Unit 6 Module 10: Suppositories, Inserts & Sticks
Learning Objectives
Upon completion of this lesson, students will be able to:
Differentiate between rectal, vaginal, and urethral suppositories based on their shape, size, and application.
Classify different types of suppository bases.
Enumerate examples for each suppository base type.
Explain the significance of suppository bases concerning drug bioavailability.
Compound suppositories effectively.
Properly package and label suppositories.
Identify appropriate storage conditions for suppositories.
Describe vaginal inserts and medication sticks.
Outline the advantages of intravaginal drug delivery.
Describe the characteristics, composition, and uses of intrauterine drug delivery systems, vaginal inserts and rings, and vaginal gels.
Introduction to Suppositories
Suppositories are an alternative drug delivery method.
They are small, round, or cone-shaped objects inserted into body orifices, commonly the rectum.
Once inserted, they melt or dissolve, releasing medication.
They are useful for patients who cannot swallow oral medication or whose stomach/intestines would not absorb drugs well.
Different types are designed for insertion into the rectum, vagina, or urethra.
Medication can act locally at the insertion site or be absorbed into the bloodstream for systemic effects.
Suppositories: General Characteristics
Definition: Solid Dosage Forms (SDFs) intended for insertion into body orifices where they melt, soften, or dissolve, exerting local or systemic action.
Etymology: Derived from Latin "supponere" ("to place under"), from "sub" (under) and "ponere" (to place), indicating they are meant to be placed under the body, such as into the rectum.
Types: Rectal, vaginal, urethral, nasal, and ear cones.
Shape and Size: Should be designed for easy insertion without undue distension and must be retained for the appropriate period.
Local Action of Suppositories
Rectal Suppositories: Used to relieve constipation (e.g., glycerin suppositories, which promote laxation by local irritation of the mucous membrane) or symptoms associated with hemorrhoids or other anorectal conditions (pain, irritation, itching, inflammation).
Laxation: Refers to loosening or relaxing of the bowels, leading to a bowel movement.
Advantages of Suppositories
Can exert a local effect on the rectal mucosa.
Promote bowel evacuation.
Avoid gastrointestinal irritation.
Applicable for unconscious patients (e.g., during seizures).
Allow systemic drug absorption, bypassing first-pass metabolism.
Suitable for infants, the elderly, post-operative patients, or those with severe nausea/vomiting who cannot take oral medication.
Disadvantages of Suppositories
Patient Acceptability: Can be a significant barrier.
Not suitable for patients with diarrhea.
Sometimes, the required drug amount might be too irritating or too large to be reasonably included in a suppository.
Absorption may be incomplete, as suppositories can promote bowel evacuation.
Vaginal Suppositories (Pessaries)
Shape: Usually globular, oviform, or cone-shaped.
Weight: Approximately 5 \text{ g} when cocoa butter is the base, though weights can vary widely depending on the base and manufacturer.
Uses (Local Effect):
Combating infections in the female genitourinary tract (e.g., Trichomonas vaginalis, Candida albicans, other microorganisms).
Restoring vaginal mucosa to its normal state.
Preventing conception (contraception).
Common Contraceptive Drug: Nonoxynol-9 (a spermicide), which melts in 10 \text{ minutes} to form an effective spermicidal barrier.
Anti-infective Agents: Nystatin, clotrimazole, butoconazole nitrate, terconazole, miconazole, triple sulfas, sulfanilamide, povidone-iodine, clindamycin phosphate, metronidazole, oxytetracycline.
Vaginal Inserts
Also known as vaginal tablets or vaginal capsules.
Vaginal Tablets:
Shape: Ovoid.
Often packaged with a plastic inserter.
Contain anti-infective and hormonal substances similar to vaginal suppositories.
Preparation: Prepared by tablet compression.
Common Components:
Lactose: As a base or filler.
Starch: As a disintegrating agent.
Polyvinylpyrrolidone: As a dispersing agent.
Magnesium stearate: As a tablet lubricant.
Advantages: Easier to manufacture, more stable, and less messy than traditional suppositories.
Vaginal Capsules: Can be used vaginally or rectally.
Rectal Suppositories
Shape: Approximately 32 \text{ mm} (1.5 \text{ inches}) in length, cylindrical, with one or both ends tapered (some are bullet-shaped).
Weight (Adult): About 2 \text{ grams} when cocoa butter (theobroma oil) is used as a base. Weight varies with base density and medicaments.
