Tablet Coating

An overview

What We Will Cover

Different Types of Coating Basics of the Process Modified Release Coats Some Typical Equipment and Materials

Types of Tablet Coating

Compression (or Dry) Coating compaction of granular material around an already formed tablet core uses similar process & equipment as standard compression especially for moisture sensitive products and for separating incompatible ingredients (one in the core and one in the coat) not in widespread use today

Sugar Coating

Sugar Coating - Pros & Cons

+ Relatively low tech and low capital costs and low complexity + Cheap, readily available and acceptable ingredients (sugar & water) + Provides an attractive, smooth & glossy finish + Good for taste masking and easing swallowing

High expertise / experience of operator required More difficult to automate / more labour intensive Long cycle times (up to 20 hours) Does not allow for embossing so identification must be by printing if required Involves a large increase in tablet size and weight

Sugar Coating - the Process

Involves the successive application of sucrose based solutions in a coating pan It can be automated in a modern coating machines but the traditional approach has been a manual operation using an open (conventional) pan and ladling the solution on tablets

Conventional (Open Pan) Coaters

low initial capital cost

low energy & space
requirements easy to maintain & clean

drying efficiency is low as it is mostly from the

tablet bed surface mixing efficiency is low and dead spot may exist in the bed poor containment for solvent vapours manual process is more dependant on operator skill difficult to instrument

Sugar Coating - A Typical Multi-stage Process

Sealing
application of a sealant to protect the tablet cores from water applied during subsequent stages over application can give disintegration issues sealants are typically water insoluble film forming materials applied in an organic solution examples of sealants are
shellac in combination with polyvinyl pyrrolidone (PVP) to prevent hardening with age polyvinyl acetate phthalate cellulose acetate phthalate acrylate polymers

Sugar Coating - the Process

Subcoating

sugar coated tablets have completely smooth edges and the subcoat is gradually built up to achieve this profile. the compressed core should have as rounded a profile as possible to assist in the process.

Method 1 apply gum / sucrose solution followed by dusting with powder then drying repeat until desired profile is achieved Method 2 apply suspension of dry powder in gum / sucrose solution followed by drying repeat until desired profile is achieved
gums used include gelatin, acacia , starch or PVP

powders used include calcium carbonate or talc solids content in the solution is as high as possible to keep drying times low

Sugar Coating
Smoothing (or Grossing)
after Sub coating the tablet surfaces are generally rough a more dilute sucrose solution is applied to make the surface smooth

Colouring
water soluble dyes demand a high degree of skill in application and have longer coating times water insoluble pigments easier to use and give more consistent results with shorter coating times

Polishing
gives an attractive finish to the tablets beeswax or carnuba wax is applied in an organic solvent sometimes a wax or canvas lined pan is used to assist in the polishing action.

Printing
the thickness of the coat would obliterate any embossing so if markings are required the tablets are printed with edible printing inks

Film Coating - Pros & Cons

+ Minimal weight gain (2-3% as opposed to 100% for sugar coating) + Coat is less likely to affect disintegration + Single stage process an so generally quicker + Easy to automate (less reliance on skilled operator / easier to meet GMP requirements of SOPs, validation etc) - Expensive equipment & plant requires large space + Maintains original shape of the core & allows for embossing - High installation & energy costs

Aqueous vs Solvent Film Coating

Solvent based coating solutions / suspensions (e.g. alcohols, methylene chloride)

+ +

rapid drying time due to inherent volatility can be applied to moisture sensitive products operator safety issues requires modification to equipment and facility (flame-proofing / intrinsically safe) environmentally responsible disposal is expensive (solvent recovery) can impart taste / smell to the product no safety issues (e.g. can allow mobile vessels) can release to atmosphere takes longer and may lead to mechanical damage as tablets are tumbled for longer requires more efficient drying air plant

Aqueous based processes are now the most common

+ +

Advances in drying efficiency has allowed aqueous processes to be developed even for moisture sensitive products

Film Coating - the Process

The coater drum rotates and the baffles in the drum mix the tablets Warm air is drawn through the bed as it enters (inlet air) and exist (outlet air) the drum through perforations The distance from the spray guns to the tablet bed is measured and the spray adjusted to achieve and even (non overlapping) coverage across ~75% of the bed The coating suspension is pumped through the spray guns with compressed (atomising) air which forms a spray of fine droplets As the suspension droplets hit the tablet surface they should spread into a film before the solvent is rapidly removed by the throughput air The aim is to gradually build up the coat as the tablets pass beneath the spray guns

