SUPPOSITORIES
Suppositories
Derived from the Latin term supponere, meaning ³to 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
Suppository
Long, cylindrical Infant: 1 gram and have one or Adult: 2 grams both ends tapered.
2.Vaginal Suppository ³Pessaries´
Globular, oviform, or conical shaped.
A bout
3. Urethral Suppositories ³Bougies´
Slender, pencilshaped suppositories.
For males: 4 g, 100-150 mm long.
1.Rectal
3 to 5
grams
Females: 2 g, 60 to 70 mm.
Types of Suppositories 1.
Rectally 2. Occasionally Urethrally 3. Nasal Insertion 4. Vaginally 5. Rarely aurally
Char ac acteristics
based on Administr ation
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. ectal Suppository are usually 32 mm (1 1/2 2. R ectal inches) in length, are cylindrical, have one or both ends tapered. ectal 3. The USP and NF NF states that the adult R ectal suppositories weigh about 2 grams when cocoa butter (theobroma oil), oil), as vehicle, is employed as based.
Suppositories - ³Burginarium´ Aural Suppositories - ³Ear Cones´ are pencil-shaped suppositories similar in shape to urethral ur ethral suppositories but shorter in length, generally about 32 mm long. Aural suppositories have been prepared with cocoa butter base Nasal
suppositories, with a glycerinated gelatin base. Nasal
Advantage and Disadvantage of Suppositories Advantages: When a drug cannot be tolerated, cause to vomit orally 2. When a drugs cannot be swallow swa llowed ed - caus causing ing choking choking 3. When a drug may 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:
1.
Inconvenient absorption is irregular and difficult to predict
Local Local
and Systemic Actions
Actions:
Once inserted, the suppository base melts, softens or dissolves, distributing the medicaments it carries to the tissues of the region. Suppositories:: relieves Suppositories constipation or pain irritation, itching and inflammation associated with hemorrhoids or otherr anor othe anorect ectal al cond conditio itions ns (pinworms, dermatitis) Vaginal suppositories: suppositories: as antiseptic in feminine hygiene and as specific agents to combat an invading pathogen.(v pathog en.(vaginiti aginitiss - by Trichomonas vaginalis and Candida albicans) Urethral Suppositories: Suppositories: as antibacterial and as a local anesthetic preparatory to urethral examination R ectal ectal
Systemic Actions: For system effects, the mucous membranes of the rectum and vagina permits absorption of many soluble drugs. ectal suppositories: suppositories: R ectal Aminophylline and Theophylline relief of asthma; rochlorperazine ne and Prochlorperazi Chlorpromazine - nausea and vomiting and as tranquilizer; Chloral hydrate -sedative and hypnotic; narco coti ticc Oxymorphine HCl - nar analgesic; Belladonna and Opium - ana analg lgesi esiaa and antispasmodic effect; rgotamin minee tart tartrate rate - migraine Ergota syndrome; Aspirin - anal analgesi gesicc and and anti antipyre pyretic tic
Factors Affecting
Drug Absorption of Suppositories Physiological Factors:
systemicc effects are are desired desired from from a.) Colonic content - When systemi 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 R oute oute - dr drug ugss ab abso sorb rbed ed 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 Buffer ing Capacity of the R ectal ectal Glands
The rectal fluids are essentially neutral in pH and have no effective buffer capacity so no chemical ch emical 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.Drug solubility of of the drug drug in lipid 1. Relative solubility and in water 2. Particle size of a dispersed drug B.Suppository base 1. A bility to melt, soften or dissolve at body temperature 2. A bility to release the drug substance 3. Its hydrophilic or hydrophobic character
A. DR UG UG 1.
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. ipid-water -water Lipid-
water soluble base: polyethylene glycols which dissolve in the anorectal fluids, release for absorption both water-soluble and oil-soluble drugs. Example
2.
suppo sitory in the size - For drugs present in the suppository undissolved state, the size of the particle will influence the amount release and dissolved in absorption. absorp tion. ³The smaller the particle size, the more readily the dissolution of the particle and the greater the chance for rapid absorption¶´ Particle
B. Suppository Base Nature of the base: base : must be capable of melting, softening, or dissolving to release its drug components for absorption. Undesirable Characteristics Of A Base 1. That which interact with the drug inhibiting inhibiting its release such that the drug absorption will 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 Bases 1.
Fatty or Oleaginous bases 2. Water-solub ater-soluble le or water-miscib water-miscible le bases 3. Miscellane Miscellaneous ous bases, (combination of lipophilic and hydrophilic)
1. Fatty Or Oleaginous Base
When a base is not specified, Cocoa Butter is used. Other
1.
oleaginous materials:
Hydrogenated fatty acids of vegetable oils - palm, Hydrogenated kernel oil, and cotton seed oil
2. Fat bases compounds - gly glyceri cerin n with with the the higher 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. WaterWater-soluble/water -soluble/water soluble/water--miscible -miscible Bases The main members members of this group are based of o f 1. Glycerinated gelatin 2. Bases of polyethylen polyethylenee glycols USP Preparation Of Glycerinated Gelatin 1. Weigh medicinal substance 2. Add water to make 10 grams 3. Dissolved or mix 20 mL of glycerin and 2 0 grams of granular gelatin. 4. Heat on a steam bath until until all gelatin gelatin dissolved 5. Pour the melted mixture into molds molds and allow to congeal.
