Suppositories - sheet 11 Flashcards
What are the four methods of manufacturing suppositories?
1️⃣ Hand Rolling
2️⃣ Cold Compression
3️⃣ Pour Molding (Fusion Method)
4️⃣ Tablet Machine Compression
What is the Hand Rolling Method?
✅ Used for small quantities (not common today).
✅ Process:
🔹 Powder API finely.
🔹 Mix API into the suppository base by kneading/trituration.
🔹 Roll into cylindrical rods or vaginal balls of required weight.
🔹 Use starch/talcum powder to prevent sticking.
🔹 Cut and shape – One end is pointed for easier insertion.
What is the Compression Molding Method?
✅ Best for thermo-labile drugs & bases (No heat needed).
Steps:
1️⃣ Grate the base.
2️⃣ Mix with API.
3️⃣ Place mass in a cylinder.
4️⃣ Use piston to extrude into molds.
What are the advantages of Compression Molding?
✔ Simple method.
✔ More elegant than hand rolling.
✔ Prevents sedimentation of solids.
✔ Suitable for heat-sensitive drugs.
What are the disadvantages of Compression Molding?
❌ Too slow for large-scale production.
❌ Air entrapment may cause oxidation.
❌ Not suitable for glycerol-gelatin or PEG bases.
What is the Pour Molding (Fusion Method)?
✅ Most commonly used (Small & Large scale).
Steps:
1️⃣ Melt base (use water/steam bath to prevent overheating).
2️⃣ Mix API (emulsified or suspended).
3️⃣ Pour into chilled metal molds (chrome/nickel-plated).
What are the lubrication tips for suppositories?
✔ Helps create smooth, elegant suppositories.
✔ Lubricant must differ from the base (prevents absorption).
✔ Water-soluble lubricant → Fatty bases.
✔ Oily lubricant → Water-soluble bases.
What is the Automatic Molding Machine?
✅ Fully automated process for large-scale production.
Production Cycle:
1️⃣ Mass fed into hopper (kept mixed & at constant temperature).
2️⃣ Mold lubrication (sprayed or brushed).
3️⃣ Mold filled with heated mass & allowed to solidify.
4️⃣ Excess material removed (scraped off & reused).
5️⃣ Ejection – Steel rods push out solid suppositories.
6️⃣ Cycle repeats (Mold re-lubricated & refilled).
What are the packaging requirements for suppositories?
✅ Each suppository must be wrapped separately to prevent sticking.
✅ Common packaging materials:
🔹 Tin or aluminum foil
🔹 Paper or plastic strips
What are the storage conditions for suppositories?
✔ Cocoa butter & glycerinated gelatin → Refrigerate ❄️
✔ Polyethylene glycol (PEG) suppositories → Room temperature 🌡️ (No refrigeration needed)
What issues arise from using water in suppository formulation?
❌ Avoid using water as a solvent in suppository bases.
🔴 Problems:
⚠️ Oxidation of fats.
⚠️ Crystallization if water evaporates.
⚠️ Microbial growth, requiring preservatives.
What are hygroscopicity issues in suppositories?
✔ Glycerinated gelatin suppositories → Lose moisture in dry climates, absorb moisture in humid conditions.
✔ Polyethylene glycol (PEG) bases → Also hygroscopic.
✔ Moisture change in PEG depends on:
🔹 Humidity & temperature
🔹 Chain length of molecules – Higher molecular weight reduces hygroscopicity.
What are incompatibilities in PEG bases?
❌ PEG bases are incompatible with:
🔹 Aspirin
🔹 Benzocaine
🔹 Sulfonamides
🔹 Silver salts
🔹 Tannic acid
🔹 Quinine
⚠️ Crystallization risk in PEG:
🔹 Sodium barbital
🔹 Salicylic acid
🔹 Camphor
What viscosity considerations are there in suppository formulation?
✔ Viscosity of melted mass affects suppository manufacturing & rectal behavior.
✔ Low viscosity: Cocoa butter & some substitutes.
✔ High viscosity: Glycerinated gelatin & PEG bases.
⚠️ Low-viscosity bases → Risk of sedimentation!
🔹 Solutions:
✔ Use a base with a narrow melting range (closer to body temp).
✔ Add 2% aluminum monostearate → Increases viscosity & prevents sedimentation.
✔ Cetyl/stearyl alcohols or stearic acid → Improves consistency.
What causes brittleness in suppositories?
✔ Cocoa butter suppositories → Elastic, less brittle ✅
❌ Synthetic fat bases (high hydrogenation & stearate content) → More brittle at room temperature.
⚠️ Causes of brittleness:
🔹 Shock cooling (rapid chilling in an extremely cold mold).
🔹 Difficulties in manufacturing, handling, wrapping, & use.
What are solutions to reduce brittleness in suppositories?
✔ Minimize temperature difference between melted base & mold.
✔ Add plasticizers:
🔹 Tween 80
🔹 Castor oil
🔹 Glycerin
🔹 Propylene glycol
Why is density important in suppositories?
✔ Needed to calculate drug per suppository.
🔹 Fixed mold volume → Weight depends on density of mass.
What is volume contraction in suppositories?
✔ Occurs in melted suppository bases after cooling.
✔ Effects:
🔹 Good mold release → Mass pulls away from mold sides ✅
🔹 No need for mold release agents (lubricants) ✅
❌ Hole formation at the open end → Reduced weight & imperfect shape.
