The document discusses different types of capsules used for pharmaceutical dosage forms. It describes hard gelatin capsules and soft gelatin capsules, including their advantages and disadvantages. The production process involves preparing gelatin solutions, manufacturing the capsule shells, and filling capsules. Hard capsules are filled using automated machinery that compresses powder into plugs using tamping pins. Soft capsules are filled and sealed in a single operation. Excipients, sizing, and quality controls are important considerations in capsule manufacturing.

1. CCAAPPSSUULLEESS

2. PPllaann
11.. CChhaarraacctteerriissttiicc ooff ccaappssuulleess aass ddoossaaggee
ffoorrmmss..
22.. MMaannuuffaaccttuurriinngg ooff HHaarrdd GGeellaattiinn SShheellllss
((ccaappssuulleess))..
33.. HHaarrdd--GGeellaattiinn CCaappssuullee ffiilllliinngg..
44.. SSoofftt--GGeellaattiinn CCaappssuulleess..
55.. MMiiccrrooccaappssuulleess..

3. CCaappssuulleess aarree ssoolliidd ddoossaaggee ffoorrmmss iinn wwhhiicchh
mmeeddiicciinnaall aaggeennttss oorr iinneerrtt ssuubbssttaanncceess aarree
eenncclloosseedd iinn ssmmaallll sshheellll ooff ggeellaattiinn..
TThheeyy aarree ooff vvaarriioouuss sshhaappeess aanndd ssiizzeess,, aanndd
ccoonnttaaiinn aa ssiinnggllee ddoossee ooff oonnee oorr mmoorree aaccttiivvee
iinnggrreeddiieennttss.. TThheeyy aarree iinntteennddeedd ffoorr oorraall
aaddmmiinniissttrraattiioonn..

4. CCaappssuullee sshheellllss aarree mmaaddee ooff ggeellaattiinn
oorr ootthheerr ssuubbssttaanncceess,, tthhee ccoonnssiisstteennccyy
ooff wwhhiicchh mmaayy bbee mmooddiiffiieedd bbyy tthhee
aaddddiittiioonn ooff ssuubbssttaanncceess ssuucchh aass
ggllyycceerrooll oorr ssoorrbbiittooll..
TThhee sshheellll sshhoouulldd ddiissiinntteeggrraattee iinn tthhee
pprreesseennccee ooff ddiiggeessttiivvee fflluuiiddss ssoo tthhaatt
tthhee ccoonntteennttss aarree rreelleeaasseedd..
TThhee ccoonntteennttss sshhoouulldd nnoott ccaauussee
ddeetteerriioorraattiioonn ooff tthhee sshheellll..

5. AAddvvaannttaaggeess ooff CCaappssuulleess
DDrruugg wwiitthh uunnpplleeaassaanntt ooddoorr aanndd ttaassttee ccaann bbee
eeaassiillyy aaddmmiinniisstteerreedd..
IIttsseellff hhaass nnoo ttaassttee..
EElleeggaanntt PPhhyyssiiccaall AAppppeeaarraannccee..
MMoorree ssttaabbllee iiff pprrooppeerrllyy ssttoorreedd..
EEaassiillyy SSwwaalllloowweedd..
SShheellllss aarree iinneerrtt aanndd aabbssoorrbbaabbllee iinn GGIITT..
FFoorr eennccaappssuullaattiioonn lleessss aaddddiittiivveess aarree
rreeqquuiirreedd..
MMaannuuffaaccttuurriinngg pprroocceedduurree iiss ssiimmppllee aanndd
ffaasstteerr..

6. CCoonntt……....
NNoott mmaannyy mmaacchhiinneess aanndd eeqquuiippmmeenntt aarree
rreeqquuiirreedd..
SShhiippmmeenntt iiss eeccoonnoommiicc ((lliittttllee oorr nnoo ddaammaaggee
dduurriinngg ttrraannssppoorrttaattiioonn))..
 MMoossttllyy uusseedd ccaarrrriieerr iinn cclliinniiccaall ttrriiaallss..
IInn ssppeecciiaall ccoonnddiittiioonnss iitt ccaann bbee ooppeenneedd
eeiitthheerr aass aa wwhhoollee oorr iinn ppoorrttiioonn ccaann bb
ddiissppeennsseedd wwiitthh ffoooodd oorr ddrriinnkk bbyy
PPhhaarrmmaacciisstt..