Weight (Infant/Child): About half the weight and size of adult suppositories, with a more pencil-like shape.
Function: Intended for both local and systemic actions.
Utility: Especially useful when patients are unwilling or unable to take medication orally.
Local Effects of Rectal Suppositories
Local Anesthetic / Analgesic: To relieve pain.
Pruritus Ani / Hemorrhoids: To relieve itching, irritation, inflammation (e.g., hydrocortisone suppositories, mesalamine suppositories).
Hemorrhoidal Suppositories: Act as astringents, protectives, anesthetics, and lubricants.
Laxative / Cathartic Suppositories: To relieve constipation (e.g., Bisacodyl (Dulcolax), glycerin).
Systemic Actions of Rectal Suppositories
The mucous membranes of the rectum and vagina permit absorption of many soluble drugs, though the rectum is more frequently used for systemic absorption.
Examples of Drugs Administered Rectally for Systemic Effect:
Relief in Nausea and Vomiting: Ondansetron suppositories.
Tranquilizers: Prochlorperazine and chlorpromazine suppositories.
Opioid Analgesia: Oxymorphone HCl suppositories.
NSAIDs for Migraine: Ergotamine tartrate (e.g., Cafergot).
Analgesic and Antipyretic: Paracetamol (e.g., Opigesic suppositories).
Smooth Muscle Relaxant for Asthma: Theophylline.
Advantages of Rectal Route over Oral Therapy for Systemic Circulation
Prevents drug destruction in the gastrointestinal (GI) tract.
Prevents irritation of the GI tract.
Bypasses first-pass metabolism in the liver.
Convenient for patients who cannot swallow.
Convenient for patients experiencing vomiting.
Drug Absorption from the Rectum
Primarily by passive diffusion.
Rate and extent of drug absorption are generally lower than the oral route, mainly due to a smaller surface area for absorption.
Example Drugs Administered Rectally for Systemic Effect: Prochlorperazine, chlorpromazine, oxymorphone HCl, ergotamine tartrate, indomethacin, ondansetron.
Factors of Drug Absorption from Rectal Suppositories
A. Physiologic Factors
Colonic Content:
An evacuant enema may be administered prior to suppository insertion to promote better absorption.
Conditions like diarrhea, colonic obstruction, and tissue dehydration can affect absorption.
Circulation Route:
Lower hemorrhoidal veins surrounding the colon receive absorbed drugs, initiating systemic circulation and largely bypassing the liver.
Lymphatic circulation also aids in absorption.
pH and Lack of Buffering Capacity of Rectal Fluids:
Rectal fluids are essentially neutral in pH and lack effective buffer capacity, meaning the drug's chemical form generally remains unchanged.
The suppository base significantly influences the release of active ingredients.
B. Physicochemical Factors of the Drug and Suppository Base
Lipid–Water Solubility:
A lipophilic drug in a fatty suppository base (in low concentration) has less tendency to escape into the surrounding aqueous fluids than a hydrophilic substance in a fatty base near saturation.
Water-soluble bases (e.g., PEG), which dissolve in anorectal fluids, release both water-soluble and oil-soluble drugs for absorption.
Higher drug concentration in the base generally leads to greater potential absorption.
Particle Size:
For undissolved drugs in a suppository, smaller particle size increases the rate of dissolution and availability for absorption.
Smaller particles dissolve more readily, leading to faster absorption.
Nature of the Base:
Potential for chemical and/or physical interactions between the medicinal agent and the suppository base, affecting drug stability and/or bioavailability.
An irritating base can initiate a colonic response and a bowel movement, preventing complete drug release and absorption.
Urethral Suppositories (Bougies)
Description: Slender, pencil-shaped suppositories inserted into the male or female urethra.
Male Urethral Suppositories:
Size: 3 to 6 \text{ mm} in diameter, approximately 140 \text{ mm} (5.5 \text{ inches}) long.
Weight: About 4 \text{ g} when cocoa butter is the base.
Female Urethral Suppositories:
About half the length and weight of male urethral suppositories.
Size: Approximately 70 \text{ mm} (2.75 \text{ inches}) long.
Weight: About 2 \text{ g} when made of cocoa butter.
Uses: May contain antibacterial agents or local anesthetics, often as preparation for a urethral examination.
