Coating of Pharmaceutical solid

dosage forms

• Benefits of the process of coating of pharmaceutical dosage forms:

1. Improved esthetic qualities of the product.

2. Masking of unpleasant taste and odor.

3. Enabling the product to be more easily swallowed by

the patient.

4. Facilitating handling, particularly in high-speed filling

& packaging lines.

5. Improving product stability.

6. Modifying drug-release characteristics.

Types of CoatingCoatings

Sugar coatings Film coatings

Conventional film coatings

Functional film coatings

Delayed-Release Film coatings

Extended-Release Film coatings

A. Film CoatingI. Introduction to film coating.

II. Ingredients used in film coating.

III. Preparation procedures of film coating liquid.

IV. Conventional film coating.

V. Modified-Release film coatings

VI. Technical procedures in film coating process

VII. Problems in film coating.

I. Introduction• The process of film coating is that one involving the application of

thin (in the range of 20- 200 um) , polymer-based coatings to an appropriate substrate (tablets, beads, granules, capsules, drug powders, and crystals).

• The process should guarantee the following criteria:

1. Balance between, and control of, the coating liquid addition rate and drying process.

2. Uniformity of distribution of the coating liquid across the surface of product being coated.

3. Optimization of the quality (both visual and functional) of the final coated product.

• Despite that the elegance of sugar-coated tablets is thought to be superior, Film-coating process has replaced sugar-coating due to the following advantages:

1. Substantial reduction in quantity of coating applied (2 - 4% for film coating,

compared with 50 -100% for sugar coating)

2. Faster processing times.

3. Improvement in process efficiency and output.

4. Greater flexibility in optimizing formulations as a result of the availability of

a wide range of coating materials and systems

5. A simplified process (compared to sugar coating) that facilitates

automation

6. Ability to be applied to a wide range of pharmaceutical products “e.g.,

tablets, capsules, granules, non-pareils, powders, drug crystals”.

II. Ingredients used in film coating• A typical formulation of film coating contains:

1. Polymer.

2. Plasticizer.

3. Colorant.

4. Solvent (vehicle).

• Certain features of film coating formulation, discussed at the following table, are important and much affected by the ingredients used in the formulation.

Important features of film coatingFeature Has impact on

1. Mechanical properties(Tensile strength & Elasticity modulus)

•Visual quality of coating.•Resistance to damage on handling.•Barrier properties of coating.•Drug-release characteristics from MR products.•Taste-masking efficiency.

2. Permeability characteristics •Barrier properties of coating.•Product stability.•Drug-release characteristics from MR products.•Taste-masking efficiency.

3. Coating solution viscosity •Spraying characteristics.•Interaction with the substrate.•Visual quality of coating.

4. Hiding power •Visual quality.•Quantity of coating needed for uniform appearance.•Stability of photo-labile APIs.

1. Polymers• the polymer is the major ingredient, Consequently, this material will

have the greatest impact on the final properties of the coating.

• Polymers are a multiplicity of differing chemical types, each in turn often having various grades (as determined by viscosity or molecular weight).

• Due to the batch-to-batch variations resulting from the polydisperse nature for a particular grade of polymers, it’s necessary to define the material in terms of:

1. Chemical structure.2. Molecular weight3. Molecular weight distribution.

• This can be determined using gel permeation (or size exclusion) chromatography, whereby average molecular weight, molecular weight distribution & polydispersity can be determined.

• Viscosity as a sole test, will not give a full image for the polydisperse nature of the polymer.

Effect of polymer M.Wt on coating propertiesProperty Effect of increasing polymer M.Wt

1. Tensile strength •Increases

2. Elastic modulus •Increases “i.e., coating becomes less elastic”

3. Film adhesion •Decreases

4. Solution viscosity •Significantly increases

5. Film permeability •Typically unaffected, unless the structural “mechanical” properties improves with the increase in the polymer M.Wt

2. Plasticizers• Plasticizers reduce the glass-transition temperature of amorphous polymers

and impart flexibility.

• below the Tg there is a critical cessation of molecular motion on the local scale, Under these temperature conditions, the polymer exhibits many of the properties of inorganic glasses, including toughness, hardness, stiffness, and brittleness.

• So the Tg is described as one below which a polymer is brittle, and above which it is flexible (temperature above which there is an increase in the temperature coefficient of expansion).

• The basic requirements to be met by a plasticizer are:1. Permanence (Plasticizer should have a low vapor pressure & low diffusion rate within

the polymeric film)…. Available in high M.Wt plasticizers.

2. Compatibility (the plasticizer should be miscible with the polymer and exhibit similar intermolecular forces to those present within the polymer).

• Sometimes there are systems needs two types of plasticization, The first is

• Internal plasticization, and refers to the situation in which chemical changes are made within the structure of the polymer itself ”Substitution and Change in polymer chain length”, as with copolymers (exemplified by many of the acrylic polymers systems used in film coating).

The second, termed • External plasticization, occurs when an external additive (the plasticizer) is

combined in admixture with the polymer.

• Effective plasticization is critical when using aqueous polymeric dispersions to ensure that sufficient free volume exists at normal processing temperatures to facilitate coalescence of the polymeric particles into a continuous film.

• the magnitude of the effect on the coating film properties is very much dependent on the compatibility, or degree of interaction, of the plasticizer with the polymer, much more than the quantity of the plasticizer in the coating formula.

