Lecture 4- Capsule Formultion Flashcards
Capsules
-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
Hard gelatin capsules advantages + disadvantages
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%)
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
- Spinning
- Drying
- Stripping
- Cutting
- Joining
Capsule filling machines
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
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: 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
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= slide 31
*dissolution test for capsules= same apparatus, dissolution medium and test are used for capsules, uncoated and coated tablets (slide 32)
Weight variation
-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
