Review Article

Recent trends in Hard Gelatin capsule delivery System
Harsha Kathpalia*, Komal
Sharma, Gaurav Doshi
Vivekanand Education Society’s
College of Pharmacy, Chembur (E),
Mumbai 400074, Maharashtra,
India.
J. Adv. Pharm. Edu. & Res.

ABSTRACT
Modifications in conventional capsule delivery system are needed to overcome
the disadvantages associated with them and to provide products of higher
selectivity for medical treatment. This review includes newer trends related tocapsule shell, capsule fill material, capsule sealing technique, and different
capsule systems to achieve modified drug release, encapsulation of various kindof materials and for modified application like mapping of the drug for clinicalevaluation
Keywords: Vegetarian capsules, capsule fill material, capsule sealing technique,modified capsule systems, drug mapping capsule systems

INTRODUCTION

soft food immediately before ingestion. In this case,

The word ‘Capsule’ is derived from the Latin word

capsules are used as a vehicle to deliver premeasured‘Capsula’ which mean small box or container. The

medicinal powder. Capsule dosage forms occupy moregelatin capsule was invented early in the 19th century

than 10% of the total dosage forms on the market. [2]as a result of the need to mask the obnoxious taste of

Capsules account for about 20% of all prescriptions

many medicinal substances such as oleoresin of

dispensed. [3]copaiba, which is extremely nauseating when taken by

Advantages of capsule over tablets [4]mouth. The first patent was granted on 25th March Fewer developmental problems in capsules,

1834 for soft gelatin capsule to Mr. François Achillehence allow quicker submission of a new drug

Barnabe Mothes, a French pharmacy student. Further

for clinical trials.

development was done in soft gelatin capsule fill It is easier to vary the dose.

formulation and soft shell manufacturing. Hard gelatin Less adjuncts are necessary than for tablets

capsule was invented by Jules Cesar Lehuby, a Capsule manufacturing requires fewer steps thanParisian pharmacist who was granted patent on 20 th
October 1846. Earlier, the soft gelatin capsule was
known as one piece capsule and hard gelatin as hardtablet manufacturing.
 Easy to swallow hence improves patientcompliance

two piece capsule. [1] A capsule is a shell or container
prepared from gelatin containing one or more
medicinal and/or inert substances. Capsules areintended to be swallowed whole by the patient. In
instances where patients (especially children) areunable to swallow capsules, the contents of thecapsule can be removed and added (e.g., sprinkled) on Simple separation of two incompatible products(combination)
 More possibilities for product identification(printing) Drug with high dose and low compressibility canbe incorporated in capsules
Types of capsule

Address for correspondence

1. Soft gelatin capsule (SGC)

Mrs. Harsha Kathpalia
Assistant Professor,
Vivekanand Education Society’s College of Pharmacy,
Chembur (E), Mumbai 400074,
Maharashtra, India.
Email:hkathpalia2007@rediffmail.com

2. Hard gelatin capsule (HGC)

Access this article online
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Journal of Advanced Pharmacy Education & Research

1. Soft gelatin capsule (SGC)
Soft capsules are for solids, liquids and semi-solids.
They may be spherical, ovoid or cylindrical withhemispherical ends. In addition to the ingredients of
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hard capsules, they contain plasticizer (e.g. sorbitol,

A. Port Capsule

propylene glycol, glycerin), which provides the

B. Hydrophilic sandwich (HS) Capsuleflexibility. They are usually filled with liquids or

C. Innercap Technology

suspensions. Dry solids are possible, including

5. Mapping the drug for clinical evaluation

compressed tablets (“Geltabs”). [5-6]A. Enterion capsules

2. Hard gelatin capsule (HGC)

B. Control of drug release from capsule using high

They consist of a cylindrical body and cap, both withfrequency energy transmission system

hemispherical end and are usually made from gelatin

C. Magnetically controlled capsuleand water with added preservative. Although quite

D. IntelliCap system

hard, they soften readily and dissolve after swallowing
with water. The problems associated with SGC are

1. Capsule shell

overcome by HGC.[5-6]