• So, plasticizers. by their very nature. are not universal, since selection is very much determined by which polymer is being used.

Effect of plasticizers on the properties of film coating

Property Effect of increasing plasticizer concentration1. Tensile strength •Decreased

2. Elastic modulus •Decreases “i.e., coating becomes more elastic”

3. Film adhesion •May be increased, but results are variable

4. Solution viscosity • Increased. and magnitude of effect dependenton molecular weight of plasticizer

5. Film permeability •Can be increased or decreased, dependingon chemical nature of plasticizer

6. Glass-transition temperature

•Decreased. but magnitude of effect dependenton compatibility with polymer

3. Colorants• Colorants are included in many film-coating formulations to improve

the appearance and visual identification of the coated product, with certain types have other physical functions.

• Colorants used in film-coating:1. Water-soluble dyes (eg. FD&C Yellow #5 and FD&C Blue #2)2. Aluminum lakes (of FD&C water-soluble dyes)3. Inorganic pigments (eg. titanium dioxide, iron oxides. calcium sulfate,

calcium carbonate)4. "Natural" colorants (eg. riboflavin, turmeric oleoresin. carmine 40).

• Using pigments is preferable to the use of water-soluble colorants due to the following:

1. Ability to increase solids content of coating solution without dramatically affecting viscosity. (particularly advantageous in aqueous film coating)

2. Ability to improve the moisture barrier properties of film coatings.

• Inadequate pigment dispersion leads to coating defects:1. Inhomogeneous Color distribution over the film.2. Surface roughness of the coating.

• Requirements of coloring in film coating:1. Create a given visual effect.2. Ensure that the appearance is as uniform as possible throughout the

particular batch of coated product.3. Coloring is consistent from batch-to-batch.

• Contrast ratio is a useful parameter in determining which type of colorant to be used and regarded as a measure of the hiding power of the coloring used:

• Contrast ratio = Yb / Yw * 100• Yb: Tristimulus value of a certain film over a black background.• Yw: Tristimulus value of the same film over a white background.

• Colored films having contrast ratios close to 100 exhibit excellent hiding power, whereas those having values close to zero are almost transparent (and thus have poor hiding power).

• Choosing a colorants with high contrast ratios greatly serves in film coating properties enhancement by:

1. Effectively mask the appearance of the substrate without requiring the use of excessive quantities of colorant (which could increase the risk of physical defects in the coated product).

2. Avoidance of applying excessive quantities of coating (which impacts total cost of the process).

• Practically, it’s been found that the best coloring are:

• certain inorganic pigments (eg. titanium dioxide and iron oxides) due to the close values of refractive indices between them and the polymer.

• those that absorb the higher wavelengths of visible light (e. g., FD&C Blue #2).

Effects of pigments on the properties of film coating

Property Effect of increasing pigment concentration1. Tensile strength •Decreased (effect may be minimized by effective pigment

dispersion).

2. Elastic modulus •Increases “i.e. elasticity decreases”

3. Film adhesion •Little effect.

4. Solution viscosity •Increased, but not substantially.

5. Film permeability •Decreased, unless critical pigment volume concentration is exceeded. “corrupt the polymer network”

6. Hiding power •Increased, but magnitude of effect dependent on refractive index of pigment, and light absorbed by pigment

4. Solvents• the rise in importance of aqueous

film coating has virtually eliminated solvent selection from the formulation process.

• However, certain types of film coatings and film-coating processes require that some organic solvents still be used. Thus, to a limited extent, selection of an appropriate solvent may still be necessary.

Common solvents used in film coating

Class Example

1. Water ---------

2. Alcohols •Ethanol•Methanol•Isopropyl alcohol

3. Esters •Ethyl acetate•Ethyl lactate

4. Ketones •Acetone

5. Chlorinated hydrocarbons

•Methylene chloride•1,1,1, trichlorothane

• Factors governing the selection of the appropriate solvent:

1. the ability to form a solution with the polymer of choice “optimal polymer solution will yield the maximum polymer chain extension, producing films having the greatest cohesive strength and thus the best mechanical properties”.

2. a controllable deposition rate of the polymer onto the surface of the substrate, the volatility of the solvent system is an important factor.

• NB: In the case of solvent system, the solubility of the polymer in the least volatile solvent component must be guaranteed, otherwise the solvent-polymer thermodynamic balance changes as evaporation progresses, leading to polymer precipitation before a cohesive film being formed.

III. Conventional film coating• The selection of coating formula ingredients is based on factors that affect:

• the mechanical properties (such as tensile strength, elasticity, and adhesion) of the coating, allowing the smoothest, glossiest coatings to be obtained, and produce coatings that readily dissolve in the human GIT.

Polymers:• The most popular class of polymers used in conventional film coating are:

1. Cellulosics, many of which have good organic-solvent and aqueous solubility, thus facilitating the transition to aqueous film coating.

2. Polyvinyl pyrrolidone, “films are brittle and hygroscopic.”

3. Polyethylene glycol, “films are waxy, hygroscopic, and soften readily at only moderately elevated temperatures.”

4. Acrylates:

1. Dimethylaminoethyl methacrylate methacrylic acid ester copolymer “Eudragit E”….“soluble in water at only low pH, making it particularly attractive for taste masking, only organic-based”.

