Pharmaceutical PVC rigid sheet production process
Abstract: PVC medicinal tablets are mainly composed of PVC (PVC) resin added with certain processing additives, through extrusion, calrolling and other processing methods, produced a new kind of packaging material that meets the medicinal requirements.
Drug aluminum and plastic blister packaging, also known as water-wrapped eye packaging, the English name is "Press Through Package", or "PTP" packaging. PTP packaging is the plastic sheet to the heater to soften it, and then put the sheet in the mold, and then from the upper mold sheet into compressed air or vacuum in the lower mold, sheet form blister or hole, after forming cooling, put the drug into the bubble, medicinal aluminum foil coated with adhesive side in raw temperature, pressure, time conditions and existing drug plastic sheet heat sealing, forming bubble packaging. The PTP packaging materials include medicinal aluminum foil, plastic hard chips, etc. This chapter mainly introduces the plastic hard sheets used for PTP packaging.
The PTP packaging was jointly developed together by German companies LAWSON MARDON SINGEN and BOSCH in the mid-1950s. The application of PTP packaging makes the single-piece packaging of drugs on the road to success.
In recent years, foreign have developed polypropylene (PP), polyethylene terephthalate (PET) PTP aluminum plastic packaging layer material, although they have advantages in some aspects, but in the processing performance, production efficiency is far less than PVC hard, and need to buy new equipment, the production cost is higher, so they have not been widely used, just used in a small number of special drug packaging, little proportion. The PVC hard sheet is the most important PTP packaging material. The choice of these materials can be determined according to the recommendations of the packaging material experts, combined with the nature of the built-in drugs and do the relevant stability tests.
1 1 Medicinal polyvinyl chloride (PVC) hard tablets
PVC medicinal tablets are mainly composed of polyvinyl chloride (PVC) resin added with certain processing additives, through extrusion, calrolling and other processing methods, produced a novel packaging material that meets the pharmaceutical requirements. It independently separate each pill, pill and capsule, make it the smallest packaging unit, improve the accuracy of medicine, safety, and because of the use of the simple processing method, small investment, easy molding processing, etc., make the production cost, production efficiency greatly improved, into the early 90s, almost all the companies are willing to use the packaging to produce pills, pills and capsules, the development trend up to now and continue. PTP aluminum and plastic packaging became the first way of packaging new and more pharmaceutical tablets, pills and capsules. PVC medicinal tablets account for more than 95% of domestic PTP packaging materials. The development trend of PTP aluminum and plastic packaging abroad is also mainly PVC materials, but now there are packaging materials such as PP, PET, PS and other packaging materials, but there is a gap between the comprehensive performance and PVC, the main thing is that the packaging appearance of drugs has no new image. Therefore, the packaging materials used in PTP aluminum-plastic packaging are mainly PVC materials in foreign countries, accounting for about 60%. Most of the rest are composite packaging materials, and other single packaging materials account for a very small proportion. In terms of the growth rate, the growth rate of composite packaging materials is 3-4 times that of single packaging materials, so, composite packaging materials will soon become the mainstream of PTP packaging.
1 2 Medicinal packaging of the PVC series of composites
PVC pharmaceutical packaging series composite tablets are mainly composed of PVC pharmaceutical tablets and another one or several new polymer material film, tablets, through extrusion, composite, coating and other processing methods, produced another new combination material that meets the requirements of pharmaceutical packaging. In the 1990s, the safety of medication is paying more and more attention. Because the ingredients of some drugs are susceptible to moisture hydrolysis and oxidation, the original PVC aluminum-plastic packaging can no longer meet the packaging requirements of these drugs. Hangzhou plastic industry co., LTD. As the leading pharmaceutical packaging materials factory according to foreign packaging materials development trend, successfully developed with PVC medicinal tablets as the substrate, increase some high barrier polymer materials (such as SOLVAY PVDC), it combines the rigidity of PVC, molding and PVDC for water vapor, oxygen, CO 2 odor excellent barrier, become a novel composite material, can meet the tide solution, oxidation drugs, and some Chinese medicine retain fragrance packaging requirements. At the same time, it still uses the PTP aluminum-plastic packaging type, packaging equipment and technology and PVC pharmaceutical packaging material is exactly the same. This series of composite materials can customize packaging materials for pharmaceutical factories according to the degree of drug susceptibility to moisture and oxidation, becoming a higher level of PTP packaging type. In addition, there are PVC/PE packaging materials to replace glass bottles to fill liquid and suppositories drugs, so that the drug safety of these drugs has been greatly improved. Because the PVC and PVC series composite materials used in PTP packaging directly contact with the drugs, the drug manufacturers should pay great attention to the sanitary conditions and health environment of the PVC manufacturers after determining the use of PVC series material packaging drugs, and must have a drug packaging material production environment consistent with the drug production environment.
