What is a suppository?
A solid dosage form intended for insertion into a body orifice where it melts, softens and/or dissolves to exert local or systemic effects.
Describe the different types of suppositories?
- Rectal: cylindrical or conical shaped. Approx. 2 g, about 1-1.5 inches long
- Vaginal: may be ovoid, globular, other shape. 3 to 5 g
- Urethral: vary depending upon male/female
- -Male: 3 – 6 mm dia, 140 mm long, 4 g wt–
- -Female: 3 mm dia, 70 mm long, 2 g wt–
What are the advantages of suppositories?
- Alternative to oral route
- By-passes the first-pass effect ->Potential for higher bioavailability
- Safe, painless, and easy administration
- Target delivery
- Admin a larger dose than is possible orally
- Pediatric, geriatrics, comatose populations
- Avoids nausea and vomiting
What are the disadvantages of suppositories?
- Unpopular route
- Leakage
- Unpredictable drug absorption
- Potential for irritation
- Induce a poop
What is the ideal suppository?
- Base should be non-irritating and non toxic
- Base should be compatible with a wide variety of active ingredients
- Uniform distribution of active ingredient throughout the dosage form
- Melt or dissolve in rectal fluids
- Stable–>Physically intact—not brittle, crumbling, etc. and chemically stable
- Pharmaceutically elegant
What physiologic factors affect rectal absorption?
- Rectum is small, approx 15-20 com long w/ 2-3 mL of fluid
- Better absorption when the colon has been ‘emptied’
- Bypass first pass effect, direct absorption into the lower hemmorhodial veins
- Neutral pH of 7.2-7.8 fluids, drug may not ionize
- Lipid-water solubility; will is be able to cross the membrane?
- Particle size, triturate down to as fine a powder as possible
- Nature of the base, pH nature or the drug and compatibility with the drug
What are the classifications of suppository bases?
- Fatty or oleaginous bases: cocoa butter and synthetic triglyceride mixtures
- Water-soluble/Water-miscible bases: glycerinated gelatin, PEG polymers, Misc Bases
What are the disadvantages of oleaginous/fatty bases?
- Designed to melt at body temperature, gamma form
- Very sensitive to temperature
What are the polymorphs of cocoa butter?
Gamma form 18° C
Alpha form 22° C
Beta prime form 27° C
Beta form 30-35° C
What are the advantages of a PEG suppository base?
- Polymers of varying molecular weights
- Water-soluble
- Relatively low melting points
- Stable
- Dissolve in body fluids
What are specific considerations for bases?
- Water
- Hygroscopicity
- Incompatibilities
- Viscosity
- Brittleness
- Density
- Volume contraction
- Dosage replacement
- Weight/volume control
Drug Release from different bases
- Oil-soluble drug w/ oily base :: Slow release; poor escaping tendency
- Water-soluble w/ oily base :: rapid release
- Oil-soluble drug w/ water-miscible base :: Moderate release rate
- Water-miscible drug w/ water-miscible base :: Moderate release; based on diffusion; all water soluble
What approach should you consider in formulations?
- Local or systemic use
- Rectal, vaginal, urethral
- Quick, slow, prolonged effect
What are the methods of preparation?
- Molding (fusion) : rectal rocket
- Compression : industrial scale
- Hand rolling : rarely done
What should you consider when preparing molded suppositories?
- Method most often employed both small scale and industrially
- Elegant appearance
- Caution must be exercised w/ heat sensitive drugs
- Wide variety of molds available
- Most bases suitable for molding
- Molds often require lubrication and calibration
- Determine the amount of base required
- Preparing and pouring the melt
What should you consider when preparing compressed (compression) suppositories?
- Mass of base and API is forced into special molds
- Useful for heat-labile substances
- Eliminates the likelihood of insoluble components settling during manufacturing
- Some limitation to the shapes of suppositories
- Rarely used in extemporaneous compounding
What should you consider when preparing hand rolled suppositories?
- Historical art
- Limited to cocoa butter suppositories
- Requires experience and good technique, lack elegant appearance
- Does not require special equipment or calculations
What are compounding hints?
- Prepare 10% overage to allow for loss
- Mark disposable molds for fill level
- Melt temperature is critical for plastic molds
- Dampen bulky powders with liquid
- Mix liquid ingredients w/ powders
How do you determine the amount of base needed?
- Dosage replacement factor method
- Density factor
- Occupied volume method
-If API < 100 mg then volume occupied is insignificant
What is the equation for the dosage replacement method?
f=[[100(E-G)] / (G*X)] + 1
f = dosage replacement factor E = weight of pure base suppository G = weight of suppository w/ X% of the API X% = percent of API in the suppository 1 = cocoa butter is arbitrarily assigned this value
What is the equation of the density factor method?
DF = B / (A-C+B)
DF = density factor A = avg weight of the blank B = weight of API per suppository C = avg weight of the medicated suppository
Explain the occupied volume method.
- Determine the average weight per mold using the designated base
- Weigh out enough base for 10 suppositories
- Divide the density of the active drug by the density of the base to obtain a ratio
- Divide the total weight of the active drug required for the total number of suppositories by the ratio obtained in step 3
- Subtract the amount obtained in step 4 from the total weight of the prescription to obtain the weight of base required
- Multiply the weight of active drug per suppository times the number of suppositories to obtain the quantity of active drug required
How should you package/label suppositories?
-Ointment Jars
-“Unwrap, moisten and insert…”
-“Moisten and insert…”
-“Insert…”
“Store in refrigerator”
How do you store suppositories?
- glass or plastic containers
- wrapped or unwrapped
- room temperature or under refrigeration
- moderate humidity