2. Ethyl acrylate-methyl methacrylate copolymers, also water insoluble, but available as aqueous latex-coating systems.

Polymers Used in Conventional Film-Coating formulations

Class Example

1. Cellulosics •Hydroxypropyl methylcellulose “HPMC”.

•Hydroxypropyl cellulose “HPC”.

•Hydroxyethyl cellulose “HEC”.

•Methylhydroxyethylcellulose “MHEC”.

•Methylcellulose

•Ethylcellulose

•Sodium carboxymethylcellulose “CMC sodium”

2. Vinyls •Polyvinyl pyrrolidone.

3. Glycols •Polyethylene glycols

6. Acrylates •Dimethylaminoethyl methacrylate methylacrylic acid ester copolymer “Eudragit E”•Ethylacrylate-methylmethacrylate copolymer

• Hints:

• HPMC films have superior tensile properties.

• HPC films tend to be more elastic (i.e., exhibit lower elastic moduli), and possess better adhesive properties.

• Since each of these polymers is available in several grades, the common practice is to use the lower molecular weight grades of each in aqueous film coating in order to optimize the properties of coating solutions with respect to solids content and solution viscosity.

• Plasticizers:

– With aqueous film-coating formulations, the general preference is to use water-soluble plasticizers, since this approach helps to facilitate interaction between the polymer and plasticizer. For this reason, plasticizers such as glycerol, propylene glycol, the polyethylene glycols and triacetin are often used with aqueous formulations.

– Specifically for HPMCs, the PEGs are the most effective plasticizers for this cellulosic polymer, with effectiveness being inversely proportional to the molecular weight of the polyethylene glycol chosen.

– Being hygroscopic, that facilitates plasticization process by helping retaining the amount of moisture in the polymeric film.

– NB: Use of triacetin as a plasticizer in aqueous formulations, although less popular, may have certain advantages when trying to improve the moisture barrier properties of the film coating.

Common Plasticizers Used in conventional film coating

Class Example1. Polyhydric alcohols •Propylene glycol

•Glycerol•Polyethylene glycols

2. Acetate esters •Glyceryl triacetate (Triacetin)•Triethyl citrate•Acetyl triethyl citrate

3. Phthalate esters • Diethyl phthalate• Dibutyl phthalate

6. Glycerides •Acetylated monoglycerides “eg. Glyceryl monostearate”.

7. Oils •Castor oil•Mineral oil

IV. Modified-Release film coating• The United States Pharmacopeia/National Formulary (USP/NF) has simplified

this terminology somewhat by defining a modified-release dosage form as: • “one in which the drug-release characteristics of time course and/or

location are chosen to accomplish therapeutic or convenience objectives not offered by conventional dosage forms….”.

• Under this umbrella definition, the USP/NF recognizes two types of modified-release dosage form:

1. Extended release: One that permits at least a twofold reduction in dosing frequency as compared to the situation in which the drug is presented as a conventional dosage form (also called sustained-release or controlled-release dosage forms).

2. Delayed release: One that releases the API at some time other than promptly after administration (e.g.. enteric-coated products).

a. Enteric Film Coatings• Enteric coatings are those which remain intact in the stomach (and

exhibit low permeability to gastric fluids). but break down readily once the dosage form reaches the small intestine.

• The purposes of use of such drug delivery system are:1. To protect & maintain the activity of drugs that are unstable

when exposed to the gastric milieu (e. g., erythromycin and pancreatin).

2. To minimize either nausea or bleeding that occurs with those drugs that irritate the gastric mucosa (e.g. aspirin and certain steroids).

• Modern enteric coatings are usually formulated with synthetic polymers that contain ionizable functional groups that render the polymer water soluble at a specific pH value. Such polymers are often referred to as polyacids.

• Since many of these polymers are esters, they may be subject to degradation (as a result of hydrolysis) when exposed to conditions of elevated temperature and humidity. Such hydrolysis can result in a substantial change in enteric properties.

Examples of Enteric-Coating Polymers

Polymer Comments• Cellulose acetate phthalate (CAP) •Subject to hydrolysis “high”.

• Cellulose acetate trimellitate (CAT) •Subject to hydrolysis

• Polyvinyl acetate phthalate (PVAP) •Subject to hydrolysis “low”.

• Hydroxypropyl methylcellulose phthalate (HP) •Subject to hydrolysis “medium”

• Hydroxypropyl methylcellulose acetate succinate (HPMCAS)

•Subject to hydrolysis “low”

•Poly methacrylic acid – ethylacrylate copolymer 1:1 “Eudragit L100-55”

•Poly methacrylic acid – methylmethacrylate copolymer 1:1“Eudragit L100”

•Relatively high dissolution pH

•Poly methacrylic acid – methylmethacrylate copolymer 1:2“Eudragit S100”

•Relatively high dissolution pH

• the special aqueous solubility requirements for an enteric polymer have delayed the routine employment of aqueous enteric-coating technology.

• More recently, various systems of aqueous enteric coating have been introduced.

• many of the coating systems exist as dry powders, with the coating liquid being prepared shortly before use by dispersing (or dissolving) the polymer in water.

• The reason for supplying many enteric coating systems as dry powders is to avoid problems of poor stability (due to hydrolysis) when these polymers are exposed to water for extended periods.

• Important factors that can influence the behavior of enteric coatings:1. The nature of the drug in the dosage form (the presence of aspirin, for example, can

greatly influence dissolution of the coating).

