Reasons for coating tablets Masking unpleasant smell or taste of drug Protecting the drug before ingestion Protection against light, air & moisture Ensuring their controlled release More elegant appearance Increase mechanical stability Avoidance of side effects

Types of Coated Tablets Sugar coated Hot melts Film coated

Aqueous Film Nonaqueous Film

Enteric coated

Characteristics of Cores• Hardness

adequate strength to withstand the rolling & frictional processes in pan and the impact stress in fluid-bed equipment.

• Shape : biconvex to prevent them sticking together less material more uniform

• Surface coarse for sugar coating smooth & dust-free for film coating

• Size• Heat sensitivity• Interaction between Core and Coating

Interaction between Core and Coating

• Hydrophilic swelling substances

cause the core swell

under the influence of moisture

• Substances migrating mottling, discoloration or fading, blooming

Sugar coatedAdvantages• Protects drug from air and humidity • Taste and smell barrier • High compliance

Disadvantages• Difficult to manufacture

– Irregular coat thickness – Irregular color

• Soft • Breakable and chip • Increased size (0.5% per shot)

and weight of tablet (25-50%)

Materials Sugar (sucrose)

50-60% (viscosity < 2 Poise)

Fillers (CaCO3, talc, TiO2) Colorants (dyes, iron oxide, TiO2) Binders (acacia gum, gelatin, cellulose derivatives, PVA, PVP)

Increase strength & elasticity

Antiadherent (talc) Flavors Surfactants (dispersion aids)

Suspension stabilizer

Materials Sugar (sucrose)

50-60% (viscosity < 2 Poise)

Fillers (CaCO3, talc, TiO2) Colorants (dyes, iron oxide, TiO2) Binders (acacia gum, gelatin, cellulose derivatives, PVA, PVP)

Increase strength & elasticity

Antiadherent (talc) Flavors Surfactants (dispersion aids)

Suspension stabilizer

Process of Sugar Coating Prime-coating layer

(sealing & subcoating)Protecting against moisture, effecting

adhesion, preventing interaction, masking odor, effecting controlled release

Rounding layer (dusting & filler syrup)

Finishing layer (coloring, smoothing or polishing,

glossing, protecting) Uniform coating layers

Requires the services of highly skilled coating operators

Process of Sugar Coating

Waterproofing and sealing Shcellacing

Subcoating (40-60C) 3-5 coats which can bond to both the tablet and the sugar Gelatin or Polyvinylpyrolidone (PVP)

Grossing, Smoothing & Final Rounding Thick Syrup of 60-70% Sucrose 5-10 coats

Finishing and coloring mulitple coats of thin sucrose syrup with pigments

Imprinting Embossed, debossed or engraved

Polishing Wax

Binder solutions Gelatin 3.3-6% Gum acacia 8-8.7% Sucrose 45-55% Water ad 100%

Dusting powder CaCarbonate 0-40% Titanium dioxide 1-5% Sucrose powdered 28-38% Gum acacia 0-2% Talc (asbestos free) 25-61%

Uniform coating layers Sucrose 58-66% Gelatin or acacia gum 0.5-1% PEG 1-3% Aerosil (colloidal silica) 0.5-1% Titanium dioxide 0.05-0.1% Dyes, pigments qs Water ad 100%

Process of Sugar Coating

Waterproofing and sealing Shcellacing

Subcoating (40-60C) 3-5 coats which can bond to both the tablet and the sugar Gelatin or Polyvinylpyrolidone (PVP)

Grossing, Smoothing & Final Rounding Thick Syrup of 60-70% Sucrose 5-10 coats

Finishing and coloring mulitple coats of thin sucrose syrup with pigments

Imprinting Embossed, debossed or engraved

Polishing Wax

Problems in sugar coating

• Tablet Core Robustness Shape, hardness

• Finished tablets Chipping: excessive use of insoluble fillers Cracking: moisture sorption Nondrying: invert sugar > 5% Twinning: shape, drying Uneven color

Enteric Coated

Enteric Coated

Function• Resists dissruption at gastric pH, then disolves

at intestinal pH

Advantages• Protects drugs from acidic hydrolisis • Protects gastric mucosa from irritating drugs • Enhanced drug absorption

Active Agent• Enteric Coats are similar to film coats, but much

thicker or with slightly different constituents • Cellulose Acetate Phthalate is a common coat

constituent • Polymeric Materials with or without Phthalate

Types of Enteric Coats

• Solution Dependent Coats– Time dependent – Hydroxyporplymethylcellulose – Ethylcellulose

• pH Dependent Coats– Cellulose acetate phthalatate pH 6 – HPMC phthalate pH 4-5 – Methacrylic acid-methacrylate co-polymer – Polyvinyl Acetate phthalate pH 4-5

Film Coated

Reasons for coating tablets Masking unpleasant smell or taste of drug Protecting the drug before ingestion Protection against light, air & moisture Ensuring their controlled release More elegant appearance Increase mechanical stability Avoidance of side effects

Types of Coated Tablets Sugar coated Hot melts Film coated

Aqueous Film Nonaqueous Film

Enteric coated

Characteristics of Cores• Hardness

adequate strength to withstand the rolling & frictional processes in pan and the impact stress in fluid-bed equipment.

