GPAT DISCUSSION CENTER

CAPSULES
Hard gelatin capsules
Telescoping capsules are primarily made up of gelatine blends.
Pin method is primarily used for production of capsules.
Capsules can be made up with methyl cellulose, polyvinyl acetate and denatured gelatine.
Formalin can modify solubility of gelatin.
Two types of gelatin Type A(Pharmagel A) acid treated, obt. frompork skin.isoelectric. pH 9.0
Type B(Pharmagel B) alkali treated, frombones and animal skin.pH 4.7
Pork skin gelatine contributes plasticity and clarity while bone gelatin forms tough and firmfilmthat forms to be hazy and brittle.
Pin method takes 45 min.
Thickness of capsule wall is controlled by viscosity of gelatin solution and speed and time of dipping.
Capsule is stored at NMT 15 deg. Fahrenheit.
Moisture in capsule should NMT 12-15%.
It should not contain iron more than 15 ppm.

FILLING EQUIPMENTS
1. Lilly Parke Davis 200000 capsules/day.
It contains Auger for forced filling of powders.
2. Rotofill-for filling of pellets.
3. Farmatic- dosator type machine.dosator means it delivers the powder as a slug to the capsule.160000 cap/hr
4. Hofliger Karg:used for powder,pellets and tablets. Auger fill principle
5. Macofar- dosator type.5000-3500 cap/hr by various models.
6. MG2 continuous motion filling.
7. Osaka vibration principle is used for filling.7000-165000 cap/hr.
8. Perry Accofil continuous rotary machine.60000 cap/hr
9. Zanasi - powder,pellets, tablets,paste and liquid filling.30000-150000 cap/hr.
10. QUALI-SEAL filling of liquids.

Filling capacity
Capsule size Approx. Vol(ml) Approx. Weight(mg)
000 1.35 950
00 0.95 650
0 0.75 450
1 0.55 300
2 0.4 250
3 0.3 200
4 0.25 150
5 0.15 100

Humidity range for capsule preparation should be 30-45%.
Amount of oil or lubricant in capsule should be less than or equal to 2%.
Weight variation test sequential test.
20-capsules taken-if 2 to 8 capsule deviates fromvariation,other 40 are taken and average of 60 capsules is
estimated.no capsule should deviate by 10-25% of specified limits.
Specified limits(IP)
Capsule weight limit
Less than 300 mg 10%
More than 300 mg 7.5


Capsule weighing machines:-
1. Rotoweigh uses reflected energy of power x-ray beam.
2. Vericarp 1200 measures capacitance variation between 2 charged plates when capsule falls.
Finishing
Accela-cota machine is used - polishes capsules. Uses polyurethane and cheese liner cloth in the pan.
Content uniformity test for capsule
30 capsule selected.10 of which are assayed.
If 1-3 deviates, 9 of themshould have 85-115%.and 10
th
should be 75-115%.


If not then take other 20 tablets,NLT 27 capsules should have 75-125% API.
Limits of capsule
Water resistance fails to dissolve in water at 20-30 deg. Celcius in 15 min.
Acid solubility dissolves in less than 5 min in 0.5%w/w aq. HCl at 36-38 deg. Celcius.
Formalin decreases solubility of gelatine by way of cross-linking of gelatine molecules initiated by aldehyde.

Capsule types
Pulvules bullet like
Kapseal a band of colored, gelatin encircles the capsules
Spansule both the ends of cap and body are similar.
Snap-fit or coni-snap a pair of matched locking rings are formed into the cap and body portions.

0.15%SO2 is used to prevent decomposition during capsule manufacturing.

SOFT GELATIN CAPSULES
3 methods of manufacture
1. Plate process: used plates. low efficient method.
2. Rotary die process: Robert Scherer developed this method. Highly efficient method.content variation comes less
than 3%.
3. Reciprocating die process.
Content of SGC may vary from0.1 30 ml.
The spherical shaped capsules are known as pearls.

Main plasticizer in SGC is glycerol. Sorbitol, propylene glycol can be used in combination with glycerol. Higher the plasticizer
concentration greater the flexibility.
Water content varies between 0.7-1.3 parts of water to each part of dry gelatine with 1:1 ration. Is generally used.
Opacifier:TiO
2
:0-0.5%.
Enteric properties to SGC cab be imparted by 4% CAP.(cellulose acetate phthalate).




