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GASTROINTESTINAL DRUG
ABSORPTION OF DOSAGE FORMS-
TABLETS AND CAPSULES
M pharm 1sem www.DuloMix.com
Department of Pharmaceutics
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Absorption of a drug is possible only when it is present in the solution
form, wherein the molecules are independent & assume molecular
dimensions.
Based on the dosage form, the variation could be depicted as:
Solution > Suspensions > Capsules > Compressed Tablets > Coated Tablets
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TABLET DOSAGE FORMS :
The tablet is the most commonly used oral dosage form.
The biggest problem is overcoming the reduction in effective surface area
produced during the compression process. One may start with the drug in a very
fine powder, but then proceeds to compress it into a single dosage unit.
INGREDIENTS:
Tablet ingredients include materials to break up the tablet formulation.
Drug : may be poorly soluble, hydrophobic or hydrophilic.
Lubricant : usually quite hydrophobic.
Granulating agent : tends to stick the ingredients together.
Filler: may interact with the drug, etc., should be water soluble.
Wetting agent : helps the penetration of water into the tablet.
Disintegration agent: helps to break the tablet apart
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TYPES OF PRODUCTS :
Matrix tablets: Matrix erodes or drug leaches from matrix.
Coated pellets: Different pellets (colors) have different release properties.
Coated ion exchange Osmotic pump: Insoluble coat with small hole. Osmotic
pressure pushes the drug out at a controlled rate.
COATED TABLETS :
Coating is generally used to mask unpleasant taste, odor and to protect the
ingredients from decomposition during storage or to improve the tablets
appearance.
This coating acts as barrier between the solid drug and drug in solution. This
barrier must break down quickly or it may hinder a drug’s bioavailability.
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SUGAR & FILM COATINGS:
Presence of water impermeable seal coating can potentially retard drug release
from sugar coated tablets.
Ex: quinine tablets coated with cellulose acetate pthalate showed a decrease in both
rate and extent of absorption with increase in thickness of coating.
Sugar coating will take more time than film coating. Care should be taken while
selecting the coating material. Ex: methyl cellulose which retards the dissolution.
ENTERIC COATED TABLETS :
It is a special film coated design to restrict the gastric fluids & to dissolve in small
intestine. It protects the drug from the degradation in the stomach.
Ex: erythromycin, aspirin. These tablets must empty the stomach before the drug
absorption can begin. The polymers with pKa values ranging from 4-7 have been
found to use. Thickness of coating will affect the bioavailability in these
formulations.
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SUSTAINED RELEASE TABLET :
For short half-life drugs, sustained release can mean less frequent dosing and thus
better compliance. Reduce variations in plasma/blood levels for more consistent
result.
PROBLEMS:
More complicated formulation, may produce more erratic results.
A sustained release product may contain a larger dose, i.e. the dose for two or
three (or more) ‘normal’ dosing intervals. A failure of the controlled release
mechanism may result in release of a large potentially toxic dose. More expensive
technology.
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FORMULATION FACTORS AFFECTING BIOAVAILABILITY OF
TABLETS:
Reduction in effective surface area- This is due to granulation and subsequent
compression into tablet. This factor is especially important for tablets
containing drugs that should disintegrate rapidly and completely in the gastro
intestinal fluids if rapid release, dissolution and absorption are required.
PHYSICOCHEMICAL PROPERTIES OF THE DRUG:
Nature and quantity of excipient. Size of the granules and their method of
manufacture.
The compaction pressure and speed of compaction used in tableting. Drug-
excipient interactions.
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CAPSULE DOSAGE FORMS:
• Powders and granules are administered as hard gelatin capsules. The hard
gelatin shell should disrupt rapidly and allow the contents to be mixed with
the GIT contents..
• The capsule contents should not be subjected to high compression forces
which would tend to reduce the effective surface area, thus a capsule should
perform better than a tablet.
• This is not always the case, if a drug is hydrophobic a dispersing agent
should be added to the capsule formulation. These diluents will work to
disperse the powder, minimize aggregation and maximize the surface area
of the powder.
• Tightly packed capsules may have reduced dissolution and bioavailability.
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FORMULATION FACTORS AFFECTING BIOAVAILABILITY OF
HARD GELATIN CAPSULES:
Generally the bioavailability of a drug from a hard gelatin capsules will be
better than or equal to that of same drug in a compacted tablet.
FACTORS:
• Dissolution rate of gelatin shell.
• The rate of penetration of GI fluids into encapsulated mass.
• The rate at which the mass disaggregates in the GI fluid.
• The rate of dissolution of dispersed drug particles.
• Packing density of the capsule contents.
• Inclusion of excipients in the capsule formulation. and effect of excipients.
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SOFT GELATIN CAPSULE:
• Soft gelatin capsule has a gelatin shell thicker than hard gelatin capsules,
but shell is plasticized by adding glycerin, sorbitol.
• Soft gelatin capsules may be used to contain non aqueous solution or
liquid or semi solid.
• Soft gelatin capsules have a better bioavailability than powder filled hard
gelatin capsules and are equivalent to emulsions.
Example:
➢ Quinine derivative was better absorbed from soft gelatin capsules
containing drug base compared with hard gelatin capsules containing HCl
salts.
➢ Grieseoflavin exhibited 88% absorption from soft gelatin capsules
compared to hard gelatin capsules (30%)
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FORMULATION FACTORS AFFECTING BIOAVAILABILITY OF
SOFT GELATIN CAPSULES:
• Solubility of drug in vehicle.
• Dissolution and splitting of flexible shell.
• Nature of the vehicle.
• Inclusion of a surfactant as a wetting or emulsifying agent.
• Particle size, density, crystal form of the drug, selection of diluents etc.,
influence bioavailability of soft gelatin capsules.
For hydrophobic drugs with a fine particle size in capsule results in decrease in
porosity of the powdered drug and thus decreased penetrability by the solvent
which results clumping of particle.
Soft gelatin capsule dissolve faster than hard gelatin capsule & tablets, which
shows better bioavailability from oily solutions, emulsions, or suspensions.
The problem with SGC is high water content of shell, moisture migrate into the
shell causes crystallization of the drug which results in altered dissolution
characteristics.
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