Tablet Coating Process PDF

Tablet coating Tablet coating Objectives: Taste, odor, or color masking. Physical and chemical protection of the drug. Controlled release. Enteric coating (protect drug from gastric fluids). Sequential r...

Tablet coating Tablet coating Objectives: Taste, odor, or color masking. Physical and chemical protection of the drug. Controlled release. Enteric coating (protect drug from gastric fluids). Sequential release of a second drug incorporated in the coat. Incorporate chemically incompatible second drug in the coat. Improve pharmaceutical elegance and appearance. Tablet coating Tablet properties Coating process Coating compositions Tablet properties Tablets must be resistant to abrasion and strong enough to withstand the coating process without chipping or being broken. The tablets should have smooth surfaces to end up with a coat that is free of imperfections. Tablets should have round surfaces to facilitate proper rolling of the tablets in the coating pan and prevents tablets from sticking together if the surfaces were flat. The coating composition must wet the surface of the tablet to ensure that the coat will adhere. Hydrophobic tablet surface are difficult to coat with aqueous based coatings. Coating process Application of a coating composition to a moving bed of tablets with the concurrent use of heated air to facilitate solvent evaporation. Coating equipment Coating pan Perforated coating pan Fluidized bed (air suspension) Conventional pan system Consists of a circular metal pan mounted angularly on a stand. The pan can be of different sizes (8-60 inch diameter) and is rotated with a motor. Heated air is directed into the pan and onto the tablet bed surface. Heated air is exhausted from the front of the pan. Conventional coating pan Conventional pan system Coating solutions are applied to the tablets by ladling or by spraying onto the rotating tablet bed. Spraying (using atomized systems) can reduce the drying time and produces a more even distribution of the coating liquid on the tablet surfaces. Conventional pan system Improvements include: The immersion sword Drying air is introduced through a perforated metal sword device that is immersed in the tablet bed. The air is more intimately mixed with the wetted tablets and so provides more efficient drying. The immersion tube system A tube that contains a spray nozzle and drying air inlet is immersed into the tablet bed. This combination produces rapid coating time. Standard coating pan Immersion sword system Immersion tube system Perforated pan systems In these systems the drum is perforated or partially perforate, and is enclosed in a housing. In such systems the drying air passes through the powder bed into the perforations to the exhaust. Or the drying air is introduced from the sides of the perforated drum and exhaust from the center of the drum into the back. These systems are widely used in industry. Perforated pan system VPC Hi coater VPC Hi coater fully perforated side-vented  for processes requiring increased air flow Perforated pan system VHC Hi coater integrated plenum side vented  more efficient use of process air. Perforated pan system, driacoater system Perforated pan systems These systems: Efficient drying systems reduce coating time. Have high capacities. Can be completely automated Fluidized bed systems The tablets are fluidized in a columnar chamber with an upward flow of dry air. The air flow is controlled such that more air flows from the center than the sides. This causes the tablets to rise in the center and then fall toward the sides and then reenter the air stream in the center again and so on. Coating liquids are sprayed onto the fluidized tablets from a nozzle located at the bottom or at the upper region of the chamber. Fluidized bed coater Spray application systems A finely divided (atomized) spray of coating liquid can be produced using one of two types of systems: High pressure- airless: Liquid is pumped at high pressure through a small orifice. Degree of atomization is controlled by: Fluid pressure Orifice size Viscosity of liquid Low pressure- air atomized: Liquid is pumped at low pressure through a larger orifice than the airless systems. Air stream contacts the liquid at the tip of the atomizer and a finely divided spray is produced. Atomization can be controlled by: Fluid pressure Fluid cap orifice Viscosity of liquid Air pressure Air cap design High pressure, airless nozzle Low pressure, air atomized nozzle Spray application systems Both types of nozzles can be used effectively. The choice usually depends on the process development of a particular product and the coating solution formula: Solids in a suspension coating liquid should be milled fine to prevent clogging of the airless type which has a smaller orifice. Coating Parameters During the coating process, the tablets are subjected to the coating liquid which is usually sprayed onto them. When the tablets are away from the spray nozzle the coating liquid can be transferred between tablets or onto the surface of the equipment. Most of the time the tablets are in a drying mode away from the spray nozzle but are repeatedly subjected to the spray nozzle. The coating application and heated air flow can be: Continuous or intermittent Coating Parameters Continuous coating application and heated airflow: The rate of application of the coating liquid equals the rate of evaporation of the volatile solvent. Deviation from this equilibrium can result in serious coating problems. Continuous operations sets the basis for automated coating systems. Mathematical models can be applied.  