Processing of Capsules Definition

• Capsules are solid dosage form that contains one or more medicinal
• Hard and soft gelatin capsules or inert substances contained in a shell most properly made of
gelatin.
• Different sizes of capsules • There are two types :
• Filling of capsules Hard gelatin capsules ( two piece).

• Handling and storage of capsules.

• Special applications of capsules.
Soft gelatin capsules ( one piece).

Standard Sizes and Volumes of EHGC

Size number Volume in ml Size in mm
Hard Gelatin Capsules (HGC) 000 1.37 26.3
00 0.95 23.7
 HGC are composed of two parts: 0 0.68 21.8
1 0.5 19.2
2 0.37 18.3
- Shorter and wider is the cap 3 0.30 15.3
4 0.21 14.7
5 0.15 11.9
- Taller and narrower is body.
 Differences between gelatin types for HGC
Manufacture of EHGC – Gelatin Production of Gelatin
• characteristics of gelatin types for HGC
• Why using gelatin? Characteristic Type A Type B
- The ability of a solution of a gel to solidify just above the ambient temperature enabling the
Production Acid hydrolysis Alkaline hydrolysis
mold pin to solidify rapidly.
Source Pork skin Other animal & bones
- Nontoxic and used in food.
Isoelectric point pH At pH 7 - 9 At pH 4.8 – 5
- Readily soluble in biological fluid at body temperature.
Physical characters Plastic and clear firm
- Produce strong flexible film.
Gel strength 240 – 300 200 - 250
- Homogeneous in structure giving good mechanical strength.
44 – 55 45 – 60
- Make a sol at 50 ˚C. Viscosity
pH 4.5 – 5.5 5.3 – 6.5
Aerobic count - Max 1000 cfm/g
• Types of gelatin? E. Coli - Negative
- Type A : Produced by acid hydrolysis of bones, skin and connective tissues of pork ( bovine).
Salmonella - Negative
- Type B : Produced by alkaline hydrolysis of bone, skin and connective tissues of animals.
Yeast & molds - Max 1000 cfu/g

Physiochemical properties of gelatin • Viscosity :

• Bloom test: Determined on 6.67% concentration of gelatin in water at 60 ˚C .
It is used to measure the strength of a gel or cohesive Viscosity range 30 – 60 millipose is considered suitable.
strength between gelatin molecules and it is proportional to
the molecular weight of gelatin. As the viscosity lowered the capsule thickness will decrease.
It is defined as the weight in grams needed by specified plunger • Microbiological tests:
( 0.5 inch diameter) to depress the surface of the gel at specified - Total microbial count
temperature to a distance of 4 mm without breaking. a- total aerobic bacteria.
The result is expressed in bloom (grade) usually between 30 – b- molds
300 using 6.67% gelatin solution kept for 17 hours at 10 ˚C prior c- preservative
to be tested.
Generally used preservative are propyl paraben, methyl paraben,
The higher the bloom value the higher the melting and gelling Antioxidant-sodium metabisulfite.
points and the shorter the gelling time.
Range of 150 – 280 is considered suitable for capsules
manufacturing.
 1- Preparation of solution for EHGC manufacture 2- Dipping
Gelatin 30% • Bloom 150 – 280 Vacuum is applied to - Pairs of stainless steel pins, lubricated are dipped into the
• Viscosity 30 -60 millpose remove the entrapped air. solution. One for caps and the other for bodies.
Water 65% Hot demineralized
-Temperature of pins is ambient while that of the solution is
Dye 5% Water soluble
Pigment As needed Water insoluble 55 ˚C kept constant by means of jacketed pan.
Surfactant 0.15% w/w Sod. Lauryl sulphate - Enhance wettability of
gelatin to metal pin - Time for dipping is 22 seconds.
during production.
- Enhance wettability of 3- Spinning
capsule shell with
Pins are elevated and rotating in spinning manner to
aqueous medium.
Preservative As needed - Sod. Metabisulfite Gelatin is ideal growth distribute the gelatin over the pins uniformly and to avoid
- Methyl paraben medium at 55 ˚C formation of bead. Stream of cool air is then applied.
- Propyl paraben

4- drying 6- Trimming
-The racks of gelatin coated pin passes through the upper and lower kilns of - The firmly held two portions of capsule rotates against knife blade which cut
trim them to the required length.
machine drying system.

- Gentle moving air of controlled temperature, humidity and volume removes
the required amount of moisture from the two halves of capsule.
5- Stripping
- A series of bronze jaws strip out the caps and bodies from the pins and pass it
to the trimming stage.
7- Joining
- The cap and body are then aligned concentrically in channels and slowly and
smoothly pushed together.
- The and body are now joined to form the capsule which is then ejected.
The entire cycle takes about 45 min , two thirds of which is in the drying
chamber.
Properties of EHGC
• Should exhibit water content 13 – 16% w/w.
- Water act as plasticizer to ensure the mechanical properties of capsule.
- If lower water content , it will become brittle and crack.
- If excessive water content, it will undergo plastic flow upon exposure to stress
and loose its shape, becoming soft.
- Water soluble at 37 ˚C and insoluble below 30 ˚C and absorb water.
• Should be stored in a sealed container at room temperature at
controlled humidity of 30% - 45%.
Assessment of Good flow properties
• Angle of repose:
- The angle that the powder makes with the horizontal plane.
- If the angle of repose exceeds 50˚ the flow properties is poor.
- Angle of repose 25 ˚ is suitable.
- Higher angle of repose requires the use of glidant.
• Torque rheometry:
- stress is applied to the powder and the rate of shear is determined to cause
deformation. The powder of high cohesion requires high shear strength to
initiate and maintain flow.
• Carr’s Compressibility index
• Hausner’s ratio
-The density of the powder before shaking to the density after shaking.
- 1.2 is acceptable but if exceed 1.6 it will be unsuitable for capsule filling.

