SUPPOSITORIES
Nov 20, 2014
SUPPOSITORIES
SuppositoriesSuppositoriesDerived from the Latin term supponere, meaning “to place under”.
SUB – under ; PONERE – to place Are solid dosage forms intended for
insertion into body orifices where they melt, soften, or dissolved and exert localized or systemic effects.
Suppositories Shape Dimensions
1.Rectal Suppository
Long, cylindrical and have one or both ends tapered.
Infant: 1 gram
Adult: 2 grams
2.Vaginal Suppository “Pessaries”
Globular, oviform, or conical shaped.
About 3 to 5 grams
3. Urethral Suppositories “Bougies”
Slender, pencil-shaped suppositories.
For males: 4 g, 100-150 mm long.
Females: 2 g, 60 to 70 mm.
Types of SuppositoriesTypes of Suppositories
1. Rectally 2. Occasionally Urethrally3. Nasal Insertion4. Vaginally 5. Rarely aurally
Characteristics based on Characteristics based on AdministrationAdministration
1. 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. Rectal Suppository are usually 32 mm (1 1/2 inches) in length, are cylindrical, have one or both ends tapered.
3. The USP and NF states that the adult Rectal suppositories weigh about 2 grams when cocoa butter (theobroma oil), as vehicle, is employed as based.
Nasal SuppositoriesNasal Suppositories - “Burginarium” Aural SuppositoriesAural Suppositories - “Ear Cones”
are pencil-shaped suppositories similar in shape to urethral suppositories but shorter in length, generally about 32 mm long.
AuralAural suppositories have been prepared with cocoa butter base
NasalNasal suppositories, with a glycerinated gelatin base.
Advantage and Disadvantage of Advantage and Disadvantage of SuppositoriesSuppositories
Advantages:
1. When a drug cannot be tolerated, cause to vomit orally
2. When a drugs cannot be swallowed - causing choking
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.
Disadvantage:
Inconvenient absorption is irregular and difficult to predict
Local and Systemic ActionsLocal and Systemic ActionsLocal Actions:
Once inserted, the suppository base melts, softens or dissolves, distributing the medicaments it carries to the tissues of the region.
Rectal Suppositories: relieves constipation or pain irritation, itching and inflammation associated with hemorrhoids or other anorectal conditions (pinworms, dermatitis)
Vaginal suppositories: as antiseptic in feminine hygiene and as specific agents to combat an invading pathogen.(vaginitis - by Trichomonas vaginalis and Candida albicans)
Urethral Suppositories: as antibacterial and as a local anesthetic preparatory to urethral examination
Systemic Actions:
For system effects, the mucous membranes of the rectum and vagina permits absorption of many soluble drugs.
Rectal suppositories: Aminophylline and Theophylline -
relief of asthma; Prochlorperazine and Chlorpromazine - nausea and vomiting and as tranquilizer; Chloral hydrate -sedative and hypnotic; Oxymorphine HCl - narcotic analgesic; Belladonna and Opium - analgesia
and antispasmodic effect; Ergotamine tartrate - migraine syndrome; Aspirin - analgesic and antipyretic
Factors Affecting Drug Factors Affecting Drug Absorption of SuppositoriesAbsorption of Suppositories
Physiological Factors:a.) Colonic content - 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 evacuate enema will be used first
Other conditions: diarrhea, colonic obstruction due to tumors, tissue dehydration can influence the rate and degree of absorption
b.) Circulation Route - 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.
c.) pH and Lack of Buffering Capacity of the Rectal Glands
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
Physiochemical Factors: A.DrugA.Drug
1. Relative solubility of the drug in lipid and in water2. Particle size of a dispersed drug
B.Suppository baseB.Suppository base 1. Ability to melt, soften or dissolve at body temperature2. Ability to release the drug substance3. Its hydrophilic or hydrophobic character
A. DRUG
1. Lipid-water solubility1. Lipid-water solubility - - 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.
Example water soluble base: polyethylene glycols - which dissolve in the anorectal fluids, release for absorption both water-soluble and oil-soluble drugs.
