In the trial and mass production of nifedipine sustained-release tablets, contraceptive tablets, stomachicangning tablets, ferrous fumarate tablets, buflomedil hydrochloride tablets, etc., we use hydroxypropyl methylcellulose (HPMC) liquid, Hydroxypropyl methylcellulose and polyacrylic acid resin liquid, Opadry (provided by Colorcon, UK), etc. are film coating liquids, which have successfully applied film coating technology, but have encountered problems in trial production and production. After some technical problems, we are now communicating with colleagues about common problems and solutions in the film coating process.
In recent years, film coating technology has been widely used in solid preparations. The film coating can protect the drug from light, moisture and air to increase the stability of the drug; mask the bad taste of the drug and facilitate the patient to take it; control the release site and release speed of the drug; prevent the compatibility change of the drug; improve the appearance of the tablet Wait. It also has the advantages of fewer processes, shorter time, lower energy consumption, and less tablet weight gain. The quality of film-coated tablets mainly depends on the composition and quality of the tablet core, the prescription of the coating liquid, the coating operating conditions, the packaging and storage conditions, etc. The composition and quality of the tablet core are mainly reflected in the active ingredients of the tablet core, various excipients and the appearance, hardness, brittle pieces, and tablet shape of the tablet core. The formulation of the coating liquid usually contains high molecular polymers, plasticizers, dyes, solvents, etc., and the operating conditions of the coating are the dynamic balance of spraying and drying and the coating equipment.
1.One-sided abrasion, film edge cracking and peeling
The hardness of the surface of the top of the tablet core is the smallest, and it is easily subjected to strong friction and stress during the coating process, and one-sided powder or particles fall off, resulting in pockmarks or pores on the surface of the tablet core, which is one-sided wear, especially with engraved Marked film. The most vulnerable part of the film in the film-coated tablet is the corners. When the adhesion or strength of the film is insufficient, cracking and peeling of the film edges are likely to occur. This is because the volatilization of the solvent causes the film to shrink, and the excessive expansion of the coating film and the core increases the internal stress of the film, which exceeds the tensile strength of the coating film.
1.1 Analysis of the main reasons
As far as the chip core is concerned, the main reason is that the quality of the chip core is not good, and the hardness and brittleness are small. During the coating process, the tablet core is subjected to strong friction when rolling in the coating pan, and it is difficult to withstand such a force without sufficient hardness, which is related to the formulation and preparation method of the tablet core. When we packaged nifedipine sustained-release tablets, due to the small hardness of the tablet core, powder appeared on one side, resulting in pores, and the film-coated tablet film was not smooth and had a poor appearance. In addition, this coating defect is also related to tablet type. If the film is uncomfortable, especially if the film has a logo on the crown, it is more prone to one-sided wear.
In the coating operation, too slow spray speed and large air intake or high air inlet temperature will lead to fast drying speed, slow film formation of tablet cores, long idling time of tablet cores in the coating pan, and long wear time. Secondly, the atomization pressure is large, the viscosity of the coating liquid is low, the droplets in the atomization center are concentrated, and the solvent volatilizes after the droplets spread, resulting in a large internal stress; at the same time, the friction between the one-sided surfaces also increases the internal stress of the film and accelerates the film. Cracked edges.
In addition, if the rotation speed of the coating pan is too fast or the baffle setting is unreasonable, the friction force on the tablet will be large, so that the coating liquid will not spread well, and the film formation will be slow, which will cause one-sided wear.
From the coating liquid, it is mainly due to the choice of polymer in the formulation and the low viscosity (concentration) of the coating liquid, and the poor adhesion between the coating film and the tablet core.
1.2 Solution
One is to adjust the prescription or production process of the tablet to improve the hardness of the tablet core. HPMC is a commonly used coating material. The adhesion of tablet excipients is related to the hydroxyl groups on the excipient molecules, and the hydroxyl groups form hydrogen bonds with the corresponding groups of HPMC to generate higher adhesion; The adhesion is weakened, and the one-sided and the coating film tend to separate. The number of hydroxyl groups on the molecular chain of microcrystalline cellulose is high, and it has a high adhesive force, and the tablets prepared from lactose and other sugars have moderate adhesive force. The use of lubricants, especially hydrophobic lubricants such as stearic acid, magnesium stearate, and glyceryl stearate, will reduce the hydrogen bonding between the tablet core and the polymer in the coating solution, making adhesion The force decreases, and with the increase of lubricity, the adhesion force gradually weakens. Generally, the more the amount of lubricant, the more the adhesion is weakened. In addition, in the selection of tablet type, the round biconvex tablet type should be used as far as possible for coating, which can reduce the occurrence of coating defects.
