CONTROLLED RELEASE

TABLET DOSAGE FORM

tablets are designed to release the drug slowly after

ingestion.

Advantages:

1.Patient compliance is improved, since only one or two

tablets need to be taken daily

2.Reduces the severity or frequency of side effects. as a

controlled-release Aspirin, has been shown to produce

less gastric bleeding

3.A controlled -release tablet produces a more constant

blood level of drug than repeated doses of a conventional

tablet e.g aminophylline

controlled-release tablets

Disadvantages:

1.The cost of controlled release tablets is more per

unit dose than conventional dosage forms.

2.Some drugs, such as riboflavin and ferrous

sulphate, are more efficiently absorbed in particular

regions of the gastrointestinal tract and therefore

controlled-release tablets are not very useful,

because they release the drug throughout the

intestinal tract.

3.Accidental poisoning with poor formulated

controlled-release where all the drug being

released at once.

4. dosage forms does present special treatment

5. The slow release of the drug into the

gastrointestinal tract, and slow clearance of drug

from the body result in problems . E.g controlled -

release tablets of potassium Chloride have been

known to cause ulceration due to delayed

gastrointestinal transit time.

6. The physical size of the dosage form may present

problems. Some patients have difficulty in

swallowing a 600-650 mg controlled -release

tablet and it is often difficult to formulate the

tablets.

FORMULATION FACTORS AFFECTING

THE RELEASE OF A DRUG FROM

TABLETS

The effective surface area of drug

releaseThe dissolution rate of a drug is directly related to

the surface area exposed to the dissolution media.

Effect of binding agentsBinding agents are incorporated into tablets to

improve the flowability of the drug & to enhance

compressibility. the rate of dissolution of the binder

in water can determine the release rate of drug from

the tablet.

tablets containing water soluble binders (hydrolysed

gelatin and PVP) had rapid dissolution rates whereas

tablets formulated with starch paste, Methyl hydroxy

ethyl cellulose (MHEC) had slow and incomplete

disintegration rates.

Effect of disintegrantsDisintegrants facilitate the rapid entrance of water

into the centre of the tablet or capsule ; result in

rapid drug release.

Tablets containing sodium starch glycollate were

superior in dissolution properties from similar tablets

containing microcrystalline cellulose and PVP .This

effect is due to the high swelling capacity of these

disintegrants.

Effect Of Lubricants

lubricating agent prevent the dosage form sticking to

the processing machinery.

The hydrophilic lubricant as sodium lauryl sulphate

allowed the drug to dissolve more rapidly

The hydrophobic lubricant magnesium stearate

produced a decrease in dissolution rate.

Effect of diluentsThe calcium salts as calcium orthophospahte and

calcium hydrogen orthophosphate promote the rapid

disintegration of the tablets and therefore give quick

drug release.

Sorbitol , lactose markedly decrease the release

rate because it dissolves very slowly and therefore

release of the drug occurs by erosion.

Effect of granule size

Granule size was not a critical factor affecting the

pharmaceutical properties of the tablets.

Formulation of controlled

release tabletsControlled -release tablets consist of two parts:

- An immediately available dose

-A sustaining part, containing the therapeutic dose,

for

prolonged blood drug levels.

The immediately available dose is incorporated in

the tablet coating with the sustaining portion.

Methods of achieving

controlled release

Diffusion-controlled release

The rate at which diffusion occurs is depend upon:

- The surface area - The diffusional pathway

- The drug concentration gradient

-The diffusion coefficient of the system.

• Diffusion-controlled release produced by:

formulating the drug in an insoluble matrix such as

methylcellulose or insoluble plastic inert

substances such as methyl methacrylate.

•The core (drug) and the matrix tableted together

by compression. Coating can be applied using a

coating pan or air-suspension technique.

• The gastro-intesinal fluids penetrate the matrix

and drug diffuses out of the matrix and absorbed.

•With coated matrix tablets the initial dose is

normally placed in the coat of the tablet.

•In non-coated systems the initial dose is normally

tableted with the matrix granulation.

Dissolution-controlled

release

• Drugs with poor dissolution rates

are prolonged release

• water-soluble drugs it is possible

to incorporate a water insoluble

carrier into the tablet formulation

to reduce dissolution.

• Prolonged drug relase can be

achieved by avoid the use of

disintegrating agent in the tablet

formulation.

• these products formulated by:

coating individual drug particles or

granules with a slowly soluble

coating material such as

polyethylene glycol of various

thickness.

•The time required for dissolution of

the coat is proportional to the

coating thickness.

•The coated particles can be

compressed directly into tablets.

