93c3coating of Solid Dosage Form

8/3/2019 93c3coating of Solid Dosage Form

1/130


2/130

2

SCHEMEOF PRESENTATION Introduction

- Why Coating is Required?

Key Factors

- Tablet Properties

Coating techniques- Film Coating

Introduction

Reasons for film Coating

Film Coating materials

Process controls Coating Equipment

Pelletization

Introduction

Preparation


3/130

3

INTRODUCTION

Tablet coating is the application of coating material to the

exterior of a tablet with the intention of conferring benefits and

properties to dosage form over the uncoated variety.

Why Tablet Coating is Required?

A number of reasons can be suggested:

The core contains a material which has a bitter taste in the

mouth or has an unpleasant odor.

Coating will protect the drug from the surroundings with a

view to improve its stability.

Coating will increase the easeby which a tablet can be ingested

by the patient.


4/130

4

CONT.

The core contains a substance which is incompatible in the

presence of lightand subject to atmospheric oxidation, i.e. a

coating is added to improve stability.

The core alone is inelegant.

The active substance is colored and migrates easily to stain hands

and clothes.

The coated tablet is packed on high-speed packaging machine.

Coating reduces friction and increasespackaging rate.

Coating can modify the drug release profile, e.g., enteric coating,

osmotic pump, pulsatile delivery.


5/130

5

KEY FACTORS

Tablet Properties

Core design is extremely important!!

Mechanical integrity (hardness, friability, etc.)

Physico-chemical stability of the core when exposed to coating

conditions (expansion or contraction, release rate, etc.)

Shape Effect!!

Coating illustrates areas on the tablet that have the highest

erosion potential. Therefore, normal concave is the preferred

shape for film coating.

Areas prone to surface erosion for flat, shallow concave, caplet

shaped and deep concave tablets respectively as shown in fig 1.


6/130

6

CONT.

Twining Occurs fig 2 Twinning less likely

Fig 1


7/130

7

TECHNIQUES

Coating Techniques

Sugar Coating

Film Coating

Compression Coating

Why not sugar coating?

Reasons are:

Skilled manipulative process

Long and vigorous

Operator must be highly skilled for such coating.


8/130

8

COMPARISON


9/130

9

Film coating is a process whereby a polymer based coating is

applied to the substrate such that:

- The rate of application of the coating fluid and the drying rate arecarefully controlled.

- The coating material is uniformly applied to the surface of the

substrate.

- The quality and the functionality of the applied coating are bothmaximized and reproducible.

- The thickness of such a coating is usually between 20-100 m.

FILM COATING


10/130

10

SCHEMETIC REPRESENTATION


11/130

11

CONT. Film coatings are applied for the following reasons:

- Their aesthetic qualities

- Improving product stability and robustness

- Enhancing flavor attributes- Facilitating ingestion and modifying drug release

characteristics.


12/130

12

CONT. Film coating is performed by two types,

1. Aqueous film coating (generally water is used as a solvent)

High quality aqueous film coating must be smooth,

uniform and adhere satisfactorily to the tablet surface

and ensure chemical stability of a drug.

Non-functional Coating


13/130

13

CONT.

2.Non aqueous film coating (generally organic solvent are used.)

(Functional Coating) (Modified-Release Coating)

Some problems are associated with the non aqueous filmcoating like employee safety (its dangerous, it smells, and

its not good to breathe.) atmosphere pollution etc. But key

problem is with the approval of the regulatory authority.


14/130

14

FILM COATING MATERIALS

An ideal film coating material should have the Following

attributes:

Solubility in solvent of choice for coating Preparation

Capacity to produce an elegant looking product

Essentially no color, taste or odor

Compatibility with common coating solution additives

Ease of printing procedure on high speed equipment

No toxicity and no pharmacological activity


15/130

15

Polymer Capable of forming smooth thin films reproducible under

conventional coating conditions and applicable to variety oftablet shapes (7-18%)

Non-enteric Polymers Enteric Polymers

Hypromellose Hypromellose phthalate

Hydroxyethyl cellulose Polyvinyl acetate phthalate

Hydroxyethylmethyl Cellulose Cellulose acetate phthalate

Carboxymethylcellulose

sodium

Polymethacrylates

Hydroxypropyl Cellulose Shellac

Ethyl Cellulose

Polyethylene Glycol


16/130

1616

IDEAL CHARACTERISTICS OF A FILM COATING POLYMER

Solubility

For conventional film coating the polymer should have good

solubility in aqueous fluids to facilitate the dissolution of the

active ingredient from the finished dosage form. However, where

a modified-release action is required then a polymer system of

low water solubility or permeability will be chosen.


17/130

1717

Viscosity

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.

Permeability

Film coating can be used to optimize the shelf-life of a tablet

preparation, as some polymers are efficient barriers against the

permeability of water vapor or other atmospheric gases. Theseproperties vary widely between the individual polymers

CONT.


18/130

1818

Mechanical properties

polymer chosen for a film coat formulation must be:

one with 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.

It should be mentioned that the polymer chosen must also comply

with the relevant regulatory and pharmacopoeial requirementscurrent in the intended marketing area.

CONT.


19/130

19

CONT


20/130

20

Plasticizer Plasticizers are simply relatively low molecular weight

materials which have the capacity to alter the physicalproperties of the polymer to render it more useful inperforming its function as a film-coating material.