The second is to adjust the prescription of the coating liquid, increase the solid content in the coating liquid or the viscosity of the coating liquid, and improve the strength and adhesion of the coating film, which is a simple method to solve the problem. Generally, the solid content in the aqueous coating system is 12%, and the solid content in the organic solvent system is 5% to 8%.
The difference in viscosity of the coating liquid affects the speed and degree of penetration of the coating liquid into the tablet core. When there is little or no penetration, the adhesion is extremely low. The viscosity of the coating liquid and the properties of the coating film are related to the average molecular weight of the polymer in the formulation. The higher the average molecular weight, the greater the hardness of the coating film, the less elasticity and the wear resistance. For example, commercially available HPMC has different viscosity grades for selection due to the difference in average molecular weight. In addition to the influence of the polymer, adding plasticizers or increasing the content of talc can reduce the incidence of film edge cracking, but the addition of colorants iron oxide and titanium dioxide can also affect the strength of the coating film, so it should be used in moderation.
Third, in the coating operation, it is necessary to increase the spraying speed, especially when the coating is first started, the spraying speed should be slightly faster, so that the tablet core is covered with a layer of film in a short time, which plays the role of protecting the tablet core. Increasing the spray rate can also reduce the bed temperature, evaporation rate and film temperature, reduce the internal stress, and also reduce the incidence of film cracking. At the same time, adjust the rotation speed of the coating pan to the best state, and set the baffle reasonably to reduce friction and wear.
2.Adhesion and blistering
In the process of coating, when the cohesion of the interface between two slices is greater than the molecular separation force, several slices (multiple particles) will briefly bond and then separate. When the balance between spray and drying is not good, the film is too wet, the film will stick to the wall of the pot or stick to each other, but also cause the film breakage at the adhesion place; In the spray, when the droplets are not fully dried, the unbroken droplets will stay in the local coating film, there are small bubbles, forming a bubble coating layer, so that the coating sheet appears bubbles.
2.1 Analysis of main reasons
The extent and incidence of this coating defect is mainly due to the coating operating conditions, the imbalance between spray and drying. The spraying speed is too fast or the volume of atomized gas is too large. The drying speed is too slow due to the low air inlet volume or low air inlet temperature and the low temperature of the sheet bed. The sheet is not dried layer by layer in time and adhesions or bubbles occur. In addition, due to improper spray Angle or distance, the cone formed by spray is small, and the coating liquid is concentrated in a certain area, resulting in local wet, resulting in adhesion. There is slow speed coating pot, centrifugal force is too small, film rolling is not good will also produce adhesion.
Coating liquid viscosity is too large, is also one of the reasons. Clothing liquid viscosity is large, easy to form larger fog drops, its ability to penetrate into the core is poor, more one-sided aggregation and adhesion, at the same time, the density of the film is poor, more bubbles. But this doesn’t have much effect on transient adhesions.
In addition, improper film type will also appear adhesion. If the flat film in the coating pot rolling is not good, will overlap together, it is easy to cause double or multi-layer film. In our trial production of buflomedil hydrochloride tablets, many overlapping pieces appeared in the common water chestnuts coating pot because of the flat coating.
2.2 Solutions
It is mainly to adjust the spray and drying speed to achieve dynamic balance. Reduce the spray speed, increase the inlet air volume and air temperature, increase the bed temperature and drying speed. Increase the coverage area of spray, reduce the average particle size of spray droplets or adjust the distance between spray gun and sheet bed, so that the incidence of transient adhesion decreases with the adjustment of the distance between spray gun and sheet bed.
Adjust the coating solution prescription, increase the content of solid in the coating solution, reduce the amount of solvent or increase the concentration of ethanol appropriately within the range of viscosity; Anti-adhesive can also be added appropriately, such as talcum powder, magnesium stearate, silica gel powder or oxide peptide. Can properly improve the speed of the coating pot, increase the centrifugal force of the bed.
Choose appropriate sheet coating. However, for flat sheets, such as buflomedil hydrochloride tablets, the coating was successfully carried out later by using an efficient coating pan or by installing a baffle in the ordinary coating pan to promote the rolling of the sheet.
3.One-sided rough and wrinkled skin
In the process of coating, because the coating liquid is not well spread, the dried polymer is not dispersed, irregular deposition or adhesion on the surface of the film, resulting in poor color and uneven surface. Wrinkled skin is a kind of rough surface, is excessive rough visual display.
3.1 Analysis of main reasons
The first is related to the chip core. The larger the initial surface roughness of the core is, the larger the surface roughness of the coated product will be.
