material should be carried out in the dust removal cover of the sieve chamber to avoid dust diffusion and cross-contamination. For the sieved material, the “material” label should be posted to identify it, and transferred to the specified location or the next process of storage. For key operations, a review and review should be carried out to ensure that the material name, code, batch number, and trait of the ingredients are in line with the regulations, and the quantity used is accurate. After each material is weighed, it should be checked in time whether the difference between the material weighing and the amount of ingredients is consistent. After weighing, the material label information on the material bag should be checked according to the formula to ensure that it is correct.

5 Points Of Attention In The Granulation Process

Since dust is generated during the granulation process, the negative pressure should be maintained to prevent dust from spreading. Before feeding, the name of the material, the material code, the material batch number, weight and other information should be carefully checked, and the double should review and sign to confirm. After the feeding is completed, the mixing time, stirring speed and other parameters should be set according to the requirements of the granulation process, and the mixing and granulation should be carried out.

For the fluidized bed dry material process, the number of filter bag shakes, cycles, inlet air volume, temperature and spray slurry and other parameters should be set according to the process requirements, and then dried. It should be noted that the amount of adhesive used in fluidized bed granulation, the rate of addition of the spray gun, the temperature and humidity of the hot air will affect the strength, particle size and drying time of the particles.

For the whole grain process of the whole pellet machine, the material should be evenly put into the hopper first, and then the speed should be selected according to the process requirements to carry out the whole grain. When you’re done, the item is status-marked. It should be noted that the moisture content is the key parameter of the success of granulation, and the speed and mixing time of the mixer in the total mixing process will affect the uniformity of the mixing.

6 Points Of Attention During Tablet Pressing

Before the start of tablet pressing, the production parameters of the tablet press should be set according to the requirements of the batch production record process parameters, and the specific points of attention are: pre-pressure and main pressure scale, filling depth, speed of the forced unloader and tablet pressing rate. Before production, it should also be debugged, that is, randomly take the plain tablets for testing, and after the visual appearance is qualified, the difference in the weight of the tablets should be checked with an analytical balance; After the vegetarian tablet is re-qualified, it is transferred to the hardness detector to test its hardness. Continuous test element pieces until the number required in the batch record is reached, if its appearance, weight, hardness test results are within the scope of the batch record requirements, then you can print the data and record the inspection data, ready for formal production.

Starting from 10 minutes after switching to the production mode state, should also be taken to detect the appearance, weight, weight difference, hardness and brittleness, and the first sampling time should be recorded on the batch production record. When there is a shutdown break in the production process or the situation of starting the machine after the elimination of faults, it is necessary to check the film weight, hardness, weight difference, film thickness and appearance again to ensure that they meet the requirements before entering the normal mode of production. In addition, in the production process, it should also be sampled regularly according to the requirements of the batch production record – to detect whether the parameters of the vegetarian tablets meet the requirements of the batch production record, and if there is any non-compliance, the equipment parameters should be immediately stopped to adjust. Special attention should be paid to the fact that the plain tablets that fall to the ground during the production process and the plain tablets after sampling and testing are strictly prohibited from being put into qualified products.

7 Points To Note In The Coating Process

Before coating, according to the requirements of the process parameters, set the production parameters of the coating machine, pay attention to the control speed in the grouting process should not be too fast, so as not to wrap the coating powder together and can not be mixed smoothly. In the coating process, the appearance and weight uniformity of the coating piece should be checked at certain intervals, and confirm whether the spraying effect and spraying atomization are normal, and pay attention to the angle of the spray gun, the air volume and temperature of the inlet and outlet air. During the coating process, the host must not stop running, and should always maintain a negative pressure state in the coating pot. In the production process, the speed of the coating pot should be adjusted according to the requirements, and the amount of spraying follows the principle of first slow and then fast – when the surface of the core is all wrapped with a layer, with the increase of the speed of the coating pot, the amount of spraying can be appropriately increased. After the coating liquid is sprayed and the spraying is stopped for 5 minutes, the hot air can be turned off; At this time, in order to make the surface of the coating sheet completely dry, the speed of the coating pot should be reduced to the minimum, and the exhaust fan and the main machine should be kept running, and then closed after the core temperature of the sheet drops to room temperature.

In the production process, the average sheet weight, weight increase ratio and appearance of the coating piece should be recorded and checked as required, and the real-time inlet air temperature, exhaust air temperature and coating pot speed should be recorded and checked. Specifically, the core temperature of the coated piece should always be strictly controlled within the required range; And should be sampled regularly according to the requirements, until the weight gain parameters of the coated tablets are detected to meet the requirements; The appearance of the intermediate products of the coated piece should be complete and smooth, without cracks and brokenness, and the printed characters should be clearly visible, and there should be no wrinkles, dry cracks, color differences and so on. Sampled coated tablets during production should be counted separately in the sampling volume. After the end of production, the bag is replaced by packaging, and those that need to be sealed should be sealed in time, and the weighing needs to be marked with materials. Similarly, coating tablets that fall to the ground during the production process and coated tablets after sampling are strictly prohibited from being put into qualified products or coating pots.

