Lecture 4- Capsule Formultion

Question 1

Capsules

Answer 1

-solid dosage forms where the drug substance is enclosed within either a hard/soft soluble shell
-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

Question 2

Hard gelatin capsules advantages + disadvantages

Answer 2

Advantages;
-better bioavailability than tabs due to fast dissolution of gelatin shell= rapid drug release
-no need for compaction of the filing material= rapid drug release
-easier to formulate than tabs
-no taste

Disadvantages;
-slower rate of capsule manufacturing
-more expensive to produce capsules
-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
-concern over maintaining proper shell moisture content (should be between 12-15%)
-too dry= brittle/ easily fractured (12%)
-too moist= too soft + sticky (15%)

Question 3

Hard gelatin capsule manufacturing

Answer 3

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

Question 4

Types of gelatin

Answer 4

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

Question 5

Physiochemical properties of gelatin

Answer 5

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

Question 6

Shell manufacture; dipping method

Answer 6

1. Dipping
2. Spinning
3. Drying
4. Stripping
5. Cutting
6. Joining

Question 7

Capsule filling machines

Answer 7

Semi automatic
-used for hospital prep labs and medium/small pharmaceutical factories
-completes the processes of positions separation, filling + locking of capsules filled with powder
Capacity; 12,500 pch/h caps size= 1-3

Fully automatic
-used for pharmaceutical manufacturer
-filling materiall powders, pellets, microtablets, tablets, powder/tab, pellet/tab and microtablets/tabs
Capacity; 140,000 pch/hr caps size= 00-5

Question 8

Design of hard gelatin capsule for powder fill

Answer 8

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

Question 9

Filling blend for hard gelatin capsules

Answer 9

-active ingredient
-fillers
-glidants
-lubricants
-disintegrates
-surfactants

Question 10

Soft gelatin capsules; advantages and disadvantages

Answer 10

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

Question 11

Composition of the shell

Answer 11

-gelatin, plasticizer, dyes, opacifiers, preservatives and flavours

Question 12

Formulation of soft gelatin capsules

Answer 12

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: pHL 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

Question 13

Requirements for the filling liquid:

Answer 13

-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

Question 14

Requirements- tests for capsules

Answer 14

*containers for dispensing capsules= container must be tight, well-closed and light resistant
*disintegration test for capsules= slide 31
*dissolution test for capsules= same apparatus, dissolution medium and test are used for capsules, uncoated and coated tablets (slide 32)

Question 15

Weight variation

Answer 15

-uniformity of dosage units may be demonstrated by determining weight variation/content uniformity

Hard gelatin capsules; slide 33
Soft capsules; slide 34
Content uniformity; slide 35