|

||

|


@ Derived from the Latin term
Ô

J meaning ³to place under´.
@ |
 under ; p
  to place
@ Gre solid dosage forms intended for
insertion into body orifices where
they melt, soften, or dissolved and
exert localized or systemic effects.
|  |
  

V.Rectal Long, cylindrical Infant: V gram

Suppository and have one or Gdult: 2 grams
both ends tapered.
2.Vaginal Globular, Gbout 3 to 5
Suppository oviform, or grams
p   conical shaped.

3. Urethral Slender, pencil- For males: 4 g,

Suppositories shaped V -V5 mm long.

  suppositories. Females: 2 g, 6
to 7 mm.
m



 

V. Rectally
2. Occasionally Urethrally
3. Nasal Insertion
4. Vaginally
5. Rarely aurally
 3







V. They have various weights and shapes, the shapes
and size of a suppository must be such that it is
capable of being easily inserted without causing
any distension and once inserted must be retained
for the appropriate period of time.
2.  | are usually 32 mm (V V
2
inches) in length, are cylindrical, have one or both
ends tapered.
3. The USP and NF states that the adult  
  
  when cocoa
butter (theobroma oil), as vehicle, is employed as
based.

|  - 
 
|  -  
are pencil-shaped suppositories
similar in shape to urethral suppositories
but shorter in length, generally about 32
mm long.
 suppositories have been
prepared with cocoa butter base

 suppositories, with a
glycerinated gelatin base.
 G

  





 
 
 
V. When a drug cannot be
tolerated, cause to vomit orally Inconvenient absorption is
2. When a drugs cannot be irregular and difficult to
swallowed - causing choking predict
3. When a drug may be
decomposed or inactivated by
the pH or enzymes in the GIT
4. Rectal suppositories
administered for its systemic
effects but containing drugs
destroyed in the liver are better
than oral administration since
rectal administration, liver is by
passed.
 ×   
 G

× | 
Once inserted, the suppository base
melts, softens or dissolves, For system effects, the mucous membranes
of the rectum and vagina permits
distributing the medicaments it absorption of many soluble drugs.
carries to the tissues of the region.
 |  relieves   
constipation or pain irritation,  
 

 -
itching and inflammation relief of asthma;
associated with hemorrhoids or p
   
other anorectal conditions 
   ! nausea and
(pinworms, dermatitis) vomiting and as tranquilizer;
 as antiseptic in 

 -sedative and
feminine hygiene and as specific hypnotic;
agents to combat an invading  
 " - narcotic
pathogen.(vaginitis - by analgesic;
Trichomonas vaginalis and
  - analgesia
Candida albicans) and antispasmodic effect;
   ! migraine
 
| as syndrome;
antibacterial and as a local  - analgesic and antipyretic
anesthetic preparatory to urethral
examination
 Õ
G

G




 
p
#
$%  - When systemic effects are desired from
the administration of a medicated suppository, greater
absorption may be expected from a rectum that is
empty than one that is distended with fecal matter
because of more absorbing surface.
So when deemed desirable, an     will be
used first


 diarrhea, colonic obstruction due to
tumors, tissue dehydration can influence the rate and
degree of absorption
$% - drugs absorbed
rectally, unlike those absorbed orally, by
pass the portal circulation during their first
pass into the general circulation, thereby
enabling drugs otherwise destroyed in the
liver to exert systemic effect.

The lower hemorrhoidal veins surrounding the

colon receive the absorbed drug and initiate
its circulation throughout the body, by
passing the liver.
$%"×&'
'' '
 
(
The rectal fluids are essentially neutral in pH and have no
effective buffer capacity so no chemical change will occur
in this area.
The suppository base has a marked influence in the release of
active constituents incorporated into it.
Cocoa butter melts rapidly at body temperature but
immiscible with body fluids and therefore fails to readily
release fat-soluble drugs.
For systemic drug action, it is preferable to incorporate the
ionized rather than the unionized form of a drug to
maximize bioavailability
p

#
$
V. Relative solubility of the drug in lipid
and in water
2. Particle size of a dispersed drug

$|
V. Gbility to melt, soften or dissolve at
body temperature
2. Gbility to release the drug substance
3. Its hydrophilic or hydrophobic character
$ (
)$×!  ! a lipophilic drug that is
)$×!
distributed in a fatty suppository base in low concentration
has loss of a tendency to escape to the surrounding
aqueous fluids than would a hydrophilic substance present
in fatty base to an extent approaching the saturation.

      polyethylene glycols -

which dissolve in the anorectal fluids, release for
absorption both water-soluble and oil-soluble drugs.

