Coating of Tablets.pptx

Coating of Tablets The application of coating to tablets, which is an additional step in the manufacturing process, increases the cost of the product; therefore, the decision to coat a tablet is usually based on one or more of the following objectives: Object...

Coating of Tablets The application of coating to tablets, which is an additional step in the manufacturing process, increases the cost of the product; therefore, the decision to coat a tablet is usually based on one or more of the following objectives: Objectives To mask the taste, odor and color of the drugs To provides physical and chemical protection of drugs To controls the release of the drugs from the tablets To protects the drugs from gastric environment with an acid resistant enteric coating To avoids chemical incompatibilities in case of more than one drugs incorporating in the tablets or to provide sequential drug release To improve the pharmaceutical elegance by use of special colors and contrasting printing  There are three primary components involved in tablet coating: 1. Tablet properties. 2. Coating compositions. 3. Coating process. 4. Coating equipment. Parameters of the coating process. Facility and ancillary equipment. Automation in coating processes. 1. TABLET PROPERTIES Tablets that are to be coated must possess the proper physical characteristics. In the coating process, the tablets roll in a coating pan or cascade in the air stream of an air suspension coater as the coating composition is applied. 1. To tolerate the intense attrition of tablets striking other tablets or walls of the coating equipment, the tablets must be resistant to abrasion and chipping. Tablet surfaces that are brittle, that soften in the presence of heat, or that are affected by the coating composition tend to become rough in the early phase of the coating process and are unacceptable for film coating. 2. The physical shape of the tablet is important. When a coating composition is applied to a batch of tablets in a coating pan, the tablet surfaces become covered with a tacky polymeric film. Before the tablet surface dries, the applied coating changes from a sticky liquid to a tacky semisolid, and eventually to a nontacky dry surface. The ideal tablet shape for coating is a sphere, which allows tablets to roll freely in the coating pan, with minimal tablet-to-tablet contact.  The worst shape is a square flat-faced tablet, in which case coating materials would collect between the surfaces to glue them together, like a stack of dominos or poker chips (Fig. A). For this reason, coated tablets have rounded surfaces (Fig B); the more convex the surface is, the fewer difficulties will be encountered with tablet agglomeration. Fig: (A) Flat-faced tablets; (B) Rounded surface tablets 3. A compressed tablet formulation includes many ingredients besides the active drug to provide a readily compressible, resilient, and rapidly dissolving dosage form. The resulting surface properties of the tablet depend on the chemical nature of the ingredients utilized in the formulation. For the coating to adhere to the tablet, the coating composition must wet the surface. Hydrophobic tablet surfaces are difficult to coat with aqueous-based coatings that do not wet the surface.  2. COATING COMPOSITIONS The coating materials may be a physical deposition of the material on the tablet substrate, or they may form a continuous film with a wide variety of properties depending upon the composition of the coating formulations. An ideal film coating material should have the following attributes: 1. Solubility in solvent of choice for coating preparation. 2. Solubility required for the intended use, e.g. free water-solubility, slow water-solubility, or 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. 7. Nontoxicity with no pharmacologic 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. A. FILM FORMERS a. Nonenteric Materials 1. Hydroxypropyl Methylcellulose (HPMC): The polymer is prepared by reacting alkali- treated cellulose first with methyl chloride to introduce methoxy groups and then with propylene oxide to introduce propylene glycol ether groups. The resulting products are commercially available in different viscosity grades. The reasons for its widespread acceptance include (1) solubility characteristics of the polymer in gastrointestinal fluid, and in organic and aqueous solvent systems, (2) noninterference with tablet disintegration and drug availability, (3) flexibility, chip resistance, and absence of taste or odor, (4) stability in the presence of heat, light, air, or reasonable levels of moisture and (5) ability to incorporate color and other additives into the film without difficulty.  The interaction of this polymer with colorants is rare. Hydroxypropyl methylcellulose closely approaches the desired attributes of an ideal polymer for film coating. When used alone, the polymer has the tendency to bridge or fill the debossed tablet surfaces. A mixture of hydroxypropyl methylcellulose with other polymers or plasticizers is used to eliminate bridging or filling problems. This polymer is also used considerably in glossing solutions. 2. Methyl Hydroxyethylcellulose This polymer is prepared by reacting alkali-treated cellulose first with methyl chloride and then with ethylene oxide. A wide variety of viscosity grades are available. Because of its structural similarity to hydroxypropyl methylcellulose, this polymer is expected to have similar properties It is marketed in Europe, but because it is soluble in fewer organic solvents, it is not used as frequently as hydroxypropyl methylcellulose. 