The document discusses innovations in capsule fill materials and technologies. Some key points: - Capsules can now be filled with various materials like powders, granules, pellets, liquids, and semisolids using advanced filling machines. - Technologies like Duo Cap, L-OROS, and Pulsincap allow for modified drug release profiles from capsules through multi-phase designs and coatings. - Newer technologies like Orbexa and Minitabs produce controlled release beads or mini-tablets that can be filled into capsules for additional control over drug release. - Liquid-filled capsules using technologies like Licaps improve bioavailability over tablets and set

1. Innovation in
capsule
fill material
Presented By :-Jyoti D.Padalkar
Roll No. 18
collage-Atmiya institute of
pharmacy

2. CONTENT
•Introduction
•Innovations in capsule system
•Newer technologies
•Current research
•Reference

3. Capsule
It is a solid dosage forms in which one or more
medicinal & or inert substances are enclosed in small
shell or container,generally made up of suitable form
of gelatin.
Types of capsule
 Hard gelatin capsule (Two piece capsule)
 soft gelatin capsule (one piece capsule.)

4.  Compendial requirements for capsules
 Official and commercially available capsules
 Inspecting, counting, packaging, and storing
capsules

5. Some of the innovations are targeted to:
 Overcome the disadvantages associated with
conventional capsules.
 Achieve modified drug release.
 Encapsulation of various kind of material.
 Modified applications
 Active ingredients were formulated into capsule in the
form of powder or granules for immediate or modified
release.
 pellets , mini-tablets , liquids, semisolids, etc. can be
filled into capsules because of innovation in filling
machines.

6. Capsules are use for filling different materials like
Powder Granules Beads
Pastes
Caplets
Tablets

7.  Non – newtonian fluids( liquid active or soln. of solid
active in liquid excipients) fill these fluids in hard
gelatin capsule, rheological consideration is imp.
 When the drug is not soluble in aq. Solvent or solvent
is incompatible with the shell then the active is
formulated as dispersion.
 Non-newtonian fluids are
1) Thixotropic gel
2) Thermosoftened system
Semi Solids

8. 1.Thixotropic gel
 It undergoes shear thinning filling followed by gel
restructing with an increase in its apparent viscosity can
be reduced by increasing the temperature of filling
process so that the formulation is molten at the filling
temp.
 Filling process temp. is usually limited up to max.70°C in
order to avoid thermal damage to the capsule shell. It
needs liquid excipients like triglyceride and gel forming
agent like silicone dioxide.

9. 2.Thermosoftened system
 Thermosoftened formulations solidify in the hard
gelatin capsule to form a non-porous crystalline plug
or solid dispersion.
 These are prepared at elevated temperature in order to
produce a formulation that is sufficiently mobile for
satisfactory filling.
 Typical formulation is based on solid excipients e.g.
PEG or Poloxomer that melt below 70°C and in which
the active melts, dissolves or disperses .The
formulation is mobile liquid at the filling temperature
and will be either solution or dispersion of active
substance.

10. DUO CAP TECHNOLOGY
• Duo Cap Technology is a single, oral-dosage unit that
comprises a capsule-in-capsule and offers broad
therapeutic applications.
• The inner and outer capsules may contain the same
active drug providing multiple release profiles from
the dosage unit, for example, an immediate- release
formulation from the outer capsule and a controlled-
release formulation from the inner capsule.
• In addition to modifying the release profiles it is also
possible to target the inner and outer capsule to
different areas of the gastro intestinal tract (small
intestine or colon), with the appropriate coating.
Alternatively, the capsules may contain

11. Capsule in capsule formation
cont…..
different actives for use with combination therapies or
actives that are incompatible in a single capsule. The
inner capsule may contain liquid, semi-solid, powder or
pellet formulations and the outer capsule contains liquid
or semi-solid formulations.

12. Types of fills in Duo Cap
1. Liquid/Semi-solid
2. Liquid/Liquid
3. Liquid/ Beads

13. INNOVATIONS IN CAPSULE SYSTEM:
 To provide modified release:
1) PORT CAPSULE TECHNOLOGY
2) HYDROPHILIC SANDWICH (HS) CAPSULE
3) L-OROS®
4) PULSINCAP
5) CHEWABLE SOFT GELATIN CAPSULE
ENCAPSULATING LIQUID FILL
6) INNERCAP TECHNOLOGY
7) GALACTICLES

14. 1.PORT CAPSULE
TECHNOLOGY
eg.Pseudoephedrine delayed release

16. 2.HYDROPHILIC SANDWHICH(HS)
CAPSULES
 Simple and time delayed probe capsule
 Based on a capsule within a capsule, in which the
inter capsular space was filled with a layer of
hydrophilic polymer (HPMC).
 This effectively created a “ Hydrophilic Sandwich “
between two gelatin capsule
 When the outer capsule dissolved, the sandwich of
HPMC formed a gel barrier layer that provided a time
delay before fluid could enter the inner capsule and
cause drug release .