Concentration (0.5-2.0 %)

Polyols Organic Esters Oils/Glycerides

Glycerol Phthalate esters Castor oil

Propylene glycol Citrate esters Fractionated Coconutoil

Polyethylene glycol

(PEG)

Triacetin Acetylated

Monoglycerides


21/130

21

CONT


22/130

22

Solvent/Vehicles

The key function of a solvent system is to dissolve ordisperse the polymers and other additives.

The major classes of solvents being used are,

Water

Alcohols

Ketones

Esters

Chlorinated hydrocarbons

Because of environmental and economic considerations, wateris the solvent of choice; however organic coating is totallycannot be avoided


23/130

23

These materials are generally used as ingredients in film-coating

formulae to contribute to the visual appeal of the product, but they

also improve the product in other ways.

Colorants for film coating are having, in more or less amount,

property of Opacifiers. So they would give protection to activeingredients in presence of light.

Concentration (2.5-8%)

Colorants/Opacquents

Organic dyes andtheir lakes

Inorganic colors Natural colors

Sunset yellow Ion oxide red, Black Carmine

Erythrosine Titanium dioxide Anthrocyanine

Tartrazine Ribofloavine


24/130

24

Miscellaneous coating solution components

To provide a dosage form with a single characteristic,

special materials may be incorporated into a solution.

Flavors and sweeteners are added to mask unpleasant odors

or to develop the desired taste. For example, aspartame,

various fruit spirits (organic solvent), water soluble pineapple

flavor (aqueous solvent) etc.

Surfactants are supplementary to solubilise immiscible orinsoluble ingredients in the coating. For example: Spans,

Tweens etc.


25/130

25

CONT

Antioxidants are incorporated to stabilize a dye system to

oxidation and color change. For example: oxides, phenols etc.

Antimicrobials are added to put off microbial growth in the

coating composition. Some aqueous cellulosic coating

solutions are mainly prone to microbial growth, and long-

lasting storage of the coating composition should be avoided.

For example: alkylisothiazloinone, carbamates,

benzothiazoles etc.


26/130

26

PROCESS CONTROLS

Pan Variables

Rotating speed of pan

Tablet motion, a factor influenced greatly by pan speed, can be a

major issue in the following cases:

Tablet breakage

Edge wear,

Surface erosion.

The uniformity of distribution of the applied coating i.e. higher

the pan speeds being better in this regard.


27/130

27

CONT It is well documented that increasing the rotating speed of the pan

improves the mixing of tablets. The pan speed affects the time the

tablets spend on the spraying zone and, subsequently, the

homogeneous distribution of the coating solution on the surface of

each tablet throughout the batch.

Increasing the pan speed decreases the thickness variation and

increase the uniformity of coatings.

Too much rotating speed of the pan will cause the tablet to

undergo unnecessary attrition and breakage.


28/130

28

Pan loading Pan loadings are usually defined in terms of volume fill, rather

than by weight. Thus, the optimum pan loading by weight will

vary from product to product, depending on the apparent density

of that product.

The difficulty arises for the following reasons:

On the laboratory scale, it isnot too difficultto ensure that a panis

appropriately loaded. Even when only a very small amount of

product is available,this problem canbe dealt with by bulking up

active tablets with placebosto make afull charge.


29/130

29

CONT.

On the production scale, total batch weight of the compressed

tablets, can be divided into a whole number of pan loads. For

example, if the total batch weight is 500kg,and these tablets are to

be coated in a pan that optimally holds 120kg per run, then the

instructions will call for five pan loadsof 100kg eachto be coated.

The result isthat each coating run will haveeach pan under loaded

byabout16%. In the example shown, a 16% under loading may not

seem to be too much of a problem, but potentially critical issuesthat may arise include:


30/130

30

CONT.

When pan is under loaded, the side walls of the coating pan, or

even baffles, become more exposed to the spray, causing

coating liquid to build up on exposed metal surfaces, often with

the result that tablets will stick to these surfaces.

This can be minimized by the following ways,

Changing the gun-to-bed distances Gun spacing

The number of guns used can minimize this problem.


31/130

31

SPRAY VARIABLES

Gun-to-tablet-bed distance:

With the help of rudimentary positioning tools, such as a ruler,

the operator is left to set up gun position. Gun positioningneeds to be optimized to:

Ensure that optimal and reproducible bed coverage is achieved.

Facilitate broad coverage while providing maximum surface

drying time. Achieve reproducible spray droplet characteristics as they

arrive at the tablet surface


32/130

32

Quality attributes of film-coated tablets that can be associated with

spray-gun performance include;

Appearance

- Coating gloss

- Coating roughness

- Existence of defects ("picking," edge chipping/edge wear, filling

in of logos)

- Colour uniformity

Functional

- Uniformity of distribution of coating

- coating porosity (which influences film permeability)

-Solvent (water) penetration into the tablet cores, and hence

product stability.

Spray gun dynamics


33/130

33

Spray rate

The spray rate is a significant parameter since it impacts the

moisture content of the formed coating and, subsequently,

the quality and uniformity of the film.

A low coating liquid spray rate causes incomplete

coalescence of polymer due to insufficient wetting, which

could effect in brittle films.

A high coating liquid spray rate may result in over wetting

of the tablet surface and subsequent problems such as

picking and sticking.


