1. Prepared by: Sabrina Rahman Archie

2.  Coating is a process by which an essentially dry, outer layer of coating material is applied to the surface of a dosage form in order to confer specific benefits that broadly range from facilitating product identification to modifying drug release from the dosage form.

3. 1. Providing a means of protecting the drug substances from the environment, particularly from the light and moisture, and thus potentially improving product stability. 2. Masking the bitter or unpleasant taste of drug substance. 3. Improving the ease of swallowing large dosage forms, especially tablets. 4. Masking any batch differences in the appearance of raw materials.

4. 5. Providing a means of improving product appearance. 6. Aiding in brand identification. 7. Facilitating the rapid identification of product by the manufacturer, the dispensing pharmacist and the patient( color and efficient labelling). 8. Enabling the coated product to be more easily handled on high speed automatic filling and packaging equipment by improving product flow, mechanical strength and reducing the risk of cross-contamination by minimizing dusting problems.

5. 9. Imparting modified release characteristics that allow the drug to be delivered in a more effective manner.

6.  Tablets must be resistant to abrasion and chipping.  Tablets should have smooth surface for proper coating.  The tablets must be in constant motion during the early drying phase to prevent tablet agglomeration.  The spherical shape of tablet is preferable for coating process. This will allow the tablets to roll freely in the coating pan with minimal tablet-to-tablet contact.

7. Tablet coating Sugar coating Film coating Compression coating

8. Reference: Aulton’s pharmaceutics (3 rd edition)

9.  Most popular technique and virtually all new coated products introduced to the market are film coated.  Involves the deposition, usually by a spraying method of a thin film of polymer formulation surrounding a tablet.

10.  Most contemporary and thus commonly used process for coating oral solid dosage forms.  It involves the deposition of a thin film of a polymer formulation to the surface of a tablet, capsule or multiparticulate core.  Now all newly launched coated products are film coated rather than sugar coated.

11. 1. Solubility in solvent of choice for coating preparation. 2. Solubility required for the intended use eg, pH- dependent solubility (enteric coating) 3. Capacity to produce an elegant looking product 4. Stability in the presence of heat, light, moisture, air, and the substrate being coated. The film properties should not change with aging. 5. Essentially no color, taste, or odor. 6. Compatibility with common coating solution additives.

12. 7. Nontoxicity with no pharmacological activity, and ease of application to the particles or tablets. 8. Resistance to cracking, and provision of adequate moisture, light, odor, or drug sublimation barrier when desired. 9. No bridging or filling of the debossed tablet surfaces by the film former. 10. Ease of printing procedure on high-speed equipment.

13. Types Immediate release film coatings Modified release film coatings

14.  Immediate release film coatings:  Also known as non-functional coatings.  It is used to imply that the coating has no effect on biopharmaceutical properties but a coating, as explained, has many other properties and functions.  Modified release film coatings:  also knows as functional coatings, which may be further categorized as either delayed release (or enteric) or extended release coatings.

15.  Immediate release coatings are usually readily soluble in water, while  enteric coatings are only soluble in water at pH values in excess of 5-6 and are intended to either  Protect the drug while the dosage form is in stomach ( in the case of acid labile drug) or  Prevent release of the drug in the stomach (in the case of the drugs that are gastric irritants)

16.  Currently, the majority of film-coating processes involves the application of a coating liquid where a significant proportion of a major component (the solvent/vehicle) is removed by means of a drying process that is concurrent with the application of that coating liquid.  Film-coating formulations typically contain: 1. Polymer 2. Plasticizer 3. Colourants 4. Solvent/vehicle (aqueous/ non-aqueous)

17. Film coating solution Aqueous solution Non-aqueous solution

18. Contain the following types of materials:  A film former capable of producing smooth, thin films reproducible under conventional coating conditions and applicable to a variety of tablet shapes. Example: cellulose acetate phthalate.  An alloying substance providing water solubility or permeability to the fi lm to ensure penetration by body fluids and therapeutic availability of the drug. Example: polyethylene glycol.

