POLYMERS FOR COATING

OVERVIEW Process of coatingProcess of coating Types of coating Mechanism of coating Factors affecting the process USP standards & specifications Principle of Plasticization Plasticizers Role of polymer Polymers used for conventional coating Polymers used for Enteric coating Commercially available coating systems Case study Future prospective

Process of Coating

Application of thin polymeric film over the core surface( tablet, pellets, granules & dosage units ) to form a smooth surface with uniform distribution optimizing the quality of product with both

-Visual

-Functional point of views.

Advantages of Coating

Improves aesthetic qualities of product Masking of unpleasant taste & odor Improving patient compliance Facilitating handling Increased product stability Modifying drug release behavior ??????

Types of Coating

Mechanism of coating

Events During Film formation Initial rapid evaporation of solvent from the

atomized droplets of coating liquid causing: a) increase in polymer concentration (viscosity) b)reduction in volume of droplets

Further loss of solvent from the film at a slower rate (diffusion controlled)

Immobilization of polymer molecules at solidification point (tablet surface)

Further gradual loss of solvent at a much reduced rate

Factors affecting the process

Factors has influence on (parameter)

1. Tablet Ingredients Porosity Surface roughness

Wetting of coating liquidDry film adhesionSpreading of coating solution

2. Coating liquid Solids content Viscosity of solution Surface tension

Coating liquid viscositySpreading and coalescenceWetting, spreading & coalescence

3. Process of drying Drying rate

Heat applied

Viscosity of coating liquid &Structure of dried coatingDevelopment of internal stress & Mechanical properties

USP Standards & Specifications

Enteric coated tablets must tolerate agitation in simulated gastric fluid test solution at 37± 2 ◦ c (no discs). After 1 hour of exposure in simulated gastric fluid, tablets must present no evidence of disintegration, cracking or softening.

Then a disc is added to each tube, and the test is continued using simulated intestinal fluid maintained at the same temperature as mentioned above. The test is conducted for 2 hours to the time specified in the individual monograph.

The batch passes the test if all tablets disintegrate. If 1 or 2 tablets fail to disintegrate completely, the test is repeated on 12 additional tablets. At the end at least 16 out of 18 tablets should disintegrate within the specified time in order to pass the test.

Plasticization Polymers used for pharmaceutical dosage

forms for coating are generally amorphous in nature.

Unfortunately Glass transition temperature of most of the polymers are in excess of conditions exposed for the pharmaceutical manufacturing. Thus one needs to incorporate plasticizer basically for two main reasons:-

1. Modification of polymer properties so as to impart flexibility which reduces the Tg of amorphous polymer.

2. To facilitate the processing of dosage form at substantial temperature conditions to protect the integrity of active ingredient.

Plasticizers

Class Examples

Polyhydric alcohols Propylene glycolGlycerolPolyethylene glycol

Acetate esters Glyceryl triacetateTriethyl citrateAcetyl triethyl citrate

Phthalate esters Diethyl phthalate

Glycerides Acetylated monoglycerides

Oils Castor and mineral oil.

Polymers

Polymers for conventional coating

Class Examples

Cellulosics HPMCHPCHECMC (Methocel)Na-CMCEC (Ethocel)

Vinyls PVP

Glycols PEG

Acrylics Co-polymers such as methyl methacrylate, ethyl methacrylate

Hydroxy propyl methyl cellulose (HPMC) Material of choice for air suspension and

pan spray coating. Reasons High moisture stability, photo-stability and

thermal stability Flexibility, tasteless and odorless. Compatible with additives with additives and

colorants. Solubility characteristic of the polymer in

GIT.

Ethyl cellulose (EC) Various viscosity grades are available.

degree of Ethoxy substitution.o Completely insoluble in water and G.I. fluids.o Soluble in wide variety of organic solventso Non-toxic odorless and tasteless.o Requires plasticizers.o Pseudo latex systems using aqueous polymeric

dispersions can be formed using ethyl cellulose having low viscosity and high solid content

Sodium Carboxy Methyl Cellulose (Na-CMC) Available in low, medium, high and extra

high viscosity grades. Easily dispersed in water to form colloidal

dispersions. Not a material of choice for coating based

on organic solvents as it is insoluble in most organic solvents.

Preferably used for aqueous film coating solutions with high coating efficiency equipment.

Polyethylene Glycol (PEG) PEG is available in grade ranging from 200-

8000 PEG has low contact angle –penetration into

powder bed and make contact with substrate surface.

Desirable melting range Molecular weight. Waxy and hygroscopic, soften readily at

moderately elevated temperatures. Low molecular weight PEG’s are used as

plasticizers in coating solutions rather than as polymers.

Acrylate polymers

Acrylate polymers are generally marketed as Eudragits.

Eudragit RL and RS are copolymers synthesized from methacrylic acid esters with low content of quaternary ammonium groups.

Polymers used for enteric coating.