2. The quantity of coating applied (application of excessive quantities of coating can substantially delay release of drug from the dosage form).

3. The presence of imperfections in the coating (fissures or "pick" marks will destroy the integrity of the coating).

4. The dissolution pH of the polymer used in the coating.

5. The effect of in vitro test conditions (dissolution of the coating, and ultimate drug release, can be affected dramatically by the pH and ionic strength of the test solutions and the agitation rate).

Examples of Aqueous Enteric-Coating Systems

Product Form Polymer CommentsEudragit L 30 D Latex dispersion Poly (MA-EA) 1:1 •System essentially contains only the polymer

Eudragit L100-55 Spray-dried latex

Poly (MA-EA) 1:1 •Requires dispersing in water with addition of alkali•System only contains polymer

HP-F Dry powder HP •Requires dispersing in water•System only contains polymer

Coateric Dry powder PVAP •Complete system.•Requires dispersing in water with addition of ammonia.

Aquateric Spray-driedpseudolatex

CAP •System essentially contains only polymer•Requires dispersing in water

HPMCAS Dry powder HPMCAS •System contains only polymer•Requires dispersing in water

CAP Dry powder CAP •System contains only polymer•Requires dissolving in water with aid of alkali (ammonia)

CAT Dry powder CAT •System contains only polymer•Requires dissolving in water with aid of alkali (ammonia)

b. Sustained-Release, or Controlled-Release film coatings

• Drug release from such sustained-release products is moderated by the film coating Which acts as a membrane that allows infusion of GI fluids and the outward diffusion of dissolved drug.

• In some instances, the release process may be augmented by a coating that slowly dissolves (e.g. shellac), or is subject to digestion by enzymes (e.g., fats and waxes).

• NB: natural substances when used do not give predictable drug release profile, unlike the synthetic ones…

Examples of coating materials used in Sustained-Release film-Coating formulations

Coating material Membrane characteristics

• Fats and waxes (e. g., beeswax, carnauba wax, cetyl alcohol, cetylstearyl alcohol)

•Permeable and erodible

• Shellac •Permeable and soluble (at high pH)

• Zein •Permeable and soluble (at high pH)

• Ethylcellulose •Permeable

• Cellulose esters (e. g., acetate) •Semipermeable

• Silicone elastomers •Permeable (when PEG added)

• Acrylic esters • Permeable

• As with other types of film coating. great interest has been shown in using aqueous-coating technology for sustained-release products.

• These coating systems typically consist of aqueous dispersions of water-insoluble polymers which form films by a process of coalescence of submicron polymer particles.

• This process can be greatly affected by conditions used in the coating process. and variable results (as they relate to ultimate drug-release characteristics) can often be attributed more to lack of control over the coating process (or choice of inappropriate processing parameters) rather than to any variability in the aqueous dispersion used.

Examples of Aqueous polymeric dispersions for sustained-release

film coating

Material Polymer CommentsSurelease Ethylcellulose •Aqueous polymeric dispersion contains requisite

plasticizers•Addition of lake colorants should be avoided because of alkalinity of dispersion

Aquacoat Ethylcellulose •Pseudolatex dispersion•Requires addition of plasticizers to facilitate film coalescence

Eudragit NE 30 D Poly(ethylacrylate-methylmethacrylate) 2: 1

•Latex dispersion•No plasticizers required unless improved film flexibility is desired

Eudragit RL 30 D Poly(ethylacrylate-methylmethacrylate)triethylammonioethyl methacrylatechloride 1: 2: 0.2

•Aqueous polymeric dispersion•No plasticizers required unless improved film flexibility is desired

Eudragit RS 30 D Poly(ethylacrylate-methylmethaeryIate)triethylammonioethyl methacrylatechloride 1: 2: 0. 1

•Aqueous polymeric dispersion•No plasticizers required unless improved film flexibility is desired

• Drug release from sustained-release systems can be described by application of Fick's first law of diffusion.

• The rate of drug release through the membrane is directly proportional to 1. surface area, 2. diffusion coefficient, 3. drug solubility in and drug concentration gradient across the membrane, and inversely proportional to membrane thickness.

• With respect to drug-release characteristics, variable results may occur through inability to control many of influencing factors. For example:

1. Variations (from batch-to-batch) in size and shape of the core material (to be coated) would certainly cause variations in surface area and coating thickness.

2. Variations in coating structure may well result from variable processing conditions that cause picking or spray drying (particularly with organic-solvent-based coating solutions) and incomplete coalescence with aqueous polymeric dispersions.

3. general variation in process efficiencies (which influence uniformity of distribution. and overall quantity applied, of the coating material)

Factors influencing drug release from a sustained-release film-coated dosage form

Parameter Influenced by

1. Surface area •Size, size distribution, and surface topography of material being coated.

2. Diffusion coefficient •Formulation of film coating

•Structure of coating

•Nature of drug

3. Drug-concentration gradient across Membrane

•Initial drug loading

•Drug content inside the membrane at any intermediate time

•Agitation rate (which influences drug concentration on outside of membrane)

4. Membrane thickness •Size, size distribution, and surface topography of material being coated•Quantity of coating material applied (related to theoretical quantity of coating to be applied, and coating efficiency)

III. Preparation procedures of film coating liquid

• Coating liquids, from the formulation aspect, are divided into two types:

1. Pseudo-dispersions “ the polymer dissolves in the solvent, and the dispersed phase results from the insoluble detackifier &/or the insoluble lakes or pigments”…e.g. HPMC-based coating liquid

2. True dispersions “the polymer is dispersed, not soluble in the solvent, beside the other dispersed ingredients”……e.g. PVAP-based coating liquid.