19.  A plasticizer to produce flexibility and elasticity of the coating and thus provide durability. Example: castor oil.  A surfactant to enhance spreadability of the film during application. Example: polyoxyethylene sorbitan derivatives.

20.  Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive. Examples: Opaquant, titanium dioxide; colorant, FD&C or D&C dyes.  Sweeteners, flavors, and aromas to enhance the acceptability of the tablet by the patient. Examples: sweeteners, saccharin; flavors and aromas, vanillin.

21.  A glossant to provide luster to the tablets without a separate polishing operation. Example: beeswax.  A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation. Example: alcohol mixed with acetone.

22.  Tablets are film coated by application or spraying of the coating solution on the tablets in ordinary coating pans.  The volatility of the solvent enables the film to adhere quickly to the surface of the tablets.

23.  Because of both the expense of the volatile solvents used in the film-coating process and the environmental problem of the release of solvents, pharmaceutical manufacturers generally favor the use of aqueous solutions.  One of the problems attendant to these, however, is slow evaporation of the water base compared to the volatile organic solvent–based solutions.

24.  One commercial water-based colloidal coating dispersion called Aquacoat (FMC Corporation) contains a 30% ethyl cellulose pseudolatex.  Pseudolatex dispersions have a high solids content for greater coating ability and a relatively low viscosity.  The low viscosity allows less water to be used in the coating dispersion, requiring less evaporation and reducing the likelihood that water will interfere with tablet formulation.  In addition, the low viscosity permits greater coat penetration into the crevices of monogrammed or scored tablets.

25.  A plasticizer may be added to assist in the production of a dense, relatively impermeable film with high gloss and mechanical strength.  Other aqueous film- coating products use cellulosic materials such as methylcellulose, hydroxypropyl cellulose, and hydroxypropyl methylcellulose as the film-forming polymer.

26. 1. Film-forming polymer (7% to 18%). Examples: cellulose ether polymers such as hydroxypropyl methylcellulose, hydroxypropyl cellulose, and methylcellulose. 2. Plasticizer (0.5% to 2.0%). Examples: glycerin, propylene glycol, polyethylene glycol, diethyl phthalate, and dibutyl subacetate. 3. Colorant and opacifier (2.5% to 8%). Examples: FD&C or D&C lakes and iron oxide pigments. 4. Vehicle (water, to make 100%).

27.  the appearance of small amounts (picking) or  larger amounts (peeling) of film fragments flaking from the tablet surface,  roughness of the tablet surface due to failure of spray droplets to coalesce (orange peel effect),  An uneven distribution of color on the tablet surface (mottling),  filling-in of the score line or indented logo on the tablet by the fi lm (bridging), and  Disfiguration of the core tablet when subjected for too long to the coating solution (tablet erosion).

28.  Solubility: is important for 2 reasons  Determines the behavior of the coated product in the GIT( the rate at which the drug will be released, and whether there will be any in the onset of drug release)  Determines the solubility of the coating in a chosen solvent system (a factor that can have great influence on functional properties of the final coating)

29.  For conventional film coating the polymer should have good solubility in aqueous fluids to facilitate the dissolution of the active ingredient from the finished dosage form. However, where a modified-release action is required then a polymer system of low water solubility or permeability will be chosen.

30.  Viscosity:  In general, polymers should have a low viscosity for a given concentration.  This will permit the easy, trouble-free spraying of their solutions in industrial film coating equipment.

31.  Permeability:  It is of significant importance when the film coating is intended to:  Mask the unpleasant taste of the API in the dosage form.  Improve stability of the dosage form by limiting exposure to atmospheric vapours and gases (water vapour and oxygen)  Modify the rate at which the API will be released from the dosage form.  These properties vary widely between the individual polymers.

32.  Mechanical properties:  The particular polymer chosen for a film coat formulation must be one with adequate strength to withstand the impact and abrasion encountered in normal handling.  Insufficient coating strength will be demonstrated by the development of cracks and other imperfections in the coating.