34/130

34

CONT

If the spray rate is high and the tablet surface temperature is

low, films are not formed during the spraying but the post

drying phase, and rapid drying often produces cracks in the

films.


35/130

35

Atomizing air pressure

In general, increasing the spraying air pressure decreases the

surface roughness of coated tablets and produces denser andthinner films.

If spraying air pressure is excessive, the spray loss is great, the

formed droplets are very fine and could spray-dry before

reaching the tablet bed, resulting in inadequate droplet

spreading and coalescence.

PROCESS AIR VARIABLES


36/130

36

CONT

If spraying air pressure is inadequate, the film thickness and

thickness variation are greater possibly due to change in the

film density and smaller spray loss.

In addition, with low spraying air pressure big droplets

could locally over wet the tablet surface and cause tablets to

stick to each other.


37/130

37

Inlet air temperature

The inlet air temperature affects the drying efficiency (i.e.

water evaporation) of the coating pan and the uniformity of

coatings.

High inlet air temperature increases the drying efficiency of

the aqueous film coating process and a decrease in the water

penetration into the tablet core decreases the core tablet

porosity, tensile strength and residual moisture content of

coated tablets.


38/130

38

CONT

Too much air temperature increases the premature drying of

the spray during application and, subsequently, decreases the

coating efficiency.

Measuring the pan air temperature helps to manage the

optimum conditions during the coating process and,

consequently, enables predicting possible drying or over

wetting problems which may result in poor appearance of thefilm or may have unfavorable effects on the moisture and

heat sensitive tablet cores.


39/130

39

Drying-air volume

Drying-air volume is selected based on,

1. The recommendations of the vendor of the equipment

2. On thebasis of the optimum conditions designed for the

air- handling system that has been installed.

- The supply and exhaustairfan speeds should be set, basedon

the equipment used, to meet the negative pressure pansettings that areusually recommended.

-


40/130

40

CONT Once the appropriate drying air volume has been

established, this setting becomes a driver for other keyprocessingvariables, such as sprayrate.


41/130

41

COATING EQUIPMENT

Most commonly used equipments are,

The standard coating pan

The perforated coating pan

The Fluidized bed coater


42/130

42

Conventional Pan System

It consists of a circular metal pan mounted somewhat angularly

on a stand and is rotated on its horizontal axis by a motor.

Heated air is directed into the pan and onto the tablet bed

surface , and is exhausted by means of ducts positioned through

the front of the pan.

UpgradedConventionalCoating Pan

Side VentedCoating Pan

ConventionalCoating Pan


43/130

43


44/130

44

CONT

A significant improvement in the particle movement & drying

efficiency of the standard coating pan is achieved by the,

Pellegrini pan

Immersion sword

Immersion tube systems


45/130

45

IMPROVEMENT IN THE PARTICLE MOVEMENT

Mixing of the core bed is important for a uniform application of

the coating material as well as for effective drying.

The most basic approach to improve the core bed movement in

pans rotating on inclined or horizontal axes was to introducebaffles and blades in the pan. One of the first pans with a single

baffle was invented by Keil in 1965

The first coating pan rotating on a horizontal axis equipped with

tapered side walls and an integral baffle system was introducedby Pellegrini and is well-known as the Pellegrini pan.


46/130

46

PELEGRINI PAN

The side walls of this pan are shaped with a pronounced taper,

which increases the efficiency of particle movement by forcing the

cores into an additional lateral movement. This results in a

composite core movement yielding improved exposure of the core

to the coating material.


47/130

47

CONT

USING BAFFLES AND BLADES INCREASES RISK of

friction between the core material and the pans, potentially

resulting in increased amounts of dust formed during the

coating process.

Hence, FOCUS was on the IMPLEMENTATION OF

PERFORATED PANS to improve the air transport in the core

bed and consequently to increase the mixing and drying

efficiency.


48/130

48

IMPLEMENTATION OF PERFORATED PANS Hostetler, for instance, has modified the peripheral wall with

perforations and positioned an air supplying inlet at the lower

peripheral area, forming the so-called side-vented pan.

The shape of the pan, the perforations in the peripheral wall, andthe side positioned air supplying inlet were not only intended to

increase core movement and air transfer, but also to increase thecontact area of the cores with the coating material.

Side-vented pan of Hostetler


49/130

49

IMPROVEMENT IN THE DRYING EFFICIENCY

Generally, the energy required for evaporating the moisture

from the coating layers is derived from the drying air.

The duration of the coating process as well as the quality of the

end product thus crucially depend on the efficiency of heat andmass transfer.

Increasing the heat and mass transfer either directly (for example

by increasing temperature and rotation speed or implementation

of perforations) or indirectly by improving the drying air supplycan improve drying efficiency.


50/130

50

CONT.

With the conventional drying method, the drying air is blown

across the surface of the core bed. As only the surface of the core

bed is exposed to the drying air, insufficient drying of core

materials and impaired spraying processes might occur.

Hence, different drying gadgets have been developed, of which

the two conventional ones are the immersion tube and the

immersion sword.


51/130

51

IMMERSION SWORD SYSTEM

With the immersion sword system, drying air is introduced

through a perforated metal sword device that is immersed in the

tablet bed.

The drying air flows upward from the sword through the bed.

Since the air is more intimately mixed with the wetted tablets, a

more efficient drying environment is provided.

As shown in figure.