1. Important measures in pseudo-dispersions preparation

• Generally, coating liquid is prepared using a high-shear mixer equipped with a homogenizing part.

• In case of soluble cellulosics “e.g. HPMC, HPC, CMC sodium” the solubility is slow due to the sudden gelling when adding to water, so it’s either:

1. to let overnight standing “ soaking”, where the formed gel dissolves slowly in water.

2. Disperse it in part of hot water “NLT 80 degree Celsius”, then adding the rest water cold.

• If the plasticizer &/or the colorant are water soluble exist, it must be added directly to the polymer solution.

• If a detackifier &/or a pigment or a lake exist, it must be homogenized externally, then added to the polymer solution with continuous stirring.

• Allover the coating process, stirring should continue so that air entrapment in the liquid is avoided, or minimized at least.

2. Important measures in true dispersions preparation• Generally, stirring must be efficient and last for a long

period to maintain the homogenous dispersity of coating ingredients esp. the polymer in the solvent.

• The polymer should be the last ingredient in addition, care must be taken upon stirring to avoid air entrapment.

• In case of enteric polymers, most of them needs the addition of an alkali to facilitate homogenous dispersion and avoid coagulation of the polymer particles, e.g. Eudragit L100-55.

• Polymers with high deviation in surface tension value from water, should be admixed with a surfactant to facilitate

1. the dispersion of the polymer. 2. wetting of the substrate by the coating dispersion. 3. coalescence of the polymeric film upon drying.

3. Important measures in pseudolatices preparation

• E.g. Eudragit E30 D, Aquacoat 30% ECD.

• Stirring is the most important measure to be taken in consideration, where air entrapment is the most hazardous factor.

• If an external plasticizer &/or detackifier is needed, addition must be done very carefully while stirring to avoid any disturbances in the pseudolatex structure.

IV. Technical procedures in film coating process

1. Mechanism of film coating process2. Coating process in general3. Process parameters to consider

1. Mechanism of film coating process

• Film coating liquids are applied almost always utilizing spray-atomization technique.

• In the spray-application process, bulk coating liquids are finely atomized and delivered in such a state that droplets “of coating liquid” retain sufficient fluidity to wet the surface of the product being coated, spread out, and coalesce to form a film.

• Because of the highly adhesive (or "tacky") nature of partially dried droplets, it is imperative that the droplets of coating liquid dry almost instantaneously the moment they contact the surface of the substrate; otherwise sticking and picking will occur.

Steps of film formation

• Uniformity of distribution of coating liquid is controlled by:1. Uniformity of application of the coating liquid i.e., number of spray

guns used, types of spray patterns used & fineness of atomization of coating liquid.

2. Uniformity of mixing (controlled by pan speed, baffle design, tablet size & shape) of the product being coated.

• Unlike sugar coating, it is not desirable in film coating to have partially dry coating material being transferred from one tablet to another, since this would create imperfections in the coating that would be readily evident at the end of the coating process.

• The tumbling action, however, has an effect on the ultimate coating structure promoting sufficient flow of the coating inducing a leveling effect.

•Factors affecting the quality of film coating• To better understand those factors affecting the quality “both visual &

functional” of the finished coated product, it’s necessary to examine the factors affecting:

1. Interaction between the core material (substrate) and the applied coating.2. The drying process.3. The uniformity of distribution of the coating.

Factors influencing interaction between substrate & coatingFactor Has influence on

1. Tablet coreIngredient

Porosity

Surface roughness

•Wetting by coating liquid.•Adhesion of dry film.

•Adhesion of dry film.

•Wetting by coating liquid.•Spreading of coating liquid across surface.•Roughness of coating.

2. Coating liquidSolids content

Viscosity

Surface tension

•Roughness of dry coating.•Coating liquid viscosity.

•Spreading of coating liquid across surface of substrate.•Coalescence of droplets of coating liquid into a continuous film.

•Wetting of surface of substrate by coating liquid.•Spreading of coating liquid across surface of substrate.•Coalescence of droplets of coating liquid into a continuous film.

3. Drying processDrying rate

Heat

•Viscosity of coating liquid at time of contact with surface of substrate•Structure of dried coating.

•Development of internal stress within film (and effect of adhesion & cohesion).•Mechanical properties of coating (and effect on defects).

Factors influencing the drying processFactor Has influence on

1. Spray equipmentNozzle design

Atomization air

Number of used spray guns

•Fineness of atomization of coating liquid (and thus evaporation rate of solvent/vehicle)

•Fineness of atomization of coating liquid (and thus evaporation rate of solvent/vehicle)

•Uniform distribution of coating liquid.•Avoidance of localized overwetting.

2. Drying ConditionsAir flow, temp, humidity •Rate at which solvent/vehicle can be removed from the coating liquid.

•Product temperature.

3. Spray rateNozzle design, no of spray guns, pumping system

•Rate at which solvent/vehicle can be removed from the coating liquid.•Product temperature.

4. Solids content of coating liquid

•Quantity of solvent/vehicle that must be removed from coating liquid.