$p  ! For drugs present in the suppository in the

undissolved state, the size of the particle will influence the
amount release and dissolved in absorption. ³The smaller
the particle size, the more readily the dissolution of the
particle and the greater the chance for rapid absorption¶´

$|

Nature of the base: must be capable of melting,
softening, or dissolving to release its drug
components for absorption.

  
  '

V. That which interact with the drug inhibiting its
release such that the drug absorption will be
prevented or delayed.
2. That which is irritating to the mucous membranes
of the rectum thus initiating a colonic response
and prompt a bowel movement, negating the
prospect of thorough drug release and absorption.
' '|
 

V. Fatty or Oleaginous bases

2. Water-soluble or water-miscible
bases
3. Miscellaneous bases, (combination
of lipophilic and hydrophilic)
)$#   

When a base is not specified, 
  is
used.


   
V. Hydrogenated fatty acids of vegetable oils - palm,
kernel oil, and cotton seed oil

2. Fat bases compounds - glycerin with the higher

molecular weight fatty acids: palmitic and stearic
acids
›xample of Suppositories with
Cocoa Butter as a Base
V.Cotmar
2.Dehydag
3.Wecobee
4.Witepsol
5.Fattybase
$* !! + !
$*   + !  
 

   '
  '
V. Glycerinated gelatin
2. Bases of polyethylene glycols

|pp  '(  ( 

V. Weigh medicinal substance
2. Gdd water to make V grams
3. Dissolved or mix 2 mL of glycerin and 2
grams of granular gelatin.
4. Heat on a steam bath until all gelatin dissolved
5. Pour the melted mixture into molds and allow
to congeal.
    Glycerinated gelatin based
suppositories have tendencies to absorb
moisture due to the hygroscopic nature of
glycerin causing the following effect:

›xample: Jell-O

V. May lose their shape and consistency

2. May lose dehydrating effect and be
irritating to the tissues upon insertion
p 
  (
Polyethylene glycols are polymers of
ethylene oxide and water, prepared to
various chain lengths, molecular weights,
and physical states. They are available in a
number of molecular weights ranges 2 ,
4 , 6 , V , V5 , V54 , 335 , 4 ,
6 and 8 .
Polyethylene glycols with average MW of
2 , 4 , and 6 are clear, colorless
liquids. Those greater than V are wax
like, white solids with hardness increasing
with an increase in molecular weight.
›xample: Polybase
‰  
 

V. Mixture of oleaginous and water-soluble materials

   Polyoxyl 4 stearate (mixture of
monostearate and distearate esters of mixed
polyethylene diols and the free glycols)
2. Mixtures of many fatty acids (including Cocoa
Butter) with emulsifying agents capable of
forming W
O emulsion. Glso referred to as


 suppository base.
3. G soap as a base like   



    J a soap as the base
are included.
p  '| 
V. Molding from a melt
Fusion (Pour
Molding)
2. Cold Compression (No heat
Gpplication)
3. Hand molding
rolling and shaping
(No Heat Gpplication)
4. Compression in a tablet press
   The method most commonly
employed in both small scale and
industrial scale is $
p 
‰

V. Melting of the base preferably in water or

steam bath to avoid local overheating.
2. Incorporating the required medicament -
either emulsified or suspend in it.
3. Pouring the melt into cooled metal molds,
which are usually chrome or nickel plate.
4. Gllowing the melt to cool and congeal
thoroughly using refrigerator in a small
scale or refrigerated air on a larger scale.
5. Removing the formed suppositories from the
mold.