52/130

52

CONT

Immersion Sword system


53/130

53

IMMERSION TUBE SYSTEM In this type of system the immersed tube delivers the heated air,

and a spray nozzle is built in the tip of the tube. During thisoperation , the coating solution is applied simultaneously withthe heated air from the immersed tube .

The drying air flows upward through the tablet bed and is

exhausted by a conventional duct.


54/130

54

CONT

Both the immersion sword and immersion tube systems are

adaptable to conventional coating pans.

Relatively rapid processing times have been reported for both

film and sugar coating with this system.


55/130

55

Pan Coaters Rotating on Vertical Axis

Represents another approach towards the improvement of pan

coating.

Designed to overcome the problem of mechanical abrasion of

cores encountered in horizontally rotating pans with baffles or

blades.

Generally, in coaters that rotate around vertical axes, the feed

material to be coated is placed in a container which is moved by a

driving motor.

This causes the circulation of particles on the axis of rotation.


56/130

56

CONT. The centrifugal force first pushes the particles outwards from the

centre to the pan wall and then upwards following the curve ofthe wall.

Particles then drop down back into the middle of the containerdue to gravity. Usually, such equipments include a return device

at the upper part of the wall which assists the feed material toroll back into the container.


57/130

57

PERFORATED PAN SYSTEM

In Accela-cota and Hi-coater systems, drying air is directed into

the drum, is then passed through the tablet bed, and is exhausted

through perforation in the drum.

.

Accela-cota
http://www.vectorcorporation.com/products/tabletcoater_prod.asp


58/130

58

Hi-coater

Stretched" Design Provides Shorter Process Times
http://www.vectorcorporation.com/products/tabletcoater_prod.asp


59/130

59

An increased spray zone is accomplished by lengthening thecoating pan while maintaining the same diameter

CONT

CONT


60/130


61/130

61

CONT Manifold Spray Bar Provides Cleaning Advantages

manifold spray bar eliminates the external nozzle air and

solution lines on the exterior of the spray bar. Instead, nozzle air

and solution is delivered within the interior of the spray bar.


62/130

62

CONT one-gasket design allows for quick assembly of the spray bar.

Changing the number of spray guns has never been easier.


63/130

63

CONTFully Perforated or Integrated Plenum


64/130

64

Driacoater

The Driacoater introducesdrying air through hollowperforated ribs located oninside periphery of the drum.

As coating pan rotates theribs dip into the tablet bed,and dying air passes throughand fluidizes the tablet bed.Air is exhausted from back ofthe pan.


65/130

65

CONT.

For hard sugar coating , DRIACOATERS with perforated

multisided drums are used. The machines are capable to handle

sugar and sugar free solutions, (Sorbitol, Xylitol, Malitol,

Isomalt, etc.), glazing and polishing solutions as well as aqueous

suspensions. Automatic loading and unloading, inside pan cleaning and

fully automatic process capabilities characterize this

DRIACOATER with batch sizes from 625 ltr to 3750 ltr.

Complete production units including:

Dosing and spraying systems for solutions, flavor and polishing

Dosing/distribution for solid powdery materials

Supply and exhaust air installations with air conditioning


66/130

66

FLUIDIZED BED SYSTEM

Process advantages

Uniform, continuous product coating.

Aqueous or organic coatings can be applied. Coating and drying

take place in one machine.

In terms of Total Containment, the coating process and the filling

and emptying of the machine can be carried out in complete

isolation and without product spreading into the environment.

When using organic solvents, the process machines can also bemade inert and used with a solvent recovery system.


67/130

67

CONT

Principle of operation

With fluid bed coating, particles are fluidized and the coating

fluid sprayed on and dried. Small droplets and a low viscosity of

the spray medium ensure an even product coating.

Glatt offers Batch Fluid Bed Systems in different batch sizes with:

Top Spray Coating

Bottom Spray Coating (Wurster Coating)

Tangential Spray Coating (Rotor Pellet Coating)


68/130

68

CONT


69/130

69

CONT

Top Spray Coating This process is used for general coatings right up to enteric

coating.

With top spray coating in the fluid bed (batch and continuous),particles are fluidized in the flow of heated air, which is

introduced into the product container via a base plate..


70/130

70

CONT The coating liquid is sprayed into the fluid bed from above

against the air flow (countercurrent) by means of a nozzle.Drying takes place as the particles continue to move upwards inthe air flow. Small droplets and a low viscosity of the spraymedium ensure that the distribution is uniform.

Coating in the continuous fluid bed is particularly suitable forprotective coatings/colour coatings where the productthroughput rates are high.

The product is continuously fed into one side of the machine and

is transported onwards via the sieve bottom by means of the airflow. Depending on the application, the system is sub-dividedinto pre-heating zones, spray zones and drying zones. The dry,coated particles are continuously extracted.


71/130

71

CONT.

Bottom Spray Coating (Continuous fluid bed) Particularly suitable for protective coatings/colour coatings

where the product throughput rates are high.

The product is continuously fed into one side of the machine andis transported onwards via the sieve bottom by means of the air

flow.


72/130

72

CONT.

Depending on the application, the system is sub-divided into pre-heating zones, spray zones and drying zones whereby sprayingcan take place from below in the form of a bottom spray. The dry,coated particles are continuously extracted.


73/130

73

CONT.

Tangential Spray Coating (Rotor pellet coating)

Ideal for coatings with high solid content.