2. Particle size2. Particle size - - For drugs present in the suppository in the undissolved state, the size of the particle will influence the amount release and dissolved in absorption. “The smaller the particle size, the more readily the dissolution of the particle and the greater the chance for rapid absorption’”
B. Suppository BaseB. Suppository BaseNature of the base: must be capable of melting, softening, or dissolving to release its drug components for absorption.
Undesirable Characteristics Of A BaseUndesirable Characteristics Of A Base1. 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.
Classification Of Suppository BasesClassification Of Suppository Bases
1. Fatty or Oleaginous bases2. Water-soluble or water-miscible
bases3. Miscellaneous bases, (combination
of lipophilic and hydrophilic)
1. Fatty Or Oleaginous Base1. Fatty Or Oleaginous Base
When a base is not specified, Cocoa Butter is used.
Other oleaginous materials:
1. 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
Example of Suppositories with Cocoa Butter as a Base
1.Cotmar
2.Dehydag
3.Wecobee
4.Witepsol
5.Fattybase
2. Water-soluble/water-miscible Bases2. Water-soluble/water-miscible Bases
The main members of this group are based of1. Glycerinated gelatin2. Bases of polyethylene glycols
USP Preparation Of Glycerinated Gelatin1. Weigh medicinal substance2. Add water to make 10 grams3. Dissolved or mix 20 mL of glycerin and 20 grams of granular gelatin.4. Heat on a steam bath until all gelatin dissolved5. 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:
Example: Jell-O
1. May lose their shape and consistency2. May lose dehydrating effect and be irritating to the tissues upon insertion
Polyethylene GlycolPolyethylene GlycolPolyethylene 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 200, 400, 600, 1000, 1500, 1540, 3350, 4000, 6000 and 8000.Polyethylene glycols with average MW of 200, 400, and 600 are clear, colorless liquids. Those greater than 1000 are wax like, white solids with hardness increasing with an increase in molecular weight.
Example: Polybase
Miscellaneous BasesMiscellaneous Bases
1. Mixture of oleaginous and water-soluble materialsExample: Polyoxyl 40 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. Also referred to as “hydrophilic” suppository base.3. A soap as a base like glycerin suppositories which have sodium stearate, a soap as the base are included.
Preparations Of SuppositoriesPreparations Of Suppositories1. Molding from a melt/Fusion (Pour
Molding)2. Cold Compression (No heat
Application)3. Hand molding/rolling and shaping
(No Heat Application)4. Compression in a tablet press
*** The method most commonly employed in both small scale and industrial scale is molding.
Preparation By MoldingPreparation By Molding
1. 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. Allowing 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.
Note: Suppositories of cocoa butter, glycerinated gelatin, polyethylene glycol and most other suppository bases are suitable for preparation by molding.
Suppository MoldsSuppository MoldsMolds 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. Scratches in the molds should be avoided especially the plastic.
Lubrication Of The MoldsLubrication Of The MoldsDepending 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.
Calibration Of The MoldsCalibration Of The MoldsIt is important the pharmacist calibrate each of his suppository molds for the suppository bases that he generally employs to have proper quantity of medicaments.1. 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.
Example of Molder
DISPOSABLE MOLDER
Suppository Molds and Suppository Molds and PackagingPackaging
Aluminum metal molds come in a variety of cavity sizes and with a variety of number of
cavities per mold Common sizes vary from 1 g to 2.5 g, and common number of
cavities range from 6 cavities up to 100 cavities
Suppository Molds and Suppository Molds and PackagingPackaging
• 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 disposable molds do not need any lubrication regardless
of the suppository mixture available in 1 g to 5 g sizes, and many different colors.
Suppository Molds and Suppository Molds and PackagingPackaging
• 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.
Suppository Molds and Suppository Molds and PackagingPackaging
Flexible rubber moldscan be packaged with the suppository still
in the mold. Generally the mold is placed in a special box.