Modifications in capsule shell help in improving

Table 1 shows comparison of advantages andphysical strength and also enhance compatibility of filldisadvantages of HGC and SGC

material with capsule shell. It aids in maintaining

Modifications in hard gelatin capsule systems

stability of fill material by limiting photo, oxidative

Need [9]and microbial degradation. It helps in regulating Overcome the disadvantages associated withmoisturelevelstherebypreventing

excessive

stickiness or brittleness of shell. [9]conventional capsules Achieve modified drug release

A. Vegetarian capsule shells

 Encapsulation of various kinds of material

There has been a great interest of the capsule industry

 Modified applications

in gelatin substitutes to be used for those people who

Recent trends related toare vegetarians, diabetics and patients with restricted

1. Capsule shelldiets. For this the capsules need to be organic, vegan,

A. Vegetarian capsule shellherbal, all natural, non-allergenic, soy or gluten free.

a. Hydroxy propyl methyl cellulose (HPMC)[10]

b. Pullulan

Table 2 shows comparison between gelatin capsulec. Starchand vegetarian capsule. [5,11-12]

d. Polyvinyl alcohol (PVA)a. Hydroxy propyl methyl cellulose (HPMC)
capsulesB. Capsule shell from animal origin
a. Gelatin/PEG

HPMC has been approved by the Europe as anb. Capsule from fish gelatin

encapsulation material for organic products sincec. Human gelatin

December 2007 (ECn780/2006)
Features of HPMC capsule [11-13]

2. Capsule fill materials
A. Pellets

 Chemically and thermally stable

B. Liquid Moisture content 4-6% less than gelatin capsule(13-16%)

C. Semisolids

 Less brittle even in low humidity (≤1% moisture

D. Capsulecontent)

3. Capsule sealing technique Fast dissolution (No change in dissolution profile

A. Banding technology
B.

Liquidencapsulated

technology (LEMST)

Microspraysealingunder stress conditions) and soluble in water atroom temperature.

4. Capsule systems
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 Lower water vapor permeability than gelatinhigher manufacturing losses, a poorer quality andhigher costs. [17]capsule (Gelatin>PEG-Gelatin>HPMC)
Table 3 shows manufacturers of HPMC capsule shellc. Starch capsule shell [18, 19]

Disadvantage of HPMC capsules

 Made from potato starchHigh manufacturing cost. HPMC shells are less

 Manufactured by the injection molding techniqueresistant to indentation and have lower tensile

developed by Capsugel (Capill®)

strength than gelatin shells, which results in Suitable for enteric coatingprocessing problem.

 Different

Nair et al. examined the process ability of HPMC
capsules versus HGC on the capsule automatic fillingmachine. A significant number of defects weresize

capsulesaremanufactured(number 0, 1, 2, 3, 4) by changing the mold.
 Officially recognized in USP 23 and NF 1
Enteric starch capsules [20]observed with size #00 HPMC capsule, including During coating with aqueous spray formulations

dimpled bodies, spilt caps, improperly closed caps andthe gelatin shell softens and becomes sticky due

large number of capsules that did not open for filling.

to solubilization.

[14]

 The gelatin shell becomes brittle due to waterb. Pullulan capsules

evaporation and drying the brittleness causes the

It is listed as a new authorized Food Additive “E 1204

capsules to lose their mechanical stability and

Pullulan” via Environment European Commission

they break under slight pressure, especially(EEC) Directive 2006/52/EC.

when coating begins.

Features of Pullulan capsule [15, 16]

 Insufficient adhesion of the film with splintering Water soluble polysaccharide which is derived

and peeling of the coat (orange peel effect) leads

by bacterial fermentation from corn starch They are odorless, tasteless, and completely

to increased cracking on handling of the capsule.
 Due to non-transparent film on capsule desired

biodegradable

glossy and attractive appearance is lost.

 Dried capsules are comparatively weak in
physical strength.