Glycerinated gelatin based suppositories have tendencies to absorb moisture due to the hygroscopic nature of glycerin causing the following foll owing effect: ***
Example:
1.
Jell-O
May lose their shape and consistency 2. May lose dehydrating effect and be irritating to the tissues upon insertion
Polyethylen olyethylenee
Glycol
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 molecular weights ranges r anges 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 Bases 1.
Mixture of oleaginous and water-solu water-soluble ble materials Example: Polyoxyl 40 stearate (mixture of monostearate monosteara te and distearate esters of mixed polyethylene polyethyl ene diols and the free glycols) 2. Mixtures of many fatty acids (including Cocoa Butter) with with emulsifying emulsifying agents capable of forming W/O emulsion. Also referred to as ³hydrophilic´ suppository base. 3. A soap as a base like glycerin suppositories which have sodium stearate, a soap as the base are included.
Preparations Of 1.
Suppositories
Molding from a melt/Fusion (Pour (Pour Molding)) Molding 2. Cold Compression ( No heat A pplication pplication)) 3. Hand molding/rolling and shaping ( No No Heat A pplication pplication)) 4. Compression in a tablet press *** The method most commonly employed in both small scale and industrial scale is molding.
Preparation 1.
2. 3. 4. 5.
By Molding
Melting of of the base base preferably preferably in water or steam bath to avoid local overheating. Incorporating the required medicam medicament ent either emulsified emulsified or suspend in it. Pouring the melt melt into cooled cooled metal metal molds, molds, which are usually chrome or nickel plate. Allowing the melt to cool and congeal thoroughly using refrigerator in a sma small ll scale or refrigerated air on a larger scale. Removing the formed suppositor suppositories ies from the mold.
Suppositories of cocoa butter, glycerinated Suppositories gelatin, polyethylene polyethylene glycol and most other suppository supposito ry bases are suitable for preparation by molding.
Note:
Suppository Molds Molds in common use are made from stainless steel, aluminum, plastic. plastic . The molds which separate into sections generally longitudinally, 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 Molds
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.
Calibration Of The Molds 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. 1. The suppositories are weighed and the total weight and average weight of each suppositories supposito ries are recorded. 2. To determine the volume volume of the the mold, the suppositories supposito ries are carefully melted in a calibrated beaker. 3. The volume volume of the the melt melt is determine determine for for the total number as well as the average of one suppository.
Example of Molder
DISPOSABLE MOLDER
Suppository Molds and Packaging
Suppository Molds and Packaging Aluminum
metal molds
come in a variety of cavity sizes and with a variety v ariety of number of cavities per mold
Common sizes vary from 1 g to 2.5 g, and a nd common number of cavities range from 6 cavities up to 100 cavities
The The tw two o ha hallves of th the e mold are held together with either nuts or some molds have 1 centered screw.
Suppository Molds and Packaging Plastic suppository shells
come in long strips that can be torn into any a ny 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.
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 supposit ory shape.
Suppository Molds and Packaging Flexible rubber molds
can be packaged with the suppository still in the mold. Generally the mold is placed in a special box.
Determination Of The Amount Amount Base R equired equired
Of
First Method Subtract 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 mold and if i f the medicaments medicaments in the formula have a collection volume of 2.8 mL the 9.2 mL of Cocoa butter will be required. 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 suppositories Active ingredient: Aminophylline Density factor: 1.1 Dosage: 0.5000 gram/suppository Suppository base: Cocoa butter Blank 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 drug 2.000 g - 0.4545 = 1.5455 g weight of cocoa butter required by the suppository 0.5000 + 1.5455 = 2.0455 g actual weight of suppository
Second Method 1.
2. 3. 4. 5. 6. 7.
Requires the following step Weigh the active ingredient for the preparation of a single suppository Dissolve or mix it with a portion of melted base insufficient to fill one cavity of the mold. Place the mixture mixture to to the mold Add additional melted base to the cavity to completely fill the mold. Remove the suppository from from mold and weigh Then subtract the weight of the ingredient from from the total total weight of the suppository to get the amount of the base ba se needed. Then multiplied by the number of suppository to made to get the total base needed.
Preparation
of Ingredient
Glycerin
Sodium Carbonate
Stearic Acid Water
3.
Preparing the Mold
Disposable molds
4.
Base preparation
5.
Mixing and Pouring
Opening
a Suppository Mold
The suppository mixture is poured into the cavities of a closed mold. When the suppository mixture has congealed, the excesss mass exces mass is rem removed oved from the top surface of the mold and the mold is separated into the two halves.
Opening
An
a Suppository Mold
efficient way to separate the mold is to remove the wing nuts or loosen the t he centered screw and place the mold so that the posts rest on the table top.
Opening
a Suppository Mold
Then apply a downward pressure only on the bottom half of the mold.
Opening
a Suppository Mold
knife or spatula should not be used to pry the two halves apart. This will damage the matching mold mold faces which have been accurately machined to A
give a tight seal.