8 Points Of Attention In The Aluminum-Plastic Packaging Process

It should be confirmed that the aluminum-plastic packaging post personnel have carefully read the batch number, batch, product name, specification, expiration date and other information after receiving the batch production records. The operator should first debug the equipment as required – take 10 empty medicine boards and visually check the appearance of the medicine board; And use the sealing tester to check its tightness to ensure that the appearance of the pharmaceutical board is qualified (clear printing, flat press, moderate cutting surface), good sealing, review by the supervisor, and ask QA to confirm the approval, and then convert the equipment to production mode. In the aluminum-plastic process, attention should be paid to the temperature of molding and heat sealing, and the speed of equipment operation.

In the production process, sample inspection should be taken – for the completed aluminum-plastic plate, the appearance of the medicine board should be visually checked one by one; Every 20 to 30 min according to the requirements of the batch production record, the drug board is extracted, and the sealing tester is used for tightness testing.
In the production process, the way of segmented isolation should be adopted, that is, the drug board that is qualified before and after the two sealing tests in any time period is a qualified product. During the production process, if excess capsules or tablets are found inside the blister, they should be cleaned with a food-grade silicone brush. The number of samples taken in the production process should be counted separately in the sampling volume. It should be noted that qualified aluminum-plastic plates are loaded with tote boxes, and after each tote box is filled, it is necessary to attach material labels and transfer to the designated location. If the product is double aluminum packaging, it is also necessary to weigh the drug board for repeated cores to ensure that the medicine board has no cavitation.

9 Points Of Attention During The Outer Packaging Process

After the operator receives the drug to be packaged according to the batch packaging record, it should be handed over to another person to review its product name, code batch number, specification, quantity and other information, and finally passed the on-site QA inspection before it can be used.

Instructions folding: According to the requirements of the batch packaging record, the instructions are folded, and the instructions after folding should be clean and flat; The material balance of the instructions must be 100%, and the unqualified products produced during the folding process of the instructions should be handed over to QA for unified centralized destruction.

Small box phase III, outer box phase three printing: according to the requirements of the batch packaging record, the small box and outer box received will be printed for three phases, and the first small box and outer box printed can be continued after the production supervisor and the on-site QA review of the third phase are correct.

Aluminum-plastic sheet packaging. Before loading the small box: before packaging, you should carefully check whether the text information on the box and the instruction manual is consistent with the drug information; When checking the packaging specifications and quantity, it should be checked at any time and reviewed at any time, and manually boxed; When packaging aluminum-plastic board, the packaging method should be standardized – first put the aluminum-plastic plate in the turnover box neatly in front of yourself, the back of the medicine board facing itself, the small box first sealed the bottom, folded neatly, check the batch number, check whether the aluminum foil is damaged, and whether the product name is clear and complete; Before loading the box, turn the medicine board to the front to check whether the batch number and expiration date of each board are clear and complete, check the appearance of the board, and confirm whether there are any unqualified drug boards such as cavitation, splintering, lamination, dirt, black spots, and uneven cutting. The unqualified drug boards are temporarily stored in the red weekly packing box, counted after the end of production, and handed over to EHS (Environmental Management System Engineer) for centralized processing.

Packing small box: According to the requirements of the batch record, the accurate quantity and good quality of the medicine board are loaded into the small box in turn along with the instructions, and the packed small box is neatly arranged in the same direction, and the side printed with the first-level traceability code is facing up.

Wrapping: The small box containing the medicine board is neatly stacked on the wrapping machine track (the side with the first-level traceability code printed on the upper side is facing up), and the wrapping machine is operated according to the requirements, and the small box is wrapped.

Traceability code scanning (electronic supervision code): Operate the equipment according to the requirements, carry out three-level traceability code scanning and registration, download the production task of the packaging relationship after scanning, check and confirm that the batch number, production date, expiration date and other information are correct, and upload it to the drug electronic supervision code system platform.

Sealing, bundling: operate the equipment according to the requirements, scan and register the traceability code, and pack, seal and bundle according to the product packaging quantity required by the batch packaging record. It should be noted that if there is a packaged small box fraction, the fraction label should be posted on the outer box and the quantity should be marked on the label; If there is A LCL, an outer box can only spell two batch numbers, and must be the same month batch number, LCL information should be marked in a conspicuous position in the outer box, easy to distinguish.

Warehousing: After the packaging is completed, the operator should truthfully report the number of finished products to the team leader, count the unqualified drugs and small boxes and hand them over to EHS for centralized processing, and fill in the quantity truthfully in the batch packaging record; Fill in the finished product warehousing list and the packaging material return list, complete the warehousing and return process, and complete the batch record in time.

10 Conclusions

In the production process, there are many factors affecting the quality of tablets, this article through the introduction of the tablet production process process, the risk factors of the tablet production process have been identified, and provide effective control measures, hoping to help pharmaceutical companies to carry out risk prevention and quality control, reduce quality and safety hazards, ensure drug quality, reduce the generation of unqualified products.