Tablet coating 322 PHT Nahla Barakat, PhD King Saud University College of Pharmacy 1432/2011 322 PHT 4/19/2017

Coating may also contain active ingredient. 322 PHT Coated tablets are defined as “tablets covered with one or more layers of mixture of various substances such as natural or synthetic resins, gums , inactive and insoluble filler, sugar, plasticizer, polyhydric alcohol ,waxes ,authorized colouring material and sometimes flavoring material . Coating may also contain active ingredient. Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates. 4/19/2017

Aspects of tablet coating 1. Therapy i) Avoid irritation of esophagus and stomach ii) Avoid bad taste iii) Avoid inactivation of drug in the stomach iv) Improve drug effectiveness v) Prolong dosing interval vi) Improve dosing interval vii) Improve patient compliance 322 PHT 4/19/2017

i) Reduce influence of moisture ii) Avoid dust formation 2. Technology i) Reduce influence of moisture ii) Avoid dust formation iii) Reduce influence of atmosphere iv) Improve drug stability v) Prolong shelve life 3. Marketing i) Avoid bad taste ii) Improve product identity iii) Improve appearance and acceptability 322 PHT 4/19/2017

- Shape - Tolerance - Surface area COATING PROCESS KEY FACTORS: TABLET PROPERTIES - Shape - Tolerance - Surface area COATING PROCESS - Equipments - Parameters - Facility and equipment - Automation COATING COMPOSITION - Polymers - Solvents - Plasticizers - Colorants 322 PHT 4/19/2017

Evaluation criteria for pre-formulated coating systems Film strength and flexibility Film adhesion Hiding power/opacity Colour uniformity Gloss Ease of use 322 PHT 4/19/2017

Types of coating processes Three main types are used in the pharmaceutical industry today; - Film coating - Sugar coating - Compression coating 322 PHT 4/19/2017

Coating pan Spray Coater 322 PHT 4/19/2017

Tablet coating machine 322 PHT 4/19/2017

Film Coating Film coating (the most popular today): Film coating is deposition of a thin film of polymer surrounding the tablet core. Conventional pan equipments may be used but now a day’s more sophisticated equipments are employed to have a high degree of automation and coating time. The polymer is solubilized into solvent. Other additives like plasticizers and pigments are added. Resulting solution is sprayed onto a rotated tablet bed. The drying conditions cause removal of the solvent, giving thin deposition of coating material around each tablet core. 322 PHT 4/19/2017

Film Coating: Appearance Dust elimination Taste masking Odour masking Isolation Protection Drug release 322 PHT 4/19/2017

Accela cota is the prototype of perforated cylindrical drum providing high drying air capacity. Fluidized bed coating, very hard tablets (hardness > 20 N) have to be used 322 PHT 4/19/2017

Types of film coating: Immediate release Modified release 322 PHT 4/19/2017

Ideal characters of coating material Solubility in the coating solution Solubility required for intended use- Free water solubility, Slow water solubility, pH- dependent solubility Capacity to produce elegant looking product Stability in presence of water, heat, moisture, air, and substrate being coated and no change in properties with aging. Essentially no color, odor, or taste Compatibility with common coating solution additives Nontoxic and ease of application Resistance to cracking and should act as barrier No bridging or filling of the debossed tablet surfaces by the film former Ease of printing procedure on high-speed equipment Low cost & Ease of application without specialized equipment 322 PHT 4/19/2017

Materials used in film coating Film coating formulation (Composition of the coating liquid) 1- Polymer 2- Plasticizer 3- Colorants 4- Solvent (vehicle): Examples: water, ethanol, methanol, isopropranol, chloroform, acetone, methylethyl ketone, and methylene chloride 322 PHT 4/19/2017

