Soft gelatin capsules, Capsules content, production,base adsorption,minim per gram factor, importance of minim,5th semester, Bpharm, Capsules, softgel capsules, determination of base adsorption,press die process, rotary die press, reciprocating die process, accogel process, seamless process, bubble method industrial pharamcy, industrial pharamcy

1. SOFT GELATIN
CAPSULES
Nirupam Kumar Verma
DELHI PHARMACEUTICAL SCIENCES AND RESEARCH UNIVERSITY

2. Contents
• Production of Softgel Capsules
• Plate press
• Rotary die process
• Reciprocating process
• Accogel process
• Bubble method
• Type of fill material
• Base adsorption
• Minim per gram factor
• Importance of minim per gram factor

3. PRODUCTION OF
SOFT GELATIN
CAPSULES

4. • Plate press/process
• Rotary die process
• Reciprocating Die process
• Accogel process
• Seamless process/Bubble method
Methods

5. Plate Press/Process
• Oldest Commercial Process
• Semi automatic process
• Equipment is no longer available
Procedure
Placing the upper half of a plasticize gelatin sheet over a die plate
containing numerous die pockets
Application of vacuum to draw the sheet into the die pockets
Filling the pockets with liquid or paste
Folding the lower half of the gelatin sheet back over the filled pockets
And inserting the sandwich under a die press where the capsules are
formed and cut out

6. Press plate
Flat die
surface
Die surface
with cavity

7. Use-
• This method is used for small scale preparation of soft gelatin
capsules had one flat side.
Drawbacks-
• Lack of dosage uniformity
• High manufacturing losses
• Labour-/cost-intensiveness(2-3 operators).

8. Rotary Die Press
• Most soft gelatin capsules are prepared by the rotary die process.
• Developed and Perfected in 1933 by Robert P. Scherer.
• Improved uniformity and high standards of accuracy.

10. Rotary Die press
• Two plasticized gelatin ribbons (prepared in the rotary-die machine).
• Continuously and simultaneously fed with the liquid, semiliquid or paste fill
between the rollers of the rotary die mechanism.
• The forced injection of the feed material between the two ribbons causes
the gelatin to swell into the left- and right-hand die pockets which govern
the size and shape of the softgels as they converge.
• As the die rolls rotate, the convergence of the matching dies pockets
hermetically seals and cuts out the filled capsules.

12. • Softgel capsules ----Drying station ------Dried on trays(in air or
under vacuum)-----Infra red step(Removes 60-70%moisture+ to
Speed up the process).
Note-
Lubrication oil is applied to increase efficiency of machine.
The lubrication oil should, therefore, be a GRAS (generally recognized as safe)
material. Immediately after manufacture, the formed capsules automatically
undergo volatile solvent(naptha solvent unit) washing to remove any traces of
lubricating oil from the exterior of the capsules.
Rotary Die press
Tumbler dryer
Toward drying station Trays

13. • Rotary die process reduces the loss of materials to a negligible
level and reduces content variation to ± 3%.
• Production capacity of the machine is determined by the die size,
the speed of the machine and the physical characteristics of the
material to be encapsulated.
• For most capsules, the gelatine thickness is between 0.25-0.32
inches. Thicker shells are used on products requiring structural
strength.
• The product cost is directly proportional to shell thickness.
Rotary Die press

14. Product Quality Consideration
The process involves careful control of three parameters:
• Temperature- this controls the heat available for capsule seal formation(37-
40°)
• Timing-The timing of the dosing of unit quantities of liquid fill matrix into the
softgel during its formation is critical.
• Pressure-the pressure exerted between the two rotary dies controls the
softgel shape and the final cut-out from the gel ribbon.
Rotary Die press

15. Reciprocating Die Process
• Continuous soft gelatin capsule processing technology
• Developed by Norton Company in 1949.
• Similar to rotary die process
• It differs in the actual encapsulating process. The gelatin ribbons
are fed between a set of vertical dies that continually open and
close to form rows of pockets in the gelatin ribbons.
• These pockets are filled with the medication and are sealed, shaped,
and cut out of the film as they progress through the machinery.
• As the capsules are cut from the ribbons, they fall into a cooled
solvent bath that prevents the capsules from adhering to one
another.

