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PharmaceuticaI Dosage Forms

Presented
By
Prof. Dr. Sanaa A. EI-Gizawy
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Pharmaceutics
Pharmaceutics is the science of dosage form
design.
There are many chemicals with known
pharmacological properties but a raw chemical
is of no use to a patient.
Pharmaceutics deals with the formulation of a
pure drug substance into a dosage form.
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ctive Drug Substance
(Active pharmaceutical ingredient - API)
Chemical compound with pharmacological (or
other direct eIIect ) intended Ior use in
diagnosis, treatment or prophylaxis oI diseases.
International non-proprietary names (INN,
generic names)
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Direct cIinicaI use of the active drug substances ,as
they are" is rare due to a number of good reasons:
P handling can be difficult or impossible (e.g.,
low mg and 3g doses)
ccurate drug dosing can be difficult or
impossible
P administration can be impractical, unfeasible
or not according to the therapeutic aims
Some P can benefit from reducing the exposure
to the environmental factors (light, moisture.), or
they need to be chemically stabilised due to the
inherent chemical instability
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Direct cIinicaI use of the active drug substances ,as
they are" is rare due to a number of good reasons:
P can be degraded at the site of administration
(e.g., low pH in stomach)
P may cause local irritations or injury when they
are present at high concentrations at the site of
administration
P can have unpleasant organoleptic qualities
(taste, smell compliance!)
dministration of active substance would mean to
have no chance for modification (improvement) of
its PK profile
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From drug substance to pharmaceuticaI
preparation
Besides the choice of the active drug
substance, you need to also make a
responsible decision regarding the route of
administration and the DOS FORM (drug
delivery system) wrong choice can cause
failure of therapy
You should also be able to handle and
administer the drug properly or advise the
patient about it wrong use can cause failure
of therapy
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Excipients
Excipients (inactive pharmaceuticaI
ingredients)
ts selection depends on technological,
biopharmaceutical and/or stability reasons.
Diluents/fillers, binders, lubricants, coatings,
preservatives, colorants and flavouring
agents
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PharmaceuticaI dosage form
PharmaceuticaI dosage form
Determines the physical form of the final
pharmaceutical preparation
s a drug delivery system which is formed by
technological processing (drug formulation)
Must reflect therapeutic intentions, route of
administrations, dosing etc.
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PharmaceuticaI preparation (PP)
PharmaceuticaI preparation (PP)
particular pharmaceutical product containing active
and inactive pharmaceutical ingredients formulated
into the particular dosage form.
Packed and labelled appropriately
Two major types of PP according the origin:
Manufactured in large scales by pharmaceutical
industry (original and generic preparations)
Compounded individually in compounding
pharmacies
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1- PharmaceuticaI preparations
manufactured by pharmaceuticaI industry
1.1- OriginaI pharmaceuticaI preparations
undergo full and very extensive
pharmacological/ toxicological and
pharmaceutical pre-clinical and clinical
development and evaluation
particularly important is the proof of
effectiveness and safety
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- Can be released after the expiration of the patent
protection of the original preparation
The approval for clinical use is easier due to the prior
experience with the original preparation
Must be pharmaceutically equivalent: same P, dose,
pharmaceutical dosage form and the same route of
administration as in original preparation
Must be clinically bioequivalent: i.e. it must be of very
close PK profile as original preparation. PK parameters
(Cmax, tmax, &C) are within 80-125 % range as
compared with the original preparation.
1.2- Generic pharmaceuticaI preparations
(,authorised copies of originaI preparations")
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2- PharmaceuticaI preparations
compounded individuaIIy
These PP are compounded individually for a particular
patient according to the physician's prescription in a
pharmacy licensed for compounding
n contrast to the past, they are used rather rarely and
mostly in specific situations
t is highly advisable that whenever the particular suitable
PP is approved and commercially available it should be
preferred over the compounding
The major disadvantage is the lack of standardization (it is
always a ,single-patient batch"), unavailability of rigorous
QC testing and the appropriate clinical evaluation.