• Shape : biconvex to prevent them sticking together less material more uniform

• Surface coarse for sugar coating smooth & dust-free for film coating

• Size• Heat sensitivity• Interaction between Core and Coating

Film CoatingTypes• Water Soluble Film • Water Insoluble Film

Advantages of Film Coats• Less Bulky than Sugar Coated Tablets • Simpler (and cheaper) than Sugar Coated Tablets

One hour for about 10 m and about 1% weight gain• Resistant to chipping • Taste and Smell barrier

Disadvantages of Film Coats In General• Cost • Possible toxicity hazard, esp non polar solvents • Environmental pollution • Increased drying time

Nonaqueous Films Polymeric Materials– Cellulose Acetate Phthalate – Methylcellulose

• Plasticizers– Castor Oil, Polyethylene Glycol & Glycerin

• Suspending Agents • Colorant & Flavoring • Solvent: isopropyl alcohol, CHCl3

– (Water in US)

• Polish– Beeswax

Aqueous Films Polymeric Materials– Ethylcellulose – Hydroxymethylcellulose

• Plasticizers

Glycerin & Polyethylene Glycol

• Colorant & Flavoring

• Water as solvent

Solvent• Depending on the solubility of film-formers water,

organic solvents or mixtures of both• Solvent selection:

Empirically Like is dissolved by like Quantitatively

• The most popular solvents :water dichloromethane:ethanol

dichloromethane:methanol dichloromethane:ethanol

dichloromethane:isopropyl alcohol acetone

dichloromethane:ethanol:acetone ethanol:water

Acetone:isopropyl alcohol:water  

Processing:

• Preheated the tablets– desired temp and dust extracted

• Thin sealing coat– Stabilize the core surfaces

• The actual film coating

• Post drying

• Polishing :10%PEG 6000 in water

Variables affecting coat application• Spraying Method

Intermittent spraying Continuous spraying

• Nozzle Distance product temperature• Spray size, rate, pressure • Batch size • Drying time (air inlet)

30-50C for organic solvents 40-60C for aqueous systems

• Moisture Content

The coating liquids were as follows: (1) HPMC 8%(wt/wt), polyethylene glycol 1.6% (wt/wt), and

purified water 90.4% (wt/wt);

(2) HPMC 8% (wt/wt), polyethylene glycol 1.6% (wt/wt), titanium dioxide 2.4% (wt/wt), and purified water 88% (wt/wt).

To prepare the coating solution and pigmented dispersion: added the polymer to the hot water (80-90°C) under

magnetic stirring. after the polymer had been dispersed, the remaining

cold water was added all the polymer was dissolved, added plasticizer and pigment to obtain a total of 1000 g

of coating liquid.

Defects in Aqueous Film Coats

Picking Little flakes

Reasons

Spray rate too high

Inadequate drying

Slow pan speed

Poor Distribution

Peeling Big flakes

Reasons

Low coating

Poor adhesion

Poor Distribution

Orange Peel Affect

Premature Drying

Film too viscous

MottlingLack of Color due to poor mixing of pigments

Bridging: Creases in the film

Erosion of the film or core

Twinning tablets sticking together

Reasons

Spray rate too high

Pan Speed too low

inappropriate shape

Cracking

Inadequate Plasticizers

Excessive pigmentation

Different thermal expansion rate

Kriteria penerimaan uji disolusi berdasarkan nilai Q :

A. Sediaan kelompok pertama (kapsul, tablet tidak bersalut dan tablet bersalut bukan enterik) = immediate release

1. 6 unit sediaan : masing-masing unit sediaan tidak < Q + 5%, bila tak terpenuhi, pengujian dilanjutkan ke tahap kedua.

2. 6 unit sediaan : purata 12 unit sediaan dari tahap pertama (1) dan kedua (2) tidak < nilai Q; tidak satu unitpun yang < Q -15%; bila syarat tak terpenuhi, pengujian dilanjutkan ke tahap ketiga.

3. 12 unit sediaan : purata 24 unit dari tahap pertama (1), tahap kedua (2) dan tahap ketiga(3) tidak < nilai Q; tidak lebih 2 unit sediaan dengan nilai < Q – 15% dan tidak boleh satu unit sediaan dengan nilai < Q -25%

B. Sediaan salut enterik (delayed release)

a. Tahap asam : 750 ml 0,1 N HCl, selama 2 Jam + 2%

1. 6 unit sediaan : masing-masing unit sediaan tidak > 10% Q, bila tak terpenuhi, pengujian dilanjutkan ke tahap kedua.

2. 6 unit sediaan : purata 12 unit sediaan dari tahap pertama (1) dan kedua (2) tidak > 10% Q; tidak satu unitpun yang terdisolusi > 25% Q; bila syarat tak terpenuhi, pengujian dilanjutkan ke tahap ketiga.

3. 12 unit sediaan : purata 24 unit dari tahap pertama (1), tahap kedua (2) dan tahap ketiga(3) tidak > 10% Q; dan tidak satu unitpun yang terdisolusi > 25% Q

b. Tahap dapar

• dalam waktu 5 menit hilangkan tahap asam, pada alikot sampel tambahkan 250 ml 0,20 M natrium trifosfat, atur pH sampai 6,8+0,05 pada 370C dengan pengadukan pada kecepatan spesifik. Uji disolusi dilanjutkan selama 45 menit atau sesuai dengan monografi. Alikot sampel kemudian dianalisis, dimana Q adalah perhitungan total dari tahap asam dan dapar.

salut enterik

• 6 unit sediaan : masing-masing unit sediaan tidak < Q + 5%, bila tak terpenuhi, pengujian dilanjutkan ke tahap kedua.

• 6 unit sediaan : purata 12 unit sediaan dari tahap pertama (1) dan kedua (2) tidak < nilai Q; tidak satu unitpun yang < Q -15%; bila syarat tak terpenuhi, pengujian dilanjutkan ke tahap ketiga.

• 12 unit sediaan : purata 24 unit dari tahap pertama (1), tahap kedua (2) dan tahap ketiga(3) tidak < nilai Q; tidak lebih 2 unit sediaan dengan nilai < Q – 15% dan tidak boleh satu unit sediaan dengan nilai < Q -25%