2. Raw materials and formula
2 1 PVC medicinal tablets
The raw materials of PVC medicinal tablets mainly include PVC resin, stabilizer, processing aid, enhancer, lubricant, plasticizer and so on. The selection of raw materials should not only consider the processing and secondary processing (PTP packaging), but also consider the hygiene of drug production, which are indispensable. In fact, PVC hard tablets contain about 90% of PVC resin, additives only account for a small part, the specific components are as follows: PVC resin: 88-92% stabilizer: 1.5% enhancer: 4.5% processing additives: 1-1.5% plasticizer: 0-1% lubricant: 1.5-2%
Therefore, the packaging material factory should first pay attention to the selection of PVC resin, which must meet the requirements of medicinal packaging, and must establish a control procedure to control each batch of raw materials strictly according to the medicinal requirements. At the same time, the improper selection of additives will also affect the internal quality of PVC medicinal tablets, and it will eventually harm the drug itself, so the selection of additives should also meet the requirements of medicinal products. Therefore, the pharmaceutical factory must carry out stability and compatibility tests before determining the packaging material factory to provide PVC pharmaceutical tablets. Once it is agreed with the packaging material factory that the raw materials and formula of PVC pharmaceutical tablets should not be changed at will.
2 2 Ingredients and formulation of 2 2 PVC series of medicinal composite hard tablets
Ingredients for the 2 2 1 PVC series of medicinal composite hard tablets:
PVC series of medicinal composite hard tablets mainly include PVC medicinal tablets, PVDC emulsion or resin, PE film, adhesive, etc. The selection of raw materials should not only consider the processing and secondary processing (PTP packaging), but also consider the hygiene of drug production, which are indispensable. Once the material composition structure is determined, the packaging material factory cannot easily change and ultimately affect the quality of the drug.
2 2 1 1 PVC medicinal tablets
Products that must be produced in a clean factory that meets the production requirements of medicinal packaging materials and are approved by the SDA in order to be used for the production of composite hard tablets.
2 2 1 2 PVDC
PVDC is a high-barrier polymer material, and its structure and formula are: - [H 2-CCl2-] m-n-, and X represents the copolymerization group. Pure PVDC is a very difficult polymer to process, so it must copolymer with other groups to be used for processing. Different copolymerization groups produce PVDC with different properties and different processing processes, and usually the copolymerize groups are methacrylate and vinyl chloride.
As a special commodity, drugs have increasingly demanding requirements on packaging. The special physical properties of PVDC have attracted more and more attention, and they are more and more used in the packaging of drugs. These special physical properties include excellent barrier properties and chemical stability for oxygen, water vapor, carbon dioxide, and organic compounds. While more and more polymer materials are being processed for drug packaging, the only one is the PVDC that has a high barrier performance to both water vapor and oxygen. In fact, many polymer materials themselves have more water vapor barrier properties, and coating on them with a thin layer of PVDC will greatly enhance this performance. In addition, the PVDC coating also blocks oxygen and other bodies and preserves its fragrance. PVDC also has acid resistance, alkali resistance, oil resistance, solvent resistance, drug resistance performance, making it more suitable for different types of drug packaging, especially some easy to moisture solution, easy to oxidation or contain chemical active substances and need to protect fragrance or block odor adsorption drug packaging.
