Coatings

By Gamal Shazly

Tablet Coatings

� What is the rationale for coating a solid dosage form?

� Main coating processes � Functional coatings

Tablet coating is the application of a coating material to the exterior of a tablet with the intention of conferring benefits and properties to the dosage form over the uncoated variety.

What is the rationale for coating a solid dosage form?

Coating of a solid dosage form is often designed to perform a specific function. For example; protection against moisture, taste masking pH or time controlled release.

Tablets can be easily coated and a variety of products are available on the market.

Generally, the coating process gives rise to; � Increased bioavailability � Improved patient acceptance � Formulation stability The rationale for coating pharmaceutical dosage form such as a tablet can be

categorised into three main headings:

� Therapy � Technology � Marketing

What is the rationale for coating a

solid dosage form? Therapy

� To minimise irritation of the oesophagus and stomach.

� Minimise inactivation in the stomach.

� Improve drug effectiveness.

� Improve patient compliance e.g. easier to swallow, masks unpleasant taste.

What is the rationale for coating a

solid dosage form? Technology

� Minimise dust formation and contamination with respect to tablets. � Masks batch differences in the appearance of raw materials.

� Facilitates their handling on high speed automated filling and packaging

equipment. � Improves drug stability e.g. Protection of active ingredient from

environment such as sunlight, moisture.

What is the rationale for coating a

solid dosage form? Marketing

� Aid sales appeal as improved appearance and acceptability with respect to gloss and colouration.

� Mask unpleasant taste.

� Improve product identity.

Main coating processes

1.Film coating 2. Sugar coating 3. Press coating

Sugar coating

6. Printing 5. Polishing 4. Colouring 3. Smoothing 2. Sub coating 1. Seal tablet core

� Traditionally sugar coatings formed the bulk of coated tablets but today film coatings are the more modern technology in tablet coating.

� Description of tablets: Smooth, rounded and polished to a high gloss. � Process: Multistage process involving 6 separate operations.

Multistage process 1. Sealing tablet core- application of a water impermeable polymer such as

Shellac, cellulose acetate phthalate and polyvinyl acetate phthalate, which protects the core from moisture, increasing its shelf life.

2. Sub coating -by adding bulking agents such as calcium carbonate or talc in combination with sucrose solution.

3. Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup.

4. Colouring - for aesthetic purposes often titanium based pigments are included.

5. Polishing - effectively polished to give characteristic shine, commonly using beeswax, carnauba wax.

6. Printing -indelible ink for characterisation.

Simplified representation of sugar coating process

Process details � Typically tablets are sugar coated by a panning technique. The simplest form would

be a traditional sugar-coating pan with a supply of drying air (preferably of variable

temperature and thermostatically controlled) and a fan-assisted extract to remove

dust- and moisture-laden air.

� Methods of applying the coating syrup include manually using a ladle, and,

automatic control. In modern equipment some form of automatic control is available

for the application of coating syrups.

Ideal characteristics of sugar-coated tablets 1-tablets must comply with finished product specifications and any

appropriate compendial requirements.

2- Sugar-coated tablets should ideally be of a perfectly smooth rounded

contour with even colour coverage. Most manufacturers take advantage of

the aethetic appeal of a sugar-coated tablet and polish to a high gloss.

3-Any printing should be distinct, with no smudging or broken print.

Coating faults These are usually associated with process defects, such as splitting of the

coat on storage, caused by inadequate drying during the coating application.

Film coating Approach to coating tablets, capsules, or pellets by surrounding them with a thin layer of

polymeric material. Advantages Produce tablets in a single step process in relatively short period of time. Process enables

functional coatings to be incorporated into the dosage form. Disadvantages There are environmental and safety implications of using organic solvents as well as their

financial expense. Process: Single stage process, which involves spraying a coating solution containing the following; 1. Polymer 2. Solvent 3. Plasticizer 4. Colourant The solution is sprayed onto a rotating tablet bed followed by drying, which facilitates the

removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet.