Factors influencing uniformity of distribution of coatingFactor Has influence on

1. Spray equipmentNozzle design

Atomizing air

Number of spray guns

•Fineness of atomization of coating liquid.•Area over which coating liquid is applied

•Fineness of atomization of coating liquid.

•Area over which coating liquid is applied.•Length of coating process.

2. Drying conditionsAir flow, temp, humidity •Efficiency of the coating process (i.e., amount of coating that ends up on core material).

3. Spray rateDrying rate •Length of coating process.

•Amount of coating liquid that is deposited on substrate at each pass through spray zone.•Amount of coating that is lost during coating.

4. Solids content of coating liquid

•Amount of coating liquid that is deposited on substrate at each pass through spray zone.•Length of coating process.•Smoothness of the dried coating.

5. Pan speed •Uniformity of mixing.•Amount of coating liquid that is deposited on substrate at each pass through spray zone.•Loss of coating due to attritional effects.

6. Baffles of coating pan •Uniformity of mixing.

FORMULATION OF FILMS FROM POLYMERIC SOLUTIONS• The film forming process & internal structure of the final dried coating

depends mainly on:• Rate of solvent evaporation.

• Rate of solvent evaporation, in turn, is controlled by: • The solvent latent heat of vaporization.• The drying conditions provided in the process.

• Film formation generally comprises:1. Initial rapid evaporation of solvent from the atomized droplets of coating liquid,

causing an increase in polymer concentration (and, hence, viscosity) and contraction in volume of the droplets.

2. Further loss of solvent from the film (that is, coalescing on the surface of the dosage form) at a slower rate which is now controlled by the rate of diffusion of solvent through the polymer matrix.

3. Immobilization of the polymer molecules at the “solidification point”.

4. Further gradual solvent loss from the film at a very much reduced rate.

• Solvent loss from the film coating will be continuous but at an ever decreasing rate.

• Solvent loss from the polymer matrix is governed by the amount of space between the polymer molecules (usually termed the free volume).

• As solvent loss progresses. the Tg of the polymer film increases and free volume decreases. Ultimately, free volume becomes so small that further solvent loss is so restricted that total removal of solvent from the coating becomes almost impossible.

• Total solvent removal requires heating the film to a temperature significantly above the Tg of the solvent-free polymer “the purpose of plasticizer”.

• Solvent loss (from the coating) that occurs beyond the solidification point creates shrinkage stresses that contribute to the internal stress within the coating, leading to mechanical defects.

FORMULATION OF FILMS FROM AQUEOUS POLYMERIC DISPERSIONS

• Film formation from aqueous polymeric dispersions requires the coalescence of polymer particles into a continuous film.

• Drying of such a system (i.e., the removal of water) is often quite rapid, whereas coalescence can be a much slower process, extending into weeks and months if appropriate formulation and processing parameters are not used.

• The actual mechanism of film formation from an aqueous polymeric dispersions is quite complex, but can be briefly described in the following steps:

1. Rapid evaporation of water, causing the particles of dispersed polymer to be brought into close contact with one another.

2. Development of pressures “associated with capillary forces within the structure”, that overcome repulsive forces between particles and cause deformation of the polymer particles.

3. Gradual coalescence of the polymer particles as a result of the viscous flow and movement of polymer molecules across the interfaces between particles.

• This process of film formation is very sensitive to process conditions used during film coating.

• The coalescence of the latex particles will be very much dependent on free volume (Which influences the movement of polymer molecules between individual latex particles).

• Consequently, aqueous polymeric dispersions must be processed at temperatures in excess of the glass-transition temperature of the polymer (or plasticized polymer in the case of, e.g., ethylcellulose).

• Thus, the optimum processing conditions for aqueous polymeric dispersions occur over a narrow range of temperatures. This explains why tackiness is a common problem cited when film coating with such aqueous dispersions.

2. Coating process in general

• Typical design of the coating machine:

• Typical behavior of tablet bed temperature and moisture content over the process time :

• Video of film coating process.

3. Process parameters to consider

I. Geometrics of system components.II. System pressures.III. Process temperature.IV. Spray rate and batch size.V. Pan speed.

I. Geometrics of system components.• Five spraygun positionings to be fixed:

• I) Gun-to-bed distance: – Production scale: approx. 15 – 20 cm,– Lab scale: approx 10 cm

• Overlapping demonstration:

II) Gun-to Gun distance:Place periodically, not too close together

to avoid the possible overwetting resuting from overlapping..

III) Gun-to-wall distance:• Accurate positioning up, saves cleaning

work !

IV) Spray target position:

II. System pressures• Spray gun pressure adjustments:

1. Atomizing air (AA)- creates the fumigation.

2. Fan air (FA),sometimes named “control air” (CA)- creates the form of the pattern, (round or oval).

• 3. Needle air (NA),- closes the liquid line.

• Influence of fan air adjustment:

III. Process temperatures• Process temperatues to consider:

1. Intake2. Exhaust.3. Tablet bed.

• Exhaust temp is a function of:- Intake Temperature- Spray rate- Process air volume- Atomizing Air pressure.

- NB: If any of these parameters vary, the exhaust temp varies as well, so exhaust temp. is used as a process control variable by almost all systems.