The product is set into a spiral motion by means of a rotating

base plate, which has air fed into the powder bed at its edge. The

spray nozzle is arranged tangentially to the rotor disc and also

sprays concurrently into the powder bed.

Very thick film layers can be applied by means of the rotor

method.


74/130

74

Spouted Bed Coaters

An effective alternative to fluidized beds for handling

coarse particles over 2 mm diameter.

Main parts of spouted bed equipment can be defined as,

Air/gas inlet chamber

Opening device

Process chamber

Spraying system

Exhaust chamber.


75/130

75

CONT

Main parts of a spouted bed equipment with differentprocessing systems


76/130

76

CONT The air/gas inlet chamber comprises the lower part of the

apparatus and - like in the fluidized bed system can beimplemented in single or divided form.

Unlike the fluidized bed processes, the spouting air/gas does not

enter the processing chamber through the air distribution baseplate, but through an opening device with relatively highvelocities, typically between 1 and 30 m/s.

The opening device can be constructed as a central orifice or alongitudinal slot at the bottom. The process chamber is usually

cylindrical with a conical base, in the centre of which the openingdevice is installed.

In general, the spraying system and the exhaust chamber aresimilar to those of fluidized bed systems.


77/130

77

Enteric Film Coatings

By definition, enteric coatings are those which remainintact in the stomach (and exhibit low permeability togastric fluids). but break down readily. once the dosageform reaches the small intestine.

The prime uses of such coatings are:

To maintain the activity of drugs that are unstable whenexposed to the gastric milieu (e. g., erythromycin andpancreatin).

To minimize either nausea or bleeding that occurs withthose drugs that irritate the gastric mucosa (e.g. aspirinand certainsteroids).


78/130

78

PELLETISATION

Pelletisation is an agglomeration process that converts finepowder blend of drugs and excipients into small, free flowing,spherical units, referred to as pellets.


79/130

79

WHY PELLETS ?

Excellent Stability

Dust free round pellets

Easy to dose

Compact structure

Very low hygroscopicity

High bulk density

Dense, Uniform surface

Narrow grain size distribution

Low abrasion

High active ingredient content possible

Controlled release application


80/130

80

PREPARATION OF PELLETS

Drum/pan pelletization

Extrusion- spheronization

Centrifugal drug-layering

Fluidized-bed pelletization

High-shear melt pelletization


81/130

81

Extrusion-spheronization

Pelletization by forming and spheronizing extrudates

Features:

Continuous processFast processEasy to up-scaleStand alone units but also fully integrated systems availableVery high drug loads possible due to special extruder designIntegration with up-and downstream equipment possible.

Applications

Forming of pellets between 0.5 and 3 mm diameter.


82/130

82

POWDER LAYERING PROCESS (ROTO SYSTEM)

PRINCIPLE OF OPERATION

With fluid bed coating, particles are fluidized and the coating/ Binderfluid sprayed on and dried. Small droplets and a low viscosity of thespray medium ensure an even product coating.


83/130

83

Liquid layering of pellets

A starting grain or a pellet can be presented as the starting material. Thepellet is built up to the required grain size by adding the layering substanceone layer at a time. Powder and binders, suspensions or solutions makesuitable layering substances.

Thick layers can be applied to the starting grains, which, in the case oflayers containing active ingredients, allow large amounts of activeingredient to be incorporated


84/130

84

Melt granulation pelletization

The active and binder powders are mixed and heated to a temperatureabove the melting point of the binder. Granulation and pelletization arethen carried out in a single operation.

Features:

Very fast process

True One-Pot operation Special polymer liners to minimize sticking

For melting a heated jacket or optional 'microwave energy' can be used

Applications

Forming of pellets between 0.5 and 2 mm diameter. By selection of thebinder material it is possible to form sustained release forms withoutadditional coating.


85/130

85

CONCLUSION In recent decades, coating of pharmaceutical dosage forms has

been subject of remarkable developmental efforts aiming to ensureand enhance end product quality.

Improvements regarding particle movement, heat and energytransfer, film distribution, drying efficiency and continuousprocessing have contributed to significantly develop thistechnology.

However, evaluation and success of further constructionalimprovements in coating methods appear to depend on accurate

analytical tools and advanced methods for process modeling andcontrol.

In this regard, achieving optimal manufacturing efficiency andhigh end product quality still remains a key challenge for future

research efforts.

POLYMERS USED IN FILM COATING


86/130

86

POLYMERS USED IN FILM COATING

CONVENTIONALCOATING POLYMERS

Cellulose ethers

HPMC(Hypromellose,

Pharmacoat)Methylcellulose

(MC)

Hydroxyethylcellulose (HEC)

Hydroxypropylcellulose (HPC)

Acrylic polymers

Methacrylate AminoEster Copolymer

POLYMERS FORMODIFIED RELEASE

APPLICATION

Methacrylate EsterCopolymers

Ethyl cellulose (EC)

ENTERIC POLYMERS

Cellulose acetatephthalate (CAP)

Polyvinyl AcetatePhthalate (PVAP)

Shellac

Methacrylic AcidCopolymers

Cellulose AcetateTrimellitate (CAT)

Hydroxypropyl

methylcellulosephthalate (HPMCP)

CONVENTIONAL COATING POLYMERS


87/130

87

CELLULOSE ETHERS

The structure of cellulose permits three hydroxyl groups per

repeating anhydro-glucose unit to be replaced.