 Suppositories of cocoa butter, glycerinated
gelatin, polyethylene glycol and most other
suppository bases are suitable for preparation by
$

|‰
Molds in common use are made from stainless
steel, aluminum, plastic. The molds which
separate into sections generally longitudinally, are
opened for cleaning before and after preparing a
batch of suppository, closed when the melt is
poured and opened again to removed the cold,
molded suppository. |

 

   especially the plastic.
× '
‰
Depending upon the formulation,
suppository molds may require
lubrication before the melt is poured to
facilitate the clean and easy removal of
the molded suppository.
Lubricant is a thin coating of
mineral oil or expressed almond oil
applied with the finger to the molding
surface is sufficient.
 '
‰
It is important the pharmacist calibrate each of his
suppository molds for the suppository bases that
he generally employs to have proper quantity of
medicaments.
V. The suppositories are weighed and the total
weight and average weight of each
suppositories are recorded.
2. To determine the volume of the mold, the
suppositories are carefully melted in a
calibrated beaker.
3. The volume of the melt is determine for the
total number as well as the average of one
suppository.

  
,|p |
׉ ×



   
  
 


   
  
Gluminum metal molds
@ come in a variety of cavity sizes and with a variety of number of
cavities per mold
@ Common sizes vary from V g to 2.5 g, and common number of
cavities range from 6 cavities up to V cavities

‡ The two halves of the

mold are held together
with either nuts or some
molds have 1 centered
screw.
 


   
  
Plastic suppository shells
@ come in long strips that can be torn into any number of cavities
@ These    do not need any lubrication regardless
of the suppository mixture
@ available in V g to 5 g sizes, and many different colors.

‡ Advantage: if the
suppository should
melt, it will not run out
of the mold. If the
material can congeals
again, it will retain the
suppository shape.
 


   
  
Flexible rubber molds
@ can be packaged with the suppository still in
the mold. Generally the mold is placed in a
special box.
    '
  '

  - 

#‰ 

Subtract the volume of the drug
substance from the total volume needed.
#   If V2 mL of Cocoa butter
are required to fill a suppository mold and if
the medicaments in the formula have a
collection volume of 2.8 mL the 9.2 mL of
Cocoa butter will be required. By mutiplying
9.2 mL times the density of cocoa butter, .86
g
mL the weight result is 7.9 g will required

  
For Cocoa butter suppositories
Gctive ingredient: Gminophylline
Density factor: V.V
Dosage: .5 gram
suppository
Suppository base: Cocoa butter
Blank weight of suppository: 2. grams


.5
V.V = .4545 g weight of cocoa butter which should be
replaced by .5 g of the drug
2. g - .4545 = V.5455 g weight of cocoa butter required by
the suppository
.5 + V.5455 = 2. 455 g actual weight of suppository
| ‰ 

Requires the following step
V. Weigh the active ingredient for the preparation of a single
suppository
2. Dissolve or mix it with a portion of melted base
insufficient to fill one cavity of the mold.
3. Place the mixture to the mold
4. Gdd additional melted base to the cavity to completely fill
the mold.
5. Remove the suppository from mold and weigh
6. Then subtract the weight of the ingredient from the total
weight of the suppository to get the amount of the base
needed.
7. Then multiplied by the number of suppository to made to
get the total base needed.
 p ',  

M

| 

| 

ë

  


  
Ú ! 


w  

 ?
 


 
@ Thesuppository mixture is poured into the
cavities of a closed mold. When the
suppository mixture has congealed, the
excess mass is removed from the top
surface of the mold
and the mold is
separated into the
two halves.
?
 


 
@ Gn efficient way to separate the mold is
to remove the wing nuts or loosen the
centered screw and place the mold so that
the posts rest on the
table top.
 ?
 


 
@ Then apply a downward pressure only on
the bottom half of the mold.
?
 


 
@G knife or spatula should not be used to pry
the two halves apart. This will damage the
matching mold faces which have been
accurately machined to
give a tight seal.
@ Suppository shells can be opened by peeling
apart the two tabs at the bottom of the shell.