• Tablet bed surface temperature is the most critical of all temperatures…

Because exactly here is happening the most important process detail:

The film forming

• Tablet bed temperature distribution:

IV. Spray rate and batch size• The higher the spray rate and the

bigger the batch size the more efficient is the process.

• Possible spray rate depends on:- Drying efficiency of equipment.- Core properties.- Film properties.- Quality of machine set up.

• Correlation between batch size and required process time to apply 3% weight gain:

V. Pan Speed• Factors governing pan speed:

1. Pan diameter.2. Amount and type of baffles.3. Tablet load “batch size”.4. Tumbling behavior of the core substrate.

• Practical hints:- Pre-heat with jog mode(or even more gentle: manually)

- Pan speed as low as possible at process beginning, but tablets MUST flow constantly.

- Permanently increase pan speed in small steps over the complete process time.

- Cool down under slow permanent rotation.

V. Problems in film coating• Unavoidable attritional effects demand that both the product being coated

and the coating itself be formulated with appropriate mechanical properties if problems associated with fragmentation (of the cores) and erosion (of the cores and coating) are to be avoided.

• The use of aqueous-based coating systems increased the complexity of the process, as water has a significantly higher latent heat of vaporization (than the previously used organic solvents). and thus greater attention must be paid to monitoring (and preferably controlling) the drying conditions in the aqueous process.

• Factors governing the interaction between a film coating and a substrate are:

1. Core characteristics : porosity, surface rugosity & surface energy all affect wetting by the coating liquid.

2. Coating liquid characteristics: viscosity & surface tension affects the initial wetting process of the substrate

3. Stresses that form within the coating, which are related to:I. Shrinkage phenomena that develop as the coating dries.II. Expansion/contraction of both coating and substrate while subjected to

heating and cooling cycles in the process.III. Other core expansion factors (as swelling due to moisture absorption).

a. Picking• Cause:

• When the coating on two adjacent tablets is not sufficiently dry before they get in contact and adhere due to the very tacky nature of the partially dried coating, and break apart later “issue of overwetting”

• In extreme cases, tablets with flat surfaces or flat edges may permanently become glued together, named “twinning” or buildup of multiplies.

• Overwetting occurs typically when the spray rate is excessive for the drying conditions in the process.

• Localized overwetting results when:1. insufficient number of spray guns is used so that certain regions got higher conc.

of coating liquid than other regions.

2. When one or more nozzles in a multiple-gun setup got blocked, causing all the coating liquid to be channeled to the remaining guns.

• Coating formulations more likely to exhibit picking are those of HPC, many of the enteric-coating formulae, acrylic aqueous latex-coating systems due to their tackier property.

b. Roughness “Orange Peel”• Cause:

• Certain process conditions are likely to induce surface roughness “orange peel”, such conditions include low spray rates coupled with excessive drying conditions, “high processing temperature and airflows” and use of excessive atomizing air pressures which accelerates premature drying of the droplets of coating liquid.

• The problem may be further complicated by spraying coating liquids of excessively high viscosities.

• It’s critical that the droplets of the coating liquid dry very soon after they make contact with the surface of the product being coated.

• Generally, all film coated tablets exhibit the Orange peel effect, but optimized coating processes will allow this characteristic to be kept at a minimum such that it’s not visible to the naked eye.

c. Edge wear “Chipping”• Usually appear as fractures at the tablet edges due to their

exposure to the attritional effects while processing in the coating pans.

• Cause:1. Tablet cores having high friability values.2. Worn tablet punches (produce “flashing” on the tablet edges).3. Minor lamination problems (with the tablet cores) which induce edge

erosion problems to get worse.4. Brittle film coatings that offer insufficient protection to tablet edges

d. Film cracking• Cause:

• Occurs when the internal stress “that develops within the coating on drying” exceeds the tensile strength of that coating.

• Cracking may be simple to catastrophic, especially when the coating film tends to serve in the alteration of the release of the API from the substrate.

• The problem is certainly exacerbated by thermal expansion effects, particularly when significant differences exist between the thermal-expansion coefficients for the core and the coating respectively.

e. Bridging of logos “Intagliations”• Cause:

• Internal stress is the major causative factor in logo bridging.

• This phenomenon occurs when a component of the internal stress becomes sufficiently high so as to cause partial or complete detachment of the coating (from the substrate) in the region of the logo.

• As a result of such detachment, the film is able to "shorten" and thus partially relieve the stress within the film, In doing so, legibility of the logo can be significantly reduced.

• Typically. this type of problem becomes progressively worse as more coating is gradually applied during the process.

• Solutions may involve:1. improving film adhesion and/or reducing stress within the film.2. require some reformation of either the tablet core or the coating.3. appropriate design of tablet punches (especially with respect to the logo) may

help to alleviate the problem.4. adjustment of process conditions

f. Film peeling• Cause:

• On occasion (particularly during application of aqueous-coating formulations). if cohesive failure (cracking) of the coating occurs, that coating may subsequently peel back from the surface of the substrate.

• while both cohesive and adhesive failure are implicated here (both phenomena being linked to internal stress).

• appropriate solutions typically involve addressing the initial cracking problem by increasing the mechanical strength of the coating.

g. In-filling of logos• Cause:

– in -filling of logos typically occurs during the spray application of aerated aqueous film-coating solutions.

• When a foamy coating solution impinges on a regular part of the tablet surface it will, under the shear forces generated, form a film with "normal“ characteristics. However, those droplets of coating liquid that reside in the logo, being protected from the shear forces at the surface, gradually dry to form a solid foam that eventually obliterates the logo.