Ideal characteristics of a film coating polymer

Solubility The polymer should have good solubility in aqueous fluids to facilitate the

dissolution of the active ingredient. However, for modified release the

polymer system should have low water solubility

Viscosity

The polymers should have a low viscosity for a given concentration. This will

permit the easy, trouble-free spraying of their solutions in industrial film

coating equipment.

Polymers used in film coating

Permeability the polymers should be efficient barriers against the permeability of water

Vapour or other atmospheric gases. These properties vary widely between

the individual polymers.

Mechanical properties polymer chosen for a film coat formulation must :

� Be of adequate strength to withstand the impact and abrasion encountered

in normal handling. Insufficient coating strength will be demonstrated by

the development of cracks and other imperfections in the coating.

� comply with the relevant regulatory and pharmacopoeial requirements

current in the intended marketing area.

Examples of the polymers used;

- Cellulose derivatives e.g. MC, HPC, HPMC

- Methacrylate amino ester copolymers.

Plasticizer used in film coating

Examples; � Polyols - Polyethylene glycol 400 � Organic esters - diethyl phthalate � Oils/glycerides - fractional coconut oil

Colourants used in film coating Examples; Iron oxide pigments, Titanium dioxide, and Aluminium lakes. Water insoluble pigments are more favourable than water soluble colours for the

following reasons; 9 Better chemically stability in light 9 Optimised impermeability to water vapour 9 Better opacity 9 Better covering ability

Plasticizers are generally added to film coating formulations to modify the physical

properties of the polymer to make it more usable. One important property is their

ability to decrease film brittleness

Solvents used in film coating Modern techniques now rely on water as a polymer solvent because of the

significant drawbacks that readily became apparent with the use of organic

solvents.

The disadvantages of organic solvents for the process:

1. Environmental: the venting of untreated organic solvent vapor into the atmosphere

is ecologically unacceptable, and efficient solvent vapor removal from gaseous

effluent is expensive. 2. Safety: organic solvents provide explosion, fire and toxic hazards to plant operators.

3. Financial: the use of organic solvents necessitates the building of flame- and

explosion-proof facilities. Ingredient cost is also comparatively high, and the

associated costs of storage and quality control must also be taken in to consideration.

4. Solvent residues: for a given process the amount of residual organic solvent in the

film must be investigated. With increasing regulatory pressure this will become an

area for additional control in the future

Process details The vast majority of film coated tablets are produced by a process which involves spraying of the coating material on to a bed of tablets. Accela Cota is one example of equipment used for film coating.

Basic process requirements for film coating 1. Adequate atomizing the spray liquid for application to the tablet cores.

2. Adequate mixing and agitation of the tablet bed.

3. Sufficient heat input to provide the latent heat of evaporation of the solvent.

This is particularly important with aqueous-based spraying

4-Good exhaust facilities to remove dust- and solvent-laden air.

Ideal characteristics of film-coated tablets

Film-coated tablets should display

� An even coverage of film and colour.

� No abiasion of tablet edges or crowns.

� Logos and break lines should be distinct and not filled in.

� The tablet must also be within specifications and any relevant compendial

requirements.

Coating faults These arise from two distinct causes: 1. Processing: for example, inadequate drying conditions will permit coating

previously deposited on the tablet surface to stick against neighbouring

tablets. When parted, this will reveal the original core surface

underneath.

2. Formulation faults: film cracking or ‘bridging’ of break lines are examples

of this type. After taking due account of the mechanical properties of the

film, reformulation will almost certainly be successful in overcoming the

problem

Why is film coating favoured over sugar coating ?

Film coating Tablet appearance 9 Retains shape of original core 9 Small weight increase of 2-3% due to

coating material 9 logo or ‘break lines’ possible Process 9 Can be automated e.g. Accela Cota 9 Easy training operation 9 Single stage process 9 Easily adaptable for controlled release

allows for functional coatings.