Coating of starch capsules appear to be lessproblematic because of the smooth seal, coupled with

 Relatively low water content (10-15%), thangelatin, low toxicity

their higher bulk density, which provide for a more
uniform coating bed. Starch capsules in conjunction

 High stability of various properties over storage

with a variety of coatings, such as a pH-sensitive

such as mechanical and dissolution properties.

material, a redox sensitive material can be used for Because pullulan offers the best oxygen barrierdelivery in the small intestine. These capsules can beof all the plant-based products, these capsules

coated with a material broken down by specific

can help mask pungent odors from ingredients

enzymes or bacteria present in the colon, for site-andspecific delivery to the colon.The coating employed isenhancetheprotectionofsensitive

ingredients.

based on a mixture of Eudragit L and S, chosen to

Table 4 shows manufacturers of pullulan capsule [15]provide a coating that starts dissolving when the

Disadvantage of pullulan capsule shell

capsule enters the small intestine after leaving the

Pullulan is more sensitive than other materials (e.g.

stomach.The thickness of the coating can be designed

gelatin or HPMC) to low moisture conditions. Thissosensitivity causes increase in shell brittleness at low

predetermined region in the intestine, such as thewater content. Unsatisfactory brittleness means

terminal ileum, the ascending-, the transverse-, or

that

the

capsuledisintegrates

withineven the descending colon. [9]Journal of Advanced Pharmacy Education & Research

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An enteric-coated starch capsule system TARGIT®

 Some products like Algae extract, Magnesium

technology is used for targeting specific sites within

peptidea, and Betacoten are available in fish

the colonic region. The TARGIT delivery systemgelatin capsule.

therefore works by both a pH and time-dependentc. Human gelatinmechanism, which is considered to be safer thanLong term availability of ‘human’ gelatin, produced

systems depending only on a pH change in thefrom recombinant human collagen, may provide aenvironment. [21]suitable low-cost gelatin for shell manufacture.
FibroGen,

Inc.

(San

Francisco)hasdeveloped

d. Polyvinyl alcohol (PVA) Capsuletransgenic plant expression technology that can

Features of PVA capsule [10, 21-22]

produce gelatin precursor collagen. FibroGen and Water soluble

Prodigene have announced collaborative work on high Less hygroscopic than gelatin

quality, high volume and low cost production of such Oxygen permeability through PVA copolymer isrecombinant human gelatin in maize. [25]significantly less than through gelatin and HPMC

2. Capsule fill materials

capsulePreviously active ingredients were formulated into

B. Capsule shell from animal origin other thancapsule

in

the

form

of

powderor granules

conventional capsulefor immediate or modified release. Apart from thea. Gelatin/PEG capsules

above,

Features of Gelatin/PEG [3, 9]

etc can be filled into capsules because of innovation inpellets, minitablets, liquids, Less brittle

filling machines.

 Good for hygroscopic and moisture-sensitive

A. Pellets
aresingledosagesemisolids,

ingredients like tocopherol niconitate, nifedipine

Multiple-units

forms

that

and captopril as combination of gelatin and PEG

disintegrate into several parts after ingestion. Hard

reduces brittleness of standard gelatin capsulegelatin capsules are particularly suitable for theirwhen exposed to low moisture.

development and manufacture. Multiple-units might Odorless, tasteless, three-year shelf life

consist of a single pellet, or homogeneous granules, or Available in sizes from 000 to 4

a combination of several pellets and granules with

 The addition of PEG improves the mechanicalvarioussubstancesanddifferent

releasecharacteristics. In this way, incompatibilities andstrength of the capsule.
 At moisture contents between 8% - 12%,

interaction between the different drug substances ingelatin/PEG capsules have equivalent mechanicalcombination products can be prevented. [26] Table 5

strength to standard gelatin capsules withshows some examples of capsule which are filled withmoisture between 13% - 16%.

pellets. [27-30]
B. Liquids

b. Capsule from fish gelatin

Features of capsule shell from fish gelatinestablished in the early 1980s as an alternative to soft

[Ocean Caps] [23, 24]
 Made from high quality, farmed fish gelatin, agelatin capsules and offered a number of specificadvantages

renewable resource.