Secondly, it has a great relationship with the coating solution prescription. It is generally believed that the molecular weight, concentration and additives of the polymer in the coating solution are related to the surface roughness of the film coating. They act by affecting the viscosity of the coating solution, and the roughness of the film coating is almost linear with the viscosity of the coating solution, increasing with the increase of the viscosity. Too much solid content in coating solution can easily cause one-sided coarsening.
Finally, it is related to the coating operation. The atomization speed is too low or too high (the atomization effect is not good), which is not enough to spread the fog droplets and form a one-sided wrinkled skin. And excessive volume of dry air (exhaust air is too large) or too high temperature, fast evaporation, especially the air flow is too large, produce eddy current, also make the droplet spread is not good.
3.2 Solutions
The first is to improve the quality of the core. On the premise of ensuring the quality of the core, adjust the coating solution prescription and reduce the viscosity (concentration) or solid content of the coating solution. Alcohol-soluble or alcohol-2-water coating solution can be selected. Then adjust the operating conditions, appropriately improve the speed of the coating pot, make the film roll evenly, increase the friction, promote the spread of the coating liquid. If the bed temperature is high, reduce the intake air volume and intake air temperature. If there are spray reasons, atomization pressure should be increased to speed up the spray speed, and the atomization degree and spray volume should be improved to make the fog drops spread forcibly on the surface of the sheet, so as to form fog drops with smaller average diameter and prevent the occurrence of large fog drops, especially for coating liquid with large viscosity. The distance between the spray gun and the sheet bed can also be adjusted. The spray gun with small nozzle diameter (015 mm ~ 1.2 mm) and high flow rate of atomizing gas is selected. The spray shape is adjusted to a wide range of flat cone Angle fog flow, so that the droplets are dispersed in a larger central area.
4.Identify bridge
4.1 Analysis of main reasons
This occurs when the surface of the film is marked or marked. Because clothing membrane owe reasonable mechanical parameters, such as high elasticity coefficient, film strength is poor, poor adhesion, etc., in the process of garment membrane drying produce high pull back, from clothing membrane surface imprinting, membrane retraction and bridging occur, make one-sided notch disappeared or logo is not clear, the reasons for this phenomenon lies in the coating fluid prescription.
4.2 Solution
Adjust the prescription of coating solution. Use low molecular weight polymers or high adhesion film forming materials; Increase the amount of solvent, reduce the viscosity of coating solution; Increase the amount of plasticizer, reduce internal stress. Different plasticizer effect is different, polyethylene glycol 200 is better than propylene glycol, glycerin. Can also reduce the spray speed. Increase the air inlet temperature, increase the temperature of the sheet bed, so that the formed coating is strong, but to prevent edge cracking. In addition, in the design of marked die, we should pay attention to the width of the cutting Angle and other fine points, as far as possible to prevent the occurrence of bridge phenomenon.
5.Clothing membrane chromatism
5.1 Analysis of main reasons
In many coating solutions there are pigments or dyes which are suspended in the coating solution and due to improper coating operation, the color distribution is not uniform and color difference is produced between slices or in different parts of slices. The main reason is that the speed of the coating pot is too slow or the mixing efficiency is poor, and the uniform coating effect can not be achieved between the pieces in the normal coating time; The concentration of pigment or dye in the colored coating liquid is too high or the solid content is too high, or the spraying speed of the coating liquid is too fast, the bed temperature is too high, so that the colored coating liquid is not rolled out in time; Adhesion of the film can also be caused; The shape of the piece is not suitable, such as long piece, capsule shaped piece, because of rolling as round piece, will also cause color difference.
5.2 Solution
Increase the speed of the coating pan or the number of baffle, adjust to the appropriate state, so that the sheet in the pan evenly roll. Reduce the coating liquid spray speed, reduce the bed temperature. In the prescription design of colored coating solution, the dosage or solid content of pigment or dye should be reduced, and the pigment with strong covering should be selected. The pigment or dye should be delicate and the particles should be small. Water insoluble dyes are better than water soluble dyes, water insoluble dyes do not migrate with water as easily as water soluble dyes, and shading, stability and in reducing water vapor, oxidation on the permeability of the film is also better than water soluble dyes. Also choose the appropriate piece type. In the process of film coating, there are often various problems, but no matter what kind of problems, the factors are many, can be solved by improving the quality of the core, adjusting the coating prescription and operation, so as to achieve flexible application and dialectical operation. With the mastery of coating technology, the development and application of new coating machinery and film coating materials, coating technology will be greatly improved, film coating will also get rapid development in the production of solid preparations.
Post time: Jan-13-2022