7. Type ooff ccaappssuulleess ddeeppeenndd oonn
ppllaassttiicciizzeerr ccoonntteenntt
aanndd tteecchhnnoollooggiiccaall pprriinncciippllee
11.. HHaarrdd--SShheellll GGeellaattiinn CCaappssuulleess;;
22.. SSoofftt-- GGeellaattiinn CCaappssuulleess
((ssooffttggeellss));;

8. CCaatteeggoorriieess ooff ccaappssuulleess
 hhaarrdd ccaappssuulleess;;
 ssoofftt ccaappssuulleess ((ssooffttggeellss));;
 mmooddiiffiieedd--rreelleeaassee ccaappssuulleess::
11.. ddeellaayyeedd--rreelleeaassee ccaappssuulleess
((ggaassttrroorreessiissttaanntt // eenntteerriicc ccaappssuulleess))
22.. ssuussttaaiinneedd--rreelleeaassee ccaappssuulleess
((eexxtteennddeedd--//pprroolloonnggeedd rreelleeaassee ccaappssuulleess))..

9. GGeellaattiinn
 pprrootteeiinn,, pprreeppaarreedd ffrroomm hhyyddrroollyyssiiss ooff ccoollllaaggeenn ((aanniimmaall
bboonneess aanndd sskkiinn))
ttyyppee AA :: ppiigg sskkiinn
ttyyppee BB :: aanniimmaall bboonneess
 ppoosssseesssseess ffoolllloowwiinngg eesssseennttiiaall pprrooppeerrttiieess
• ssttaabbllee wwhheenn ddrryy
• ssuubbjjeecctt ttoo mmiiccrroobbiiaall ddeeggrraaddaattiioonn wwhheenn mmooiisstt
• ddiiggeesstteedd aanndd aabbssoorrbbeedd
9

10. HHaarrdd CCaappssuulleess
HHaarrdd ccaappssuulleess hhaavvee sshheellllss ccoonnssiissttiinngg ooff
ttwwoo pprreeffaabbrriiccaatteedd ccyylliinnddrriiccaall sseeccttiioonnss tthhaatt
ffiitt ttooggeetthheerr..
OOnnee eenndd ooff eeaacchh sseeccttiioonn iiss rroouunnddeedd aanndd
cclloosseedd,, aanndd tthhee ootthheerr iiss ooppeenn.. TThhee
ccoonntteennttss ooff hhaarrdd ccaappssuulleess aarree uussuuaallllyy iinn
ssoolliidd ffoorrmm ((ppoowwddeerr oorr ggrraannuulleess))..

11. HHaarrdd GGeellaattiinn CCaappssuulleess
AAddvvaannttaaggeess
ttaasstteelleessss aanndd ooddoouurrlleessss
sswwaalllloowwiinngg iiss eeaassyy
fflleexxiibbiilliittyy iinn ffoorrmmuullaattiinngg
uunniiqquueellyy ssuuiittaabbllee ffoorr bblliinnddeedd cclliinniiccaall ttrriiaallss
uusseeffuull ffoorr eexxtteemmppoorraanneeoouuss ccoommppoouunnddiinngg bbyy
pphhaarrmmaacciisstt
1111

12. DDiissaaddvvaannttaaggeess
tteenndd ttoo bbee mmoorree eexxppeennssiivvee ttoo pprroodduuccee tthhaann
ttaabblleettss
nnoott ssuuiittaabbllee ffoorr hhiigghhllyy ssoolluubbllee ssaallttss

13. HHaarrdd GGeellaattiinn CCaappssuulleess
SSiizzeess
SIZE VOLUME (cm3)
000 1.37
00 0.95
0 0.68
1 0.50
2 0.37
3 0.30
4 0.21
5 0.13
1133

14. Soft gelatin capsules
(softgels) are hermetically sealed one-piece capsules
containing a liquid or a semisolid fill.
Soft capsules are usually formed, filled, and sealed in
one operation.
shells are softened by addition of glycerin or polyhydric
alcohol (ex. sorbitol)

15. Advantages of soft-gelatin capsules
1. Improved bioavailability, as the drug is presented in a
solubilized form.
2. Enhanced drug stability.
3. Consumer preference regarding ease of swallowing,
convenience, and taste can improve compliance.
4. Offer opportunities for product differentiation via colour,
shape, and size and product line extension.
5. The softgels can be enteric coated for delayed release.
6. may contain liquids, suspensions, pastes
7. rapid release of contents
8. useful for drugs prone to oxidation
They are popular for pharmaceuticals, cosmetics, and
nutritional products.