16. 16
• The rotary die process and reciprocating die process were capable of producing
soft gelatin capsules containing oily liquids and pastes, but not for powders and
granules.
• Lederle Laboratories in 1949 developed accogel process, a continuous process
that produces soft gelatin capsules containing powders and granules.
Accogel Process
What was the need?
Vaccum Vaccum
Vaccum
Rotary die press

17. 17
• The process involves a measuring roll that
holds the fill formulation in its cavities under
the vacuum and rotates directly above the
elasticized sheet of the gelatin ribbon.
• The ribbon is drawn into the capsule cavities of
the capsule die roll by vacuum.
• The measuring rolls empty the fill material
into the capsule-shaped gelatin cavities on the
die roll.
• The die roll then converges with the rotating
sealing roll covered with another sheet of
elasticized gelatin. The convergence of two
rotary rolls creates pressure to seal and cut the
formed capsules

18. 18
• The seamless technique produces one-piece soft gelatin capsules
without the use of dies.
• Referred to as a bubble method that creates seamless, spherical soft
gelatin capsules.
Seamless process (Bubble Method)

19. 19
In this process, a molten gelatin stream flows though the outer nozzle of a
concentric tube at a constant rate, and the medicated liquid formulation is
dispensed through the inner orifice by means of a precision metering pump. The
emerging stream is broken up into an intermittent but steady flow of uniform-sized by
a pulsating mechanism, leading to the formation of droplets enveloped in molten
gelatin. The formed capsules are quickly removed from the nozzle, slowly
congealed(on cooling), and automatically ejected from the system.

20. 20
Soft gelatin capsules may contain
• a single liquid,
• a combination of miscible liquids,
• a solution of a drug in a liquid,
• or a suspension of a drug in a liquid.
All these are formulated to produce smallest calsules with maximum ingredients and
physical stability, therapeutic effectiveness and production efficiency.(why not Gelatin
shell filling?)
• The pH of the liquid can be between 2.5 and 7.5pH.
• Aqueous emulsions,water, alcohol (upto 5% as minor constituent) cannot be filled
because inevitably water will be released, which will affect the
shell(Hydrophillic)(_Gelucire44/14).
• Plasticizers like glycerine, propylene glycol(upto 10% with PEG) can’t act as major
constituent as they will Show softening effect on shell.
Types of Fill Material for Softgel capsules

21. 21
Combinations of miscible liquids(why)-
• To increase absorption of active ingredient (vitamin A and polysorbate
80);
• To produce desired physiochemical results, such as improved flow
properties (dilution or partial substitution with a thinner liquid),
• To improved solubility (steroid with oil and benzyl alcohol).
• The most widely used liquids for human use are-
• Oily active ingredients(clofibrate)
• Veg. Oils(soyabean oils), mineral oils
• Non ionic surface active agents(polysorbate 80)
• PEG 400and 600
• Fish oil used as solvent or suspending agent in vit. Capsules.
• Usually, a solution is more easily capsulated and exhibits better uniformity,
stability, and biopharmaceutical properties than does a suspension.
Types of Fill Material for Softgel capsules

22. 22
• Base adsorption is defined as the number of grams of liquid base required to
produce a capsulated mixture(medicament) when mixed with 1 gram of
solid(API).
Base adsorption = Weight of base/Weight of solid
• Solids that are not sufficiently soluble in liquids are capsulated as
suspensions. Such materials should be 80 mesh or finer in particle size.
Base Adsorption
• The base adsorption mixture is milled or homogenized, and deaerated (a
desiccator under vacuum is suitable), and the specific gravity is taken.

23. 23
Base Adsorption
(Solid~API)
(Liquid Base)
Capsulated
mixture
= 1gm =?

24. 24
When the mixture tend to stop flowing,note
down the weight of liquid base

25. 25
Influenced by factors as –
• solid's particle size and shape,
• physical state (fibrous, amorphous, or crystalline),
• density,
• moisture content,
• and oleophilic or hydrophilic nature.
• In the determination of base adsorption solids must be completely
wetted by the liquid base. For glycol and nonionic type bases, the
addition of a wetting agent is required, but for vegetable oil
bases,complete wetting of the solid(s) is not achieved without an
additive. Soy lecithin, at a concentration of 2 to 3% by weight of the oil,
serves excellently for this purpose.
Base Adsorption

26. 26
• Solid + liquid base(ex. PEG400)= Capsulated mixture- it can be
used to determine minimum calsule size but Suspending agent
(Ex.Liquid wax) or Gelucire 44/14(prevent crystallization) is added
to make the mixture stable, uniform, ⬆️ bioavailability and
lubricity.
• Mostly used suspending agent for oily bases is wax mixture,and in
nonoily bases, the polyethylene glycols 4000 and 6000.
Minim per gram factor

27. 27
Minim per gram factor
1ml=16.23minim

28. 28
Importance

29. 29
References
• Lachman/Lieberman’s the Theory and Practice of Industrial Pharmacy
• Aulton’s Pharmaceutics: The Design and Manufacture of Medicines
• Gibson, M. (2009). Pharmaceutical Preformulation and Formulation: A
Practical Guide from Candidate Drug Selection to Commercial Dosage
Form. New York: Taylor & Francis Group.
• Allen L. and Ansel H. (2014). Ansel’s Pharmaceutical Dosage Forms and
Drug Delivery Systems. Philadelphia: Lipincott Williams and Wilkins.
• https://youtu.be/YvTXNHsoshk
• https://youtu.be/__GUEeh2oYQ