Coating (pharmacy)
In pharmacy, coating is the coating or encapsulation of solid particles with coating substances. With the help of these coatings, the surface properties of the particles should be changed in a targeted manner, for example to protect them from external influences, to mask taste or smell or for the controlled release of the active ingredient.
function
Solid drug preparations are coated so that they can e.g. B. easier to take and more resistant to moisture and oxygen. Other reasons are greater stability against light or mechanical influences during packaging and shipping. Depending on the dissolving behavior of the coating substances, a certain local or time-delayed release of active ingredient can be achieved, such as. B. gastro-resistant tablets .
Coating substances
The substances used for the coating are liquids such as solutions, suspensions or melts .
Procedure
There are essentially two methods available for coating pharmaceutical dosage forms: on the one hand drum coating and on the other hand fluidized bed coating.
Drum coating is a process that is mainly used to coat large, non-fluidizable particles such as tablets and capsules. The drum coating is also suitable for coating pellets .
Drum coating
There are partially perforated and fully perforated drums. The devices differ among other things in the type of air flow, which is carried out either according to the cocurrent or countercurrent process. With the direct current method, the supply air comes from above, the exhaust air is discharged through the product bed downwards. In the countercurrent process, the supply air comes from below through the product bed, the exhaust air goes upwards.
The cocurrent process is predominantly used for pharmaceutical purposes, with the countercurrent process being used more in the food industry.
With the co-current method, the spray liquid and drying air flow in the same direction. This may lead to spray drying effects in the area of the spray nozzle.
In the countercurrent process, the spray liquid and drying air flow in the opposite direction; this can lead to turbulence in the area of the spray cone.
With the drum coater, the particles are kept in motion by the rotating drum rotating around its longitudinal axis. This contains so-called harassment, which is responsible for the wilting of the tablet bed. The wilting of the filling material ensures, among other things, a more homogeneous coating of the particles.
Fluidized bed coating
Fluid bed processes can be used for film coating. In this process, the material to be coated is held in suspension by a stream of air. While the particles are in motion all the time, they are sprayed with a film-forming liquid, evenly wetted and dried.
As a film former predominantly water-insoluble macromolecular compounds such as natural are polymers (. E.g. shellac ), semi-synthetic polymers (eg. Cellulose - derivatives ), as well as synthetic polymers (eg. Polymethacrylates ) used. They are used as organic or aqueous solutions or suspensions. The aqueous preparations are preferred, although the resulting film is more uneven. The reason for this is the properties of organic solvents that are harmful to the environment and health. When using organic solvents, a solvent recovery system must be connected.
The solvent contained is evaporated and only the solid dissolved or dispersed therein remains as a film. Coated particles of uniform shape and size result.
In addition to film coating, the fluidized bed system is also suitable for drying, granulating or pelleting.
During the drying process, liquid is removed from the goods during the flight phase. The drying takes place in a gentle way.
Another area of application is the build-up wet granulation. The granulate build-up takes place in two steps: First, there is a build-up of particles, a liquid containing solids is deposited on the powder particles in the process and the grain size increases. In the next step, particle accumulation, the existing particles accumulate on each other and become larger as a result.
Depending on the choice of granulating liquid used, a distinction is made between adhesive granules and crust granules. For example, 2-5% gelatin solutions, 1-6% cellulose derivative solutions or even 3% PVP solutions can be used to produce adhesive granules. The particles are bound by the formation of adhesive bridges. The granulating liquid is then removed by the drying process down to the solid content of the adhesive.
In the production of crust granules, for example, ethanol or ethanol-water mixtures can be used. The prerequisite for this is that part of the substance to be granulated dissolves in the granulating liquid. The powder particles accumulate through the formation of crystal bridges. The granulating liquid is then also evaporated here.
Due to the stability and strength of the adhesive bridges, adhesive granules can be easily produced in a fluidized bed. Crust granules, on the other hand, are unstable and can break in the fluidized bed.
Another option for using fluidized bed technology is pelleting.
When pelleting, powder is mixed and moistened with a solvent or binder. Agglomerates are formed, which round out to form uniform and dense pellets.
The fluidized bed coating can be divided into top spray, bottom spray and tangential spray coating, depending on the position of the nozzles in the drum.