Determination Of The Amount Of Determination Of The Amount Of Base RequiredBase Required
First MethodFirst MethodSubtract the volume of the drug
substance from the total volume needed. For example: If 12 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, 0.86 g/mL the weight result is 7.9 g will required
Another Example:For Cocoa butter suppositoriesActive ingredient: AminophyllineDensity factor: 1.1Dosage: 0.5000 gram/suppositorySuppository base: Cocoa butterBlank weight of suppository: 2.000 grams
Calculations:0.5000/1.1 = 0.4545 g weight of cocoa butter which should be replaced by 0.5 g of the drug2.000 g - 0.4545 = 1.5455 g weight of cocoa butter required by the suppository0.5000 + 1.5455 = 2.0455 g actual weight of suppository
Second MethodSecond Method
Requires the following step1. Weigh the active ingredient for the preparation of a single
suppository2. Dissolve or mix it with a portion of melted base
insufficient to fill one cavity of the mold.3. Place the mixture to the mold4. Add additional melted base to the cavity to completely fill
the mold.5. Remove the suppository from mold and weigh6. 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.
Glycerin
Sodium Carbonate
Stearic AcidWater
Preparation of Ingredient
3. Preparing the Mold
Disposable molds
4. Base preparation
5. Mixing and Pouring
Opening a Suppository MoldOpening a Suppository MoldThe suppository mixture is poured into the
cavities of a closed mold. When the suppository mixture has congealed, the excess mass is removed from the topsurface of the mold and the mold is separated into the two halves.
An 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.
Opening a Suppository MoldOpening a Suppository Mold
Then apply a downward pressure only on the bottom half of the mold.
Opening a Suppository MoldOpening a Suppository Mold
A 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.
Opening a Suppository MoldOpening a Suppository Mold
Suppository shells can be opened by peeling apart the two tabs at the bottom of the shell.
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2
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6. Cooling and Finishing
7. Packaging
Suppository PackagingSuppository PackagingStrip wareStrips (bars) with 10, 12, 20 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, “short”
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"
Suppository PackagingSuppository Packaging
Preparing and Pouring of the MeltPreparing and Pouring of the Melt
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 “layering” 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.
2. Preparation By Compression2. Preparation By CompressionSuppositories 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.
Advantages and Disadvantages Advantages and Disadvantages of Preparation by Compression: of Preparation by Compression:
AdvantagesAdvantages1. The method is simple2. The resulting suppository
is more elegant than that of hand molding
3. Avoid the possibilities of sedimentation of the insoluble solids in the
suppository base
DisadvantagesDisadvantages1. Too slow for large scale
operation2. Air entrapment in
molding fat type base suppositories. This results in uncontrolled weight variation and favors the possible oxidation of the base and active ingredients.
Preparation by hand rolling and shaping Preparation by hand rolling and shaping (no longer used today)(no longer used today)