33.  Film strength which greatly affects the ability of the coating to resist the mechanical stresses to which it will be exposed during the coating process.  Film flexibility, which imparts similar benefits to film strength and minimizes film cracking during handling and subsequent storage.  Film adhesion which is necessary to ensure that the coating remains adherent to the surface of the dosage form right up to the point of being consumed by the patient.

34. Immediate release coatings Cellulose derivatives (HPMC) Vinyl derivatives (PVP) Aminoalkyl methacrylate copolymers Modified release coatings Cellulose derivatives (EC, CA) Methylmetha crylate copolymers Methacrylic acid copolymers Phthalate esters (HPMCP, CAP, PVAP)

35.  Added to modify physical properties of the polymer.  This is necessary because most acceptable film-coating polymers are brittle in nature.  It is generally accepted that the mechanisms by which plasticizers exert their effect is for plasticizer molecules to interpose themselves between the polymer molecules, thus increasing free volume and facilitating increased polymer chain motion within the structure of the coating.

36.  The positive benefit of this interaction include:  Increased film flexibility  Reduced residual stresses within the coating as it shrinks around the core during drying.  Example:  Polyols (PEG, PG)  Organic ester( diethyl phthalate, triethyl citrate)  Oils/glycerides, (fractionated coconut oil)

37.  Pharmaceutically accepted colorants are available in both water-soluble form (known as dyes) and water insoluble form (known as pigments)  The insoluble form is preferred in film coating formulations, based on the fact that pigments tend to be more chemically stable towards light, provide better opacity and covering power and provide a means of optimizing the permeability properties of the applied film coating.

38.  Water insoluble pigments will not suffer from mottling that can be observed with water soluble dyes.  Example:  Iron oxide pigments  Titanium dioxide  Aluminum lakes(a pigment formed by bonding water soluble colorants to approved fine alumina hydrate particles.

39.  Film coating processes are very much dependent on the use of organic solvents (methanol/dichloromethane combinations or acetone) in order to achieve the rapid drying characteristics demanded by the process.  Organic solvents possesses many disadvantages that are related to the following factors:  Environmental issues (solvent vapor)  Safety issues (flammable)  Financial issues (explosion-proof processing area and storage area, raw materials)  Solvent residue issues (quantify and limit the residual levels)

40.  The defects that are commonly attributed to film coating are usually:  Visual defects (usually seen with film coated tablets)  Defects that affect functional properties (those influencing drug release, associated with modified release product)

41.  Visual defects can be categorized as those relating to:  Processing issues- these are typically associated with an imbalance between the rate of delivery of coating liquid and the rate of evaporation during the drying process. This imbalance results in either over-wetting ( where tablets or multiparticulates might become stuck together) or over drying.

42.  Formulation issues- these are usually associated with some deficiency in the core or the coating. Core formulation issues often result in mechanical defects so that the core is not able to withstand the attritional effects of the coating process, leading to tablet breakage or erosion. Coating formulation issues often result in inadequate film mechanical strength leading to Film cracking and chipping Inadequate film adhesion leading to film peeling and logo bridging.

43.  Adequate means of atomizing the spray liquid for application to the tablet cores.  Adequate mixing and agitation of the tablet bed.  Sufficient heat input in the form of drying air to provide the latent heat of evaporation of the solvent. This is particularly important with aqueous based spraying.  Good exhaust facilities to remove dust and solvent-laden air.

44.  Should display an even coverage of film and color.  Should be no abrasion of tablet edges or crowns.  Logos and break lines should be distinct and not filled in.  The tablet must also be compliant with finished product specifications and any relevant compendial requirements.

45.  Enteric-coated solid dosage forms are intended to pass through the stomach intact to disintegrate and release their drug content for absorption along the intestines.  The design of an enteric coating may be based on the transit time required for passage to the intestines and may be accomplished through coatings of sufficient thickness.  Usually an enteric coating is based on factors of pH, resisting dissolution in the highly acid environment of the stomach but yielding to the less acid environment of the intestine.