How can volume contraction be prevented?
✔ Pour mass slightly above congealing temp into a warmed mold.
✔ Overfill the mold → Scrap off excess after cooling.
What are lubricants in suppository manufacturing?
✔ Cocoa butter tends to adhere to molds due to low volume contraction.
❌ Problem: Difficult to remove suppositories from molds.
🔧 Solutions:
🔹 Mineral oil
🔹 Aqueous solution of sodium lauryl sulfate
🔹 Silicones
What factors influence weight & volume control in suppositories?
✔ Factors influencing drug amount per suppository:
🔹 Concentration of active ingredient in the mass.
🔹 Specific gravity of the base.
🔹 Volume variation between molds (should be within ±2%).
❗ Weight variation tolerance:
🔹 ±5.0% (due to manufacturing inconsistencies like mold closure and scraping).
What is rancidity in suppositories?
✔ Rancidity occurs due to oxidation of unsaturated fats, producing:
🔹 Aldehydes
🔹 Ketones
🔹 Acids
❗ Result: Strong unpleasant odors.
What is the purpose of calibration of the mold?
✔ Molds usually hold 1-2 grams of suppository mass.
✔ Why calibration is necessary:
🔹 Mold size remains constant but weight varies due to different densities of bases and medicaments.
✔ Solution: The mold should be calibrated for each base and medicament.
What is the displacement value?
✔ Definition:
🔹 The amount of suppository base displaced by a given amount of API (Active Pharmaceutical Ingredient).
🔹 Or, it’s the amount of drug that displaces 1g of base.
✔ How density affects displacement:
🔹 If drug density = base density, the drug will displace the same amount of base.
🔹 If drug density > base density, the drug will displace less base.
🔹 If drug density < base density, the drug will displace more base.
What are the evaluation criteria for appearance and uniformity of suppositories?
✔ Uniformity:
🔹 Suppositories should be uniform in size and shape.
🔹 Internal and external surfaces should match when cut longitudinally.
✔ Examine for defects:
🔹 Look for cracks or pits caused by air entrapment in the molten mass.
✔ Color:
🔹 Verify color intensity, nature, and homogeneity.
✔ Odor:
🔹 Ensure the odor is consistent to avoid confusion with other suppositories.
🔹 Changes in odor can indicate degradation.
What is the method for uniformity of weight in suppositories?
✔ Method:
🔹 Weigh 20 suppositories individually.
🔹 Calculate average weight and check the % deviation.
✔ Acceptance criteria:
🔹 No more than 2 suppositories should deviate more than 5% from the average.
🔹 None should deviate by more than 10%.
What is the purpose of the mechanical strength/crushing (breakage test)?
✔ Purpose:
🔹 Evaluate the brittleness or elasticity of suppositories.
🔹 Test the tensile strength, which measures the force required to break or crush the suppository.
✔ Tensile Strength:
🔹 Indicates the maximum force a suppository can withstand during production, packing, and handling.
🔹 Higher tensile strength = less tendency to fracture.
✔ Test Method:
🔹 Place suppository upright.
🔹 Gradually add weights until the suppository collapses.
✔ Result:
🔹 A good result = at least 1.8–2 kg pressure.
What is the purpose of the content uniformity test?
✔ Purpose:
🔹 Ensure dose-to-dose uniformity of active ingredients in suppositories.
✔ Test Method:
🔹 Assay of the individual content of the drug substance(s) as per the monograph.
✔ Official Limits:
🔹 Active content should be between 95%–105% of the labeled amount.
✔ Goal:
🔹 All suppositories must contain the same labeled quantity of the drug.
What is the purpose of the melting range test?
✔ Purpose:
🔹 Ensure the suppository melts at or below 37°C.
✔ Test Method:
🔹 Place the suppository on water at 37°C and verify it melts completely within a few minutes.
🔹 Also known as the macromelting range test.
✔ Ideal Outcome:
🔹 The suppository should melt completely at 37°C in a short time (usually within a few minutes).
What is the purpose of the disintegration test?
✔ Purpose:
🔹 Breaks up solid dosage units into small fragments to increase the surface area for enhanced drug dissolution.
✔ Test Method:
🔹 Suppositories are placed in each tube of the disintegration apparatus.
🔹 Basket rack assembly is submerged in a 1-liter beaker containing water or simulated gastric/intestinal fluid at 37°C ± 2°C.
🔹 The suppository must remain 2.5 cm from the bottom of the beaker.
🔹 A standard motor moves the basket up and down through a distance of 5-6 cm, at a frequency of 28-32 CPM (cycles per minute).
✔ Acceptance Criteria:
🔹 Passes if all suppositories disintegrate and the particles pass through the mesh screen within 30 minutes.
What is the purpose of the dissolution test?
✔ Purpose:
🔹 Measures the rate and extent of drug release from the suppository.
✔ Test Method:
🔹 The suppository is placed in a beaker containing medium at 37°C ± 0.5°C.
🔹 At different time intervals, samples are taken and drug content is determined.
🔹 UV-visible spectrophotometry is used to analyze the drug, with absorbance measured using a suitable blank solution.
✔ Why it’s important:
🔹 Tests for hardening and polymorphic transitions of active ingredients and suppository bases.
✔ Final Calculation:
🔹 The drug release rate is calculated using the calibration curve and a suitable equation.