) .


à   " 
`
#
 


   
Strip ware
@ Strips (bars) with V , V2, 2 or 24 individual
cells
@ with or without punching
@ one side target printing
@ white or transparency or one side white and
one side transparency foil
@ various opening methods like tear open slot,
tear open strap, peel off strap, ³short´
 


   
Roll ware
@ with or without perforation between the cells
@ one or two side target printing
@ white or transparency or one side white and one side
transparency foil
@ various opening methods like tear open slot, tear
open strap, peel off strap "long", peel off strap
"short"
p p'
‰ 
Using the least possible heat, the weighed suppository base material is melted,
generally over a water bath.
The medicinal substance are usually incorporated into portion of the melted
base by mixing on glass or porcelain tile with spatula, stir and allowed to
cool almost to its congealing point.
It is generally best to chill the mold in the refrigerator before pouring the
melt. Then, the melt is placed carefully and continuously in the filling of
each cavity in the mold.
The pouring must be continuous to prevent   which may lead to a
product easily broken on handling.
When solidified the excess material is scraped off the top of the mold with
spatula. The mold is placed in the freezer to hasten hardening of the
suppository.
When suppositories are hard, the mold is removed from the freezer and
dislodged the suppositories from the mold.
Generally, little pressure is required to let fall the suppository of their mold.
$p 
  
Suppositories may be prepared by forcing the mixed mass
of the suppository base and the medicament into special
molds using suppository making machines.
On a small scale, a mortar is heated in warm water before
use and then dried, the softening of the base and the
mixing process are greatly facilitated forming a paste-like
consistency.
The compression process is especially suited for making
suppositories which contain substances that are heat labile
and for suppositories containing a great deal of substances
insoluble in base.
The suppository mass is placed in the cylinder which is
then closed, pressure is applied from one end, by turning
wheel and the mass is forced out of the other end into the
suppository mold or die. When the die is filled with the
mass, a movable end plate at the back of the die is removed
and when additional pressure is applied to the mass in the
cylinder, the formed suppositories are ejected.
 G

  




 
 
   
V. The method is simple V. Too slow for large scale
2. The resulting suppository operation
is more elegant than that 2. Gir entrapment in
of hand molding molding fat type base
3. Gvoid the possibilities of suppositories. This results
sedimentation of the in uncontrolled weight
insoluble solids in the variation and favors the
suppository possible oxidation of the
base base and active
ingredients.
p 


/  %

V. G plastic mass is formed from the base of grated

Cocoa butter and other ingredients.
2. Triturate in a mortar, then formed into a ball in
the palms of the hands, previously cooled in the
ice water.
3. G broad bladed spatula or flat board is used to roll
it into a cylinder on a pile tile.
4. Cut with a spatula into sections and shaped as
desired.
Ú$  , p 
)$ -releasing tablet - made up of
dried sodium biphosphate, sodium bicarbonate and
starch. This compressed rectal suppository is
dipped or sprayed with a coating of water soluble
polyethylene glycol to add film for protection of
the core and for the aid in insertion into rectum.

$     - in addition to the

active ingredient, it contains lactose and
or
phosphoric acids for adjusting the acidity of the
vagina to an approximate pH 5.
 
, / JJ
 
%

)$  ! Vaginal Tablets
Inserts

$  J  J # !
ProtoFoam
.$0  ( 
Ú$  |
1$,  p     | !
Progestasert
2$p 
3$|! vaginal Douches
4$ ! Retention and ›vacuation ›nemas
5$| ! Barium Sulfate Suspension
PGCKGGING GND STORGG›
V. Glycerin Suppository  tightly close glass container
2. Suppositories prepared with cocoa butter  wrapped individually
3. Suppositories containing light sensitive  individually wrapper  metallic
foil
4. Commercially suppositories  individually wrapped  foil or plastic
5. Some packaged with continuous strips
6. Cocoa butter 3 C
7. Glycerinated  2 C to 25 C
8. Polyethylene glycol  room temperature
9. With humidity- absorbed moisture and tend to become spongy
V .With excessive dryness  lose moisture and become brittle
GLPROSTGDIL UR›THRGL MICROSUPPOSITORY