Polymers for film coating Immediate release coating polymers Modified release coating polymers 1- Cellulose derivatives Ex: HPMC Extended release coating polymers Enteric coating polymers It is readily soluble in aqueous media Form film with good mechanical properties (strength, flexibility and adhesion to the tablet core Other examples: MC, HPC They are dissolved in organic solvent or dispersed in aqueous medium Ex: Ethyl cellulose 1- Methacrylic acid copolymers: Eudragit they are insoluble in water at low pH (stomach) but gradually soluble as pH rises towards neutrality (small intestine) 2- vinyl derivatives: PVP, it has a limited use in film coating because of its inherent tackiness. Copolymer of PVP and vinyl acetate forms better films PVPVA copolymer 2- Phthalate esters: e.g. Cellulose acetate phthalate (CAP) 322 PHT 4/19/2017

plasticizer Combination of plasticizer may be used to get desired effect Concentration of Plasticizer Expressed As The amount of polymer being plasticized. Recommended Level of Plasticizer : 1 to 50% by weight of the film former. EXAMPLES : Castor oil; Polyethylene glycol of 200 and 400 series; surfactants eg; Tweens; Spans; organic acid esters. water- soluble plasticizer : PEG, propylene glycol. organic- soluble plasticizer : castor-oil and Spans. 322 PHT 4/19/2017

Used to provide distinctive color and elegance to a dosage form. COLORANTS Colorants may be soluble in the solvent system or suspended as insoluble powders. Used to provide distinctive color and elegance to a dosage form. To achieve proper distribution of suspended colorants in the coating solutions requires the use of fine-powdered colorants (< 10 microns ). Most of colorants are synthetic Dyes or Lakes of Dyes approved by the FD&C and D&C. 322 PHT 4/19/2017

Inorganic materials: iron oxides LAKES : Examples Inorganic materials: iron oxides Natural coloring materials :Anthocyanins, caramel, carotenoids, chlorophyll, indigo, flavones, and carminic acid. Various concentrates promoted as achieving less lot-to-lot color variation Opalux – Opaquant color concentrate for sugar coating. Opaspray- Opaque color concentrate for film coating. Opadry – Complete film coating concentrate 322 PHT 4/19/2017

Examples: Silicates (talc, aluminium silicate); OPAQUANT-EXTENDERS These are very fine inorganic powders used in the coating solution formulation to provide more pastel colors and increase film coverage. Opaquant provides a white coating or mask the color of the tablet core, and thus the less amount of the colorants are required. Examples: Silicates (talc, aluminium silicate); Carbonates (magnesium carbonate); Sulfates (calcium sulfate); Oxides (Mg oxides, titanum oxide) 322 PHT 4/19/2017

ENTERIC COATING The technique involved in enteric coating is protection of the tablet core from disintegration in the acidic environment of the stomach by employing pH sensitive polymer, which swell or solubilize in response to an increase in pH to release the drug. Aims of Enteric protection: To mask taste or odour Protection of active ingredients, from the acidic environment of the stomach. Protection from local irritation of the stomach mucosa. Release of active ingredient in specific target area within gastrointestinal tract. 322 PHT 4/19/2017

Examples of enteric coated OTC products : Enteric coated aspirin E.g. Micropirin® 75mg EC tablets Enteric coated peppermint oil E.g. Colpermin® 322 PHT 4/19/2017

Sugar coating Compressed tablets may be coated with colored or uncolored sugar layer. The coating is water soluble and quickly dissolves after swallowing. The sugarcoat protects the enclosed drug from the environment and provides a barrier to objectionable taste or order. The sugar coat also enhances the appearance of the compressed tablet and permit imprinting manufacturing’s information. Sugar coating provides a combination of insulation, taste masking, smoothing the tablet core, colouring and modified release. The disadvantages of sugar coating are the time and expertise required in the coating process and thus increases size, weight and shipping costs. 322 PHT 4/19/2017

Each coat is applied only after the previous coat is dried. Typically, tablets are sugar coated by panning technique, using traditional rotating sugar-coating pan with a supply of drying air (thermostatically controlled). The pan is automatically rotated, allowing tablets to tumble over each other while making contact with the coating solutions which are gently poured or sprayed, portion wise onto the tablets with warm air blown to hasten drying. Each coat is applied only after the previous coat is dried. 322 PHT 4/19/2017

Composition of sugar coat Seal coating Sub coating Syrup coating Color coating Polishing printing 322 PHT 4/19/2017