If all three hydroxyl groups are replaced the degree of

substitution (DS) is designated as 3, and so on for lower

degrees of substitution.

The term molar substitution (MS) covers the situation where a

side chain carries hydroxyl groups capable of substitution and

takes into account the total moles of a group whether on thebackbone or side chain.

CONT


88/130

88

CONT

Both DS and MS profoundly affect the polymer properties withrespect to solubility and thermal gel point.

The polymer chain length, together with the size and extent of branching, will of course determine the viscosity of the

polymer solution.

As a generality, film coating demands polymers at the lowerend of the viscosity scale.

It is soluble in both aqueous media and the organic solventsystems normally used for film coating

CELLULOSE ETHERS


89/130

89

(HPMC) (Hypromellose, Pharmacoat)

Provides aqueously soluble films which can be colored by the

use of pigments or used in the absence of pigments to form clear

films.

Non-tacky Typical low-viscosity polymer can be sprayed from an aqueous

solution containing around 1015%w/w polymer solids

(HPMC) (Hypromellose Pharmacoat) Cont


90/130

90

(HPMC) (Hypromellose, Pharmacoat) Cont..

Advantages:

It does not affect tablet disintegration and drug availability,

It is cheap, flexible, and highly resistant to heat, light and

moisture, it has no taste and odor, color and other additives can

be easily incorporated.

Disadvantage:

When it is used alone, the polymer has tendency to bridge or fill

the debossed tablet surfaces. So mixture of HPMC and other

polymers/ plasticizers is used

Different available grades of HPMC


91/130

91

Different available grades of HPMC

Available in a number of viscosity designations defined as the

nominal viscosity of a 2%w/w aqueous solution at 20C.

Thus a 5mPa s grade will have a nominal viscosity of5 mPa-s in 2% aqueous solution in water at 20C and

similarly with 6 mPa-s, 15 mPa-s and 50 mPa-s grades.

Commercial nomenclature for these grades may still

describe them as 5 cP.


92/130

92

Commercial designations such as E5 (Methocel) or 606

(Pharmacoat) also correspond with the viscosity designation,

such that for example Methocel E5 has a nominal viscosity of

5mPa s under the previously described standard conditions.

While Pharmacoat 606 would have a nominal viscosity of

6 mPa s under the same conditions.

The first two digits of the four-digit designation specify the

nominal percentage of methoxyl groups while the final two

specify the nominal percentage of hydroxypropoxyl groups.


93/130

93

PHARMACOAT


94/130

94

PHARMACOAT

PHARMACOAT Cont.


95/130

95

PHARMACOAT film has the hardness and strength

characteristic of cellulose derivatives.

Although PHARMACOAT film is not brittle, as acrylic

polymers, addition of a plasticizer such as polyethylene glycol

(PEG 6,000) is effective when highly flexible film is required.

Moreover, addition of a water-insoluble polymer such as

Ethylcellulose (EC) or Hydroxypropyl methylcellulose phthalate

(HPMCP) to PHARMACOAT delays dissolution of the film,which is useful for the masking of bitter taste or unacceptable

texture, as well as delaying drug dissolution.

SOLUBILITY OF MIXED FILM IN SIMULATEDGASTRIC FLUID AND SIMULATED


96/130

96

GASTRIC FLUID AND SIMULATED

Methylcellulose (MC)


97/130

97

Substituent group:CH3

This polymer is used rarely in film coating possibly because of

the lack of commercial availability of low viscosity material

meeting the appropriate compendial requirements.

It is not frequently used as HPMC because soluble in fewer

organic solvents.

DIFFERENT AVAILABLE GRADES


98/130

98

DIFFERENT AVAILABLE GRADES

Hydroxyethyl cellulose (HEC)

Substituent group CH (OH) CH3


99/130

99

Substituent group:CH (OH)CH3

This water-soluble cellulose ether is generally insoluble in

organic solvents.

The USNF is the sole pharmacopoeial specification; there is no

requirement on the quantity of hydroxyethyl groups to be

present.

The USNF allows the presence of additives to promote

dispersion of the powder in water and to prevent caking on

storage.

Hydroxypropyl cellulose (HPC)

S b i CH2 CH (OH) CH3


100/130

100

Substituent group:CH2CH (OH)CH3

HPC has the property of being soluble in aqueous below 40oc

(insoluble above 45 C), gastric fluid and many polar organic

solvents.

Its films unfortunately tend to be rather tacky , which possess

restraints on rapid coating; HPC films also suffer from being

weak.

Currently this polymer is very often used in combination with

other polymers to provide additional adhesion to the substrate.

Hydroxypropyl cellulose (HPC) Cont.


101/130

101

y yp py

The EB/BP has no requirements on hydroxypropoxyl content.

The USNF states this must be less than 80.5% while the JP has

two monographs differing in substitution requirements. The

monograph most closely corresponding to the USNF material

has a substitution specification of 53.477.5%.

ACRYLIC POLYMERS

M th l t A i E t C l


102/130

102

Methacrylate Amino Ester Copolymer

This polymer is basically insoluble in waterbut dissolves in

acidic media below pH 4.

In neutral or alkaline environments, its films achieve solubility

by swelling and increased permeability to aqueous media.