‰ |  single use in male urethra

Medicated pellet measuring V.4 mm in
diameter by 3 mm or 6 mm long
Gdministered by inserting the applicator tip
after urination
Gvailable strength are V25, 25 , 5 , and
V ug
#  '
 „



 
Suppository Product ›ffect Category

V. Bisacodyl Dulcolax local Cathartic

2. Chlorpromazine Thorazine systemic Gnti-emetic, tranquilizers

3. ›rgomine Tartrate Cafergot systemic Gdrenergic blocking

agents

4. Hydrocortisone Gnusol-HC local Pruritis, Inflammed

Hemmarhoids
5. Indomethacin Indocin systemic Gnti-inflammatory,
analgesic

6. Prochlorperazine Compazine systemic Gnti-emetic

7. Promethazine HCl Phenergan systemic Gnti-histaminic,

antiemetic, sedative
› 
„




 
 6 


  m

Product Gctive Constituents Category

V. GVC Suppositories Sulfanilamide, V. 5 Gm Candida albicans infections

2. Betadine Medicated Povidone-iodine, V  relief of vaginitis due to Candida

albicans, Trichomonas, and Gardnerella
vaginalis

3. Gyne- Lotrimin Clotrimazole, V mg Vulvovaginal yeast (candida) infections

4. Monistat 7 Miconazole nitrate, 2 g Gntifungal for vulvovaginal candidiasis

(moniliasis)

5. Semicid vaginal contraceptive insert nonoxynol-9,V mg Non-systemic reversible method of birth

control

6. Sultrin vaginal Tablet Sulfathiazole, sulfacetamide Haemophilus

sulfabenzamide, 5 mg
vaginalis vaginitis

7. Terazol 3 Terconazole, 8 mg same # 4

› 
6 


  m

 


M |

 


 |

 

|

 
$ |

 
 


% |

  |

   

|

   

 


 $ 'w   |

 

$ &$ 'w  $ &$ 'w 

G   





 
 V
„



 
V. If possible, go to the toilet and empty bowels.
2. Wash hands carefully with soap and warm water.
3. Remove any foil or plastic wrapping from the suppository.
4. Lubricate the tapered end of the suppository with a small
amount of K-Y® Jelly. If the jelly is not available,
moisten the suppository with a small amount of water.
5. ›ither stand with one leg on a chair, or lay on one side
with one leg straight and the other leg bent toward your
stomach.
V
„



 

|tanding
position

Lying Position
 V
„



 

6. Separate buttocks to expose the rectal area.

`. Gently but firmly
push the suppository
into the rectum until it
passes the sphincter
(about 1/2 to 1 inch in
infants, and 1 inch in
adults.
 V
„



 

8. Close your legs and sit (or lay) still for about
V5 minutes. Gvoid emptying bowels for at
least one hour (unless the suppository is a
laxative). Gvoid excessive movement or
exercise for at least one hour.
9. Wash hands again with soap and warm water
immediately after inserting the suppository.
V
„



 
 V


|


V. Wash your hands carefully with soap and
warm water.
2. Remove any foil or plastic wrapping from
suppository.
3. Place suppository in applicator.
4. Hold the applicator by the opposite end from
where the suppository is.
 V


|


5. ›ither lay on your back with your knees bent,
or stand with your feet spread a few inches
apart and your knees bent.
6. Gently insert the applicator into the vagina as
far as it will go comfortably. Once you are
ready, push the inside of the applicator in and
place the suppository as far back in the
vagina as possible.
 V


|


7. Remove the applicator for the vagina.
8. Wash your hands again with soap and warm
water.
 0××,|
 ' 




  


'- 
' 
& 
 
‰
 '  
 
›xample of Jellies
V.Lidocaine HCl Jelly
2.Cyclomethycaine Sulfate Jelly
3.Promoxine HCl Jelly  local anesthetic
4.›phedrine Sulfate Jelly -
symphatomimetic