17. The time delay was controlled by :
Molecular weight of polymer
Inclusion of a soluble filler eg. Lactose

19. 3.L-OROS®: For Controlled Release of
Non - Aqueous Liquid Formulation
A) L-OROS Hard cap
B) L-OROS Soft cap
C) Delayed liquid bolus delivery system
 consists of liquid drug, an osmotic engine or push
layer and a semi permeable membrane coating .
ADVANTAGES:
 Enhanced bioavailability of class II drugs
 Uniform blood levels over specific period of time

20. cont…..
 Reduced first pass effect
 Reduced dose
 Patient compliance
 Made of pharmaceutical acceptable excipient

21.  A) L-OROS HARD CAP:
•The drug layer and the osmotic engine are
encased in hard capsule which is surrounded

22. cont….
by the rate controlling semi permeable
membrane.
• A barrier layer composed of an inert substance
separates the drug layer from osmotic engine.
 A delivery orifice is laser drilled at the
opposite end of the osmotic engine providing
an outlet for the drug

23. •The liquid drug formulation is encased in soft capsule. It is
in turn surrounded by a barrier layer, osmotic engine, and a
semi permeable membrane in order.
B)L-OROS SOFT CAP

24. cont….
• A delivery orifice in drilled through semi-
permeable membrane,osmotic engine and
barrier layer
• When the osmotic engine expands it compresses
the soft capsule and the drug formulation
is pushed out through the delivery orifice.

25. Manufacturing Flow chart :-
Mixing(drug-
layer)
Encapsulation
Inner coating
Osmotic coating

26. Coating
membrane
Drilling
Drying

27. C)Delayed liquid bolus system
 Delivers the pulse of the liquid drug.
 The system consists of the placebo delay layer, a liquid
drug layer, an osmotic engine all encased by a subcoat and
then surrounded by semi-permeable membrane.
 The delivery orifice is drilled on the placebo layer of the
system.
 When the osmotic engine expands, the placebo is released
first delaying the drug release.
 Delay in drug release can be srom 1-10 hours depending
on the permeability of the rate controlling membrane and
the size of the placebo layer.

29. 4)PULSIN CAP:
 Used for pulsatile drug delivery.
 consists of insoluble capsule body and a soluble capsule cap.
1st concept :
 separation of a plug form an insoluble capsule
body.
 It comprised of a water permeable body prepared from a
water-swellable hydrogel cross linked PEG polymer
 A swelling agent mixed with the drug was filled into the
internal cavity of capsule body and a plug was used to seal the
contents into the internal cavity.

30.  Upon oral administration by the patient, cap
dissolves. Water diffuses through capsule body.
Swelling causes plug to move in upward
direction causing drug release.
 Water diffusion into the core through
semi-permeable membrane is controlled by-
Hydrogel composition and Wall thickness of the
capsule.

31. PLUG, CROSS LINKED HYDROGEL
SWELLING
AGENT
DRUG
FORMULATION
PERMEABLE CROSS LINKED
HYDROGEL

32. 2nd concept
 capsule body is made of gelatin coated with
ethyl cellulose.
 In the presence of fluid, the plug swelled at a
controlled rate that was independent of the
nature of pH of the medium.
 As the plug swells it attains frustroconical
shape and it gets slowly pulled out of the
capsule.

33. Pulse time is controlled by:
 The length of the plug and insertion distance of
plug into the capsule.
 Disadvantage :not adopted for large scale
manufacturing because of high cost.

35. 3rd concept
•In this approach in place of hydrogel
plug,simple erodible compressed tablet is
placed.
• This overcomes the need for the precise
dimensional tolerance between capsule
and plug for sliding mechanism of the
plug.