such

as

lower

moistureandgastransmission, use of high melting point excipients,

 Excellent machinability.

plasticizer - and preservative-free, lower moisture Transparent capsule.
 Great versatility: the dosage form is adapted tomany liquid, pasty and powdered formulations.
168

Liquid-fill hard gelatin capsule technology wascontent, ease of coating and choice of capsulecomposition(gelatin

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methylcellulose, HPMC). In many instances a liquid-

viscosity in the filled capsule. The viscosity can be

filled hard capsule may be a more appropriate

reduced by increasing the temperature of filling

formulation for numerous reasons including [31-32]

process so that the formulation is molten at the filling Better bioavailability for Active Pharmaceuticaltemperature. Filling process temperature is usuallylimited up to maximum 70°C in order to avoid thermal

Ingredient (API) Protects hygroscopic and oxidation sensitive

damage to the capsule shell. It needs liquid excipientscompounds including proteins and peptides

like triglyceride and gel forming agent like silicone

 Removes issues caused by API variability

dioxide. [31](Particle size, shape, crystal habit, density,

2. Thermosoftened system

polymorphic form or moisture) and ideal for

Thermosoftened formulations solidify in the hardcytotoxic APIs

gelatin capsule to form a non-porous crystalline plug Eliminates compatibility issues between shellor solid dispersion. These are prepared at elevatedtemperature in order to produce a formulation that is

and APIsufficiently mobile for satisfactory filling. Typical Provides a scalable formulation
Rheological consideration

formulation is based on solid excipients e.g. PEG or

Newtonian liquids like liquid active or solution of solid

Poloxomer that melt below 70°C and in which theactive in liquid excipients are filled in hard gelatin

active melts, dissolves or disperses .The formulation iscapsule. Newtonian liquid with viscosity in the range

mobile liquid at the filling temperature and will be

0.1-25Pa can be filled with accuracy and precision, so

either solution or dispersion of active substance. [31]the coefficient of variation (CV) of fill at value <1% is

D. Capsuleoften achieved. Table 6 shows product formulated as

Duo Cap Technology is a single, oral-dosage unit thatliquid filled capsules. [32]comprises a capsule-in-capsule and offers broad

C. Semisolids

therapeutic applications. The inner and outer capsules

Need [9]may contain the same active drug providing multiple

 Enhancement of bioavailability

release profiles from the dosage unit, for example, an Low melting point

immediate- release formulation from the outer Critical stability

capsule and a controlled-release formulation from the Sustained release

inner capsule. In addition to modifying the release

Semisolids are non- Newtonian fluids. To fill these
fluidsinhardgelatincapsule,rheologicalconsideration is important. When the drug is not
soluble in aqueous solvent or solvent is incompatible
with the shell then the active is formulated as

profiles it is also possible to target the inner and outercapsule to different areas of the gastro intestinal tract(small intestine or colon), with the appropriate
coating. Alternatively, the capsules may containdifferent actives for use with combination therapies ordispersion. It has to be filled in a semisolid form. Nonactives that are incompatible in a single capsule. The

Newtonian fluids are

inner capsule may contain liquid, semi-solid, powder

1. Thixotropic gelor pellet formulations and the outer capsule contains

2. Thermosoftened system

liquid or semi-solid formulations. [33]Table 7 shows formulation of semi solid in capsule[33]
1. Thixotropic gel
It undergoes shear thinning during filling followed by

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

gel restructuring with an increase in its apparent
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Micro-FloraGuard™ is presented in a unique DuoCap

During this process the capsules were subjected to- capsule in a capsule providing plant oils in the outerconsiderable stress. In contrast to this, in thecapsule and probiotic bacteria with garlic in the innerredesigned process every capsule is individuallycapsule, ingredients which would not normally be able

sprayed with a micro amount of sealing fluid at the

to be taken together. It helps to promote the health ofbody and cap junction. Drying takes place by gently

the gastrointestinal system. The design enhances

tumbling of capsules in a rotating drum. Control of the

product stability by protecting the probiotic inner

filled and sealed capsules is carried out as follows:

capsule in an HPMC capsule. This creates an effective

 Inspection on trays after 24 hours.

barrier to moisture, which helps the probiotic remain

 Inspection after depression test at - 0.8 bar for 20

inactive until it is consumed. [34]minutes.