At present, all the PVDC used in the production of pharmaceutical packaging materials in China are imported from foreign countries. These products are all recognized by the FDA in the United States, and can be used in the packaging of drugs and food. Domestic manufacturers have produced PVDC emulsion, but the quality is still compared with the gap between the imported universities, mainly manifested in the barrier, coating uniformity, stability, hygiene and other aspects. Due to the hygiene requirements of the PVC series of medicinal composite tablets, the VDCM (vinyl dee-chloride monomer) content of the PVDC emulsion selected must be less than 3ppm.
2 2 1 3 PE membrane
The selection of PE film, like PVC medicinal tablets, must be produced in a clean factory that meets the production requirements of pharmaceutical packaging materials, and approved by SDA, can be used for the production of composite hard tablets.
2 2 1 4 Adhesive
The adhesives currently used in composite hard tablets are all two-component polyurethane adhesives, which consists of the main agent and the curing agent. The main agent, curing agent and solvent are evenly mixed in a certain proportion and used for production. The quality of adhesives directly affects the quality of products, the domestic mainly use of imported adhesives. There are many foreign manufacturers of adhesives, such as: German Henkel company, American Morton company, etc. These products are recognized by the American FDA, and can be used in medicine and food packaging. Domestic manufacturers have produced two-component polyurethane adhesive, but compared with foreign products, there is still a large quality gap, mainly manifested in the bonding strength, heat resistance, hygiene, transparency, coating uniformity and other aspects.
2 2 2 Formula 2
The PVC series of medicinal composite hard tablets are mainly composed of PVC medicinal tablets, PVDC, PE membrane, adhesives, etc. In fact, the composite hard tablets contain about 70-90% PVC hard tablets, and other raw materials only account for a small part. The specific components are listed in Table 3:
Therefore, the packaging material factory should first pay attention to the selection of PVC hard tablets, must meet the requirements of medicinal packaging, must establish a control procedure to each batch of raw materials strictly according to the medicinal requirements. At the same time, the improper selection of PVDC and other raw materials will also affect the internal quality of PVC series pharmaceutical composite tablets, and eventually harm the drug itself, so the selection of raw materials should also meet the requirements of medicinal materials. Therefore, the pharmaceutical factory must carry out stability and compatibility tests before determining the packaging material factory to provide PVC series pharmaceutical composite tablets. Once it is determined that with the packaging material factory agreement, the raw material and formula of PVC series pharmaceutical composite tablets cannot be changed at will.
3. Production process procedures
3 1 PVC medicinal tablet process flow
The production process of PVC medicinal tablet mainly includes calendering method and extrusion method.
Caldering process: PVC resin and additives added to the high speed mixing kettle pinch and kneading, After the temperature rises to 100-120℃, unload it into the cooling mixing kettle, Cooling to 50-80℃ into the mix intermediate tank, The extruder is plasticized at a temperature of 120-180℃, Further plasticizing on the two-roller making machine, Fully plasticized melt blocks are formed by a belt conveyor, The molding temperature is 190-210℃, The lead roller strips the formed sheet from the last roller of the press, After the sheet is cooled and rolled down, Use the cutting machine to cut into a variety of different specifications of products. Shesheet thickness is achieved by adjusting the gap of the roller.
Extruding process: the mixing preparation process is consistent with the rolling method, sheet molding is through the extruder and mold head extrusion molding, cooling, winding, cut into a variety of different specifications of products. Plate thickness is achieved by adjusting the mold-lip gap.
3 2 PVC/PE composite sheet process flow:
The production process of PVC/PE composite sheet is dry composite. Adhesive preparation: add the main agent, curing agent and solvent to the stainless steel bucket and mix well, and then add to the coating head glue tank. After releasing the PVC hard sheet, adjust the surface tension through the corona processor, apply the adhesive on the coating head, enter the hot air drying to dry the solvent contained in the adhesive; after the PE film is released, adjust the surface tension through the corona processor, compound with the adhesive coated PVC hard sheet, and cool. The composite material roll is cooked at 50-60℃ and cut into different specifications with a cutting machine.
