Suppositories - sheet 11

Question 1

What are the four methods of manufacturing suppositories?

Answer 1

1️⃣ Hand Rolling
2️⃣ Cold Compression
3️⃣ Pour Molding (Fusion Method)
4️⃣ Tablet Machine Compression

Question 2

What is the Hand Rolling Method?

Answer 2

✅ 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.

Question 3

What is the Compression Molding Method?

Answer 3

✅ 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.

Question 4

What are the advantages of Compression Molding?

Answer 4

✔ Simple method.
✔ More elegant than hand rolling.
✔ Prevents sedimentation of solids.
✔ Suitable for heat-sensitive drugs.

Question 5

What are the disadvantages of Compression Molding?

Answer 5

❌ Too slow for large-scale production.
❌ Air entrapment may cause oxidation.
❌ Not suitable for glycerol-gelatin or PEG bases.

Question 6

What is the Pour Molding (Fusion Method)?

Answer 6

✅ 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).

Question 7

What are the lubrication tips for suppositories?

Answer 7

✔ Helps create smooth, elegant suppositories.
✔ Lubricant must differ from the base (prevents absorption).
✔ Water-soluble lubricant → Fatty bases.
✔ Oily lubricant → Water-soluble bases.

Question 8

What is the Automatic Molding Machine?

Answer 8

✅ 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).

Question 9

What are the packaging requirements for suppositories?

Answer 9

✅ Each suppository must be wrapped separately to prevent sticking.
✅ Common packaging materials:
🔹 Tin or aluminum foil
🔹 Paper or plastic strips

Question 10

What are the storage conditions for suppositories?

Answer 10

✔ Cocoa butter & glycerinated gelatin → Refrigerate ❄️
✔ Polyethylene glycol (PEG) suppositories → Room temperature 🌡️ (No refrigeration needed)

Question 11

What issues arise from using water in suppository formulation?

Answer 11

❌ Avoid using water as a solvent in suppository bases.
🔴 Problems:
⚠️ Oxidation of fats.
⚠️ Crystallization if water evaporates.
⚠️ Microbial growth, requiring preservatives.

Question 12

What are hygroscopicity issues in suppositories?

Answer 12

✔ 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.

Question 13

What are incompatibilities in PEG bases?

Answer 13

❌ PEG bases are incompatible with:
🔹 Aspirin
🔹 Benzocaine
🔹 Sulfonamides
🔹 Silver salts
🔹 Tannic acid
🔹 Quinine
⚠️ Crystallization risk in PEG:
🔹 Sodium barbital
🔹 Salicylic acid
🔹 Camphor

Question 14

What viscosity considerations are there in suppository formulation?

Answer 14

✔ 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.

Question 15

What causes brittleness in suppositories?

Answer 15

✔ 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.

Question 16

What are solutions to reduce brittleness in suppositories?

Answer 16

✔ Minimize temperature difference between melted base & mold.
✔ Add plasticizers:
🔹 Tween 80
🔹 Castor oil
🔹 Glycerin
🔹 Propylene glycol

Question 17

Why is density important in suppositories?

Answer 17

✔ Needed to calculate drug per suppository.
🔹 Fixed mold volume → Weight depends on density of mass.

Question 18

What is volume contraction in suppositories?

Answer 18

✔ 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.

Question 19

How can volume contraction be prevented?

Answer 19

✔ Pour mass slightly above congealing temp into a warmed mold.
✔ Overfill the mold → Scrap off excess after cooling.

Question 20

What are lubricants in suppository manufacturing?

Answer 20

✔ 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

Question 21

What factors influence weight & volume control in suppositories?

Answer 21

✔ 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).

Question 22

What is rancidity in suppositories?

Answer 22

✔ Rancidity occurs due to oxidation of unsaturated fats, producing:
🔹 Aldehydes
🔹 Ketones
🔹 Acids
❗ Result: Strong unpleasant odors.

Question 23

What is the purpose of calibration of the mold?

Answer 23

✔ 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.

Question 24

What is the displacement value?

Answer 24

✔ 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.

Question 25

What are the evaluation criteria for appearance and uniformity of suppositories?

Answer 25

✔ 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.

Question 26

What is the method for uniformity of weight in suppositories?

Answer 26

✔ 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%.

Question 27

What is the purpose of the mechanical strength/crushing (breakage test)?

Answer 27

✔ 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.

Question 28

What is the purpose of the content uniformity test?

Answer 28

✔ 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.

Question 29

What is the purpose of the melting range test?

Answer 29

✔ 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).

Question 30

What is the purpose of the disintegration test?

Answer 30

✔ 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.

Question 31

What is the purpose of the dissolution test?

Answer 31

✔ 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.