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Concept
• Definition: semisolid preparations intended for exter
nal application are termed ointments.
• Ingredient: drug substance +bases+ adjuvants
Classification
According to the
dispersion system:
(1) solutions type
(2) suspension type
(3) emulsions type
According to the bases:
(1) oleaginous dosage form
(2) emulsions dosage form
(3) pastes dosage form
(4) collodions dosage form
(5) ophthalmic dosage form
Quality requirement
the product is required smooth and uniform with
certain stickiness to skin
the drug in bases even distributed
stability of the ointment
Skin infection preparations are designed to be sterile
Ointment bases
Ointment bases are classified into four general groups:
• (1) Hydrocarbon bases
• (2) Absorption bases
• (3) Water-Removable Bases
• (4) Water-Soluble Bases
(1) hydrocarbon bases
Hydrocarbon bases (oleaginous bases) are water-free, and a
queous preparations may be incorporated into them only in s
mall amounts and then with difficulty.
Hydrocarbon bases are retained on the skin for prolonged pe
riods, do not permit the escape of moisture from the skin to t
he atmosphere, and are difficult to wash off.
As such they act as occlusive dressings. They do not "dry ou
t" or change noticeably upon aging.
• Petrolatum
a mixture of semisolid hydrocarbo
ns obtained from petroleum
an unctuous mass, varying in color
from yellow to white
It may be used alone or in combina
tion with other agents as an ointme
nt base
Commercial product is Vaseline
• Paraffin
A purified mixture of solid hydrocarbons obtained from petroleum.
A colorless or white, more or less translucent mass that may be used
to harden or stiffen oleaginous semisolid ointment bases.
• Liquid paraffin• a colorless, odorless
oily liquid consisting of a mixture of hydrocarbons obtained from petroleum
• has the same character with paraffin
• be used in combination with paraffin to adjust viscosity
•Hydrophilic Petrolatum is composed of cholesterol, stearyl alcohol, white wax, and white
petrolatum
has the ability to absorb water, with the formation of a water-in-o
il emulsion.
Aquaphor is a highly refined variation of Hydrophilic Petrolatum
and because it can absorb up to 3 times its weight in water, it has
proven useful to incorporate extemporaneously a water-soluble d
rug into an oleaginous base.
may contain no more than 0.25
% of water.
insoluble in water, but mixes wi
thout separation with about twi
ce its weight of water
The incorporation of water resu
lts in the formation of a water-i
n-oil emulsion.
Anhydrous Lanolin (refined wool fat)
a semisolid, fatlike substance
obtained from the wool of she
ep.
a water-in-oil emulsion that c
ontains between 25 and 30%
water.
Additional water may be inco
rporated into lanolin by mixi
ng.
Lanolin (hydrous Wool Fat )
• Beeswax and spermaceti
They are weak sufactants (W/O) and used as stabilizati
on agents in O/W emulsive ointment.
Mineral Oil
• a mixture of liquid hydrocarbons.
• It is useful as a levigating substan
ce to wet and to incorporate solid
substances into the preparation o
f ointments that consist of oleagin
ous bases as their vehicle.
(2) Absorption bases
Absorption bases may be of two types:
(1)those that permit the incorporation of aqueous solut
ions, resulting in the formation of water-in-oil emuls
ions (e.g. Hydrophilic Petrolatum and Anhydrous lan
olin) and those that are already water-in-oil emulsio
ns (emulsion bases) that permit the incorporation of
small, additional quantities of aqueous solutions (e.g.
lanolin and Cold Cream).
These bases are useful as emollients although they do
not provide the degree of occlusion afforded by the ol
eaginous bases.
Absorption bases are not easily removed from the ski
n with water washing.
They are also useful pharmaceutically to incorporate
aqueous solutions of drugs, e g., sodium sulfacetamid
e, into oleaginous bases.
(3)Water-Removable Bases
oil-in-water emulsions that are capable of being washed from skin or clothing with water. For this reason, they are frequently referred to as "water-washable" ointment bases
may be diluted with water or with aqueous solutions.
have the ability to absorb serous discharges in dermatologic conditions.
Certain medicinal agents may be better absorbed by the skin when present in a base of this type than in other types of bases.
•Emulsifying agents
sodium lauryl sulfate :O/W emulsion
stearyl alcohol and cetyl alcohol representing the oleaginous phase of the W/O emulsion to improve the stabilization and viscosity.
sodium stearate and calcium stearate.
