First of all, I am an intern in the preparation workshop. By studying the preparation technology of Jisheng Shenqi tablets, Guifu Dihuang capsules, Zhenyuan capsules and other dosage forms, the production technology of solid preparations was intuitively understood.
Take Guifu Dihuang Capsule and Zhenyuan Capsule as examples to illustrate:
1, Guifu Dihuang Capsule:
It is mainly made of Poria cocos fine powder, Chinese yam fine powder, extract, silicon dioxide, starch, etc. The main difficulty of its preparation is that the viscosity of the water extract is high, and it is not easy to mix evenly during the stirring process, resulting in agglomeration, so that it needs to be crushed by hand before boiling and drying. In addition, because the viscosity of water extract is too high, there are many residues in the container during the preparation process, causing unnecessary losses. In order to solve this problem, we can consider methods to reduce the viscosity of raw water extract, such as extracting with alcohol or further treating the water extract, such as alcohol precipitation.
2. Zhenyuan Capsule:
It is mainly made of ginsenoside powder, magnesium stearate, calcium hydrogen phosphate, talcum powder, ethanol, etc. The dust flying in the production process is serious, so it is necessary to wear protective equipment. In addition, a large number of talcum powder, calcium hydrogen phosphate and magnesium stearate are used as auxiliary materials in production, but the application of this auxiliary material has not been further studied. Take talcum powder as an example. As we all know, its main component is magnesium silicate. Many documents have pointed out that talcum powder is not suitable for common use, and Zhenyuan capsule is mainly taken by heart patients for a long time. So should we pay more attention to the side effects of long-term accumulation?
Then, it is the study of painting workshop:
1, sugar coating:
The process of icing is generally: coating isolation layer, powder coating, icing layer, colored icing layer and polishing. It is a tablet coated with sucrose as the main coating material, which has the advantage of strong adhesion. It can be used to increase the hardness of the tablet and make the surface of the tablet smooth and beautiful, but it has the disadvantages of strong hygroscopicity and excessive hardness after long-term storage.
(1) encapsulation isolation layer. Its purpose is to form an impermeable barrier to prevent the moisture in syrup from infiltrating into the tablet core. Available coating materials are: 10% zein ethanol solution, 15% ~ 20% shellac ethanol solution, 10% cellulose acetate phthalate (CAP) ethanol solution and 10% ~ 15% gelatin slurry.
(2) Powder coating. In order to eliminate the edges and corners of tablets as soon as possible, syrup and talcum powder are added alternately, and a thick powder coating is wrapped outside the isolation layer. In operation, high-concentration syrup (65% ~ 75%, g/g) and talcum powder with 100 mesh are generally used, and the pulp powder is sprinkled once each, and then dried with hot air for 20 ~ 30 min (40 ~ 55℃), and the above operation is repeated 15 ~ 18 times. In order to increase the viscosity of the syrup, 10% gelatin or Arabic gum can also be added to the syrup.
(3) sugar coating. The surface of powder coating film is rough and loose, so it should be wrapped with sugar coating to make its surface smooth, flat, delicate and firm. The key points of operation are to add slightly diluted syrup, gradually reduce the dosage (only wet one side), and slowly dry at low temperature (40%), generally making 10 ~ 15 layer.
(4) wrapping with colored sugar coating. It is exactly the same as the sugar coating process mentioned above. The purpose is to make the tablets beautiful and easy to identify. The only difference is that food pigments are added to the syrup. The concentration of pigment in colored syrup added each time should be from shallow to deep to avoid color spots. Generally, 8 ~ 15 floors should be installed.
(5) lighting. Its purpose is to increase the luster and surface hydrophobicity of tablets. Generally, rice wax produced in Sichuan is used, which is often called Sichuan wax; Before use, it needs refining, that is, heating to 80 ~ 100℃ to melt, then passing through 100 mesh sieve to remove suspended impurities, and mixing 2% silicone oil evenly. After cooling, it is planed into 80 mesh fine powder for use, and the dosage is about 3 ~ 5 kg per 10,000 tablets.
2, film coating:
The materials for film coating are mainly divided into three types: gastric soluble type, enteric soluble type and water insoluble type;
(1) gastric soluble type. That is, some polymer materials that can be dissolved in the stomach are suitable for general tablet film coating. Materials include hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), acrylic resin ⅵ and polyvinylpyrrolidone (PVP).