Enteric Coating PolymersPolymer Characteristics

Cellulose Acetate Phthalate Susceptible to Hydrolysis

Cellulose Acetate Trimellitate Susceptible to Hydrolysis

Polyvinyl Acetate Phthalate Susceptible to Hydrolysis

HPMC-Phthalate Susceptible to Hydrolysis

HPMC-Acetate Succinate Susceptible to Hydrolysis

Poly (MA -EA) 1 : 1 ------

Poly (MA -MMA) 1 : 1 High Dissolution pH

Poly (MA -MMA) 1 : 2 High Dissolution pH

Cellulose Acetate Phthalate (CAP)

Relatively hygroscopic and permeable to gastric fluids and moisture.

Films formed from CAP are brittle. Usually formulated with hydrophobic excipients

to achieve a better enteric film. Colloidal dispersion of latex particles comprising

of polymeric spheres of CAP (aquateric) have been developed and commercially utilized.

Dissolves only above pH 6 and delays the absorption of drugs

HPMC-phthalate

Dissolves at a relatively lower pH (5-5.5) than CAP or acrylic copolymers.

This Solubility characteristic may result in higher bioavailability of certain drugs.

Different grades are available HPMCP-50,HPMCP-55 and HPMCP-55S.

Stability is higher compared to CAP

Absence of labile acetyl groups

Commercially available enteric coating systems

Product Polymer Form Characteristic

Eudragit L30D Poly (MA-EA) 1:1 Latex Dispersion Essentially contains only polymer

Eudragit L 10055 Poly (MA-EA) 1:1 Spray Dried latex Dispersed in water + allkali

Coateric PVAP Dry powder Dispersed in water + ammonia

Aquateric CAP Spray dried pseudo latex

Dispersed in water

CAP CAP Dry powder Dissolved in water + alkali

CAT CAT Dry powder Dissolved in water + alkali

HPMC-P HPMC Dry powder Dispersed in water

Eudragits

Eudragits Eudragits Availability applications Dissolution properties

Eudragit L 100-55

Powder Drug delivery in duodenum

> 5.5

Eudragit D 100-55

Aqueous dispersion 30%

Drug delivery duodenum

>5.5

Eudragit L 100 Powder Drug delivery in jejunum

>6.0

Eudragit S 100 Powder Drug delivery in ileum

>7.0

Eudragit FS 30 D

Aqueous Dispersion 30%

drug delivery in colons.

>7.0

Cont’d The EUDRAGIT grades for enteric coatings are based on

anionic polymers of methacrylic acid and methacrylates. They contain –COOH as a functional group. They dissolve at ranges from pH 5.5 to pH 7.

Application benefits of enteric EUDRAGIT coatings:

PH-dependent drug release Protection of actives sensitive to gastric fluid Protection of gastric mucosa from aggressive actives Increase in drug effectiveness Good storage stability GI and colon targeting

Use of Hot melt extrusion in Enteric coating of tablets “The manufacture and characterization of hot-melt

extruded enteric tablets” Eudragit L100-55, an enteric polymer, was pre-plasticized

with triethyl citrate (TEC) and citric acid and subsequently dry-mixed with 5-aminosalicylic acid, a model active pharmaceutical ingredient (API).

Powder blends were hot-melt extruded as cylinders, cut into tablets.

The authors concluded that Increasing the concentration of TEC significantly lowered the glass transition temperature (Tg) of Eudragit L100-55 and reduced temperatures necessary for extrusion as well as the die pressure.

Release profile

Influence of method of manufacture on the release of 5-ASA from Eudragit L100-55 tablets in 0.1 N HCl dissolution media (pH 1.2). () HME tablet; (■) compressed tablet with hardness value of 62 ± 2 N; (○) compressed tablet with hardness value of 230 N ± 12 N.

Cont’d..

This leads to suggest that hot melt extrusion, a versatile process can be utilized to decrease the compression pressure in order to optimize formulation parameters affecting compressional behavior of materials such as MCC that in conventional enteric coating techniques employ high compressional pressures.

Case study 2 Controlled release of dual drug-loaded

hydroxypropyl methylcellulose matrix tablet using drug-containing polymeric coatings. By Beom-Jin Lee, , Seung-Goo Ryu and Jing-Hao Cui.

Dual drug loaded HPMC matrix tablet that conatins drug in inner tablet core and outer coated layers.

Aqueous based Eudragit RS 30 D dispersionis used.

Cont’d.. The dual drug-loaded HPMC matrix tablet gave a

biphasic linear release, showing a zero-order for 4 h (first) followed by another zero-order release.

The current dual drug-loaded HPMC matrix tablet, showing biphasic release profiles may provide an alternative to deliver drugs with circadian rhythmic behaviors in the body.

The dual drug-loaded coating method is also interesting for the modified release of poorly water-soluble drugs because solubilizers and other additives can be added in drug-containing polymeric coating dispersions.

Future prospects

Coating can be dated as back as in ancient times when an experienced individual would dip a bitter tablet into sugar syrup.

Since then the process of coating has been constantly an area of interest for oral dosage forms.

With the emergence of newer polymers that are pH dependent, acid resistant and many other properties.

Cont’d…

Utilization of dual coating in case of polymers such as HPMC may result into development of newer techniques in case of coating.

Thus it can be concluded that coating has been, is and shall continue to be one of the most promising area in formulation of oral dosage forms for improved health care.

Thank us“If we knew what we were

doing, it would not be called research”