16. Soft Capsules
 DISADVANTAGES
have a greater tendency to adhere to each
other
more expensive
increased possibility of interactions between
drug and shell
16

17. Stage of capsules production:
1. Preparing of gelatin
solutions.
2. Preparing of gelatin
shells.
3. Hard-gelatin
capsule filling.
4. Packing and
labeling.
1. Preparing of gelatin
solutions.
2. Preparing and filling
of soft-gelatin
capsules.
3. Packing and
labeling.

18. In the manufacture of capsules,
measures are taken to:
ensure that the active ingredient(s) when
present in solid state form have appropriate
solid-state properties such as particle-size
distribution and polymorphic form;
ensure that mixing with excipients is carried
out in a manner that ensures homogeneity;
minimize the degradation of the active
ingredient(s);
minimize the risk of microbial contamination;
minimize the risk of cross contamination.

19. Excipients for production
of the Capsule shells :
 solvents,
 surface-active substances,
 opaque fillers,
 antimicrobial agents,
 sweeteners,
 colouring matter,
 flavouring substances,
 disintegrating agents,
 substances capable of modifying the behaviour of the active
ingredient(s) in the gastrointestinal tract.

20. Methods obtaining
of gelatin solutions
Obtaining
of gelatin solutions
with stage of
swelling
Obtaining
of gelatin solutions
without stage of
swelling

21. Obtaining of gelatin solutions
with stage of swelling
1. Swelling of gelatin in cold water (15 - 18 °C, 1.5 -
2 hours).
2. Dissolving of gelatin.
3. Adding preservatives, plasticizers and others
excipients.
4. Remove of air bubbles from the solution of the
gelatin by the vacuum.
5. Stabilization of solution of the gelatin (45-60 °C).

22. Obtaining of gelatin solutions
without stage of swelling
1. Heating of purified water (70-75 °C).
2. Dissolution of preservatives, plasticizers and
others excipients in the water.
3. Dissolution of the gelatin.
4. Remove of air bubbles from the solution of the
gelatin by a vacuum.
5. Stabilization of the solution of the gelatin (45-60
°C).

23. Hard capsules production
 To manufacture the shells, pairs of molds, for the
body and the cap, are dipped into an aqueous gelatin
solution (25 – 30 % w/w), which is maintained at
about 50 °C in a jacketed heating pan.
 As the pins are withdrawn, they are rotated to
distribute the gelatin evenly and blasted with cool air
to set the film.
 Drying is carried out by passing dry air over the shell
as heating temperatures are limited due to the low
melting point of gelatin.
 The two parts are removed from the pins, trimmed,
and joined using a prelock mechanism.

27. Preparation of Filled Hard Gelatin
Capsules
Following Steps:
 Developing and Preparing the formulation
 Selection of Capsule Size
 Filling Capsule Shells
 Capsule Sealing
 Cleaning and polishing filled capsules

28. Hard - Gelatin Capsule Filling
Powders and granules are the most common filling
materials for hard - shell gelatin capsules, although
pellets, tablets, pastes, oily liquids, and nonaqueous
solutions and suspensions have been used.
 Filling machines are differentiated by the way they
measure the dose of material and range in capacity
from bench - top to high - output, industrial, fully
automated machines.

29. Hard - Gelatin Capsule Filling
Most automated machinery is of the
independent type and compresses a
controlled amount of powder using a low
compression force (typically 50 – 200 N ) to
form a plug. Most are piston - tamp fillers
and are dosator or dosing disk machines.
The powder is passed over a dosing plate
containing cavities slightly smaller than the
capsule diameter, and powder that falls into
the holes is tamped by a pin to form a plug.

32. Process flow diagram for automated capsule filling.

33. NJP-3000,3500 series automatic
capsule filling machine It comply with volume-produce.
This machine adopts full sealed filling
and turret parts and easy to clean,
upper and lower die assemblies move in
one-way, imported double-lip sealing
ring made of polyurethane and have
high performance,
die assemble cleaning work station
combine blowing and breathing to
ensure no powder in die hole during
high speed running,
there is no absorb device in locking
work station, lubricant be added
timing in transmission work station.

34. Storage
 Optimum moisture content 12-16%
 At very low Humidity, Loses moisture and
becomes brittle.
 At high humidity, becomes flaccid and
loses shape
 High temp. also affect adversly.
The best Storage conditions are at temp.
20C to 25C and with humidity 35 to 40%

35. Methods of
softgels production
Droplet method Pressing method

36. Droplet method
1. Container with
medicines substance
2. Hoper with
medicines substance
3. Container with
gelatin solution
4. Conical nozzle
5. Pulsater
6. Cooler
7. Container with
Vaseline oil

37. Characteristic of Droplet
method
It is based on formation of spherical
gelatinous drop filled with a solution or
suspension of medicinal substance at
simultaneous drop dosage of medicinal
substance solution followed by subsequent
cooling of heated gelatinous mass in cool
liquid petrolatum. As the result joinless
spherical gelatious capsule with elastic
shell is formed.

