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Biopharmaceutics and

Pharmacokinetics Task
topic 2
the relation between
Dosage form and
Absorption
Group 3:
1. Nita Yulisa 1311011018
2. Dhena Marichy Putri 1311011022
3. Rhesty Winanda 1311011027
4. Ghea Rofifah 1311011028
5. Ayu Fadhilla Rahmi 1311011029
The drug dose and the dosage form must be chosen
to provide sufficiently high unbound drug
concentrations so that an adequate amount of
drug reaches the site of drug action (receptor).
The onset of drug action depends on the rate of the
free (unbound) drug that reaches the receptor
and produces a minimum effective concentration
(MEC) to produce a pharmacodynamic response.
(Shargel, Leon et.al, 2004)
Drug products are designed to deliver drug for
local or systemic effects. Common drug
products include liquids, tablets, capsules,
injectables, suppositories, transdermal
systems, and topical products such as creams
and ointments.
The design and formulation of drug products
requires a thorough understanding of the
biopharmaceutic principles of drug delivery.
(Shargel, Leon et.al, 2004)
Drugs are not generally given as pure chemical
drug substances but are formulated into
finished dosage forms (drug products), such as
tablets, capsules, ointments, etc, before being
administered to patients for therapy.
Formulated drug products usually include the
active drug substance and selected
ingredients (excipients ) that make up the
dosage form.
(Gibson, Mark. 2009)
a dosage form refers to the package or
container of which the drug has taken the
shape that have the ability to release the
active ingredient over an extended period
(Gibson, Mark. 2009)
The main purpose of incorporating a drug in a delivery
system is to develop a dosage form that possesses the
following attributes:
contains the labeled amount of drug in a stable form
until its expiration date
consistently delivers the drug to the general circulation
at an optimum rate and to an optimum extent
is suitable for administration through an appropriate
route
is acceptable to patients.
(Jambhekar, Sunil S and Philip J Breen. 2009)
Recognizing the fact that drug must dissolve in
the gastrointestinal (GI) fluid before it can ben
absorbed, the bioavailability of a drug would be
expected to decrease in the following order:

solution > suspension > capsule > tablet


>coated tablets

Although this ranking is not universal, it does


provide a useful guideline.
(Jambhekar, Sunil S and Philip J Breen. 2009)
1. Solution (elixir, syrup and
solution) as a dosage form
is a mixture of 2 or more components that form
a single phase that is homogeneous down to the
molecular level. Solutions offer several
advantages over other dosage forms. Compared
with solid dosage forms, solutions are absorbed
faster and generally cause less irritation of the GI
mucosa.

Drugs are generally absorbed more rapidly from


solution.
(Jambhekar, Sunil S and Philip J Breen. 2009)
The rate limiting step is likely to be gastric
emptying, particularly when the drug is
administered after meals.
Many drugs, unless converted to water-
soluble salts, are poorly soluble. Solutions of
these drugs can be prepared by adding co-
solvents such as alcohol or polyethylene glycol
or surfactants.
Certain materials such as sorbitol or
hydrophilic polymers are added to solution
dosage forms to improve pourability and
palatability by increasing viscosity. This higher
viscosity may slow gastric emptying and
absorption.
The major problem of the solution dosage
form is the physicochemical stability of the
dissolved drug(s).
(Jambhekar, Sunil S and Philip J Breen. 2009)
The disadvantages of solutions include
susceptibility to microbial contamination and
the hydrolysis in aqueous solution of
susceptible active ingredients. In addition, the
taste of some drugs is more unpleasant when
in solution.
2. Suspension as a dosage form
A well-formulated suspension is second to a
solution in efficiency of absorption.
Dissolution is the rate-limited factor in
absorption of a drug from a suspension.
However, drug dissolution from a suspension
can be rapid if very fine or micronized
powders are used. (These have a larger
surface area or specific surface.)
(Jambhekar, Sunil S and Philip J Breen. 2009)
Drugs formulated in tablet and capsule dosage
forms may not achieve the state of dispersion in
the GI tract that is attainable with a finely
subdivided, well-formulated suspension