3. Ethylcellulose It is manufactured by the reaction of ethyl chloride or ethyl sulfate with cellulose dissolved in sodium hydroxide. Depending on the degree of ethoxy substitution, different viscosity grades are obtained and available commercially. This material is completely insoluble in water and gastrointestinal fluids, and thus cannot be used alone for tablet coating. It is usually combined with water-soluble additives, e.g. hydroxypropyl methylcellulose, to prepare films with reduced water solubility properties. A combination of ethylcellulose with water-soluble additives has been widely used in preparing sustained-release coatings of fine particles and tablets.  4. Hydroxyproylcellulose This material is manufactured by treatment of cellulose with sodium hydroxide, followed by a reaction with propylene oxide at an elevated temperature and pressure. It is soluble in water below 40°C (insoluble above 45°C), gastrointestinal fluids and many polar organic solvents. This polymer is extremely tacky as it dries from a solution system and may be desirable for a subcoat, but not for a color or gloss coat. The polymer yields very flexible films. It is usually not used alone, but it is used in combination with other polymers to improve the film characteristics. 5. Povidone Povidone is a synthetic polymer consisting of linear l-vinyl-2-pyrrolidinone groups. The degree of polymerization results in materials of various molecular weight range. Povidone is usually available in four viscosity grades identified by their K values, which approximate K-15, K-30, K-60, and K-90. The average molecular weight of these grades are 10,000, 40,000, 160,000, and 360,000 respectively. The most common uses of povidone in pharmaceuticals (frequently K-30) are as a tablet binder and a tablet coating. It has excellent solubility in a wide variety of organic solvents, in water, and in gastric and intestinal fluids. When dry, povidone films are clear, glossy, and hard. 6. Sodium Carboxymethylcellulose This material is sodium salt of carboxymethyl-cellulose and is manufactured by the reaction of soda cellulose with the sodium salt of monochloroacetic acid. It is available in low, medium, high, and extra high viscosity grades. Sodium carboxymethylcellulose is easily dispersed in water to form colloidal solutions, but it is insoluble in most organic solvents, and therefore is not a material of choice for coating solutions based on organic solvents. Films prepared with sodium carbo-xymethylcellulose are brittle, but adhere well to tablets. Partially dried films are tacky, however, so coating compositions must be modified with additives. Conversion to aqueous-based film coating with high coating efficiency equipment probably increases the usefulness of this polymer in coating systems.  7. Polyethylene Glycols Polyethylene glycols (PEG) are manufactured by the reaction of ethylene glycol with ethylene oxide in the presence of sodium hydroxide at elevated temperature and under pressure. The materials with low molecular weights (200 to 600 series) are liquid at room temperature and are used as plasticizers for coating solution films. The materials with high molecular weights (series 900 to 8,000) are white, waxy solids at room temperature. These polymers are used in combination with other polymers to modify film properties. Combinations of polyethylene glycol waxes with cellulose acetate phthalate provide films that are soluble in gastric fluids. Such systems constituted one of the first commercially used nonenteric film coating processes. 8. Acrylate Polymers A series of acrylate polymers is marketed under the trademark Eudragit. Eudragit E is a cationic copolymer based on dimethyl-aminoethyl methacrylate and other neutral methacrylic acid esters, and is the only Eudragit material that is freely soluble in gastric fluid up to pH 5, and expandable and permeable above pH 5. This material is available as (1) organic solution (12.5%) in isopropanol/acetone, (2) solid material, or (3) 30% aqueous dispersion. Eudragit RL and RS are copolymers synthesized from acrylic and methacrylic acid esters with a low content of quaternary ammonium groups. These are available only as organic solutions and solid materials. These polymers produce films for the delayed-action (pH independent) preparations similar to ethylcellulose formulations. b. Enteric Materials Some most important reasons for enteric coating are as follows: 1. To protect acid-labile drugs from the gastric fluid, e.g. enzymes and certain antibiotics. 2. To prevent gastric distress or nausea due to irritation from a drug, e.g. sodium salicylate. 3. To deliver drugs intended for local action in the intestines, e.g. intestinal antiseptics could be delivered to their site of action in a concentrated form and bypass systemic absorption in the stomach. 4. To deliver drugs that are optimally absorbed in the small intestine to their primary absorption site in their most concentrated form. 5. To provide a delayed-release component for repeat-action tablets. An ideal enteric coating material should have the following properties: 1. Resistance to gastric fluids. 