Glyceryl monostearate: weak W/O emulsifying agents and used as stabilization agents and emollient in the O/W emulsion.
• Stearic acid, beewax and paraffin are the main oleaginou
s bases.
• propylene glycol and water representing the aqueous ph
ase
• Methylparaben and propylparaben are used to preserve t
he ointment against microbial growth
(4) Water-Soluble Bases
• contain only water-soluble components.
• are water washable
• Because they soften greatly with the addition of water,
aqueous solutions are not effectively incorporated into
these bases. Rather, they are better used for the incor
poration of nonaqueous or solid substances.
•Polyethylene Glycol Ointment
Polyethylene glycols are polymers of ethylene oxide
and water
The chain length may be varied to achieve polymers
having desired viscosity and physical (liquid,
semisolid, or solid) form.
The general formula for this base calls for the
combining of polyethylene glycol 3350(a solid) and
polyethylene glycol 400 (a liquid) to prepare base.
•Antioxidants
preparations Antioxidants
aqueous Sodium sulfite(Na2SO3)
sodium bisulfite(NaHSO3), hypophosphorous acid(H3PO2)
ascobic acid( vitamin C)
oleaginous Alpha tocopherol(vitamin E)
Butylhydroxyanisole(BHA)
ascorbyl palmitate
•Antimicrobial preservatives
frequently require the addition of chemical antimicr
obial preservatives to the formulation to inhibit the
growth of contaminating microorganisms
These preservatives include: para-hydroxybenzoates
(parabens), phenols, benzoic acid, sorbic acid, quater
nary ammonium salts and other compounds.
Selection of the Appropriate Base
The selection of the base to use in the formulation of an
ointment depends upon the careful assessment of a
number of factors, including :
(a) the desired release rate of the particular drug subst
ance from the ointment base
(b) the desirability for enhancement by the base of the
percutaneous absorption of the drug
(c) the advisability of occlusion of moisture from the
skin by the base
(d) the short-term and long-term stability of the drug
in the ointment base
(e) the influence, if any, of the drug on the consistency
or other features of the ointment base.
(f) patient factors also play an important role in a
base's selection
Preparation of Ointments Both on a large and a small scale, ointments are
prepared by three general methods:
(1) incorporation method
(2) fusion method
(3) emulsification method
The method for a particular preparation depends
primarily upon the nature of the ingredients
(1) incorporation the components of the ointment are mixed together by
various means until a uniform preparation has been
attained.
On a small scale, the pharmacist may mix the
components of an ointment in a mortar with a pestle,
or a spatula and an ointment slab (a large glass or
porcelain plate) may be used to rub the ingredients
together.
(2) fusion
By the fusion method, all or some of the components of an
ointment are combined by being melted together and cooled
with constant stirring until congealed.
Those components not melted are generally added to the
congealing mixture as it is being cooled and stirred.
Naturally, heat-labile substances and any volatile components
are added last when the temperature of the mixture is low
enough not to cause decomposition of volatilization of the
components.
• In the preparation of ointments having an emulsion type of
formula, the general method of manufacture involves a
melting process as well as an emulsification process.
(3) emulsification
the water-immiscible components such as the oil and
waxes are melted together in a steam bath to about 70 to
75°C
Meantime, an aqueous solution of all of the heat-stable,
water-soluble components is being prepared in the
amount of purified water specified in the formula and
heated to the same temperature as the oleaginous
components.
Then the aqueous solution is slowly added, with
constant stirring (usually with a mechanical stirrer),
to the melted oleaginous mixture, the temperature is
maintained for 5 to 10 minutes to prevent
crystallization of waxes
the mixture is slowly cooled with the stirring
continued until the mixture is congealed.
Notice:
• If the aqueous solution were not the same
temperature as the oleaginous melt, there would
be solidification of some of the waxes upon the
addition of the colder aqueous solution to the
melted mixture.
Emulsification ointments
Ⅱophthalmic ointments
• Concept
semisolid preparations intended for
application to the eye are specially prepared
and are termed ophthalmic ointments.
•Preparation of ophthalmic ointments
The methods of preparation just like
ointments,but under the aseptic condition
for prevent eye infection.
•The bases
must be non-irritating to the eye and must permit the diffusion of
the medicinal substance throughout the secretions bathing the e
ye.
Ointment bases utilized for ophthalmics have a melting or softeni
ng point close to body temperature.
In most instances, mixtures of petrolatum and liquid petrolatum
(mineral oil) are utilized as the ointment base.