Talc, magnesium stearate or similar materials are useful

additions to the coating formula as they assist in decreasing the

sticky or tacky nature of the polymer. In general, the polymer

does not require the addition of a plasticizer.

POLYMERS FOR MODIFIED RELEASE APPLICATION

Methacrylate Ester Copolymers


103/130

103

Methacrylate Ester Copolymers

These materials are insoluble over the entire physiological pH

range. However they do possess the ability to swell and

become permeable to water and dissolved substances so that

they find application in the coating of modified release dosage

forms.

The two polymers Eudragit RS and RL can be mixed and

blended to achieve a desired release profile. The addition of

hydrophilic materials such as the soluble cellulose ethers,

polyethylene glycol (PEG), etc., will also enable modifications to

be achieved with the final formulation.


104/130

104

The polymer Eudragit RL is strongly permeable and thus only

slightly retardant. Its films are therefore also indicated for use in

quickly disintegrating coatings.

For aqueous spraying a latex form of each polymer is available.

In addition the polymer Eudragit NE30D has been made for this

purpose.

This material is also used as an immediate-release nonfunctional

coating in film coat formulations where relatively large quantities

of water-soluble materials are added to ensure efficient disruption

of the coat.

Ethyl cellulose (EC)

Substituent group CH2 CH3


105/130

105

Substituent groupCH2CH3

It possesses good solubility in common solventsused for film

coating.

Apart from its extensive use in controlled release coatings, ethyl

cellulose has found a use in organic solvent-based coatings in a

mixture with other cellulosic polymers, notably HPMC.

Ethyl cellulose also conveys additional gloss and shine to thetablet surface.


106/130

106

In many ways ethyl cellulose is an ideal polymer for modified

release coatings.

It is odorless, tasteless and it exhibits a high degree of

stability not only under physiological conditions but also

under normal storage conditions, being stable to light and

heat at least up to its softening point of c. 135c

Only the USNF contains a monograph, an ethoxy group contentof between 44.0 and 51.0% is specified.


107/130

107

The USNF also contains a monograph Ethyl cellulose Aqueous

Dispersion which defines one type of such material which finds

a use in aqueous processing. The monograph permits the

presence of cetyl alcohol and sodium lauryl sulphate which are

necessary to stabilize the dispersion.

ENTERIC POLYMERS

Cellulose acetate phthalate (CAP)


108/130

108

Cellulose acetate phthalate (CAP)

Enteric polymers are designed to resist the acidic nature of the

stomach contents, yet dissolve readily in the duodenum.

Of the generally accepted solvents used for tablet coating, CAP is

insoluble in water, alcohols and chlorinated hydrocarbons.

A pseudo latex version of CAP is available (Aquateric) as a dry

powder for reconstitution in water and offers the convenience of

aqueous-based processing.


109/130

109

CAP is a white free-flowing powder usually with a slightly

odor of acetic acid.

The JP has requirements for the content of acetyl and phthalyl to

be respectively 1722 and 3040% while the USNF requires

21.526 and 3036% respectively.

CAP is somewhat prone to hydrolysis.

Aquacoat CPD

Sepifilm LP

Klucel

Aquacoat ECD

Metolose

Enteric Coatings

Taste masking Sustained release coating

Sub coat moisture and

barrier sealant pellet coating

Polyvinyl Acetate Phthalate (PVAP)


110/130

110

Polyvinyl acetate phthalate possesses the following solubility

characteristics, with the extent of solubility given in parentheses:

methanol (50%)

methanol/methylene chloride (30%)

ethanol 95% (25%)

ethanol/water 85:15 (30%)

An aqueous dispersible form (Sureteric) is available for water-

based spraying.

Shellac


111/130

111

Shellac is insoluble in water but shows solubility in aqueous

alkalis; it is moderatelysoluble in warm ethanol.

Shellac suffers from the general drawback that it is a material

of natural origin and consequently suffers from occasional

supply problems and quality variation

EmCoat 120 N Enteric Coatings

Marcoat 125 Taste/Odor Masking

Methacrylic Acid Copolymers


112/130

112

Because these polymers possess free carboxylic acid groups they

find use as enteric-coating materials, forming salts with alkalis

and having an appreciable solubility at pH in excess of 5.5.

Of the two organic solvent soluble polymers, Eudragit S100has

a lower degree of substitution with carboxyl groups and

consequently dissolves at higher pH than Eudragit L100. Used

in combination, these materials are capable of providing films

with a useful range of pH over which solubility will

occur.


113/130

113

Polyethylene glycols are frequently added as they provide a

measure of gloss to the final product. They also assist in

stabilizing the water-dispersible form, Eudragit L30D.

Both Eudragit L100 and S100 are available in powder form and

for convenience purposes they are also available as concentrates

in organic solvent solution, which are capable of further dilution

in the common processing solvents used in organic solvent-

based film coating.

Cellulose Acetate Trimellitate (CAT)Substituent Groups (COCH3, COC6H3


114/130

114

(COOH) 2

The useful property of this polymer is its ability to start to

dissolve at the relatively low pH of 5.5 , which would help

ensure efficient dissolution of the coated dosage form in the

upper small intestine.

Chemically this polymer bears a strong resemblance to cellulose

acetate phthalate but possesses an additional carboxylic acid

group on the aromatic ring.