37. 5)CHEWABLE SOFT GELATIN CAPSULE
ENCAPSULATING LIQUID FILL
 Chewable SGC require mixture of gelatin having
different bloom values.
 Most preferable combination ratio - 3:1 to 5:1
 It contains ingredients like,
Low bloom gelatin
Medium bloom gelatin
Plasticizers
Water
Moisture retaining agent
Other

38. 6) INNERCAP TECHNOLOGY
 The combination example consists of a high potency
insoluble active in a lipid emulsion, sustained release
tablet and a cocktail of two crystalline active
materials.
 A combination of release profiles can be incorporated
in the system.
 It Can deliver incompatible and compatible drugs
using different physical phases.
 The combination dosage form consists of a primary
HPMC capsule containing an emulsion, pH coated
tablet, crystalline filled HPMC capsule and a beadlet
filled gelatin capsule.

39. INNERCAP TECHNOLOGY

41. 7)GALACTICLES™
 Oral Lipid Matrix in Liquid-Filled Softgel
Capsules
 A Novel Drug Delivery System for Improved
Oral Bioavailability
 The Galacticles™ Lipid Matrix consists of a
mixture of galactolecithin
 & one or more other lipids, for example, mono-
, di-, and/or tri- glycerides

44. Potential for Improved Drug Absorption
improve oral bioavailability for hydrophilic and lipophilic
drugs with low solubility
• Potential for Reduced Degradation in the
GI Tract
• Tolerability & Taste
The favorable taste of Galacticles™ formulations compared to
corresponding formulations with phospholipids and synthetic
surfactants
• Safety
Preliminary safety studies indicate no toxic effects of oral
administration

45. CONTROLLED RELEASE
SOFTGEL
 Banner’s scientists have developed a controlled release
technology that is able to achieve a large variety of
release patterns.
 The controlled release softgel can be applied to a wide
range of active molecules. Banner’s controlled release
softgel technology uses a lipid matrix in a standard softgel
shell.
 Depending on the physicochemical properties of the active
molecule, an emulsion or a suspension is chosen as a
matrix.

46.  By applying these, or combinations of these,almost
any release profile can be engineered simply by
varying the formulation.
 The result is an oral dosage form offering controlled
release of the active moiety, combined with all the
benefits that the softgel dosage form offers.
 Its release properties, combined with the advantages
of a softgel, make the CR-softgel a preferred form for
those insoluble compounds that require enhanced
absorption as well as a prolonged and controlled
release.

48. • Licaps® two-piece gelatin capsules with liquid
formulations containing pumpkin seed; pumpkin seed
oil or herbal extracts such as saw palmetto or hop
extract.
 The filled capsules are then sealed using Capsule's
LEMS® automated capsule sealing system and the
finished capsules are marketed by GSK as
pharmaceuticals to treat several types of urological
conditions or as nutraceuticals . Licaps® Liquid
Delivery System doesn’t just offer better bioavailability
® Liquid - Filled Capsules®:

49.  It’s also fast-acting and gentle on the stomach. The
capsule protects against degradation and oxidation to
preserve the efficacy of your formulation.
 Liquid capsules are also visually appealing, and
offering a liquid option sets your brand apart from
your competition.
 Licaps® Liquid Delivery System is available in
liquid-filled gelatin or vegetarian HPMC-based
capsules. Every Licaps® capsule is sealed with our
proprietary LEMS sealing process and fused with
nitrogen to protect your supplement against oxidation.

50.  Innovative multi-phase capsule designs are also
available.
 Like all of Capsugel’s capsules, Licaps® can
be colored and printed to reflect your brand.
 Capsugel is meeting growing demand for liquid
filled capsules with Licaps®, a two piece hard
capsule specially designed for secure
containment of liquid and semi-solids.

51. Some of the benefits of using Licaps® capsules include:
Proprietary Liquid Encapsulation Microspray Sealing
(LEMS®) sealing process means no balancing and
outstanding product integrity.
 Available in both gelatin and non animal capsules and a
wide variety of sizes and colors.

52. Opportunity for improved absorption and bioavailability
over the tablets.
Improved time-to-market versus tablet due to less
complex formulation and development processes.

53. NEWER TECHNOLOGIES :
1. ORBEXA® TECHNOLOGY:
 It produces beads that are of controlled size and density
and suitable for formulation as controlled release
multiparticulates - using granulation, spheronization and
extrusion technique.
 The resultant beads can be coated with functional polymer
membrane for additional release rate control and may be
filled into capsules.