•A pulsed dosing effect can be also

obtained by utilizing different coat

types.

Release controlled by ion exchange •Ion exchange materials are water-insoluble resine

containing salt-forming groups.

•Either anionic or cationic groups can be used to

produce the desired ion exchange resin.

•The drug-charged resin is prepared by:

mixing the resin with drug solution, then washing

to remove contaminant ions and then dried to form

beads or particles which are tableted.

•Drug release is achieved in the presence of a high

concentration of charged ions in the

gastrointestinal tract; the drug molecule is

exchanged and diffused out of the resin to the

gastrointestinal fluids.

Ion-exchange resine Ion-exchange resine

(styrene di-vinyl benzene copolymer)(styrene di-vinyl benzene copolymer)

Ananionic groupAnanionic group Cataionic groupCataionic group

COOHCOOH, ,

++ cataionc drug cataionc drug ++ Anaionic drug Anaionic drug

(Atropin)(Atropin) (Deltiazem HCL)(Deltiazem HCL)

Resin-SOResin-SO33-- D D+ + Resin-N(CHResin-N(CH33)) 3 3

++ D D--

GI (HCL) GI (HCL) GI (HCL) GI (HCL)

Resin-SOResin-SO33- - H H + + + D Resin-N(CH+ D Resin-N(CH33)) 3 3

++ CL CL- - + D+ D

The main disadvantage:

1. The drug release depend only on the ionic

environment of the resin not on pH or enzyme

content at the absorption site.

1.The ionic content of the gastrointestinal tract

varies with diet and water content, and therefore

variable drug release results.

Release controlled by osmotic

pressure •A semipermeable membrane is placed around a

tablet or drug particle which allows transport of

water into the centre of the tablet by osmosis.

•As a result of increased internal pressure, drug

solution is then pumped out of the tablet through a

small hole in the tablet coating is bored with the use

of a laser beam. .

Advantages :

1.The delivery rate is constant where that excess

drug present inside the tablet rapidly declines to

zero once the concentration drops to below

saturation.

2. the system delivers drug based on osmotic

pressure, independent of stirring rate and

environment pH.

Types Of Tablet Coating

There are three types in common use:

1.Sugar coating

2.Film coating

3.Press coating (compression coating).

Of these the most important are sugar coating and

film coating.

Tablet Coating as a Technique for controlling release

Reasons for coating tablets

1. Protection of ingredients from the environment,

light and moisture.

2 .For taste masking that aid patient compliance

with

dosage schemes.

3. Coloured coatings aid in the rapid identification

of

product tablets with differing appearance.

4. Coating confers an added mechanical strength to

the

tablet core.

5. Functional film coatings are used to impart

enteric or

controlled release properties to the coated

tablet.

Enteric coatingThis technique is used to protect the

tablet core from disintegration in the

acid environment of the stomach for

one or more of the following reasons:

1. Prevention of acid attack on active constituents

unstable

at low pH

2. To protect the stomach from the irritant effect of

certain

drugs

3. To facilitate absorption a drug preferentially

absorbed

distally to the stomach.

The following polymers are commonly used for the

purposes of enteric coating:

1. Cellulose acetate phthalate

2. Polyvinyl acetate phthalate

3. Acrylates (Eudragit L100).

Due to the presence of free carboxylic acid groups

on the polymer backbone, they exhibit a differential

pH solubility profile. These are almost insoluble in

aqueous media at low pH but as the pH rises they

experience a sharp, well defined increase in

solubility at a specific pH, e.g. pH 5.2 for cellulose

acetate phthalate.

Enteric sugar coating

The sealing coat is modified to comprise one of the

enteric polymers in sufficient quantity

The subcoating and subsequent coating steps are

then as for conventional sugar coating.

Enteric film coating

Sufficient weight of enteric polymer has to be used to

ensure an efficient enteric effect. This is normally two

or three times that required for a simple film coating.

Enteric coating is possible using both sugar and film

coating techniques.

Press coatingsThe polymers used in coating include:

1. Modified acrylates

2. Water-insoluble celluloses e.g. ethyl cellulose.

Press coatings

Chewable TabletsAdvantages of the chewable tablet

1)provide a unit dosage form easily

administered to infants and children or to

the elderly, who may have difficulty

swallowing a tablet intact. E.g Many antacid

tablet products are of the chewable type.

Tablets Used in the Oral Cavity

The chewable tablet offers two major advantages to

the delivery of a solid antacid dosage form:

1) The dose of most antacids is large, so that the

typical antacid tablet would be too large to swallow.

