Transcript CONTROLLED RELEASE TABLET DOSAGE FORM

CONTROLLED RELEASE
TABLET DOSAGE FORM
controlled-release tablets
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
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 controlledrelease 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 release
The dissolution rate of a drug is directly related to the
surface area exposed to the dissolution media.
Effect of binding agents
Binding 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 disintegrants
Disintegrants 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 diluents
The 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
pharmaceutical properties of the tablets.
affecting
the
Formulation of controlled release tablets
Controlled -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
achieved
drug
relase
by
avoid
disintegrating
agent
formulation.
the
in
can
be
use
of
the
tablet
• 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
(styrene di-vinyl benzene copolymer)
Ananionic group
Cataionic group
COOH,
+ cataionc drug
(Atropin)
Resin-SO3- D+
GI (HCL)
Resin-SO3- H + + D
+ Anaionic drug
(Deltiazem HCL)
Resin-N(CH3) 3+ DGI (HCL)
Resin-N(CH3) 3+ CL- + 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.
Tablet Coating as a Technique for
controlling release
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.
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 coating
This 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 coating is possible using both sugar and film
coating techniques.
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.
Press coatings
The polymers used in coating include:
1. Modified acrylates
2. Water-insoluble celluloses e.g. ethyl cellulose.
Press coatings
Tablets Used in the Oral Cavity
Chewable Tablets
Advantages 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.
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 Tablets
Buccal 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 20to 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 nearnetural 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.