1. A 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. A 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.
4. Compression In A Tablet Press4. Compression In A Tablet Press
1. Carbon dioxide-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.
2. Vaginal Compressed Tablet - 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.
Other Inserts (rectally, Vaginally, and Other Inserts (rectally, Vaginally, and Urethrally)Urethrally)
1. Tablets and capsules - Vaginal Tablets/Inserts2. Ointments, Creams, and Aerosol Foams -
ProtoFoam3. Jellies and Gels4. Contraceptive Sponge5. Intrauterine Progesterone Drug Delivery System -
Progestasert6. Powders7. Solutions - vaginal Douches8. Enemas - Retention and Evacuation Enemas9. Suspensions - Barium Sulfate Suspension
PACKAGING AND STORAGE1. 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 –300C
7. Glycerinated – 200C to 250C
8. Polyethylene glycol – room temperature
9. With humidity- absorbed moisture and tend to become spongy
10.With excessive dryness – lose moisture and become brittle
ALPROSTADIL URETHRAL MICROSUPPOSITORY
MUSE – single use in male urethra
Medicated pellet measuring 1.4 mm in diameter by 3 mm or 6 mm long
Administered by inserting the applicator tip after urination
Available strength are 125, 250, 500, and 1000ug
For Erectile Dysfunction
Rectal Suppositories:Rectal Suppositories:
Suppository Product Effect Category
1. Bisacodyl Dulcolax local Cathartic
2. Chlorpromazine Thorazine systemic Anti-emetic, tranquilizers
3. Ergomine Tartrate Cafergot systemic Adrenergic blocking agents
4. Hydrocortisone Anusol-HC local Pruritis, Inflammed Hemmarhoids
5. Indomethacin Indocin systemic Anti-inflammatory, analgesic
6. Prochlorperazine Compazine systemic Anti-emetic
7. Promethazine HCl Phenergan systemic Anti-histaminic, antiemetic, sedative
Examples of Rectal Examples of Rectal SuppositoriesSuppositories
Vaginal Suppositories and TabletsVaginal Suppositories and TabletsProduct Active Constituents Category
1. AVC Suppositories Sulfanilamide, 1.05 Gm Candida albicans infections
2. Betadine Medicated Povidone-iodine, 10% relief of vaginitis due to Candida albicans, Trichomonas, and Gardnerella vaginalis
3. Gyne- Lotrimin Clotrimazole, 100 mg Vulvovaginal yeast (candida) infections
4. Monistat 7 Miconazole nitrate, 200g Antifungal for vulvovaginal candidiasis (moniliasis)
5. Semicid vaginal contraceptive insert nonoxynol-9,100 mg Non-systemic reversible method of birth control
6. Sultrin vaginal Tablet Sulfathiazole, sulfacetamide sulfabenzamide, 500 mg
Haemophilus
vaginalis vaginitis
7. Terazol 3 Terconazole, 80 mg same # 4
Examples of Vaginal Suppositories and TabletsExamples of Vaginal Suppositories and Tablets
Examples
Glycerin Suppository
Eucalyptol Suppository
SuppositoryHerbal Suppositories
Examples
Vaginal Suppository Suppository for Adult
Suppository for Children
Examples
Hemril-HC 25 mg
Anucort HC 25 mg Cotecxin Suppository
Hemorrhoidal-HC 25mg
Administration of Administration of SuppositoriesSuppositories
Inserting Rectal SuppositoriesInserting Rectal Suppositories
1. 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. Either stand with one leg on a chair, or lay on one side with one leg straight and the other leg bent toward your stomach.
Inserting Rectal SuppositoriesInserting Rectal Suppositories
Standing position
Lying Position
6. Separate buttocks to expose the rectal area.
Inserting Rectal SuppositoriesInserting Rectal Suppositories
7. 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.
8. Close your legs and sit (or lay) still for about 15 minutes. Avoid emptying bowels for at least one hour (unless the suppository is a laxative). Avoid excessive movement or exercise for at least one hour.
9. Wash hands again with soap and warm water immediately after inserting the suppository.
Inserting Rectal SuppositoriesInserting Rectal Suppositories
Inserting Rectal SuppositoriesInserting Rectal Suppositories
Inserting Vaginal Inserting Vaginal SuppositoriesSuppositories
1. 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.
5. Either 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.
Inserting Vaginal Inserting Vaginal SuppositoriesSuppositories
7. Remove the applicator for the vagina.
8. Wash your hands again with soap and warm water.
Inserting Vaginal Inserting Vaginal SuppositoriesSuppositories
JELLIES
Are class of gels in which the structural coherent matrix contains a high portion of liquid usually water
Usually formed by adding a thickening agent: tragacanth or CMC
Usually clear and uniform semisolid consistency
Example of Jellies
1.Lidocaine HCl Jelly
2.Cyclomethycaine Sulfate Jelly
3.Promoxine HCl Jelly – local anesthetic
4.Ephedrine Sulfate Jelly - symphatomimetic