2) As the activity of an antacid is related to its

particle size. If the tablet is chewed prior to

swallowing, better acid neutralization may be

possible from a given antacid dose.Disadvantages :

Bitter or foul-tasting drugs are not good candidates

for this type of tablet, and this fact restricts the use

of the chewable tablet dosage form.

Buccal and Sublingual

TabletsBuccal tablet

are intended to be held between the cheek and teeth

or in the cheek pouch

Sublingual tablets

beneath the tongue

Advantages: 1.The gastric environment, where decomposition may be

extensive (for certain steroids and hormones), may be

avoided for drugs that are well absorbed in the mouth.

2.A more rapid onset of drug action occurs than for tablets

that are swallowed (an advantage with vasodilators given

by this route).

3.Avoids first-pass metabolism

4.formulated with tasteless excipients, which do not

stimulate salivation. This reduces the fraction of the drug

that is swallowed rather than being absorbed through the

oral mucosa.

5.these tablets designed not to disintegrate but to slowly

dissolve, typically over a 15 to 30-min period, to provide

effective absorption.

Lozenges and Troches

Lozenges are originally termed pastilles,

but are more commonly called cough drops.

They are usually made with the drug

incorporated in a flavored hard-candy sugar

base.

Lozenges may be made by compression but

are usually formed by fusion or by a candy-

molding process.

Troches are manufactured by compression

as other tablets.

Advantages :

1.they are exert a local effect in the mouth or throat.

2.These tablet forms are commonly used to treat sore

throat or to control coughing in the common cold.

3.They may contain local anesthetics, various

antiseptic and antibacterial agents, demulcents,

astringents, and antitussives.

4.These two classes of tablets are designed not to

disintegrate in the mouth but to dissolve or slowly

erode over a period of perhaps 30 min or less.

Dental Cones

designed to be placed in the empty socket remaining

following a tooth extraction.

The usual vehicle of these tablets is

sodium bicarbonate, sodium chloride,

or an amino acid.

Advantages :

1.prevent the multiplication of bacteria in the socket

by employing a slow-releasing antibacterial

compound, or to reduce bleeding by containing an

astringent or coagulant.

2.The tablet formulated to dissolve or erode slowly in

the presence of a small volume of serum or fluid,

over a 20- to 40-min period, when loosely packed in

the extraction site.

Tablets Administered by Other

Routes

Implantation Tablets

Implantation or depot tablets are designed for

subcutaneous implantation in animals or man for the

administration of growth hormones to food-

producing animals.

Advantages:

1. provide prolonged drug effects, ranging from one

month to a year.

2.provide constant a drug delivery release rate as

possible.

Disadvantages:

1. this dosage form has achieved little use in

humans.

2.need for a surgical technique to discontinue

therapy

3.cause tissue toxicity problems in the area of the

implantation site.

Vaginal Tablets

Vaginal tablets or inserts are designed to undergo

slow dissolution and drug release in the vaginal

cavity.

The tablets are typically ovoid or pear-shaped to

facilitate retention in the vagina.

The tablets designed to be compatible with some

type of plastic tube inserter, which is usually

employed to place the tablet in the upper region of

the vaginal tract.

Advantages:

1.used to release antibacterial agents, antiseptics, or

astringents to treat vaginal infections, or possibly to

release steroids for systemic absorption.

2.The vehicle of these tablets is typically a slowly

soluble material similar to agents described for the

preparation of buccal tablets.

•Tablets Used to Prepare

Solutions

•Effervescent Tablets• The tablets are typically prepared by compressing

the active ingredients with mixtures of organic acids-

such as citric acid or tartaric acid-and sodium

bicarbonate.

•When such a tablet is dropped into a glass of water,

a chemical reaction is initiated between the acid and

the sodium bicarbonate to form the sodium salt of

the acid, and to produce carbon dioxide and water

completed within one minute or less.

The advantage

1.it provides a means of preparing a solution

containing an accurate drug dose As in the case of

effervescent aspirin tablet has a pH of about 8.

If pH of the gastric contents raise to neutral or

near-netural pH, the aspirin remains in solution and

is rapidly available upon emptying from the stomach,

that this form of aspirin is less irritating to the

stomach mucosa.

1.having the capability of producing clear solutions,

also produce a pleasantly flavored carbonated drink,

which assists in masking the taste of certain drugs.

The disadvantage

1. is the difficulty of producing a chemically stable

product where the moisture in the air during product

preparation may be adequate to initiate effervescent

reactivity.

2. During the course of the reaction, water is

liberated from the bicarbonate, which autocatalyzes

the reaction.

3.Need adequate protection of effervescent tablets in

the hands of the consumer where the moisture to

which tablets are exposed after opening the

container result in a rapid loss of product quality.