Characteristics of Suppositories (Summary Table)
Characteristic | Rectal | Vaginal | Urethral |
|---|---|---|---|
Other Names | Pessaries | Bougies | |
Weight | \approx 2 \text{ g} | \approx 5 \text{ g} | Male: \approx 4 \text{ g}, Female: \approx 2 \text{ g} |
Length | 32 \text{ mm} | Male: 140 \text{ mm}, Female: 70 \text{ mm} | |
Shape | Bullet, Torpedo, | Globular, Oviform, | Pencil-shaped |
Little finger | Cone-shaped | ||
Base Used | Cocoa butter | Cocoa butter, | Cocoa butter, PEG |
Glycerinated gelatin |
Local Therapeutic Actions of Suppositories
Rectal: Laxative (e.g., glycerin suppositories), hemorrhoids.
Vaginal: Contraceptives, antiseptics, antibiotics, antifungals.
Urethral: Antibacterial, anesthetics.
Suppository Bases
Important Requisites for a Suppository Base
Remains solid at room temperature.
Softens, melts, or dissolves readily at body temperature.
Ensures the contained drug is fully available soon after insertion.
Classification of Suppository Bases
1. Fatty or Oleaginous Bases
a. Cocoa Butter / Theobroma Oil:
Fat obtained from roasted Theobroma cacao seeds.
Properties: Yellowish-white solid at room temperature, faint chocolate-like odor.
Chemical Composition: Primarily triglycerides of oleopalmitostearin and oleodistearin.
Melting Point: \text{30°C - 35°C}, making it ideal.
Polymorphism: Exhibits marked polymorphism, meaning it can exist in multiple crystalline forms with different melting points.
Preparation Considerations:
Avoid Overheating: Must not be heated above \text{35°C} during preparation. Overheating converts it to a metastable (\beta') structure which melts at \text{25°C - 30°C}. This results in finished suppositories that melt at room temperature and are unusable.
Melting Point Changes with Drug Addition: Certain drugs (e.g., chloral hydrate, phenol) can lower its melting point. In such cases, stiffening agents like spermaceti or beeswax may be added to raise the finished suppository's melting point back to the desired range.
b. Newer Synthetic Triglycerides:
Consist of hydrogenated vegetable oils.
Advantage over Cocoa Butter: Do not exhibit polymorphism, though they are more expensive.
Examples (often single-entity formulations or series of bases):
Fattibase: Triglycerides from palm, palm kernel, and coconut oils.
Wecobee: A series (FS, M, R, S) made from triglycerides of coconut oil.
Others: Dehydag, Hydrokote, Suppocire, Witepsol.
2. Water-soluble/Water-miscible Bases
Contain glycerinated gelatin or polyethylene glycol (PEG) polymers.
a. Glycerinated Gelatin:
Useful base for vaginal suppositories, accommodating various medicaments (alkaloids, boric acid, zinc oxide).
Properties: Translucent, resilient, gelatinous solids that dissolve or disperse slowly in mucous secretions, providing prolonged release.
Storage: Must be kept in well-closed containers in a cool place to prevent atmospheric moisture absorption (hygroscopic).
Preservatives: Methylparaben, propylparaben, or a combination may be added to extend shelf-life.
Composition:
Vaginal: Granular gelatin (20\%), glycerin (70\%), Active Ingredient (AI) (10\%).
Urethral: Granular gelatin (60\%), glycerin (20\%), AI (20\%).
Disadvantage: Easily absorb moisture; can have a dehydrating effect and irritate tissues upon insertion. May need to be moistened with water prior to insertion.
b. Polyethylene Glycol (PEG) Polymers (Macrogols):
Polymers of ethylene oxide and water, prepared with various chain lengths, molecular weights (MW), and physical states.
Desirable Properties as Suppository Bases:
Chemically stable.
Non-irritating.
Miscible with water and mucous secretions.
Can be formulated by both molding and compression.
3. Miscellaneous Bases
Mixtures of oleaginous and water-soluble or water-miscible materials.
Can be chemical or physical mixtures, some are pre-formed emulsions (generally water-in-oil (w/o) type).
May be capable of dispersing in aqueous fluids.
Example: Polyoxyl 40 stearate.
Composition: Mixture of monostearate and distearate esters of mixed polyoxyethylene diols and free glycols.
Properties: Waxy, white to light tan solid, water-soluble.
Melting Point: Generally between \text{39°C} and \text{45°C}.