Top spray coating
This process is preferred in the food industry and the fine chemical industry. The coating serves in particular to improve the storage stability.
The relaxation zone with the nozzles is located above the product container. The liquid is sprayed onto the particles from above. Compressed air is used to atomize the liquid jet. Since this method is sprayed against the direction of air flow, part of the sprayed solution is dried by the air flow before a film is formed. The distance between the nozzles and the particles is different for each particle, which results in slightly porous film structures, which is not a problem for the application area mentioned.
Bottom spray coating
With this coating technique, the product to be coated is sprayed from below.
Tangential spray
The particles are moved evenly by a rotor disk. Air flows through the inflow base into the vortex chamber and the particles are set in motion. These are sprayed from the nozzles protruding from the side of the product container.
Wurster process
The Wurster method is a Glatt-specific method that was developed by Dale E. Wurster (1918-2007) in 1952.
It describes a coating process that is used in the context of fluidized bed coating. The bottom spray method can be used as a variation of the Wurster method.
Here the spray liquid is sprayed from the bottom up. The spray nozzles are integrated in the base plate (inflow base) and thus completely surrounded by the particles to be coated.
The process is suitable for coating very small particles, micropellets and mini-tablets. An advantage of the method is that one can achieve a uniform coating, i.e. This means that even with particles that are not spherical, the coating can produce a uniform layer thickness. This can be done by spray coating with an active ingredient-containing solution or suspension. Another advantage is that this method can be used to achieve a targeted change in the release profile of the active ingredient from the coated tablets or pellets.
The basis of the coating by the Wurster process is a circulating fluidized bed. This fluidized bed is generated by using a cylinder with a riser pipe and a base plate that contains drill tubes of different sizes. This results in a controlled movement of the particles and thus also a homogeneous amount of the coating applied to the tablets / pellets. The coating liquid is injected into the ascending particle stream and the coating is slowly built up through frequent and repeated thin application of the liquid droplets.
The Wurster riser pipe is designed in such a way that areas with different air flow rates are obtained, i.e. H. Areas with more and less air flow. The areas below the riser pipe have larger boreholes and thus enable a stronger air flow. The particles contained therein are accelerated upwards and wetted by the spray liquid. As they continue to rise in the riser pipe, they are dried and discharged at the upper edge.
construction
The center of the fluidized bed is the Wurster riser, a cylindrical insert that serves as a partition to the outer space. This insert has a gap above the inflow base at the lower end. The air flow is higher in the inner cylinder than in the outer one.
In the inner cylinder, the particles in the inflow base are coated by the spray nozzle. The particles are accelerated up to a certain height during the spraying process. The drying process then takes place in the upper part of the Wurster riser pipe. Here they fall back into the outer space and again enter the interior of the cylinder through the gap at the bottom of the inner parting line. This process is repeated until the desired layer thickness of the coating is achieved. The uniformity of the coating depends on the cycle time and the number of times the particles pass. The circulation depends on the particle properties, the process parameters and the coating system. The process parameters that influence the circulation of the particles include the flow rate, the parting line within the inner ring, the speed of the atomizing air and the configuration of the atomizer.
literature
- Mont Kumpugdee-Vollrath, Jens-Peter Krause (Hrsg.): Easy Coating: Basics and trends in the coating of pharmaceutical products. Vieweg + Teubner Verlag, Wiesbaden 2011, ISBN 978-3-8348-0964-3 .
Individual evidence
- ^ Coating - Glatt Integrated Process Solutions
- ↑ Gerhard Waßmann, M. Kumpugdee-Vollrath et al .: Coatings in the pharmaceutical industry. In: Easy Coating: Basics and trends in coating pharmaceutical products. Vieweg + Teubner Verlag, Wiesbaden 2011, p. 52; ISBN 978-3-8348-0964-3 .
- ↑ Drum Coating - Glatt Integrated Process Solutions
- ↑ Gerhard Waßmann, Mont Kumpugdee-Vollrath, Jens-Peter Krause: Introduction and History of Coatings. In: Easy Coating: Basics and trends in coating pharmaceutical products. Vieweg + Teubner Verlag, Wiesbaden 2011, p. 5; ISBN 978-3-8348-0964-3 .