46.  The coating system may be aqueous or organic solvent based and effective so long as the coating material resists breakdown in the gastric fluid.  Among the materials used in enteric coatings are pharmaceutical shellac, Hydroxypropyl methylcellulose phthalate, Polyvinyl acetate phthalate, Diethyl phthalate, and cellulose acetate phthalate.

47.  Fluid bed coating, which uses equipment of the type shown in Figure, is spray coating of powders, granules, beads, pellets, or tablets held in suspension by a column of air.  Fluid bed processing equipment is multifunctional and may also be used in preparing tablet granulations.

49.  In the Wurster process, named after its developer, the items to be coated are fed into a vertical cylinder and are supported by a column of air that enters from the bottom of the cylinder.  Within the air stream, the solids rotate both vertically and horizontally.  As the coating solution enters the system from the bottom, it is rapidly applied to the suspended, rotating solids, with rounding coats being applied in less than an hour with the assistance of warm air blasts released in the chamber.

50.  In another type of fluid bed system, the coating solution is sprayed downward onto the particles to be coated as they are suspended by air from below.  This method is commonly referred to as the top-spray method.  This method provides greater capacity, up to 1,500 kg, than the other air suspension coating methods.

51.  A third method, the tangential-spray technique, is used in rotary fluid bed coaters.  The bottomspray, top-spray, and tangential- spray methods are depicted in following Figure.

53.  The three systems are increasingly used for application of aqueous or organic solvent– based polymer film coatings.  The top-spray coating method is particularly recommended for taste masking, enteric release, and barrier films on particles or tablets.  It is most effective when coatings are applied from aqueous solutions, latexes, or hot melts.

54.  The bottom-spray method is recommended for sustained-release and enteric-release products;  The tangential method is used for layering coatings and for sustained-release and enteric-coated products.

55.  Among the variables requiring control to produce the desired and consistent quality are equipment and the method of spraying (e.g., top, bottom, tangential), spray nozzle distance from spraying bed, droplet size, spray rate, spray pressure, volume of the air column, batch size, method and time for drying, and air temperature and moisture content in the processing compartment.

56.  More traditional process closely resembling that used for coating confectionery products.  It has been used in the pharmaceutical industry since the late 19 th century.  Involves the successive application of sucrose based coating formulations, usually to tablet cores, in suitable coating equipment.  The water evaporates from the syrup, leaving a thick sugar layer around each tablet.  Sugar coats are shiny and highly colored.

57.  The sugarcoating of tablets may be divided into the following steps: (a) waterproofing and sealing if needed, (b) subcoating, (c) Smoothing and final rounding, (d) finishing and coloring if desired, and (e) polishing.

58.  The entire coating process is conducted in a series of mechanically operated acorn- shaped coating pans of galvanized iron, stainless steel, or copper.

59.  For tablets containing components that may be adversely affected by moisture, one or more coats of a waterproofing substance, such as pharmaceutical shellac or a polymer, are applied to the compressed tablets before the subcoating application.  The waterproofing solution (usually alcoholic) is gently poured or sprayed on the compressed tablets rotating in the coating pans.  Warm air is blown into the pan during the coating to hasten the drying and to prevent tablets from sticking together.

60.  After the tablets are waterproofed if needed, three to five subcoats of a sugar-based syrup are applied.  This bonds the sugar coating to the tablet and provides rounding.  The sucrose and water syrup also contains gelatin, acacia, or PVP to enhance coating.  When the tablets are partially dry, they are sprinkled with a dusting powder, usually a mixture of powdered sugar and starch but sometimes talc, acacia, or precipitated chalk as well.  Warm air is applied to the rolling tablets, and when they are dry, the process is repeated until the tablets are of the desired shape and size (next Fig. )

62.  The subcoated tablets are then scooped out of the coating pan and the excess powder is removed by gently shaking the tablets on a cloth screen.