Rotating Perforated Pan

A Typical Side Vented Drum Coater

Tablet Bed

Mixing Baffl

Control Panel

Spray Arm

Coating Pan Perforations

Baffle

Baffle

Mobile Solution Vessel

Peristaltic Solution Pump

Spraying The Tablets

Spray Arm Tablet Coater

Solution Vessel

Peristaltic Pump

Floor Balance

Coating Spray Arm

Spray Guns

Supply of Coating Suspension and Atomising Compressed Air

Common Components of a Film Coat

Solvents
water solvents
alcohols (e.g. methanol, ethanol, isopropanol) esters (e.g. ethyl acetate, ethyl lactate) chlorinated hydrocarbons (e.g. methylene chloride, 1:1:1 trichloroethane)

Polymers / Film Formers

form a clear, non-tacky, mechanically strong film must be soluble in the chosen solvent and also allow release of drug in the body must be compatible with the core contents most common example is Hydroxy propyl methyl cellulose (HPMC)

Common Components of a Film Coat Plasticisers

modify the properties of the polymer to assist the coating process (e.g. by reducing brittleness of the coat) need to be miscible with the polymer e.g. propylene glycol, polyethylene glycol (PEG),

Colourants
water insoluble pigments or water soluble dyes e.g. yellow or red iron oxide, aluminium lake dyes

Opacifiers
provide a hiding function preventing the coat from being see through used to mask core colour and / or provide light protection some water soluble pigments have opacifier properties e.g. titanium dioxide

Modified Release Coatings

Preparations which have been designed in such a way that the rate or place at which the active ingredients are released has been modified (BP) Coating can be applied directly to the tablet or indirectly by coating small pellets before compression

Enteric Coating

GI REGION Stomach Duodenum Jejunum Ileum Colon Rectum

pH 1.0 - 3.5 6.5 - 7.6 6.3 - 7.6 7.6 7.9 - 8.0 7.8

Enteric Coating
GI REGION Stomach Duodenum Jejunum Ileum Colon Rectum pH 1.0 - 3.5 6.5 - 7.6 6.3 - 7.6 7.6 7.9 - 8.0 7.8

Enteric coating uses materials with solubility profiles dependent upon pH

Reasons for Enteric coating: to protect the tablet from the acidity of the stomach to protect the stomach from irritant effect of some drugs e.g. Aspirin to specifically target drug absorption in the GI Tract downstream of the stomach

Enteric Sugar coating the sealant includes an enteric polymer, other steps remain the same Enteric Film coating an enteric polymer is incorporated into the suspension weight of suspension applied is more critical (and greater) than standard film coating Enteric polymers include cellulose acetate phthalate, polyvinyl acetate phthalate and acrylates

Controlled / Sustained
Coating includes specialist materials which are insoluble but allow water to enter and the drug in solution to diffuse out Designed to give uniform and sustained drug release at a rate determined directly by the coating thickness Examples are modified ethylcelluloses

Laser Drilled Hole

Tablet Core

Selectively Permeable Membrane Coat After swallowing, water can enter via the coat and

the hole but the membrane prevents dissolved active getting out

Water entry causes the table to swell and a build up of pressure inside the coat

Pressure build up forces out active in solution via the laser drilled hole. This controls the release over a period of time. Also known as an Osmotic Pump.

Some Common Tablet Coating Problems & Solutions

Coating Problems
Main Causes:
Poor Tablet Design (e.g. fine embossing, flat surfaces) Physical Damage (e.g. overloading the coater, loading / unloading operations) Overwetting - the suspension droplets hit the tablet surface whilst still wet and the drying air does not dry quickly enough. This can lead to surface pitting. Spray Drying - the suspension droplets hit the tablet surface after the moisture has been removed. This can lead to lack of / poor adherence of the coat.