54. Advantages of Orbexa
 Aqueous or solvent-based granulation
 High-speed process is well suited for sensitive molecules
like proteins
 Suitable for high drug loading

55. 2. EURAND MINITABS®
TECHNOLOGY:
 Eurand's microencapsulated drugs can be taste-masked
and directly compressed with Advatab to ensure an
optimised drug delivery process.
Microcaps®- microencapsulation of drug
particles via a proprietary coacervation technique for
uniform, precise taste-masking

56. 3. SODAS® Technology
 SODAS® (Spheroidal Oral Drug Absorption System)
is particulate drug delivery system.
 SODAS® Technology is based on the production of
uniform spherical beads of 1-2mm in diameter
containing drug plus excipients and coated with
product specific controlled release polymers.

57. 4. CODAS® TECHNOLOGY:
 Chronotherapeutic Oral Drug Absorption
System(CODASTM Technology) was developed
to achieve this prolonged interval.
 Delay is introduced by the level of release
controlling polymer applied to the drug loaded
beads. The release controlling polymer is a
combination of water soluble and water
insoluble polymers.

58. cont….
 As water from the GIT contacts the polymer coat
beads, the water soluble polymer slowly dissolves and
the drug diffuses through the resulting pores in the
coating.
 The water insoluble polymer continues to act as a
barrier, maintaining the controlled release of the drug.

59. 5. PRODAS® TECHNOLOGY:
 which is unique
in that it
combines the
benefits of
tabletting
technology
within a capsule.
 It can be used to
pre-program the
release rate of a
drug.

60. PRODAS® technology, by incorporating
minitablets with different release rates, can
display the characteristics of a number of
different conventional dosage forms:
 delayed release component for site/regional
release and/or food resistance
 sustained release component for additional
controlled release/profile extension

61. 6. Banner’s VersetrolTM
Technology:
 Drug is incorporated in lipophilic or hydrophilic
matrix and that is than incorporated in soft gelatin
capsule shell.
7. Bijel Capsules: Co-release
Micro- gel

62.  new generic route to gel capsule formulation,
involving particles suspended in fluid-
bicontinuous mixture of two solvents.
 The bijel capsules are made of two fluids and
hence they are both a gel and an emulsion. The
water and oil domains inside the capsules can
be used to deliver chemically different active
ingredients. The capsules can be designed to
release or mix the active ingredients in
response to a specific external stimulus.

63. Jintan Capsule Mira
cell
Soft Capsule Hard capsule
APPEARNCE
MANUFACTU
RING
DROPPING METHOD
FILLER ROTARY DIE PROCESS DIPPING METHOD
SHELL
RATIO
10%~ 30%~ 20~50%
DIAMETER 0.3mm~10mm 5mm~20mm 10mm~21mm
CONTENT
LIPOPHILIC
HYDROPHILIC
POWDER
LIPOPHILIC
POWDER IN SUSPENSION
POWDER
SHELL
MATERIAL
GELATIN
AGAR
NATURAL GELLING
SUBSTANCE
GELATIN
GLYCERIN
GELATIN
GLYCERIN
SHELL
FUNCTION
HEAT RESISTANCE
ACID RESISTANCE
FREEZING RESISTANCE
NO FUNCTION NO FUNCTION
CHARACTERI
STICS
FUNCTIONS CAN BE
ADDED TO THE SHELL.
POSSIBLE TO DESIGN
MULTIPLE LAYER
CAPSULES
SHELL THICKNESS IS
LARGE ENOUGH TO JOINT
TWO PCS OF GELATIN
SHEETS.
USE OF GLYCERIN CAN
CAUSE BLOCKING.
ONLY AVAILABLE FOR
POWDER, NOT
LIQUID AS CONTENT.
NO USE FOR SMALL
CAPSULES.

64. Nifedipin
e
Gel-filled
Capsule
Procardia
(Pratt)
Adalat
(Bayer)
10 and
20
mg/capsul
e
Glycerin,
peppermint
oil, PEG,
soft
gelatin
capsule
Swallow
whole,
bite and
swallow,
or bite
and hold
sublingua
ll
10 Approx 2
hr
Drugs and Dosage Forms Used for Oral Transmucosal
system
Drug Brand Name Availability Formulation/ Dose/ Onset of Duration of
(Manufacturer) Excipients Directions Action (min) Action

