Lecture 4- Capsule Formultion Flashcards
Capsules
-Solid dosage forms where the medicine is inside a soft or hard shell that dissolves in the body
-hard/soft = made of gelatin, difference between both= design + manufacturing technology
-swallowing is easier
-majority of capsules produced today= hard
-most are swallowed but some used for rectal/vaginal as suppositories
Hard vs soft - slide 5
Hard gelatin capsules advantages + disadvantages
Advantages;
-better bioavailability = rapid drug release
-no need for compaction of the filing material= rapid drug release
-easier to formulate than tabs
-no taste
Disadvantages;
-slower manufacture rate
-more expensive
-not suitable for use with highly soluble substances like highly soluble salts (gastric irritation due to high drug conc)
-not ideal for use with hygroscopic substances = may dry out the capsule shell
-may stick to the oesophagus where some drugs can cause irritation
Hard gelatin capsule manufacturing
Gelatin- produced from hydrolysis of collagen taken from animal connective tissue, bone, skin
*bone gelatin (type B) = alkaline hydrolysis
*skin gelatin (type A) = acid hydrolysis
Types of gelatin
Type A- acid hydrolysis
-manufactured mainly from porcine skin
-isoelectric point: 7.0-9.0
-plasticity + clarity
Type B- alkaline hydrolysis
-manufactured mainly from animal bones
-isoelectric point: 4.8-5.0
-firmness
-differ in viscosity + film forming characteristics
-can be combined to achieve best shell characteristics
Physiochemical properties of gelatin
Bloom strength- measure of cohesive strength of gelatin film using gleometer
-peak force is the gel strength in bloom-grams
*viscosity = important factor controlling shell thickness
Shell manufacture; dipping method
- Dipping- pairs of stainless-steel pins are dipped into solution to form caps and bodies
*pins are lubricated with a mold release agent - Spinning- pin withdrawal from the dipping solution, elevation and rotation= helps for even distribution
- Drying
- Stripping
- Cutting
- Joining
Capsule filling machines
Semi automatic
-used for hospital prep labs and medium/small pharmaceutical factories
-completes the processes of position, separation, filling + locking of capsules filled with powder
Fully automatic
-used for pharmaceutical manufacturer
-filling material; powders, pellets, microtablets, tablets, etc
Design of hard gelatin capsule for powder fill
Requirements;
-Stability
-Manufacturability
-Patient acceptability
-Physical and chemical stability of shell and its contents
-Rate and extent of drug release must be constant
-Efficient cost-effective production of the required batch sizes
-Uniformity of drug content within acceptable limits
-Attractive appearance, including colour, size easy to swallow, not have an unpleasant odour or taste
Filling blend for hard gelatin capsules
-active ingredient
-fillers
-glidants
-lubricants
-disintegrates
-surfactants
Soft gelatin capsules; advantages and disadvantages
Advantages;
-high reproducibility + bioavailability
-hermetically sealed due to manufacturing procedure- suitable for liquids etc
-wide variety of sizes and shapes
Disadvantages;
-limited expertise and necessary filling equipment
-additional quality controls are required
-possible risks of interactions between the liquid + soft gelatin shell
Composition of the shell
-gelatin, plasticizer, dyes, opacifiers, preservatives and flavours
Formulation of soft gelatin capsules
Aim= to produce the smallest possible capsule consistent with maximum stability, therapeutic effectiveness and manufacturing efficiency
Liquids can be: single, combo of miscible liquids + solution/suspension of a drug in a liquid
Requirements: pH 2.5-7.5 (<2.5= leakage due to gelatin hydrolysis, >7.5- solubility reduction due to polymerization)
-aqueous emulsions cannot be used- water will leak
Requirements for the filling liquid:
-liquids including > 5% water and small molecular weight alcohols = not appropriate
Types of vehicles used in soft gelatin capsules;
1. Water-immiscible, volatile/ non-volatile liquids
2. Water-miscible, non-volatile liquids
Manufacture- slide 29
Requirements- tests for capsules
*containers for dispensing capsules= container must be tight, well-closed and light resistant
*disintegration test for capsules=
- according to boiling point and which applies to both soft and hard capsules
1. Introduce one capsule in each tube and suspend the apparatus in a beaker containing 600ml of water at 37 degrees
2. Operate the apparatus for 30 min, remove assembly from the liquid
- capsules must disintegrate completely into a soft mass = having only some fragments of gelatin shell
*dissolution test for capsules= same apparatus, dissolution medium and test are used for capsules, uncoated and coated tablets
-The capsule is put in a metal basket attached to a stirring shaft
-It’s placed in 1 litre of fluid (usually water) at 37°C (body temp)
-The basket rotates at a set speed
-Samples of the liquid are taken at set times to measure how much drug has dissolved
-The rule is: at least 85% of the drug should dissolve within 30 minutes
-If the capsule shell affects the test, empty shells are tested first for comparison
Weight variation - hard capsules
-uniformity of dosage units may be demonstrated by determining weight variation/content uniformity
*Hard gelatin capsules;
-Weigh 20 capsules individually
-Calculate the average weight
-Each capsule must be within ±10% of that average (so, 90–110%)
*Weight variation;
If Some Capsules Are Out of Limit:
Weigh the 20 capsules again
Remove the contents carefully (e.g., using a brush)
Weigh the empty shell
Net content = Gross weight – Shell weight
Calculate the average net content weight
Not more than 2 capsules should differ by more than 10% from the average
No capsule should differ by more than ±25%
🔁 If 2–6 Capsules Are Between 10–25% Off:
-Test 40 more capsules = In total (60 capsules):
Max 6 capsules can vary by more than 10%
None can be off by more than 25%
Storage, packaging and stability
Moisture content of hard gelatin capsule = 12-15%
<12%= brittle shells/capsules
>15%= softened shells/ capsules
Weight variation - soft capsules
Weigh each capsule individually then cut open the capsule
Remove contents by washing with a suitable solvent
Let the solvent evaporate from the empty shell for 30 minutes at room temp
➤ Important: ensure there’s no moisture gain or loss
Weigh the empty shell
Net content = Original capsule weight – Empty shell weight
Content uniformity
This test is done only if required by the monograph or if capsules fail the weight variation test.
Test starts with 30 capsules total.
-First, 10 capsules are assayed individually.
Pass criteria for the first 10:
At least 9 out of 10 must be within 85%–115% of the average content (±15%)
None should be outside 75%–125% (±25%)
If 1–3 capsules fail the ±15% limit:
The remaining 20 capsules must be tested
In total, at least 27 out of 30 must be within ±15%
No capsule should be beyond ±25%
Content Labelling:
All official capsules must be labelled with the exact amount of each active ingredient per capsule.
Go through end of lecture questions
