Tablet CoatingAn 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

- Aqueous based processes are now the most common+ 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

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

• A Typical Side Vented Drum CoaterMixing Baffle

Rotating Perforated Pan

Spray Arm

Tablet Bed

Control Panel

Coating Pan Perforations Baffle Baffle

Mobile Solution Vessel Peristaltic Solution Pump Spraying The Tablets

Tablet Coater

Spray Arm

Solution Vessel

Peristaltic PumpFloor Balance

Spray Guns

Coating Spray Arm

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 pH

Stomach 1.0 - 3.5

Duodenum 6.5 - 7.6

Jejunum 6.3 - 7.6

Ileum 7.6

Colon 7.9 - 8.0

Rectum 7.8

Enteric Coating

• 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

GI REGION pH

Stomach 1.0 - 3.5

Duodenum 6.5 - 7.6

Jejunum 6.3 - 7.6

Ileum 7.6

Colon 7.9 - 8.0

Rectum 7.8

• 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

• Enteric coating uses materials with solubility profiles dependent upon pH

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

Possible Causes Solutions • Spray rate too high Reduce spray rate and/or increase

efficiency atomising

• Pan speed too low Increase pan speed

• Inappropriate tablet shape 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 Reformulate the suspension

• Spray guns too close to Increase gun to tablet bed distance

tablet bed

TWINNING

Possible Causes Solutions • Low mechanical strength of coating, Select formulation with improved mechanical

strength exacerbated by and elasticity characteristics inadequate plasticiser or excessive pigmentation

• Core has significantly different thermal Avoid use of mineral-type fillers (e.g. expansion characteristics than coating calcium carbonate, calcium sulphate,

magnesium carbonate) where possible • Extended elastic recovery of core after Extend holding period for tablets prior to submitting

them to compaction coating process • Inadequate plasticization

CRACKING

Possible Causes Solutions

• Low mechanical strength of coating Select formulation with improved mechanical strength

• Poor adhesion of coating to tablet surface Select formulation for improved adhesioncharacteristics

• Excess lubricant usage in formulation Use an excipient with good lubrication

properties like STARCH 1500

PEELING

Possible Causes Solutions

• Viscosity of coating liquid too high Reduce solids content of coating liquid / viscosity

• Poor atomisation of coating liquid Increase atomising air pressure / volume (n.b. excessive atomisation may

exacerbate spray drying)

ORANGE PEEL ROUGHNESS

Possible Causes Solutions • Inadequate adhesion of the film coating Select formulation for improved adhesion

characteristics • Surface characteristics of the product Modify core formulation to include more being

coated(e.g. hydrophobic substrate) hydrophilic ingredients (where possible) or increase core porosity

Inappropriate design of logo(e.g. too Select a different logo design (with detailed or too fine) increased area within the debossing and

modified angles) • Insufficient plasticiser in film / Reduce spray rate / increase drying rate

high internal stress

LOGO BRIDGING

Possible Causes Solutions • Spray rate too high Reduce spray rate • Inadequate drying conditions Improve drying conditions • Pan speed too low Increase pan speed • Inadequate atomisation of coating Increase atomising air pressure / volume

liquid • Poor distribution of coating liquid Select formulation for improved adhesion

characteristics

PICKING / STICKING

Possible Causes Solutions • Inappropriate design of logo Select a different logo design (with increased area (e.g. too

detailed or too fine) within the debossing and modified angles)

• Logo "disappearance" can be due Reduce erosion potential by reformulating core, to erosion of tablet surface around changing logo design or modifying curvature of faces logo of tablet

• Logo Bridging See solutions for Logo Bridging • In-filling of logo with spray-dried Reduce spray-drying potential by:

coating material - increasing spray rate - reducing inlet air temperature / air flow

- reducing atomising air pressure - reducing distances between spray guns and surface of tablet bed

LOGO INFILLING

Possible Causes Solutions • Inherent softness or high friability 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

• Excessive pan speed in coating Reduce pan speed process

• Spray rate too low Increase spray rate • Low solids content of spray Select formulation with high solids solution content • Premature swelling of hydrophilic Replace super disintegrant with less hydrophilic super

disintegrant in formulation disintegrant like STARCH 1500

CORE EROSION

Possible Causes Solutions • Low mechanical strength of coating Select formulation with improved mechanical

strength • Excessive pan speed Decrease pan speed • Low solids content in coating liquid Increase solids content of coating liquid • Low spray rate Increase spray rate • Sharp edges on tablets Replace or use modified punch design (use dual

radius punch tips) • Worn tablet punches Refurbish or replace punches • Low tablet hardness / friability 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)

EDGE CHIPPING / EROSION