Some important factors to consider in formulating a


suspension for better bioavailability are:
(1) particle size
(2) inclusion of a wetting agent
(3) crystal form and
(4) Viscosity
(Jambhekar, Sunil S and Philip J Breen. 2009)
3. Capsule as a dosage form
The capsule has the potential to be an efficient
drug delivery system. The hard gelatin shell
encapsulating the formulation should disrupt
quickly, and expose the contents to the GI fluid,
provided that excipients in the formulation
and/or the method of manufacture do not
impart a hydrophobic nature to the dosage
form.
(Jambhekar, Sunil S and Philip J Breen. 2009)
Unlike the tablet dosage form, drug particles in a
capsule are not subjected to high compression forces,
which tend to compact the powder or granules and
reduce the effective surface area.
Hence, upon disruption of the shell, the encapsulated
powder mass should disperse rapidly to expose a large
surface area to the GI fluid.
This rate of dispersion, in turn, influences the rate of
dissolution and, therefore, bioavailability. It is,
therefore, important to have suitable diluents and/or
other excipients in a capsule dosage form, particularly
when the drug is hydrophobic
(Jambhekar, Sunil S and Philip J Breen. 2009)
4. Tablet as a dosage form
Whereas solutions represent a state of maximum
dispersion, compressed tablets have the closest
proximity to particles. Since problems
indissolution and bioavailability are generally
inversely proportional to the degree of
dispersion, compressed tablets are more prone to
bioavailability problems.
This is primarily because of the small surface area
exposed for dissolution until the tablets have
broken down into smaller particles
(Jambhekar, Sunil S and Philip J Breen. 2009)
Most solid dosage forms for oral administration
(tablets, capsules, and powders) must first undergo
disintegration followed by dissolution of drug particles
and transport of drug molecules into the gut.
Oral suspensions require dissolution and molecular
transport for absorption to occur. Extended- or
modified-release oral dosage forms may release the
drug by surface erosion, biodegradation, osmotic
pressure, or other mechanisms.
Diffusion of the active drug molecules across the gut
mucosa into the systemic circulation occurs either by
active transport or by passive diffusion process.
(Shargel, Leon et.al, 2004)
Factors responsible for the primary breakdown of
tablets into granules and their subsequent
breakdown into finer particles include:
type and concentration of a binder
disintegrating agent
diluents
lubricants
hydrophobicity of the drug
method of manufacture (wet granulation, dry
granulation and direct compression)
coloring and coating agents used.
(Jambhekar, Sunil S and Philip J Breen. 2009)
Tablet disintegration and granule
deaggregation are important steps in the
dissolution and absorption processes. A tablet
that fails to disintegrate or which disintegrates
slowly may result in incomplete and/or slow
absorption; this, in turn, may delay the onset
of action.
The importance of disintegration in drug
absorption is evident froma study of
dipyridamole (Persantine), a coronary
vasodilator.
(Jambhekar, Sunil S and Philip J Breen. 2009)
The dissolution of solid dosage forms is a prerequisite,
before absorption across biological barriers can occur.
Even when solutions with limited aqueous solubility
are given via the oral route, they may precipitate in the
stomach or intestinal region, because of either pH
changes or solubility limitations, and then they must
redissolve before absorption can occur.
Drugs with low solubilitymay dissolve slowly in the
gastrointestinal tract. The rate of in vivo dissolution
may be the ratedetermining step in the absorption
process.
THE KIND OF DRUG PRODUCT
1. Modified-Release Drug Product
The term modified-release drug product is used
to describe products that alter the timing and/or
the rate of release of the drug substance. A
modified-release dosage form is defined "as one
for which the drug-release characteristics of
time course and/or location are chosen to
accomplish therapeutic or convenience
objectives not offered by conventional dosage
forms such as solutions, ointments, or promptly
dissolving dosage forms as presently
recognized" ().
Several types of modified-release drug products
are recognized:
- Extended-release drug products. A dosage
form that allows at least a two fold reduction
in dosage frequency as compared to that drug
presented as an immediate-release
(conventional) dosage form. Examples of
extended-release dosage forms include
controlled-release, sustained-release, and
long-acting drug products.
- Delayed-release drug products. A dosage form
that releases a discrete portion or portions of
drug at a time or at times other than promptly
after administration, although one portion may
be released promptly after administration.
Enteric-coated dosage forms are the most
commondelayed-release products.
- Targeted-release drug products. A dosage form
that releases drug at or near the intended
physiologic site of action. Targeted-release
dosage forms may have either immediate- or
extended-release characteristics.
2. prolonged-action drug product
is designed to release the drug slowly and to
provide a continuous supply of drug over an
extended period.
The prolonged-action drug product prevents very
rapid absorption of the drug, which could result
in extremely high peak plasma drug
concentration.
Most prolonged-release products extend the
duration of action but do not release drug at a
constant rate. A sustained-release drug product
can be designed to deliver an initial therapeutic
dose of the drug (loading dose), followed by a
slower and constant release of drug.
The rate of release of the maintenance dose is
designed so that the amount of drug loss from
the body by elimination is constantly replaced.
With the sustained-release product, a
constant plasma drug concentration is
maintained with minimal fluctuations. shows
the dissolution rate of three sustained-release
products without loading dose. The plasma
concentrations resulting from the sustained-
release products are shown in .
Food can also affect the integrity of the dosage
form, causing an alteration in the release rate
of the drug. For example, theophylline
bioavailability from Theo-24 controlled-
release tablets is much more rapid when given
to a subject in the fed rather than fasted state
because of dosage form failures, known as
dose-dumping.
(Shargel, Leon et.al, 2004)
Daftar Pustaka
Gibson, Mark. 2009. Pharmaceutical
Preformulation and Formulation. USA:
Informa Healthcare
Jambhekar, Sunil S and Philip J Breen. 2009.
Basic Pharmacokinetics. UK: Pharmaceutical
Press
Shargel, Leon et.al., 2004. Applied
Biopharmaceutics & Pharmacokinetics, 5th
Edition. UK: The McGraw-Hill Companies
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