(2) enteric type. Refers to the polymer film coating material which is insoluble in gastric acid and begins to dissolve in intestinal juice environment. The coating method is the same as film coating, or it can be coated with sugar coating to powder coating, then coated with enteric coating, then coated with sugar coating and polished. The most commonly used enteric coating materials are cellulose acetate phthalate (CAP), hydroxypropyl methylcellulose phthalate (HPMCP), polyethylene phthalate (PVAP), styrene-maleic acid copolymer, 1, No.2 and No.3 acrylic resins (copolymer of methacrylic acid and methyl methacrylate Eudragit L).
(3) water insolubility. Refers to the water-insoluble polymer film coating material. Materials include ethyl cellulose (EC), cellulose acetate (EA) and ethylene-vinyl acetate copolymer (EVA).
(4) Other auxiliary materials. Include plasticizers, anti-sticking agents, sunscreens and the like. Commonly used plasticizers are propylene glycol, castor oil, polyethylene glycol, silicone oil, glycerol, diethyl phthalate or dibutyl ester. Commonly used anti-sticking agents are talcum powder and stearic acid; Commonly used sunscreen is mainly titanium dioxide; Commonly used pigments are amaranth, carmine, lemon yellow and indigo.
Film coating technology can be widely used in tablets, pills and granules, especially for Chinese medicine tablets with strong hygroscopicity, easy cracking and mottling. Compared with sugar coating, film coating has the following advantages:
1. Good quality. As the film-forming agent and most auxiliary additives are polymer materials with excellent physical and chemical properties, the coated film-coated tablets are not only moisture-proof, light-proof, taste-masking and wear-resistant, but also not easy to mildew and disintegrate, which greatly improves the dissolution, bioavailability and expiration date of drugs, greatly expands the countries and regions where drugs can be sold, and effectively promotes the export of drugs, especially Chinese patent medicines.
2. Less weight gain. Only the weight of the tablet core is increased by 2% ~ 4%, while the sugar-coated tablets (in which the main auxiliary ingredient is talcum powder that has been eliminated abroad) often increase the weight of the tablet core by 50% ~ 100%.
3. Dry it quickly. The coating operation time is short, generally only 2 ~ 3h hours, while the sugar coating generally needs16 hours, which is simple and easy to master, especially for Chinese and western medicines that are easily damaged at high temperature.
4. The image is beautiful. Beautiful shape, bright colors, fresh logo and vivid image. The drug core can adopt various plane bending shapes, and the trademark and logo of the enterprise can be directly washed on the drug core, and it is still clear and obvious after being wrapped with a film coating, which can not only improve the corporate image, but also play an anti-counterfeiting role.
5. There are many varieties. There are many materials for film coating. By designing the coating formula and changing the release position and characteristics of the drug core, film coatings with different characteristics can be made Now, besides stomach-soluble film and intestinal-soluble film, there are oral-soluble film (buccal tablet), sustained-release film, controlled-release film, composite film (besides drug core, the film also contains other main drugs) and the latest multilayer film, microporous film, osmotic pump coating and targeted drug delivery coating, which greatly improves the drug effect.
6. Widely used. At present, film coating is not only widely used in tablets and pills of Chinese and western medicines, but also widely used in mini-tablets, pellets, granules, soft capsules and hard capsules, and even drug powders. Film-forming materials can also be directly used in film (such as contraceptive film, that is, the film contains the main drug but not the drug core), suspension and hydrophobic drug dispersant.
7. standardization. The design, technology, material and quality of film-coated tablets can be standardized and then computerized, which is particularly important for GMP management and entering the international market.
8. Little pollution. This process can reduce or avoid dust flying in the workshop, which is beneficial to environmental protection and labor protection, and can prevent workshop pollution at the same time, which is of great significance to meet GMP cleaning requirements under dynamic conditions.
9. There are many solvents. Generally, water is used as the solvent of coating agent to prepare coating liquid, which not only reduces the cost, but also makes the operating environment more comfortable and safe. However, for some drugs that absorb water quickly or decompose easily in water, only non-aqueous solvents can be used, and there are many solvents to choose from.
10. Low cost. Although the film coating material is more expensive than sugar and talcum powder, the overall calculation is not higher than the sugar coating cost because of its small dosage, labor saving (1 ~ 2 operators), less requirements for workshop and equipment (only one standard workshop and one coating pan), and material saving and energy saving.
Based on these advantages, with the acceleration of GMP implementation, the application of film coating technology in China is in the process of acceleration, and the market prospect of film coating is very broad. The improvement and innovation of coating materials and coating technology is imperative. We have made some explorations in the selection of coating materials, prescription design and the progress of coating technology.