• when the viscosity of coating solutions is too high, libration of the foam (on standing) does not occur. Thus, the coating liquid that is sprayed on during the coating process will still be extremely aerated.

B. Sugar Coating

Summary of Advantages vs. Disadvantages of Sugar Coating

1. Raw materials are inexpensive and readily available.

2. Raw materials are widely accepted with few regulatory problems (with the exception of perhaps colors)

3. Inexpensive, simple equipment can be used.

4. Sugar-coated products are esthetically pleasing and have wide consumer acceptability

5. The process is generally not as critical (as film coating) and recovery (or rework) procedures are more readily accomplished

1. The size and weight of the finished product results in increased packaging and shipping costs.

2. The brittleness of the coatings renders the coated tablets susceptible to potential damage if mishandled.

3. The achievement of high esthetic quality often requires the services of highly skilled coating operators.

4. The final gloss is achieved by a polishing step which can make imprinting difficult

5. The inherent complexity (from the standpoint of the variety of procedures and formulations used) of the process makes automation more difficult

Process of Sugar Coating

1. Sealing: – Offer initial protection to the tablet cores and prevent migration of core

ingredients to the coating layer.

– Sealing is done using application of polymer-based coating (eg: Shellac, Zein,

HPMC, PVAP & CAP) …. Made at 30% w / w conc. in an appropriate organic

solvent, preferably denatured ethanol.

– Because sealing polymers are water-insoluble, the layer must be minimized to

avoid the alteration in the API release.

– IF the final product is to have enteric properties, the use of enteric polymers as

PVAP or CAP for seal coat is preferable, ensuring that sufficient coating material

is applied.

2. Subcoating:

– Provides the means for rounding off the tablet edges and building up the core weight.

– provides the foundation for the remainder of the sugar-coating process. with any weakness in the final sugar coat often being attributable to weaknesses in the subcoat.

– Subcoating formulations almost always contain high levels of fillers such as talc. calcium carbonate. Calcium sulfate, kaolin, and titanium dioxide, beside auxiliary film formers as acacia, gelatin, or one of the cellulose dvs to improve the structural integrity of the coating.

– It’s very critical during subcoating to get effective coverage of the coating material over the tablet corners and on the edges…”Tablet shapes play a critical role”.

3. Grossing “Smoothing”

• Assure the smoothness of the substrate, free from irregularities prior to the application of the color coat.

• Depending on the degree of smoothing required, the smoothing coating simply consists of a 70% sugar syrup, containing titanium dioxide as an opacifier, may be with other colorants to make a good base for the subsequent color coat.

• If the substrate to be smoothed requires excessive work, as in case which subcoat tablets have a pitted surface, other additives as calcium carbonate, talc or corn starch may be used in low conc. to enhance and accelerate the smoothing process.

4. Color Coating:• Has the most impact on appearance of the substrate.

• Occurs using either water-soluble dyes or water-insoluble pigments in sugar-coating syrups.

• Using pigments has solved many coating defects caused by the soluble dyes “mottling, variation in color from batch-to-batch, a skilled operator & light sensitivity with subsequent fading by time”.

• Color properties is optimized using opacifiers as titanium dioxide.

• Most efficient process of color coating involves the use of predispersed, opacified lake suspensions, with controlling ratios of lake & opacifier, various shades can be produced.

• If using pigments, careful attention must be paid to the pigment dispersion process, otherwise specking in colour would be produced.

• It’s inadvisable to keep coating systems containing lakes “typically acidic” hot, otherwise excessive amounts of inverted sugar will be formed

5. Polishing “Glossing”:• Polishing is a step achieving the gloss that is typical of finished sugar-coated

tablets.

• generally recommended that tablets should be trayed overnight (prior to polishing) to ensure that they are sufficiently dry.

• Excessively high moisture levels in tablets submitted for polishing will:1. Make achievement of a good gloss difficult2. Increase the risk of "blooming" and "sweating" over longer periods of time.

• Glossing or polishing can be carried out in various types of equipment (e. g.. canvas- or wax-lined pans), including that used for applying the sugar coating itself.

• Polishing systems that may be used include:1. Organic-solvent-based solutions of waxes (beeswax, carnauba wax, candelilla wax)2. Alcoholic slurries of waxes3. Finely powdered mixtures of dry waxes 4. Pharmaceutical glazes (typically alcohol solutions of various forms of shellac, often

containing additional waxes)

5. Printing:• Typically, such printing involves the application of a pharmaceutical branding ink to

the coated tablet surface by means of a printing process known as offset rotogravure.

• Adhesion of printing inks can be enhanced by application (prior to printing) of a modified shellac, preprint base solution.

Basic application procedures of sugar coating

1. Application of an appropriate volume (sufficient to completely cover the surface of every tablet in the batch) of coating liquid to a cascading bed of tablets.

2. Distribution of the coating liquid uniformly across the surface of each tablet in the batch.

3. Drying of the coating liquid once uniform distribution is achieved.

• NB: the main mechanism for coating liquid distribution relates to the shearing action that occurs as tablets cascade over one another, so it is not necessary to finely atomize the coating liquid in order to ensure effective distribution of that liquid.

• It’s not necessary for each tablet to pass through the zone of application, unlike the film-coating process.