NATURE OF GELATINE SHELL

Bloom/gel strength measure of cohesive strength of capsule.
Determined by measuring the wt in grams req. to move a plastic plunger that is 0.5 inches in diameter and 4 mm
immersed into 6.66%gel that is cooled at 10 deg. Celcius for 17 hrs.
Bloomstrength should be 150-250 gms.
Higher the bloomstrength, stable the gelatine shell.
Viscosity determined by keeping gelatine (6.66%) in water at 60 deg. celcius. optimumvalue 25-45 mili poise.
Plasticizers glycerine, sorbitol, CAP, PG.
Ratio of dry plasticizer and dry gelatine determines the hardness of gelatin shell.
Hardness Ratio Usage
hard 0.4/1 Oral/oil-based/softening
shells, used in humid areas
medium 0.6/1 Oral/tube/shell, for
temperate areas
soft 0.8/1 Tube/vaginal for cold dry
areas.

Accogel machine (STERN machine) solids are filled into the SGC either in formof solution or suspension. Powders can also be
filled.

Base adsorption no. Of grams of liquid base req. to produce a capsulate mix mixed with one gramof solid. For this solid must be
completely wetted by liquid base.liquid base used is soy lecithin.
Base adsorption value is used to determine minimper gramof solid.

Gelatin disk method is ude to determine effects of agitation,temperature,dissolution medium and shell composition on the
dissolution rate of capsules.
ALSO SEE TABLE OF LACHMAN PG NO:401



v Lower the base adsorption of solid, smaller the capsule due to higher density of mixture.

Gelatin preparation department:
Temp: 20-22 deg. celcius.
Humidity: max 40% in operating areas and 20-30% in drying areas.
Deaeration done at 60 deg. celcius.
Gelatine is mixed with the liquid constituents(7 deg. Celcius) in Pony mixture.melting time for gelatine
3hrs.
Thickness of capsule shell 0.025-0.032 inch
Sealing of capsule done at 37-40 deg. Celcius.
Accepted seal thickness is one half of ribbon thickness.
After manufacturing of capsule, naptha wash is given to remove mineral oil.
IR-drying 60-70% loss of water.
Final capsule 20-30% Relative humidity at 21-24 deg. celcius is considered as dry.capsule shell contains 6-10% of water.
Moisture content of capsule is determined by toluene distillation method.
Accogel is also known as stern machine
Fill contents in SGC (variation allowed is 1-3%).
Commonly used preservatives in SGC (methyl and propyl parabens).
Formic acid is also used to decrease aldehyde tanning of capsule.
Dry shells of SGC contain 9-4 % of water.
Flavours can be used in concentration of NMT2% E:g Ethylvanilllin.
Sugar upto 5% can be used.

Veterinary capsules
v Capsule no. 10, 11 and 12 for 30, 15 and 7.5 grams respectively.
Oxides and carbonate of calciumand magnesiumare used as protective sorbents.
Edible oils are used as anti-dusting compounds in capsule.
Rotosort capsule sorting machine by Eli Lilly -150000 cap/hr
Erweka Kea is a dedusting machine.

Special types of capsules
1. Enteric coated CAP(10%) is widely used as coating material. Formaldehyde and mix. of waxes
with fatty acids can also be used.
2. Sustained release capsules cellulose esters, fats, waxes like beeswax and carnauba wax is used
with glyceryl monostearate. total thickness of coating should be about 0.1mm.
3. Rectal capsules
4. Ophthalmic capsules SGC is used.
The max. Size of capsule and shape suitable for human use is 20 minim oblong,26 minim oval and 9 minim round.
Upto 10% of glycerine and propylene glycol can be used as co-solvents with PEG.

Glycerine exhibits tackiness of 954 cp at 25 deg. Celcius.
Preparations that have to be capsulated should have pH 2.5-7.5.
For oral products medicine should have such a solubility in SGC taht 16-20 minimfill volume can be attained.
Organic/inorganic compounds that are to be capsulated must be lesser than 80 mesh.
The most widely used oily bases is wax mixture and in non-oily bases, the polyethylene glycols 4000 to 6000.

Read table of lachman on page - 405

Proteolytic effect of chloral hydrate on gelatine shell is greatly reduced when Polyethylene glycol base is used instead of oily base.

Soft gelatin capsules are protected by polyethylene bags (0.003) inch which act as moisture bearer.

For information (very imp.) - Aminophylline is a mixture of theophylline and ethylene diamine.


Still more to come ..................................!!!!