3. Capsule sealing techniques

 Inspection after 18 hours at 45°C after cooling to

Need [5]room temperature.

 Tamper resistance/tamper evidence Prevents

inadvertent

separation

By incorporation of a dye tracer into the sealing ﬂuid
onhandling/shippingand observation of the liquid in the overlapping space
it could be verified that the sealing liquid does not Makes liquid/semi-solid filling of hard gelatin
capsules possible

pass beyond the interlocking rings of capsule. The
machine is freestanding and in practice is connected Sealed capsules are excellent barriers to oxygen.

to the output of a capsule ﬁlling machine by means of

A. Banding technology

a conveyor. [31]Processing [35]S. Robin et.al studied that all capsules filled with

 The capsules are first rectified and then passed

various products and sealed with LEMST are robust

once or twice over a wheel that revolves in aover time when stored in room conditions: 50%RH ±temperature controlled gelatin bath.

15% and 22°C± 2°C. Furthermore, it was confirmed A quantity of gelatin is picked up by the edges ofthat transparent capsules are even more robust thanwheel and applied to the junction of the cap andopaque capsule. [37]body.

4. Modified capsule systems

 The banded capsule are transferred to

A. Port system

continuous loop conveyor belt in the drying unit

Port technologies offer significant flexibility in The bands are dried using filtered air at ambientobtaining unique and desirable release profile tomaximize pharmacological and therapeutic effect.The

room condition.
Fig.1 shows the banding technology

dosage form consists of a hard gelatin capsule coatedExamples of products that use banding technology forwith the semi permeable, rate controlling polymer.

sealing

Inside coated capsule is the osmotic energy source,

capsuleare

Benadryl®,

Metamucil® and

Zegarid.

which normally contains the therapeutic agents to beB.

delivered in the body. The capsule is sealed with the

Liquid Encapsulated Microspray Sealing

Technology (LEMST)

water insoluble lipid separators plug and immediate

This capsule sealing process uses the principle ofrelease dosage can be incorporated above the plug tolowering of the melting point of gelatin by thecomplete the dosing options. Examples of port

application of moisture to the area between thetechnologies are delayed release pseudoephedrine

capsule body and cap. The first machine developed toandseal capsules, involved dipping the capsules into a

propanolamine. [37-39]

multiple

programreleaseofphenylbath of liquid and drying in a fluidized bed chamber.
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B. Hydrophilic sandwich (HS) capsules

melatonin found in the beadlets at a set dose over a

These are simple and time delayed probe capsules.

fixed period of time.

Based on a capsule within a capsule, in which inter5. Mapping the drug for clinical evaluation

capsular space is filled with a layer of hydrophilic

Mapping out the human absorption profile, it ispolymer (HPMC). This effectively creates Hydrophilic

possible to fast-track drug development by selection

sandwich between two gelatin capsules. When theof optimal enabling technology for the molecule,outer capsule dissolves the sandwich of HPMC forms adetermine whether a change of delivery route isgel barrier layer that provides a time delay before

required, or decide to terminate drug development.

fluid can enter the inner capsule and cause drug

Human absorption studies are increasingly being usedrelease. [40] The time delay is controlled byin early drug development to rationalize possible

 Molecular weight of polymer

strategies for oral drug delivery. This approach has

 Inclusion of a soluble filler e.g. Lactose

facilitated an integration of drug delivery into theSoutar et.al employed a gastro resistant version of the

discovery/development interface and has put thelarger HS capsule in cohort of 13 volunteers to deliver

selection of appropriate enabling technologies at the

500mg Paracetamol to the ileocecal junction /heart of drug development.

proximal colon. Absorbed drug was monitored using

A. Enterion Capsulesalivary analysis and a mean Tmax value of 79 hour

The Enterion capsule has recently been developed for(s.d. ±0.96) was observed. [41]targeted delivery of a wide range of different drug

C. Inner cap technology

formulations into any region of the gut.