Preparation of Suppositories
Three primary methods:
(a) Molding from a Melt: Most common method.
(b) Compression: Suitable for heat-labile drugs or large amounts of insoluble substances.
(c) Hand Rolling & Shaping: Oldest method, requires skill, less common today.
1. Preparation by Molding
Steps:
Melting the base.
Incorporating any required medication.
Pouring the melt into molds.
Allowing the melt to cool and congeal into suppositories.
Removing the formed suppositories from the mold.
Suppository Molds:
Can produce individual or large numbers of suppositories in various shapes and sizes.
Commonly made from stainless steel, aluminum, brass, or plastic.
Individual plastic molds are also available for single suppositories.
Lubrication of the Mold:
May be required before pouring the melt to facilitate clean and easy removal.
Not needed for cocoa butter or PEG bases.
Necessary for glycerinated gelatin suppositories.
Calibration of the Mold:
Each mold opening holds a specific volume of material.
Pharmacists must calibrate each mold with the usual base to ensure medicated suppositories contain the proper quantity of medicaments.
Determination of Amount of Base Required:
Volume of base = Total volume of the mold - Volume of the drug substance.
Example Calculation: If 12 \text{ mL} of cocoa butter fill a mold and medicaments have a collective volume of 2.8 \text{ mL}, how much cocoa butter is needed? (Density of cocoa butter = 0.86 \text{ g/mL})
Volume of base needed = 12 \text{ mL} - 2.8 \text{ mL} = 9.2 \text{ mL}
Weight of cocoa butter = 9.2 \text{ mL} \times 0.86 \text{ g/mL} = 7.912 \text{ g}
Determination of Density Replacement Factor Method:
Formula: f = \frac{100(E-G)}{GX} + 1
E = weight of pure base suppositories.
G = weight of suppositories with X\% of the active ingredient.
X = percentage of active ingredient.
Determination of Density Factor Method (Detailed Steps):
Determine the average blank weight, A, per mold using the suppository base.
Weigh the quantity of suppository base for 10 suppositories.
Weigh 1.0 \text{ g} of Active Pharmaceutical Ingredient (API).
Melt the suppository base, incorporate API, mix, pour into molds, cool, trim, and remove.
Weigh the 10 suppositories and determine average weight (C).
Calculate density factor: \text{Density factor} = \frac{B}{A - C + B}
A = average weight of blank suppository.
B = weight of medication per suppository.
C = average weight of medicated suppository.
Divide the weight of medication per suppository by the density factor to find the replacement value of the suppository base.
Subtract this quantity from the blank suppository weight.
Multiply by the number of suppositories required to get the total suppository base for the prescription.
Multiply the weight of drug per suppository by the number of suppositories to get the total active drug required.
Determination of Occupied Volume Method (Detailed Steps):
Determine the average weight per mold (blank) using the suppository base.
Weigh the quantity of suppository base necessary for 10 suppositories.
Divide the density of the active drug by the density of the suppository base to get a ratio.
Divide the total weight of active drug required for the total number of suppositories by the ratio from step 3 (this gives the amount of suppository base displaced by the active drug).
Subtract the amount from step 4 from the total weight of the prescription to get the weight of suppository base required.
Multiply the weight of active drug per suppository by the number of suppositories to be prepared to get the quantity of active drug required.
2. Preparation by Compression
Process: The mixed mass of base and medicaments is forced into special molds using suppository-making machines.
Consistency: Friction during mixing softens the base into a paste-like consistency.
Advantages:
Suitable for heat-labile medicinal substances.
Suitable for suppositories containing a large amount of substances insoluble in the base.
Eliminates the possibility of insoluble matter settling during manufacture (unlike molding).
Disadvantage: Requires a specialized suppository machine, which limits shapes.
3. Preparation by Hand Rolling and Shaping
Historical Context: Oldest and simplest method, predates readily available molds. Today, it is less common due to advanced molds.
Process (Requires considerable skill):
Combine prescribed medicinal substances with grated theobroma oil (or other base).
Thoroughly incorporate ingredients with a pestle to create a pill-like mass.
Knead the mass vigorously until plastic, then transfer to a filter paper.
Roll the mass into a ball with quick, rotary movements.
Place the ball on a pill tile and roll between fingers into rod-shaped units.
Cut rods into pieces and point one end with a spatula.
Challenges: The suppository