Typical values for timellityl and acetyl percentages are 29 and

22% respectively

Hydroxypropyl methylcellulose phthalate

(HPMCP


115/130

115

(HPMCP) HPMCP is insoluble in waterbut soluble in aqueous alkalis

and acetone/water 95:5 mixtures.

The degree of substitution of the three possible substituents

determines the polymer characteristics, in particular the pH of

dissolution.

HPMCP may be plasticized with diethyl phthalate, acetylated

monoglyceride or triacetin. Mechanically it is a more flexible

polymer and on a weight basis will not require as much

plasticizer as CAP or CAT.


116/130

116

HPMCP is a white powder or granular material. USNF and JP

describe two substitution types, namely HPMCP 200731 and

220824. The six digit nomenclature refers to the percentages of

the respective Substituent methoxyl, hydroxypropoxyl and

carboxy-benzoyl groups.

For example, HPMCP 200731 has a nominal methoxyl content

of 20% and so on for the other two substituents.

Fine particle size grades designated with a suffix F are intended

for suspension in aqueous systems, with suitable plasticizers

prior to spray application.


117/130

117

Commercial designations such as 50 or 55 refer to the pH (10)

of the aqueous buffer solubility.

TRUE LATEXES


118/130

118

These are very fine dispersions of polymer in an aqueousphase and particle size is crucial in the stability and use ofthese materials. They are characterized by a particle size rangeof between 10 and 1000 nm.

At the other end of the size range the characteristic of colloidalparticles is approached where such dispersions are barelyopaque to light and are almost clear.

One of the chief ways of producing latex dispersions is byemulsion polymerization.

The reaction is quenched when the particle size is in the range50200 nm. Using this process the following acrylate polymersare produced: Eudragit L10055 and NE30D.

PSEUDO LATEXES


119/130

119

Commercially there are two main products which fall into thiscategory, both of them utilize ethyl cellulose as the film formerbut are manufactured in quite a different way and their methodof application also differs significantly.

Characteristically pseudo latexes are manufactured startingwith the polymer itself and not the monomer. By a physicalprocess the polymer particle size is reduced thereby producingdispersion in water; the characteristics of this dispersion neednot differ significantly from true latex, including particle sizeconsiderations. The pseudo latex is also free of monomerresidue and traces of initiator, etc.

Aqueous dispersions have significant advantages, enablingprocessing of water-insoluble polymers from an aqueousmedia.

CONT..


120/130

120

Mechanism

Minimum film-forming temperature (MFT) this is theminimum temperature above which film formation will takeplace using individual defined conditions. It is largelydependent on the glass transition temperature (Tg) of thepolymer.

With aqueous dispersions Lehmann recommends to keep thecoating temperature 1020C above the MFT to ensure thatoptimal conditions for film formation are achieved.

COATING DEFECTS


121/130

121

Picking and sticking: This is when thecoating removes apiece of

the tabletfrom the core.

Causedby over-wetting the tablets, by under-drying, or by poor

tablet quality.

Solution

A reduction in the liquid application rate

Increase in drying air temperature or air volume

Bridging: This occurs when the coating fills in the lettering or

logo on the tablet..


122/130

122

Is typically caused by , improper application of the solution,

poor design of the tablet embossing,

high coating viscosity,

high percentage of solids in the solution, or

improper atomization pressure

Increasing the plasticizer content or changing the plasticizer can

solve this problem.


123/130

123

Capping: This is when the tablet separates in laminar fashion.

The problem stems from

improper tablet compression

How you operate the coating system, however, can

exacerbate the Problem

over-dry the tablets in the preheating stage. That can make

the tablets brittle and promote capping.

Erosion: This can be the result of soft tablets, an over-wetted tablet

surface, Inadequate drying or lack of tablet surface strength.


124/130

124

Peeling and frosting: This is a defectwhere the coatingpeels away

from thetablet surface in asheet.

This couldbe due to a defect inthe ,

coating solution,

over-wetting or

high moisture contentin the tabletcore

Chipping: This is the result of high pan speed, a friable tablet core,

or a coating solution that lacks a good plasticizer.


125/130

125

Mottled color: This can happen when the ,

coating solution is improperly prepared

the actual spray rate differs from the target rate

the tablet cores are cold, or the drying rate is out of spec.

Use of lake dye may eliminate the problem.

Orange peel: This refers to a coating texture that resembles the

surface of an orange.

It is usually the result of high atomization pressure in

combination with spray rates that are too high.

Thinning the solution with additional solvent can solve the

problem


126/130

126

Twinning: This is the term for two tablets that stick together,

and its a common problem with capsule shaped tablets.

We can solve this problem bybalancing the pan speed and

spray rate.

Try reducing the spray rate or increasing the pan speed.

EVALUATION OF COATING SYSTEMS


127/130

127

Evaluating coating systems requires evaluation of both the

coatings and the coated tablets.

Physical characterization of the coating system should include

particle size, preparation time and viscosity because each

affects the handling and use of the powdered on step coating

systems.

Large particles minimizes dust and short process time have

obvious advantages. Low viscosity enables to create a coating

with high ration of solids, which leads to faster tablet coating.


128/130

128

Once coated tablet should be evaluated for the,

Gloss

Opacity

Color uniformity

Disintegration

Adhesion time

Logo bridging

Film strength and flexibility

Edge wear


129/130

129


130/130

Documents

93c3coating of Solid Dosage Form