Sometimes a water-miscible agent as lanolin is added. This per
mits water and water-insoluble drugs to be retained within the del
ivery system.
•The advantage and disadvantage
The primary advantage of an ophthalmic ointment
over an ophthalmic solution is the increased ocular
contact time of the drug.
One disadvantage to ophthalmic ointment use is the
blurred vision which occurs as the ointment base
melts and is spread across the lens.
Suppositories are semisolid dosage forms intended for
insertion into body orifices where they melt, soften, or
dissolve and exert localized or systemic effects.
1.Definition
Suppositories are commonly employed rectally, vagi
nally and occasionally urethrally.
They have various shapes and weights depending up
on the density of the base and the medicaments prese
nt in it, and the individual manufacturer's product.
2. Body orifices for using
3.character of action
Rectal suppositories are most frequently employed to relieve
constipation or the pain, irritation, itching, and inflammation a
ssociated with hemorrhoids or other anorectal conditions.
Vaginal suppositories or inserts are employed mainly as cont
raceptives, antiseptics in feminine hygiene, and as specific a
gents to combat an invading pathogen.
Urethral suppositories may be used as antibacterial and as a
local anesthetic preparative to urethral examination.
1)Local Action
(a) for the relief of nausea and vomiting and as a tranquilizer
(b) for narcotic analgesia
(c) for the relief of migraine syndrome
(d) anti-inflammatory analgesic and antipyretic.
2)Systemic Action
administered rectally in the form of suppositories for
systemic effects include:
3) advantages over oral therapy(rectal route for achieving systemic effects )
(a) drugs destroyed or inactivated by the pH or enzymatic
activity of the stomach or intestines need not be exposed
to these destructive environments;
(b) drugs irritating to the stomach may be given without
causing such irritation;
(c) drugs destroyed by portal circulation may bypass the liver
after rectal absorption (drugs enter the portal circulation
after oral administration and absorption);
(d) the route is convenient for administration of drugs
to adult or pediatric patients who may be unable or
unwilling to swallow medication;
(e) it is an effective route in the treatment of patients
with vomiting episodes.
4.Quality control of suppository
the medicaments and base mixed uniformly with certain
hardness under condition of shipment and storage
capable of being easily inserted into the intended body
orifice without causing undue distension.
once inserted, the base melts, softens, or dissolves,
distributing the medicaments it carries to the tissues of the
region. It must be retained for the appropriate period of time
for local effects or quickly absorbed for systemic effects .
The shape and size of a suppository must be such that
contains drug,base and other adjuvant ,which the affec
ting factors for preparation are the physicochemical n
ature of the drug, the nature of the suppository vehicle
and its capacity to release the drug and clinical desired
effects from administration 。
Drug
properties as the relative solubility of the drug in lipid
and in water , the particle size of a dispersed drug.
Ⅱ Ingredients of suppositories
1.requisites for a suppository base is that :
1)it remains solid at room temperature but softens, melts,
or dissolves readily at body temperature so that the dru
g it contains may be made fully available soon after inse
rtion
2)with certain hydrophilic or hydrophobic character
3)melting point near to solidifying point
4) easily ejectable from mold
5) don’t irritate to the mucous membranes
Base
2.Classification of Suppository Bases
According to bases physical characteristics the
bases can be classified into
(1) fatty or oleaginous bases
(2)water-soluble or water-miscible bases
(1) fatty or oleaginous bases:
Fatty bases are perhaps the most frequently employed s
uppository bases . A lipophilic drug that is distributed i
n a fatty suppository base in low concentration has less o
f a tendency to escape to the surrounding aqueous fluids
than would a hydrophilic substance present in a fatty ba
se to an extent approaching its saturation.
fatty bases contains:
(a) Cocoa Butter and (b) compounds of glycerin
the fat obtained from the r
oasted seed of theobroma c
acao.
At room temperature it is
a yellowish, white solid hav
ing a faint, agreeable choco
late-like odor.
(a) Cocoa Butter
Chemically, it is a triglyceride (combination of gly
cerin and one or different fatty acids) primarily of
oleopalmitostearin and oleodistearin.
It melts between 30 to 36 , an ideal supposito℃ ℃
ry base, melting just below body temperature and
yet maintaining its solidity at usual room tempera
tures.
because of its triglyceride content, cocoa butter exhibi
ts marked polymorphism, or different crystalline for
ms α, β,β’,γ.