Formulation of the Powder Fill

Excipient function Examples Soft Gelatin Capsules softgels
Diluent Provide powder mass - Lactose monohydrate
- Starch • Soft gelatin capsules are capsules in which the mechanical properties of
- Microcrystaline cellulose

Lubricant Reduce the adhesion to metal dossator - Mg Stearate gelatin have been manipulated by addition of a plasticizer ( glycerol,
and to metal of machine.
Glidant Reduce the interparticle attraction to - Talc polyhydric alcohols as sorbitol) resulting in more flexible capsule.
provide powder flow. - Aerosil
Disintegrant To break the powder mass following - Maize Starch – crospovidone
release into the stomach. - Microcrystaline cellulose • Soft gelatin capsules SGC may have a various shapes and sizes.
Surface active To enhance wettability - Sod lauryl sulphate
agent
Protective sorbent To prevent absorption of moisture by - Mg Oxide
hygroscopic materials - Ca Carbonate
Antidusting To prevent dusting of powder - Inert edible oil
 Advantages of softgels Disadvantages of Softgels
• Requires special manufacturing equipment.
1. Patient compliance: easy to sallow, no taste, tamper proof, unitdose delivery.
• Stability issues for water soluble drugs.
2. Versatile: filled as semisolid, liquid, gel or paste. Various colours, shapes, sizes.

3. Improved bioavailability: immediate or delayed by delivering drug in solution. • Possibility of interactions between liquid and gelatin shell.

4. Improve stability: drug is protected by lipophilic vehicle and capsule shell. • Limited choices for excipients.
5. Liquid flow in filling is more precise than powder flow. No dust. Homogeneity. • Highly moisture sensitive.
6. Can be enteric coated for delayed release.

7. Popular for pharmaceutical and nutritional products.

Composition of Softgel shell Plasticizer in Softgels

• Incorporated to provide flexibility of the shell.
• Gelatin type B – alkali processed, constitutes 40% of melt gel.
• 20 -30 % of the wet gel formulation.
• Plasticizer • The compatibility with the fill formulation determine the plasticizer.

• Water. • The mechanical properties of the capsule determine the

concentration. Above 30% result in too flexible capsules and below
• Other additives which may be added as colorants, opacifier, 20% will result in too brittle capsules.
preservative or flavouring agents. • Glycerol, Sorbitol, propylene glycol or mixtures are frequently used.
Water in Softgel Other additives in gel formulation
• Water accounts for 30 – 40% of the wet gel to facilitate proper • Insoluble pigments, soluble pigments with or without opacifier can be
processing during gel preparation.
used.
• Excess water is removed by controlled drying.
• Opacifier Titanium dioxide isgenerally used for suspension or to guard
• Water content in the finished capsule should be 5 – 8%, to keep the
physical stability . against light.

• Improper storage conditions may make the capsules too soft or too
• Methy paraben, propyl paraben, sod sulfite may be used as preservative.
hard and embrittled.

Composition of Soft Gelatin Capsule Shell

Gelatin
• Formulation of Suspension for SGC involves Base Adsorption consideration.
• Plasticizer – Glycerin, sorbitol, Propylene Glycol, Water or
• Base Adsorption (BA) = weight of Base/Weight of Solid Moisture Content (6 to 10%)
• BA is number of grams of liquid base required to produce a capsutable mixture • (Moisture Content is determined by Toluene Distillation Method or
with 1 gram of solid. Azeotropic Distillation.)
• Preservatives-Methyl and Propyl Paraben (4:1)
• Minim per gram (M/G) = (BA + S) × V/w
• Colourants–FD and C, Certified Lakes
• Base adsorption is used to determine minim per gram factor of solid. • Opacifier–Titanium Dioxide (0.2 to 1.2%)
• M/G is volume in minim that is occupied by one gram of solid(S) plus weight of • Flavouring Agent–Ethyl Vanillin (0.1%)
• Fumaric acid is added to aid solubility and to reduce aldehyde
liquid base required to produce a capsutable mixture.
tanning of gelatin.
• Lower the BA of solid, higher the density of mixture and thus smaller the • While Formalin treatment reduces the solubility of shell.
capsule size.
 Quality Control Tests for Capsules
• Visual inspection
- Appearance : shape, colour, size , thickness of the shell,
leakage test for soft gels.
Capsule weighing machine
1. Roto weigh–It is capsule weighing machine. It • Disintegration test.
measures the reflected energy (backscatter) of low
power X-ray beam.
2. Vericap 1200–It measures the change in dielectric • Microbiological Testing • Dissolution test.
constant or capacitance variation.(2000/min)
Finishing
• Moisture permeation test
1. Pan Polishing-Accelacota tablet coating pan using • Weight variation
polyurethane cloth. Salt polishing using crystalline
NaCl. • Content uniformity test
2. Cloth dusting–Cloth impregnated with inert oil
3. Erweka kea–Dedusting and polishing machine