Coating Parameters Continuous coating application and heated airflow, the balancing act between drying and coat application depends on: Inlet and outlet air temperature and humidity (for aqueous coating liquids). Outlet air temperature is usually less and more humid. Coating liquid composition: Coating liquid viscosity Coating liquid drying rate (aqueous based or organic solvent based) Tablet surface area: Tablets of larger size of the same weight of a smaller size ones requires less coating materials. Equipment efficiency: It is the value obtained by dividing the net increase in coated tablet weight by the total non-volatile coating weight applied to the tablets. 90% to 95 % of the applied film coating should be on the tablet for a perforated pan method. Little coating material accumulates on the pan wall. Low efficiency can result from low application rates of the coating liquid which leads to drying of the liquid before reaching the tablet surfaces and be exhausted as dust. 60% of the applied sugar should be on the tablet for a perforated pan Automated coating systems The system contains a series of sensors and regulating devices for: Temperature Airflow Spraying rate Pan speed All of these are controlled with a computer program. Automated coating system Tablet coating process Sugar coating Film coating Sugar coating In the pan-ladling method, the coating liquids are poured on the tablet cores. The operator determines: Quantity of solution to add Rate of pouring When to apply drying air Duration and speed of tumbling in the pan Newer techniques utilize spray systems and automation to improve coating efficiency and product uniformity. A successful sugar coating process yields elegant highly glossed tablets. Sugar coating The process steps include: Sealing Subcoating Syruping (smoothing) Finishing polishing Seal coating To prevent moisture penetration into the tablet core. This is especially needed in pan-ladling processes. Without a seal coat the tablets could become overwetted and absorb excess moisture which makes them soft or they could disintegrate. Shellac is an effective sealant but it could retard tablet disintegration upon aging because of shellac polymerization. Zein is an alcohol soluble protein derivative from corn That is also used as an effective sealant without retarding disintegration. Shellac and zein Shellac: a natural polymer (obtained from the secretion of an insect – coccus lacca). Zein: a protein type that is found in maize (corn). Subcoating It is applied to round the edges and build up the tablet size. It consists of applying a sticky binder solution followed by dusting of subcoating powder (insoluble) and drying. This is repeated until the desired thickness is achieved. For spray processes the subcoating suspension containing both the binder and the insoluble powder is sprayed intermittently with control over drying rates. Syrup coating To cover and fill the imperfections on the tablet surface caused by the subcoating step and to impart color to the tablet. Syrup solutions containing a dye are applied until the final color and size are achieved. Finishing Application of the syrup solution without colorants. This gives depth to the color and enhance elegance of the coat. Polishing Polishing can be achieved by applying powdered wax (beeswax) or warm solution of wax in a volatile solvent. Film coating Film coating and sugar coating are processed on the same equipment and share the same process parameters. Film coating can be achieved by: Pan-pour methods Pan-spray methods Fluidized bed methods Film coating, pan-pour methods This is an old technique which takes long and time and produces high degree of variability. The method is relatively slow and relies on the skill of the operator. The coating liquid is poured onto the tablets in the moving pan and dried. This repeated until the desired coat thickness is achieved. Aquous based coating liquids are not suitable for this method because of the localized over wetting which could lead to surface erosion of the tablets or product instability. Film coating, pan-spray methods Spray nozzles provide a continuous band across the tablet bed surface. A number of nozzles (1 to 5) is (are) chosen such that the entire width of the tablet bed is covered. Film coating, pan-spray methods Process variables: Pan variables: Pan design/baffling Speed Load Process air: Air quality (filtered, degree of humidity) Temperature Flow rate Spray variables: Spray rate Degree of atomization (droplet size in the spray) Spray pattern Nozzle to bed distance  Fluidized bed methods The coating liquid formulations are similar to those used in for pan processes. Fluidized bed methods The coating solution formulations are similar to those used in for pan processes. Process variables include: Chamber design Air flow volume, rate, and temperature Too high airflow can lead to breakage of tablets Too low air flow rate can lead to the tablets not become appropriately fluidized and they move slowly through the spray region which could lead to overwetting. Tablet shape, size, and density Quantity of load  Development of film coating formulations The choice of formulation depends on: Purpose of coating: Taste masking Color masking Odor masking Control drug release Physical protection (seal coating for water unstable drug) Film strength/ flexibility: The strength of the formulated film can be tested for its strength and flexibility (elasticity) by testing strips of films on a tester that applies a known force at a constant rate until the film breaks. Addition of plasticizers to the formulation increases the flexibility of a film that is brittle. Tablet size, shape, and color (tablet appearance) Products of the same company should be of different appearance by varying size, shape and color this can be Coated tablet evaluations Evaluation tests for the quality of the coating include: Adhesion test: The force required to peel the coat from the tablet surface. Crushing strength: The additional strength of the tablet as a result of the coat is indicative of its quality. Coated tablet disintegration and dissolution. Temperature and humidity effects on the quality of the coat. Visual inspection of the coated tablet for surface roughness, and color uniformity. Materials used in film coating An ideal material should: Soluble in the coating solvent. Serve its purpose: rapid dissolution or enteric coating…etc Produce elegant looking product Stable in heat, light, moisture, and in contact with the coated substrate. Have properties that does not change with time. Have no color, taste, or odor. Compatible with other coating additives. Non-toxic and have no pharmacologic activity. Be resistant to cracking Provide a coated surface that can be printed on. Materials used in film coating Film formers Solvents Plasticizers Colorants Opaquants Others Flavors Sweeteners Antioxidants Antimicrobials: prevent microbe growth during the preparation and storage of the coating liquid. Surfactants: solubilize insoluble ingredients Film formers Film formers are usually polymers that form a continuous film with a wide range of properties depending upon other additives included in the coating liquid. In sugar coating there is physical deposition of the coating material on the tablet surface Film formers can be non enteric or enteric. Non-enteric film formers The coating of such material provide rapid disintegration and dissolution. These materials should have some solubility in the GIT fluid or soluble additives should be combined with them. examples: Hydroxypropyl methylcellulose Ethylcellulose, water insoluble can be combined with Hydroxypropyl methylcellulose Hydroxypropylcellulose Povidone Sodium carboxymethyl cellulose Polyethylene glycol 8000 Enteric film formers Reasons for enteric coating: Protect acid-labile drugs from gastric fluids, e.g. eryhtromycin. Prevent gastric distress due to irritation from the drug, e.g. NSAID Local action drugs in the intestines. Delayed release action. Enteric film formers An ideal material should: Be acid resistant. Release the drug in the small intestine. (dissolve or becomes permeable to intestinal fluid). Have previously mentioned properties of film forming materials. Enteric film formers According to USP: The enteric coated tablet should tolerate (remain intact with no crack or softening) agitation in simulated gastric fluid solution at 37°C for 1 hour. The tablets should disintegrate within 2 hours if transferred to a simulated intestinal fluid at 37°C and agitated. Enteric film formers Examples: Cellulose acetate phthalate: Dissolve only at pH above 6 this could delay absorption of drugs. Permeable to gastric fluid. Susceptible to hydrolysis which could lead to film property change with time. Usually mixed with hydrophobic film formers to to improve enteric properties. Acrylate polymers: Eudragit L and S, insoluble in gastric fluid and soluble in intestinal fluid (pH above 6). Hyddroxypropyl methylcellulose phthalate: Dissolve at pH above 5 Solvents Its function is to dissolve or disperse polymers and other additives and to convey them to the surface of the tablet. An ideal solvent should: Dissolve or disperse the polymer and the additives. The viscosity after dissolving or dispersing the coating materials should remain low