Sealing 1- Sealing (Waterproofing) This involved the application of one or more coats of a waterproofing substance in the form of alcoholic spray, such as pharmaceutical Shellac (traditionally) or synthetic polymers, such as CAP. ( Unless a modified-release feature needs to be introduced, the amount of the sealing coat applied should be carefully calculated so that there is no negative effect on the drug release characteristics in case of immediate release product.) (WHY Sealing?) a- Sugar-coatings are aqueous formulations which allow water to penetrate directly into the tablet core and thus potentially affecting product stability and possibly causing premature tablet disintegration. b- Application of many coats of partially or completely water-insoluble polymers in this step, enables sugar-coated product to exhibit modified- release pattern (extended release or delayed "enteric“-release characteristics). 322 PHT 4/19/2017

2- Subcoating Large quantities of sugar-coatings are usually applied to the tablet core (typically increasing the tablet weight by( 50- 100%) WHY? In order to round off the tablet edge. Much of this material build-up occurs during this stage and is achieved by adding a bulking agent such as Calcium carbonate, to the sucrose solution. Antiadherents e.g. Talc may be added after partial drying to prevent sticking of the tablets together. 322 PHT 4/19/2017

3- Smoothing The subcoating stage results in tablets with rough surfaces. To facilitate the color application (which requires smooth surface), subcoated tablets are smoothed out by a thick sucrose syrup coating. 4- Coloring Color coatings usually consist of thin sucrose syrup containing the requisite coloring materials. (water-soluble dyes or water-insoluble pigments may be used) This step must be done into a clean pan deprived of any residues from the previous operations 322 PHT 4/19/2017

5- Polishing After the coloring step, the tablet surfaces tend to be smooth but somewhat dull in appearance. To achieve glossy finish, final stage involving application of waxes (beeswax carnuba wax) is employed. 6- Printing Different tablets could be identified by manufacturer' logo, product name, dosage strength or other appropriate code. For sugar-coated tablets, such identification could be only achieved by printing process using special edible inks 322 PHT 4/19/2017

Example of sugar coated tablets Brufen® POM Available in 200mg and 400mg strength Premarin® POM Conjugated oestrogens 625mcg (maroon) and 1.25mcg (yellow) Colofac ® P Mebeverine hydrochloride 100mg Round, white, sugar coated Kalms ® GSL 45mg Hops powder,90mg Gentian powdered extract, and 135mg Valerian powdered extract 322 PHT 4/19/2017

The constituents of coating solution used for sugar coating Seal coating Sub coating Syrup coating Polishing solution Zein/shellac Gelaatin colorant Carnauba wax Oleic acid Acacia Sub coating powder beeswax Propylene glycol Sugar cane powder Cal. carbonate Paraffin wax PEG 4000 Corn syrup Naphtha Methylene chloride Syrup Corn starch Alcohol Distilled water syrup 322 PHT 4/19/2017

Summary of polymers used as coating solution Trade name Application Shellac EM Coat 120 N Marcoat 125 Enteric coatings Taste/odor masking Cellulose acetate Aquacoat CPD Sepifilm LP Klucel Aquacoat ECD Metolose Taste masking Sustained release coating Sub coat moisture and barrier sealant pellet coating Polyvinylacetate phthalate Sureteric Enteric coating methylacrylate Eudragit Sustained release coatings Moisture protection Rapidly disintegrating films 322 PHT 4/19/2017

TABLE. Comparison between Film coat and Sugar coat Features Film Coating Sugar coating Tablet: Appearance    Weight increase because of coating material   Logo or ‘break lines Retain contour of original core.  Usually not as shiny as sugar coat type 2-3% Possible Rounded with high degree of polish 30-50% Not possible Process Operator training required Adaptability to GMP Process stages Functional coatings Process tends itself to automation and easy training of operator High Usually single stage Easily adaptable for controlled release Considerable Difficulty may arise Multistage process Not usually possible apart from enteric coating

Compression-coating of tablets Although less popular, it gained increased interest in recent years for creating modified-released products involves the compaction of granular materials around preformed tablet core using specially designed tableting equipment. Compression coating is a dry process 322 PHT 4/19/2017

After tablet core manufacture, it is transferred (centrally positioned) to another slightly larger die that is partially filled with the coating powder. More coating powder is filled on the top of the core and compressed again resulting in tablet within tablet. 322 PHT 4/19/2017