63.  After the tablets are subcoated, 5 to 10 additional coatings of a thick syrup are applied to complete the rounding and smooth the coatings.  This syrup is sucrose based, with or without additional components such as starch and calcium carbonate.  As the syrup is applied, the operator moves his or her hand through the rolling tablets to distribute the syrup and to prevent the tablets from sticking to one another.  A dusting powder is often used between syrup applications.  Warm air is applied to hasten the drying time of each coat.

64.  To attain final smoothness and the appropriate color to the tablets, several coats of a thin syrup containing the desired colorant are applied in the usual manner.  This step is performed in a clean pan, free from previous coating materials.

65.  Solid dosage forms may be passed through a special imprinting machine (Fig. 8.33) to impart identification codes and other distinctive symbols.  By FDA regulation, effective in 1995, all solid dosage forms for human consumption, including both prescription-only and over- the-counter drug products, must be imprinted with product specific identification codes.

66.  Some exemptions to this requirement are allowed: those used in clinical investigations; those that are extemporaneously compounded in the course of pharmacy practice; radiopharmaceutical drug products; and products that, because of their size, shape, texture, or other physical characteristics, make imprinting technologically not feasible.

67.  Technically, the imprint may be debossed, embossed, engraved, or printed on the surface with ink.  Debossed means imprinted with a mark below the surface; embossed means imprinted with a mark raised above the surface; and engraved means imprinted with a code that is cut into the surface during production.

68.  Coated tablets may be polished in several ways.  Special drum-shaped pans or ordinary coating pans lined with canvas or other cloth impregnated with carnauba wax and/or beeswax may be used to polish tablets as they tumble in the pan.  Or, pieces of wax may be placed in a polishing pan and the tablets allowed to tumble over the wax until the desired sheen is attained.

69.  A third method is light spraying of the tablets with wax dissolved in a non-aqueous solvent.  Two or three coats of wax may be applied, depending upon the desired gloss.  After each coat has been applied, the addition of a small amount of talc to the tumbling tablets contributes to their high luster (following Fig) Fig: Coated, polished, and monogrammed tablets.

70.  Technically and practically a difficult process that requires a great deal of skill and experience.  Common sugar coating defects include: Tablets that are rough in appearance Tablets that are smooth but dull in appearance Tablets that have pieces of debris (usually from the broken tablets from the same batch) stuck to the surface Tablets exhibiting poor color uniformity Tablets that split on storage as a result of inadequate drying (causing the tablets to swell).

71.  Less popular process.  Has gained increased interest in recent years as a means of creating specialized modified release products.  Involves the compaction granular material around a preformed tablet core using specially designed tableting equipment.  A dry process.

72.  Tablet cores are first prepared and then mechanically transferred, on the same machine, to another slightly larger die that has partially been filled with the coating powder.  The tablet core is positioned centrally into this partially filled die, more coating powder is filled on top of the core and the whole composite mass undergoes a second compaction event.

73.  Traditionally, it has been used mainly to separate chemically incompatible materials, one or more being placed in the core and the other(s) in the coating layer.  There is still an interface layer (between the two layers) that may potentially compromise product stability.  Thus it is also possible to apply two coating layers where the first coating layer is an inert, placebo formulation that effectively separates the core and the final coating layer, each of which contains a drug substance that is incompatible with the other.

74.  Disadvantages  It is a mechanically complex process that requires careful formulation and processing of the coating layer.  Large or irregularly sized agglomerates of granules will cause the core to tilt in the second die used for compression of the coating. Thus there is the possibility of an uneven or incomplete coating, with the core being visible at the tablet surface.

75.  Compression coatings are generally made from powdered ingredients that either dissolve, or readily disintegrate, in aqueous media and thus have been commonly used for immediate release tablet products.  There has been increased use of compression coatings for the purpose of creating modified release products.

76. Standard (conventional) coating pan Perforated coating pan Fluidized bed (air suspension) coater Immersion Sword System Immersion Tube System Accela-Cota System Pellegrini Pan System Driacoater System Glatt Coater System Hi-Coater Systems Air Suspension System

77.  Ansel’s Pharmaceutical Dosage Forms and Drug Delivery System  Aulton’s Pharmaceutics- The science of Dosage Form