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The individuaIIy compounded PP
can be a justified choice when:
The drug in a particular dosage form is not
commercially available on the market
The extraordinary low or high dose is needed (young
children, elderly people, special situations e.g.,
intoxications). n this case right dosage strength need
not be readily commercially available for every patient
The patient suffers from the allergy on a specific
excipients (e.g., lactose a filler, some
colorizing/flavouring or antimicrobial agents -
parabens) or another drug appearing in the PP
Patient is unable to use a PP in its commercially
available dosage form (e.g., children, elderly)
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CIassification of pharmaceuticaI dosage
forms according to physicaI properties
aseous dosage forms
Liquid dosage forms
Semisolid dosage forms
Solid dosage forms
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Gases
Medicinal gases, inhalation/volatile
anaesthetics (vaporised before administration
by inhalation)
erodispersions of solid particles (e.g.,
antiasthmatic inhalations) or liquid particles
(antiasthmatic inhalations or sprays)
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Liquids
Solutions one homogenous phase, prepared by dissolving one or
more solutes in a solvent
mulsions
a dispersion system consisting of two immiscible liquids
o/w or w/o
cloudy appearance
Suspensions
dispersion system where solid particles (dispersed phase) are
dispersed in liquid phase (dispersion medium)
ccording to the size of dispersed particles (1 nm- 0,5 mm) a
molecular, colloidal and coarse dispersions can be distinguished
May require shaking before administration
Not intended for systemic administration of drugs with high
potency
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SemisoIid dosage forms
1- Unshaped (without specific physicaI shape)
els - semisolid systems in which a liquid phase is
constrained within a 3D cross-linked matrix.
Creams semisolid emulsion systems (o/w, w/o)
containing more than 10% of water.
o/w creams - more comfortable and cosmetically
acceptable as they are less greasy and more easily
water washable
w/o creams accommodate and release better
lipophilic P, moisturizing, Cold creams
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SemisoIid dosage forms
1- Unshaped (without specific physicaI shape)
Ointments semisolid dosage forms with the
oleaginous (hydrocarbon), water-soluble or
emulsifying base
Oleaginous (hydrocabon) base: Petrolatum
(Vaseline white, yellow)
Water-soluble base: Polyethylenglycol (P)-
ointment syn. macrogol ointments
Pastes semisolid dispersion system, where a solid
particles (> 25%, e.g. ZnO) are dispersed in
ointments mostly oleaginous (Petrolatum)
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SemisoIid dosage forms
2- Shaped
Suppositories (for rectal administration)
different shapes
Melting/dissolving at body temperature
Oleaginous (cacao butter, adeps
neutralis) or aqueous (Ps,
glycerinated gelatine)
Pessaries (vaginal suppositories)
Similar as above, Ps or glycerinated
gelatine are often used as base.
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SoIid Dosage Forms
Unshaped (without specific shape)
- powders for external/internal use
Shaped
- TabIets
- CapsuIes
- ImpIantates (Sterile disks inserted surgically into
body tissues and designed to release drug(s) over
extended period of time)
- TransdermaI patches
- Lozenges (consists of sugar and gum to medicate
the mouth and throate)
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CIassification of pharmaceuticaI dosage forms
according to the route of administration
for systemic administration
Peroral (p.o)
Sublingual (S.L) and buccal.
Rectal
Parenteral
Transdermal
nhalation
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CIassification of pharmaceuticaI dosage forms
according to the route of administration
for local administration
Topical (on the skin or mucosa)
nto/onto - the eye, nose, ear
- the oral cavity
- the vagina, rectum
- the brochi
- the skin
Local parenteral (viz Parenteral above)
Oral (local effect within T; antacids, adsorbents)
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Prescription Writing
The prescription is one of the most important
therapeutic transactions between physician and
patient.
The art of prescription writing is an ancient inheritance.
The ancients started their prescription with an appeal
to the gods for its success.
The ancient symbol, Rx, signifying the appeal, was
established centuries ago and has been carried down
to the present time.
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Prescription Writing
To avoid undesirable and/or serious effects on
the patient, both physician and pharmacist
must render the highest of professional
services.
ccurate diagnosis; proper selection of
medication, dosage form and route of
administration; proper size and timing of dose;
precise dispensing; accurate labeling; and
correct packaging all must be provided.
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Parts of prescriptions
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For rthur H. Recipe
Take thou
Potassium cetate of.............................one drachm.
Of Solution of cetate of mmonium........three and a half
drachms.
Of Spirits of Nitrous ther...........................two drachms.
Of nfusion of Buchu (a quantity sufficient) up to four
ounces.........
Signa: -Mix. Let a mixture be made.
Label: -One drachm three times a day after meals.