Because of this, when cocoa butter is hastily or careles
sly melted at a temperature greatly exceeding the min
imum required temperature and then quickly chilled,
As a result a metastable crystalline form (α crystals)
with a melting point much lower than the original coc
oa butter that the cocoa butter will not solidify at roo
m temperature.
Since the form represents a metastable condition, ther
e is a slow transition to the more stable β form of cryst
als having the greater stability and the higher melting
point.
Cocoa butter must be slowly and evenly melted. Prefe
rably over a water bath of warm water, to avoid the fo
rmation of the unstable crystalline form and ensure th
e retention in the liquid of the more stable β crystals t
hat will constitute nuclei upon which the congealing m
ay occur during chilling of the liquid.
Substances such as phenol and chloral hydrate have a
tendency to lower the melting point of cocoa butter wh
en incorporated with it.
If the mp is lowered to such an extent that it is not feas
ible to prepare a solid suppository using cocoa butler
alone as the base, solidifying agents like cetyl esters w
ax (about 20%) or beeswax (about 4%) may be melted
with the cocoa butter to compensate for the softening
effect of the added substance.
However, the additions of hardening agents must
not be so excessive as to prevent the melting of
the base after the suppository has been inserted
into the body,
nor must the wax material interfere with the
therapeutic agent in any way so as to alter the
efficacy of the product.
The higher molecular weight fatty acids, such a
s palmitic and stearic acids, may be found in fa
tty suppository bases.
Such compounds as glyceryl monostearate and
glyceryl monopalmitate are examples of this ty
pe of agent.
(b) compounds of glycerin
This base is slower to soften and mix with the physiologic fluids , therefore provides a more prolonged release;
Because it have a tendency to absorb moisture due to the hygroscopic nature of glycerin, the suppository must be protected from atmospheric moisture in order for them to maintain their shape and consistency
Due also to the hygroscopicity of the glycerin, the suppository may have a dehydrating effect and be irritating to the tissues upon insertion.
(2) water-soluble or water-miscible bases
(a) Glycerinated gelatin
The water present in the formula for the suppositories
minimizes this action; however, if necessary, the
suppositories may be moistened with water prior to
their insertion to reduce the initial tendency of the
base to draw water from the mucous membranes and
irritate the tissues.
A glycerinated gelatin base is most frequently used in the
preparation of vaginal suppositories, where the prolonged
localized action of the medicinal agent is usually desired.
vaginal suppositories are much more easily inserted than
suppositories with a cocoa butter base, owing to the
brittleness of cocoa butter and its rapid softening at body
temperature.
They are available in a number of molecular weight
ranges, the more commonly used being polyethylene
glycol 200,400, 600,1000,1500,1540, 3350, 4000,6000,
and 8000. The numerical designations refer to the
average molecular weights of each of the polymers.
(b) Polyethylene glycols
Various combinations of these polyethylene glycols
may be combined by fusion, using two or more of the
various types to achieve a suppository base of the
desired consistency and characteristics.
Polyethylene glycol suppositories do not melt at
body temperature but rather dissolve slowly in
the body's fluids.
If the polyethylene glycol suppositories do not
contain at least 20%of water to avoid the irritation
of the mucous membranes after insertion, they
should be dipped in water just prior to use.
a surface-active agent with the average polymer l
ength being equivalent to about 40 oxyethylene u
nits.
The substance is a waxy, white to light tan solid t
hat is water-soluble. Its melting point is generally
between 39℃ and 45 ℃ .
(c) polyoxyl 40 stearate
Ⅲ Preparation of Suppositories
Suppositories are prepared by two methods:
(1) Preparation by compression
(2) Fusion or preparation by mold
(1) Preparation by Compression:
Suppositories may be prepared by forcing the mixed
mass of the suppository base and the medicaments int
o special molds using suppository making machines.
In preparation for compression into the molds, the su
ppository base and the other formulative ingredients a
re combined by thorough mixing, the friction of the p
rocess causing the base to soften into a paste-like consi
stency.
(a)cold Compression:
The process of compression is especially suited for the
making of suppositories containing medicinal
substances that are heat labile and for suppositories
containing a great deal of substances insoluble in the
base.
(b) hand rolling and shaping:
With the ready availability of suppository molds of
accommodating shapes and sizes, there is little
requirement for today's pharmacist to shape
suppositories by hand.
Hand rolling and shaping is a historic part of the
art of the pharmacist.
(2) Fusion or preparation by mold
The method is most frequently employed in the
preparation of suppositories both on a small scale and
on an industrial scale.