65. EXAMPLES OF MARKETED PRODUCTS FORMULATIONS
Drug Name Compound Dosage form Company Indication
Neoral® Cyclosporine Soft gelatin Capsule Novartis Immune
Suppressant
Norvir® Ritonavir Soft gelatin capsule Abbott
Laboratories
HIV antiviral
Fortovase® Saquinavir Soft gelatin capsule Hoffmann-La
Roche
HIV antiviral
Agenerase® Amprenavir Soft gelatin capsule Glaxo
Smithkline
HIV antiviral
Convulex® Valproic acid Hard gelatin Capsule Ligand Antiepileptic
Lipirex® Fenofibrate Soft gelatin capsule Genus Antihyperlipoprotei
nemic
Sandimmune® Cyclosporine Soft gelatin capsule Pharmacia Immuno
Suppressant

66. Current research
 Invitro – invivo evaluation of a novel capsule for colon
specific drug delivery (JPS Vol. 98 No. 08 Aug. 2009
Page no. 2626)
 A novel approach to prepare insulin-loaded poly
(lactic –co-glycolic acid microcapsule) (JPS Vol. 98
no.05 May 2009 page no.1712)
 Effect of lipophilic compounds on the compatibility of
lipid based formulation with HG capsules. (JPS Vol. 99
no.01 Jan 2010 )
 The Bilayer floating capsule : A stomach – directed
drug delivery system for misoprostol. (Pharmaceutical
research Vol. 9 No.3 1992)

67.  Self micro emulsifying drug delivery system
(IJPS Vol-1, Issue-2, 2010) Self micro
emulsifying drug delivery systems are isotropic
mixtures of oil, surfactant, co-surfactant and drug
with a unique ability to form fine oil in water
microemulsion upon mild agitation following
dilution with aqueous phase

68.  Pulsatile delivery systems: An approach for
chronotherapeutic diseases (Year : 2010 | Volume :
1 | Issue : 1 | Page : 55-61)
Marketed technologies such as PULSYS™, CODAS® ,
TIMERx® , and DIFFUCAPS® follow one of the above
mechanisms to render a sigmoidal drug release profile.
 Novel iron- polysaccharide multilayered microcapsule for
controlled insulin release.
(C.A. vol. 150 no. 22, 2009 page no. 1469)
 cholesterol mediated anchoring of enz. Loaded liposomes
within disulfide stabilized polymer carrier capsule. (C.A. vol.
150 no. 21 , 2009 page no. 1479)
achieved by non covalently sandwiched the liposomes b/w
a tailor made cholesterol modified poly(-lysine) precursor
layer & a poly ( methacrylic acid) –co- (cholesteryl
methacrylate) capping layer.

69.  COATING METHOD FOR SOFT GELATIN CAPSULES
WITH IMPROVED STABILITY .
(Ref: Chemical Abstracts, Vol 151, Number 13, September
28,2009 , Page2156, 297838p)
Adding 10-90% ethanol into mixture of HPMC 20-
150parts, Tween80 8.5-25vol parts, Titanium white powder
7.5-25wt parts, Talc powder 7.5-25wt parts, 2%chocolate
brown solution, 7.5-25wt parts, castor oil 15-40 vol parts to
obtain coating solution, regulating flow rate of coating
material at 25-40°C under relative moisture of 20-60%.
 Hydrocapsule : A new method for aqueous drug
delivery.
(C.A. vol. 149 no. 2 2008 page no. 1479)
 development of boron nanocapsule for neutron capture
therapy.
(C.A. vol. 150 no. 22, 2009 page no. 1455)

70.  Cross-linked DNA capsules templated on porous
calcium carbonate microparticles: (Colloids and
Surfaces A: Physicochemical and Engineering
Aspects, Volume 356, Issues 1-3, 5 March 2010,
Pages 126-133)
first, DNA was adsorbed onto calcium
carbonate microparticles, and then the adsorbed
DNA was covalently cross-linked with each other
by using ethylene glycol diglycidyl ether.
This method has the potential to be used for the
preparation of various single-component polymer
capsules.
 Capsule endoscopy

71.  Novel drug delivery system N.K.Jain
 www.authorstream.com-presentation
 Pharmaquest.weebly.com
 Journal of Advanced Pharmacy Education & Research,
Issue 2 ,Vol 4 ,Apr-Jun 2014 ,pg no.169
 www.ijrrpas.com -Patented techno. In Soft gelatin
capsule
 Review on –Duo cap ,Capsule in capsule techno.
Kanabar vishvesh,doshi sumit ,Patel vipul
Int.Res.J.Pharm.2015;6(2)86-89
REFERENCES