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Parts of prescriptions
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Form of the Written Prescription
prescription consists of the superscription,
the inscription, the subscription, the signa, and
the name of the prescriber
1- Superscription
The date when the prescription order is written;
the name, address and age of the patient; and
the symbol Rx (an abbreviation for "recipe," the
Latin for "take")
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Form of the Written Prescription
2- nscription
The body of the prescription, containing the
name and amount or strength of each
ingredient.
3- Subscription
The directions to the pharmacist, usually
consisting of a short sentence such as: "make
a solution," "mix and place into 10 capsules,"
or "dispense 10 tablets."
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Form of the Written Prescription
- Signature
From the Latin "signa," meaning "write," "make," or
"label," this sections contains the directions to the
patient.
These should always be written in nglish; however,
physicians continue to insert Latin abbreviations, e.g.
"1 cap t.i.d. pc," which the pharmacist translates into
nglish, "take one capsule three times daily after
meals." Since the pharmacist always writes the label in
nglish, the use of such abbreviations or symbols
should be discouraged.
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Form of the Written Prescription
Follow: - Signature
The instruction, "take as directed," is not
satisfactory and should be avoided.
The directions to the patient should include a
reminder of the intended purpose of the
medication by including such phrases as "for
pain," "for relief of headache," or "to relieve
itching"
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Form of the Written Prescription
5- Labeling
When the physician wants his patient to know
the name of the drug, the box on the
prescription form marked "label" should be
checked.
6- Refills
The physician should designate the number of
refills he wishes the patient to have.
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Proprietary vs. Non-Proprietary
("Generic") Prescriptions
n recent years, some hospitals and private
physicians are indicating on the prescription
their willingness or desire that the pharmacist
dispense a non-proprietary or "generic-named"
preparation instead of the trade name item
written on the prescription. Some have a box
on the prescription designated "N.P.P." n this
way, the pharmacist can use a form of the drug
which may be less expensive to the patient.
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Types of Drugs
Legend Drugs: These drugs may not be
dispensed by a pharmacist without a
prescription from a physician.
ControIIed Drugs: n addition to requiring a
prescription, these drugs require additional
safeguards for storage. Refills are also limited.
Over-the-Counter (OTC) Drugs: These drugs
do not require a prescription.
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ControIIed Substances
Schedules of Controlled Drugs: These drugs are
divided into five schedules.
Drugs can be scheduled, unscheduled, or moved from
one schedule to another as the need arises.
ScheduIe I
Drugs in this schedule have a high abuse potential
(narcotic and hallucination effects). xamples are
heroin, marijuana.
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ControIIed Substances
ScheduIe II
Drugs in this schedule have a high abuse potential with
severe psychic or physical dependence liability.
ncluded are certain narcotic analgesics, stimulants,
and depressant drugs. xamples are opium, morphine,
codeine, hydromorphone, methadone, meperidine,
oxycodone, anileridine, cocaine, amphetamine,
methamphetamine, phenmetrazine, methylphenidate,
amobarbital, pentobarbital, secobarbital,
methaqualone, and phencyclidine.
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ControIIed Substances
ScheduIe III
Drugs in this schedule have an abuse potential less
than those in Schedules and and include
compounds containing limited quantities of certain
narcotic analgesic drugs, and other drugs such as
barbiturates, glutethimide, methyprylon, and
chlorphentemine. ny suppository dosage form
containing amobarbital, secobarbital, or pentobarbital
is in this schedule.
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ControIIed Substances
ScheduIe IV
Drugs in this schedule have an abuse potential
less than those listed in Schedule and
include such drugs as barbital, phenobarbital,
chloral hydrate, ethchlorvynol, meprobabmate,
chlordizepoxide, diazepam, oxazepam,
chloroazepate, flurazepam, etc.
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ControIIed Substances
ScheduIe V
Drugs in this schedule have an abuse potential
less than those listed in Schedule V and
consist primarily of preparations containing
limited quantities of certain narcotic analgesic
drugs used for antitussive and antidiarrheal
purposes.
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Requirements for Prescriptions
Written for ControIIed Substances
Required nformation on the Prescription
Must be dated and signed on the day it is
issued. Must have the full name and address of
the patient.
Must have the name, address, and registration
number of the physician.
May be prepared by the secretary, but must be
signed by the physician.
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RefiIIing Prescriptions for
ControIIed Substances
Refills for Schedule drugs are not permitted.
Refills for Schedule , V, and V drugs are
permitted if the number of refills is indicated
on the prescription. However, the prescription
order may be renewed only up to five times
within six months after the date of issue. fter
five renewals or after six months a new
prescription order is required.