Sugar coating Tablet appearance 9 Rounded with high degree of polish 9 Larger weight increase 30-50% due to

coating material 9 Logo or ‘break lines’ are possible Process 9 Difficult to automated e.g. traditional coating pan 9 Considerable training operation required 9 Multistage process 9 Not able to be used for controlled release

apart from enteric coating.

coating pans

fluid beds

PRESS COATING involves the compaction of granular material around an already preformed

Core using compression equipment similar to that used for the core itself,.

press coating is used

� to separate chemically incompatible materials, one or more being placed in the core

and the other(s) in the coating layer. However, there is still an interface contact left

between the two layers. In cases where even this is important then the process of

pre coating can be taken one stage further. It is possible to apply two press coatings

to a tablet core using suitable equipment. This equipment produces press-coated

tablets with perfect separation between active core and coating, as the two can be

separated by an inert middle layer.

Functional coatings Functional coatings are coatings, which perform a

pharmaceutical function. These include; � Controlled release coating � Enteric coating Multiparticulates (Pellets’ or ‘Beads), find favor over conventional non-

disintegrating tablets for controlled release use, owing to a number of factors:

1. Their small size (typically 0.7—2.00 mm) allows them to pass through the

constricted pyloric sphincter and distribute themselves along the

gastrointestinal tract. This tends to overcome the disadvantage that whole

tablets have of a rather irregular passage through the gastrointestinal tract

and consequent irregular absorption

2. Whole, non-disintegrating tablets can be liable to lodge in restrictions within the

gastrointestinal tract, and this can lead to ulcerative damage to the gastric mucosa

as the drug solution is leached out from the tablet. Because of their small size, this

is not a problem with multiparticulates

3-Should an individual bead or pellet fail and release all of its contents at once the

patient Would not be exposed to any undue risk. This is Certainly not the case if a

non-disintegrating tablet failed, when the consequences would Potentially be

serious

Types of multiparticulate

Extruded/spheroflized granulates

produced in modified granulating equipment , with the drug granulation extruded through

a mesh or other device under pressure to form small granulates which are

subsequently spheronized.

Non-pareilsThese are sucrose spheres which are coated with the drug plus an adhesive

water-soluble polymer (Fig 28.4). After their formation and any necessary intermediate

steps such as drying, they may be coated with the controlled-release coating.

Mechanisms of drug release from multiparticulates

1. Diffusion

On contact with the aqueous fluids of the gastrointestinal tract, water will enter

the interior of the particle by diffusion. Dissolution of the drug will occur and

drug solution will diffuse across the controlled-release coat to the exterior.

2. Erosion

Some coatings can be designed to erode gradually with time, thereby

releasing the drug contained within the pellet.

3. Osmosis

In allowing water to enter, an osmotic pressure can be built up within the

interior of the pellet. drug solution will be forced out of the pellet to the

exterior .

Enteric coating The technique involved in enteric coating is protection of the tablet core from

disintegration in the acidic environment of the stomach by employing pH sensitive polymer, which swell or solubilize in response to an increase in pH to release the drug.

The enteric polymers (CAP,PVAP, suitable acrylic derivative ) are capable of forming a direct film in a film-coating process. Sufficient weight of enteric polymer must be used to ensure an efficient enteric effect. This is normally two or three times that required for a simple film coating.

Aims of Enteric protection: 9 To mask taste or odour 9 Protection of active ingredients, from the acidic environment of the stomach. 9 Protection from local irritation of the stomach mucosa. 9 Release of active ingredient in specific target area within gastrointestinal tract.

The pH status of enteric coated polymers in the stomach

The polymers used for enteric coatings remain unionise at low pH, and therefore remain insoluble. As the pH increases in the gastrointestinal tract the acidic functional groups are capable of ionisation, and the polymer swells or becomes soluble in the intestinal fluid. Thus, an enteric polymeric film coating allows the coated solid to pass intact through the stomach to the small intestine, where the drug is then released for absorption through the intestinal mucosa into the human body where it can exert its pharmacologic effects.

The ideal properties of enteric coated material?

9 Permeable to intestinal fluid 9 Compatibility with coating solution and drug 9 Formation of continuous film 9 Nontoxic 9 Cheap and ease of application 9 Ability to be readily printed 9 Resistance to gastric fluids