TABLET-TO-TABLET COLOR VARIATION

Possible Causes Solutions Too little coating applied Increase quantity of coating applied Inadequate mixing of tablets during coating Increase pan speed and/or improve baffle system Poor opacity (or hiding power) of coating Reformulate coatings to improve opacity or use an opacified white pre-coat (for coloured tablet cores) Solids content of coating liquid is too high Reduce solids content of coating liquid Insufficient number of spray guns Increase number of spray guns Poor spray pattern bed distribution Ensure gun position is correct and provides optimum bed coverage Pan speed too low Increase pan speed

TWINNING
Possible Causes
Spray rate too high efficiency Pan speed too low Inappropriate tablet shape

Solutions
Reduce spray rate and/or increase atomising Increase pan speed Select new tablet shape that minimises chances of flat surfaces

coming into contact during

application of coating liquid (e.g. avoid capsule-shaped tablets with straight edges or thick side walls)

Tacky coating formulation

Spray guns too close to tablet bed

Reformulate the suspension

Increase gun to tablet bed distance

CRACKING

Possible Causes Low mechanical strength of coating, characteristics pigmentation

Solutions Select formulation with improved mechanical strength exacerbated by and elasticity inadequate plasticiser or excessive

Core has significantly different thermal characteristics than coating

Extended elastic recovery of core after submitting them to compaction Inadequate plasticization

Avoid use of mineral-type fillers (e.g. expansion calcium carbonate, calcium sulphate, magnesium carbonate) where possible Extend holding period for tablets prior to coating process

PEELING
Possible Causes Low mechanical strength of coating Poor adhesion of coating to tablet surface Excess lubricant usage in formulation Solutions Select formulation with improved mechanical strength Select formulation for improved adhesion characteristics Use an excipient with good lubrication properties like STARCH 1500

ORANGE PEEL ROUGHNESS

Possible Causes Viscosity of coating liquid too high Poor atomisation of coating liquid Solutions Reduce solids content of coating liquid / viscosity Increase atomising air pressure / volume (n.b. excessive atomisation may exacerbate spray drying)

LOGO BRIDGING
Possible Causes Inadequate adhesion of the film coating Surface characteristics of the product coated(e.g. hydrophobic substrate) Inappropriate design of logo(e.g. too detailed or too fine) Insufficient plasticiser in film / high internal stress Solutions Select formulation for improved adhesion characteristics Modify core formulation to include more being hydrophilic ingredients (where possible) or increase core porosity Select a different logo design (with increased area within the debossing and modified angles) Reduce spray rate / increase drying rate

PICKING / STICKING

Possible Causes
Spray rate too high Inadequate drying conditions Pan speed too low Inadequate atomisation of coating liquid Poor distribution of coating liquid

Solutions
Reduce spray rate Improve drying conditions Increase pan speed Increase atomising air pressure / volume Select formulation for improved adhesion characteristics

LOGO INFILLING
Possible Causes
Inappropriate design of logo detailed or too fine) Logo "disappearance" can be due of tablet surface around Logo Bridging In-filling of logo with spray-dried coating material

Solutions
Select a different logo design (with increased area (e.g. too within the debossing and modified angles) Reduce erosion potential by reformulating core, to erosion changing logo design or modifying curvature of faces logo of tablet See solutions for Logo Bridging Reduce spray-drying potential by: - increasing spray rate - reducing inlet air temperature / air flow - reducing atomising air pressure - reducing distances between spray guns and surface of tablet bed

CORE EROSION
Possible Causes
Inherent softness or high friability

Solutions
Improve mechanical strength of core by increasing of core compaction force, modifying core formulation or changing process by which core is produced (e.g. use granulation process instead of direct compaction Reduce pan speed Increase spray rate Select formulation with high solids solution content Replace super disintegrant with less hydrophilic super disintegrant like STARCH 1500

Excessive pan speed in coating process Spray rate too low Low solids content of spray Premature swelling of hydrophilic disintegrant in formulation

EDGE CHIPPING / EROSION

Possible Causes
Low mechanical strength of coating Excessive pan speed Low solids content in coating liquid Low spray rate Sharp edges on tablets Worn tablet punches Low tablet hardness / friability

Solutions
Select formulation with improved mechanical strength Decrease pan speed Increase solids content of coating liquid Increase spray rate Replace or use modified punch design (use dual radius punch tips) Refurbish or replace punches Improve mechanical strength of core by increasing compaction force, changing tablet shape, modifying core formulation or hanging process by which core is produced (e.g. use granulation process instead of direct compaction)