3 3 PVC / PVDC composite sheet process:
The production process of PVC / PVDC composite sheet is reverse concave coating. Adhesive preparation: add the main agent, curing agent and solvent to the stainless steel bucket and mix well, and then add to the coating head glue tank. PVC emulsion preparation: Add lubricant additives to the PVDC emulsion and stir, add the PVDC intermediate groove, and push into the PVDC coating head with a pump. PVC hard sheet to adjust the surface tension through the corona processor, coat the coating head, enter the hot air oven to dry the solvent contained in the adhesive, then after the PVDC cloth roll coated with PVDC, enter the moisture contained in the PVDC to dry the hot air dryer, cool the roll, and then apply PVDC several times to meet the required PVDC coating amount. After 3-4 days of ripening at 50-60℃, be cut into different specifications with a minute cutting machine.
3 4 PVC/PE / PVDC composite sheet process flow
The production process of PVC/PE / PVDC composite sheet is actually the synthesis of the above two processes.
Because PVC medicinal tablets and PVC series medicinal composite tablets are directly in contact with drugs, the above process must be produced under the same net environmental conditions as the pharmaceutical factory. National Medical Products Administration in 2000 issued the 21 order "direct contact drug packaging materials production management specification (GMP)", has clear provisions, so pharmaceutical packaging materials manufacturers in the hardware and software to meet the requirements of GMP, so as to ensure product quality, process quality management level also directly affect the stability of PVC pharmaceutical quality, so before determining the use of packaging material, must be to the packaging material factory comprehensive audit and confirmation.
4. Main equipment and plant requirements
The main equipment of pharmaceutical PVC hard chip production is high-speed kneading and machine, extruder, plastic-making machine, four-roll rolling machine, split-cutting machine and so on.
The main equipment of medicinal composite hard tablets are coating machine and cutting machine. PVC hard chip production from the cooling setting process and the entire composite chip production plant requirements are 100,000 level cleanliness. The plant cleanliness of foreign class products is disturbing to 100,000 level.
5 Product standards
According to the standard series search, the above products have no unified international standards. International common practice is each drug factory according to the specific situation of the package drugs set standard to regulate the packaging materials used, and at the same time conform to the general performance requirements of packaging materials, from the current contact of the foreign pharmaceutical factory standard, domestic foreign owned or joint venture pharmaceutical factory are equivalent or equivalent to the foreign standards. Domestic national standard of medicinal PVC hard tablets, the standard number is GB5663-1985. The industry standards of pharmaceutical PVC series composite tablets are being formulated. Now the enterprise standards of Hangzhou Plastic Industry Co., Ltd. guides and standardizes the production and sales of products. These standards all refer to the standards of foreign pharmaceutical manufacturers, and most of the technical indicators have reached the international advanced level, and the table 4 are shown for the specific technical indicators.
6 Scope of application and the impact of packaging and packing equipment:
7. Notes and basic principles for choosing such products
What kind of packaging material selection is mainly determined by the nature of the drug (moisture, oxidation, fragrance retention, etc.) and shelf life requirements. It should be noted that this is a very careful choice, not only to consider the quality of drugs, but also to consider the development and cost of the enterprise, it is suggested to have a powerful packaging material factory or packaging material experts to jointly determine the packaging material choice. Basic selection principle: ordinary drugs, the moisture-proof requirements are not high can choose PVC medicinal tablets. Either PVC / PVDC or PVC/PE / PVDC composite tablets can be used for drugs with moisture-proof and antioxidant requirements, or long shelf life requirements. PVC/PE compound tablets can be used for oral liquid and suppositories drugs.
General procedure for selecting packaging materials:
1 First, determine to use PTP aluminum-plastic packaging;
2. According to the nature and shelf life requirements of the choice of the packaging material, the specific technical experts of the packaging material factory, or the material selection test, to take full consideration to the versatility of the equipment, the novelty of the appearance, the minimum cost;
3. Conduct the machine test to determine the applicability of packaging material to equipment and the satisfaction of product quality and appearance;
4. Do a good job of stability and compatibility test, each drug must be done, because the nature of their own drug factory is different;
5. Review the environment, equipment, process, quality, determine the raw materials, formula and material structure of the packaging material, and sign the agreement finally.