Why Compression coating Mostly, the coat is water soluble and disintegrate easily after swallowing, in order to achieve immediate-release product 1- traditionlayy, to separate incompatible materials (one in the core, the other in the coat). There is an interface between the two layers and thus compromize product stability. 2- May be used to create modified relaese products 322 PHT 4/19/2017

SPECIALIZED COATING TECHNIQUICS Dip-coating In this, cores to be coated are a held in a suitable device eg: baskets Dipped into coating solution and then dried taking care to prevent adherence to one another. For obtaining more perfect or heavier coats the dipping and drying steps may be repeated several times one after another. Several dipping arrangements are obtainable, amongst them the sophisticated devices comprise tiny suction tubes, which hold the individual tablets apart until drying is accomplished. Before proceeding to coat additional tablets or begin recoating cycles. 322 PHT 4/19/2017

LAMINATED-COATING Laminated coating provides multiple layers for incorporation of medicament; for example Repeat-action tablet, here a portion of the drug is kept in outer lamella or coating Enteric tablet, here one drug could be made available for gastric absorption while another for release in intestine Buccal-swallow tablet, this could first be administered sublingually, and upon a signal, such as release of flavour from the inner core, the same may be swallowed as a normal peroral tablet. 322 PHT 4/19/2017

Dry coating It avoids the use of water or, at least, allows it to be reduced to very small amounts with respect to the coating material, thus overcoming the need for time- and energy-consuming drying phases, as well as possible drug stability issues. In this technology, powdered coating materials are directly coated onto solid dosage forms without using any solvent, and then heated and cured to form a coat. 322 PHT 4/19/2017

Coating defects Since spraying, coating distribution, and drying take place at the same time, tablet coating is a dynamic, complex process that is affected by many variables. In no particularorder, here are some of the parameters that you should check when evaluating your coating operation to determine the source of defective coated tablets. Many problems occur in coating when you can’t control every important parameter, such as temperature, pan pressure, spray rates, and atomization pressure. 322 PHT 4/19/2017

Picking and sticking. This is when the coating removes a piece of the tablet from the core. It is caused by over-wetting the tablets, by under-drying, or by poor tablet quality. 322 PHT 4/19/2017

Bridging. This occurs when the coating fills in the lettering or logo on the tablet and is typically caused by improper application of the solution, poor design of the tablet embossing, high coating viscosity, high percentage of solids in the solution, or improper atomization pressure. 322 PHT 4/19/2017

Capping. This is when the tablet separates in laminar fashion Capping. This is when the tablet separates in laminar fashion. The problem stems from improper tablet compression, but it may not reveal itself until you start coating. Be careful not to over-dry the tablets in the preheating stage. That can make the tablets brittle and promote capping. 322 PHT 4/19/2017

Twinning. This is the term for two tablets that stick together, and it’s a common problem with capsuleshaped tablets. Assuming you don’t wish to change the tablet shape, you can solve this problem by balancing the pan speed and spray rate. Try reducing the spray rate or increasing the pan speed. 322 PHT 4/19/2017

Mottled color. This can happen when the coating solution is improperly prepared, the actual spray rate differs from the target rate, the tablet cores are cold, or the drying rate is out of spec. 322 PHT 4/19/2017

Orange peel. This refers to a coating texture that resembles the surface of an orange. It is usually the result of high atomization pressure in combination with spray rates that are too high. 322 PHT 4/19/2017

attribute the peeling in this photo to excessive moisture within the tablet, which prevented the coating from adhering. However, the tablet coating also pulled the granulation out of the tablet, a picking defect. That is usually caused by over- wetting the tablet or by a tablet that is 322 PHT 4/19/2017

This photo shows a very porous tablet that prevented the coating from adhering to the surface. These tablets should have been coated longer, and the atomization pressure should have been reduced to decrease the slight orange peel, or textured, surface. 322 PHT 4/19/2017

This photo shows multiple defects. The initial problem was erosion of the tablet edge due to a soft or friable tablet or because the pan was turning too fast or both. Peeling and breakage also appear here. 322 PHT 4/19/2017

These tablets likely broke because they had poor hardness. Just one broken tablet can distribute particles to all the other tablets and mar their appearance. These tablets likely broke because they had poor hardness. 322 PHT 4/19/2017