Mold shape
Molds in common use today are made from stainless
steel.
The molds, which separate into sections, generally
longitudinally, are opened for cleaning before and
after the preparation of a batch of suppositories.
Care must be exercised in cleaning the mold for the
desired smoothness of the resulting suppositories.
LUBRICATION OF THE MOLD
Depending upon the formulation, suppository molds may require lubrication before the melt is poured to facilitate the clean and easy removal of the molded suppositories.
Lubrication is seldom necessary when the suppository base is cocoa butter or polyethylene glycol.
Lubrication is usually necessary when glycerinated gelatin suppositories are prepared.
Any materials which might cause irritation to the mucous membranes should not be employed as a mold lubricant.
(a) the melting of the base
(b) incorporating of any required medicaments
(c) pouring the melt into molds
(d) allowing the melt to cool and congeal into suppositories
(e) removing the formed suppositories from the mold.
Notice:Suppositories of cocoa butler, glycerinated gelatin,
polyethylene glycol, and most other suppository bases are
suitable for preparation by molding.
the steps in molding
Each individual mold is capable of holding a specific volume of material in each of its openings.
If the material is changed, the weight of the resulting suppositories will differ from the weight of suppositories prepared in the same mold because of the difference in the densities of the materials.
Similarly, any added medicinal agent would further alter the densities of the bases, and the weights of the resulting suppositories would be different from those prepared with base material alone.
CALIBRATION OF THE MOLD
It is important that the pharmacist calibrate each of
his suppository molds for the suppository bases that
he generally employs in order that he may prepare
medicated suppositories each having the proper
quantity of medicaments.
First step : to prepare molded suppositories from
base material alone. After removal from the mold,
the suppositories are weighed, and the total weight
and the average weight of each suppository are
recorded as G
Second step :
to prepare molded suppositories from base and
drug. After removal from the mold, the
suppositories are weighed, and the total weight
and the average weight of each suppository are
recorded as M
Third step : to calculate the displacement
value by the equation below:
G
G-(M-W)
W
M
)( WMG
WDV
n
DV
yGx )(
For example:
Prepare the suppositories using cocoa buffer. The
average weight of each blank suppository is 3.5g. Then
adding 1.5g drugs into cocoa buffer and preparing a
medicated suppository. The weight of the medicated
suppository is 4.2g.
Please calculate the dosage of cocoa buffer if 10
medicated suppositories, every medicated
suppositories contain 1.0g drug, want to be prepared.
individually wrapped in either foil or a plastic material. Some
are packaged in a continuous strip with suppositories being
separated by tearing along perforations placed between
suppositories
Suppositories are also commonly packaged in slide boxes or
in plastic boxes.
maintain in a cool place.
stored in environments of fitting humidity
Ⅳ Packaging and Storage
Most commercially available suppositories are:
flash1 flash2
Ⅴ Treating role and Clinical applying
systemic action: medicaments may be intended to be
absorbed for the exertion of systemic effects
local action :medicaments may be intended for
retention within the cavity for localized drug effects.
Systemic Action
For systemic effects, the mucous membranes of
the rectum and vagina permit the absorption of
many soluble drugs. Although the rectum is
utilized quite frequently as the site for the
systemic absorption of drugs, the vagina is not as
frequently used for this purpose.
Absorption route:
According to the course of venous flow, a drug
absorbed in the lower part of the rectum should
enter the vena cava;
A drug placed in the upper part of the rectum
should diffuse into blood vessels which lead to the
liver.
The factors affecting the rectal absorption of a drug admini
stered in the form of a suppository may be divided into :
(1)physiologic factors: colonic contents, circulation route, and
the pH and lack of buffering capacity of the rectal fluids
(2) physicochemical factors of the drug and the base: The lipi
d-water partition coefficient;particle size; nature of the bases
Affecting factors for absorption
GlossaryOintments bases; oleaginous; hydrocarbon bases; absorptio
n bases; water-removable bases;water-soluble bases ; Petrol
atum ; Vaseline; Paraffin ; Anhydrous lanolin ; Hydrophilic;
Antioxidants; incorporation method; fusion method; emulsif
ication method; ophthalmic ointments;
Suppositories; Body orifices ; Rectal; Vaginal; melting point ;
Cocoa Butter ; polymorphism; hygroscopicity; Glycerinated
gelatin ; Polyethylene glycols; polyoxyl 40 stearate; displace
ment value