Suppository shells shells can be opened by peeling apart the two tabs at the bottom of the shell.
1
3
2
6.
Cooling and Finishing
7.
Packaging
Suppository Packaging Strip ware Strips (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 slot, various opening methods like tear open slot, tear open strap strap,, peel off off strap, strap, ³shor ³short´ t´
Suppository Packaging 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"
Preparing 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 continuo continuously usly in the filling of each cavity in the mold. The pouring must be continuous to prevent ³layering´ 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 Com Compression pression 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 filled with the mass, a movable end plate at the back of the die d ie is removed and when additional pressure is applied to the mass in the cylinder, the formed suppositories are ejected.
Advantages and Disadvantages of Prepar ation by Compression: Advantages 1. The method is simple 2. 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
Disadvantages 1. Too slow for large scale operation 2. 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 (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, mortar, then formed into into a ball in the palms of the hands, previously cooled in the ice water. 3. A broad bladed spatula 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 Press
1. Carbon dioxide-relea -releasin sing g tablet tablet - mad madee 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. rectum. 2. Vaginal Compressed Tablet - in addi additio tion n to the the active ingredient, it contains lactose and /or phosphoricc acids for adjusting the acidity phosphori acidity of the vagina to an approximate pH 5.
Other
Inserts (rectally, Vaginally, and Urethrally)
1. Tablets and capsules - Vaginal Tablets/Inserts 2. Ointments intments,, Creams, and Aerosol Foams ProtoFoam 3. Jellies and Gels 4. Contraceptive Sponge 5. Intrauterine Progesterone Drug Delivery System Progestasert 6. Powders 7. Solutions - vaginal Douches 8. Enemas - Retention and Evacuation Enemas 9. Suspensi Suspensions ons - Barium Sulfate Suspension
PACK AGING A ND STOR AGE 1.
Gly Gl yce ceri rin n Su Supp ppos osit itor ory y ± tightly close glass container
± wrapped individually 2. Sup Suppos posit itori ories es prepa prepared red with with cocoa cocoa butte butter r ±
3. Suppositor Suppositories ies conta containin ining g light light sensi sensitiv tivee ± individually wrapper ± metallic foil 4. Com Comme merci rcial ally ly sup suppos posit itori ories es ± individually wrapped ± foil or plastic 5. Som Somee packag packaged ed wit with h continu continuous ous str strips ips ± 300C 6. Cocoa bu butter ±
7. Gl Gly yce ceri rina natted ± 200C to 250C 8. Pol Poly yet ethy hyle lene ne gl gly yco coll ± room temperature 9. With hu hum mid idit ity y- absorbed moisture moisture and tend to become spongy 10. With excessive dryness ± lose
moisture and become brittle
ALPROSTADIL
UR ETHR AL MICROSUPPOSITOR MICRO SUPPOSITORY Y
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, 1000ug
For Erectile Dysfunction
250, 500, and
Rectal
Suppositories:
Suppository
Product
Effect
Category
1. Bisacod yl
Dulcolax
local
Cathartic
2. Chlorpromazine
Thorazine
systemic
Anti-emetic,
3. Ergomine Tartrate
Cafergot
systemic
Adrenergic
tranquilizers
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 Suppositories
Vaginal
Suppositories and Tablets
Product
1. AVC
Active
Suppositories
Constituents
Category
Sulfanilamide, 1.05 Gm
Candida albicans infections
2. Be 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
5. Se Semi micid cid va vagi ginal nal con contra tracep ceptiv tivee ins insert ert
nonox non oxyn ynol ol-9 -9,,100 mg
Non-systemic reversible method of birth control
6. Sultrin vaginal Tablet
Sulfathiazole, sulfacetamide sulfabenzamide, 500 mg
Haemophilus
Terconazole, 80 mg
same # 4
7. Terazol 3
for vulvovaginal candidiasis (moniliasis)
vaginalis vaginitis
Examples
of Vaginal Suppositories and Tablets
Examples
Glycerin Suppository
Eucalyptol Suppository
Herbal Suppositories
Suppository
Examples
Vaginal Suppository
Suppository for Adult
Suppository for Children
Examples
Anucort HC 25 mg
Hemril-HC 25 mg
Cotecxin Suppository
Hemorrhoidal-HC 25mg
Administr ation of Suppositories
Inserting 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, a vailable, moisten the suppository with 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
Suppositories
Standing
position
Lying Position
Inserting Rectal
Suppositories
6. Separate buttocks to expose the rectal area. 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.
Inserting Rectal
Suppositories
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 imm ediately after inserting the suppository.
Inserting Rectal
Suppositories
Vaginal Suppositories
Inserting
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.
Vaginal Suppositories
Inserting 5.
6.
Either
lay on your back with your y our knees bent, or stand with your feet spread a few inches apart and your knees bent. 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.
Vaginal Suppositories
Inserting 7.
Removee the applicator for the vagina. Remov
8.
Wash your hands again with soap and warm water.
JELLIES Are class of gels in which the structural coherent cohere nt matri m atrix 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.E phedrine Sulfate Jelly symphatomimetic