2. Ready susceptibility to or permeability to intestinal fluids. 3. Compatibility with most coating solution components and the drug substrates. 4. Stability alone and in coating solutions. The films should not change on aging. 5. Formation of a continuous (uninterrupted) film. 6. Non toxicity. 7. Low cost. 8. Ease of application without specialized equipment. 9. Ability to be readily printed or to allow film to be applied to debossed tablets.  Pharmaceutical formulators have a wide choice of materials for use in developing an enteric coated granule, pellet, or tablet product. These materials range from water-resistant films to pH-sensitive materials. Some are digested or emulsified by intestinal juices, and some slowly swell and fall apart when solvated. Many formulators use a combination of the actions just listed to achieve the desired objective. Most commercially available enteric materials fail to display two or more of the ideal properties of an enteric coating material. 1. Cellulose Acetate Phthalate Cellulose acetate phthalate (CAP) has been widely used in the industry. It has the disadvantage of dissolving only above pH 6, and possibly delaying the absorption of drugs. It is also hygroscopic and relatively permeable to moisture and gastric fluids, in comparison with some other enteric polymers. CAP films are brittle and usually formulated with hydrophobic-film forming materials or adjuvants to achieve a better enteric film. 2. Acrylate Polymers Two forms of commercially available enteric acrylic resins are Eudragit L and Eudragit S. Both resins produce films that are resistant to gastric fluid. Eudragit L and S are soluble in intestinal fluid at pH 6 and 7, respectively. Eudragit L is available as an organic solution (Isopropanol), solid, or aqueous dispersion. Eudragit S is available only as an organic solution (Isopropanol) and solid. 3. Hydroxypropyl Methylcellulose Phthalate hydroxypropyl methyl-cellulose are marketed as HPMCP 50, 55, and 55S (also known as HP- 50, HP-55, and HP-55-S) HPMCP is the trade name for hydroxypropyl methylcellulose phthalate. These polymers dissolve at a lower pH (at 5 to 5.5) than CAP or acrylic copolymers, and this solubility characteristic may result in higher bioavailability of some specific drugs 4. Polyvinyl Acetate Phthalate Polyvinyl acetate phthalate (PVAP) is manufactured by the esterification of a partially hydrolyzed polyvinyl acetate with phthalic anhydride. This polymer is similar to HP-55 in stability and pH-dependent solubility. It is supplied as ready-to-use or ready-to-disperse enteric systems. B. Solvents The primary function of a solvent system is to dissolve or disperse the polymers and other additives and convey them to the substrate surface. Some important considerations for an ideal solvent system are as follows: It should either dissolve or disperse the polymer system. It should easily disperse other coating solution components into the solvent system. Small concentrations of polymers (2 to 10%) should not result in an extremely viscous solution system (>300 cps), creating processing problems. It should be colorless, tasteless, odorless, inexpensive, nontoxic, inert, and nonflammable. It should have a rapid drying rate (the ability to coat a 300 kg load in 3 to 5 hours). It should have no environmental impact.  The most widely used solvents, either alone or in combination are water, ethanol methanol, isopropanol, chloroform, acetone, methyl-ethyl ketone, and methylene chloride. Because of environmental and economic considerations, water is the solvent of choice; however, several polymers cannot be applied from aqueous systems. Drugs that readily hydrolyze in the presence of water can be more effectively coated with non- aqueous-solvent-based coatings. Such a process might require applying an initial sealing coat from an organic based sub- coating, followed by aqueous color and gloss coating. C. Plasticizers The quality of a film can be modified by the use of “internal” or “external” plasticizing techniques. Internal plasticizing pertains to the chemical modification of the basic polymer that alters the physical properties of the polymer. Most often, the formulator uses external plasticizers as additives to the coating solution formula so that the desired effects are achieved for the film. An external plasticizer can be a nonvolatile liquid or another polymer, which when incorporated with the primary polymeric film former, changes the flexibility, tensile strength, or adhesion properties of the resulting film. The choice of plasticizer depends upon the ability of plasticizer material to solvate the polymer and alter the polymer-polymer interactions. When used in correct proportion to the polymer, these materials impart flexibility by relieving the molecular rigidity. The type of plasticizer(s) and its ratio to the polymer can be optimized to achieve the desired film properties.  Examples of plasticizers are castor oil; propylene glycol; glycerin; low-molecular-weight polyethylene glycols of 200 and 400 series; and surfactants, e.g. polysorbates (Tweens), sorbitan esters (Spans), and organic acid esters. D. Colourants Coating solution formulations may contain a wide variety of components in addition to the film former, solvents, and plasticizers. Colorants may be soluble in the solvent system or suspended as insoluble powders. They are 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 (