38. RRGG22--220000 225500 330000 SSeerriieess SSoofftt
GGeellaattiinn EEnnccaappssuullaattiioonn MMaacchhiinnee
• For volume-production,
increase the utilization
ration of gelatin skin;
• convey gelatin skin with
a plane surface more
steady running
condition;
• oil saving;
• suitable for volume-production,
continually
for 24 hour.
(Huizhou Pingfang
pharmaceutical
machinery co. ltd.)

39. Pressing method (Plate
method)
Preparing of an initial gelatinous
tape, placing it into metal plates
and rolls having deepening holes
resembling half of the capsules.
While heating gelatin fills this
mould. Drug is fed into a hollow
in a gelatinous tape, then this
half of a capsule is joined with
another one formed and filled in
the same way. Obtained
capsules have a horizontal weld.

40. Pressing (rotary or reciprocating
die) method
The glycerol – gelatin solution is heated
and pumped onto two chilled drums-1
to form two separate ribbons-2, which
form each half of the softgel.
The ribbons are lubricated and fed into
the filling machine, forcing the gelatin
to adopt the contours of the die.
The fill-4 is manufactured in a separate
process and pumped in, and the
softgels are sealed by the application
of heat and pressure.
Once cut from the ribbon (5), they are
tumble - dried and conditioned at
20 % relative humidity.

41. Uses of Soft Gelatin Capsules
 Water immiscible volatile and non-volatile
liquids (vegetable, aromatic oils chlorinated
hydrocarbons, ethers, esters and alcohol)
 Water miscible nonvolatile liquids
(polyethylene glycols ,nonionic surfactant
polysorbate 80)
 Water miscible and relativly nonvolatile
compounds (propylene glycol, IPA)

42. Compendial Requirements
Added Substances
 Should harmless in the quantities used.
 Do not exceed the minimum amounts
required.
 Do not impair the products bioavailability,
therapeutic efficacy, and safety.
 Do not interfere with requisite compendial
assays and tests.

43. Compendial Requirements
Containers for Dispensing Capsules
Should be according to USP or BP
Specifications
Tight, well-closed, light resistant container

44. Cont…….
 Disintegration test
 Dissolution test
 Weight Varioation
 Content uniformity
 Content Labeling requirement
 Stability Test
 Moisture Permeation Test

45. Oral administration
 Place the dose upon tongue
 Swallow with glass of water or beverage
 Dry intake causes ulcers
 Oral dosage forms with special coating
must not be chewed, broken or crushed.
 If patient cannot swallow, suggest
chewable or liquid form of drug.

46. Modified-release
capsules
 They are hard or soft capsules in which
the contents or the shell or both contain
excipients or are prepared by special
procedures such as microencapsulation
which, separately or together, are
designed to modify the rate, place or
time of release of the active
ingredient(s) in the gastrointestinal
tract.

47. Sustained-release capsules
(Extended- or Prolonged-release
capsules) are designed to slow the
rate of release of the active
ingredient(s) in the gastrointestinal
tract.

48. Delayed-release capsules
(gastro-resistant/enteric capsules)
are hard or soft capsules prepared in
such a manner that either the shell or
the contents resist the action of gastric
fluid but release the active ingredient(s)
in the presence of intestinal fluid.

49. Microcapsule is a small sphere with
a uniform wall around it.
Micro-encapsulation is a process in which
tiny particles or droplets are surrounded by a
coating to give small capsules many useful
properties.
The material inside the microcapsule is
referred to as the core, internal phase, or fill,
whereas the wall is sometimes called a shell,
coating, or membrane.
Most microcapsules have diameters between
a few micrometers and a few millimeters.

50. The reasons for microencapsulation
 In some cases, the core must be isolated from its
surroundings, as in isolating vitamins from the
deteriorating effects of oxygen,
 retarding evaporation of a volatile core,
 improving the handling properties of a sticky material,
or isolating a reactive core from chemical attack.
 In other cases, the objective is not to isolate the core
completely but to control the rate at which it leaves the
microcapsule, as in the controlled release of drugs or
pesticides.
 The problem may be as simple as masking the taste or
odor of the core, or as complex as increasing the
selectivity of an adsorption or extraction process.

51. The end