One of the recent trends in encapsulation isParts of capsule: Dimension: 32-mm long, roundcontrolled-release and multi-release products, which

ended capsule with opening of 9 mm in diameterentails

which is then sealed by inserting a push-on cap fitted

putting

multiplecomponents

in

one

with a silicone O-ring

convenient package.
 A combination of release profiles can be

Drug reservoir: Volume capacity of approximately 1
mL the capsule can be loaded with either a liquidincorporated in the system.
 Can deliver incompatible and compatible drugs

formulation (e.g. solution, suspension) or a particulate
formulation (e.g. powder, pellets, minitablets, etc)

using different physical phases.
The combination dosage form consists of a primaryWorking of capsule:

HPMC capsule containing an emulsion, pH coatedWhen the capsule reaches the target location in thetablet, crystalline active material filled in HPMC

gastrointestinal tract, the contents are actively ejectedcapsule and a bead filled gelatin capsule.

by the external application of an oscillating magnetic

Lipo-6X is the most advanced fat burner using

field The power induced in the coil by the magnetic

Innercap multi-phase technology. This unique multi-

field (few tenths of a watt) is fed to a tiny heaterphase technology combines rapid liquid capsule

resistor located within a separate sealed electronics

deliverycompartment inside the capsule. The heater resistor iswithcontrolled-releaseinsidecapsuletechnology. [42]in direct contact with the restraining filament, causing

AquaCap developed “time-release beadlets suspended

it to soften and break with the increase inin a liquid active ingredient that allow for a multi-

temperature. This in turn, releases the spring andphase or delayed release formula,” which can be used

drives the piston which is held back against ato enhance the delivery of nutrients. Melatonin is ancompressed spring by a high-tensile strength polymer

example. “In the initial phase, melatonin in the liquidfilament. The resulting increase in pressure within thephase quickly releases, followed by the release of the

drug reservoir forces off the O-ring sealed cap andJournal of Advanced Pharmacy Education & Research

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rapidly ejects the drug or drug formulation into thesense the force between it and the capsule and vary

surrounding GI fluids. The piston motion is stopped

that force. By varying the external magnetic force thenear the end of the capsule, which maintains a seal

capsule can be held at a specific location. The

and prevents contact of the internal electronicmagnetic force is precisely controlled to avoid

components with the GI fluids. Detection of this signal

damaging surrounding tissue. The capsule’s retention

externally confirms that the capsule has opened

works by creating an inter-magnetic force between

successfully A radioactive marker is placed inside athe magnetic gelatin capsule and an external magnet.

separate sealed tracer port to allow real-time

Magnetic capsule in the body is placed at right placevisualization of the capsule location using the imaging

by the magnet outside which create a magnetic

technique of gamma scintigraphy. [43]attraction and forces to locate the magnetic capsule.

Application[45]

The Enterion capsule offers the opportunity to obtain

Application [45]data on the intestinal absorption of drugs in humans

 This technology is applicable for GI diseases likeusing a range of complex formulations both easily andGI cancers, Crohn’s disease and acid reflux. it canefficiently. By delivering the drug in different physicaleven be used in case of diabetes.

forms into a specific region of the intestine, the Targeted release by the use of magnet helps therespective contribution of intestinal permeability

drug’sand/or in vivo dissolution to bioavailability is easily

damaging intestinal tissues.

assessed. [43]uptakeandbioavailability

without Magnetic localization of chemotherapeutics at

B. Control of drug release from capsule using highthe site of GI tumors, which are simultaneously

frequency energy transmission system

identifiable

New drug delivery systems have been developed,

intravenousadministration ofwhich are controlled by a computer and a highcontrast, would enable localized dosing while

frequency energy transmission system. The capsules

minimizing side effects associated with systemic

consisted of a drug reservoir, a high frequency

administration.

receiver, a gas generating section and a piston to

D. IntelliCap systempump a drug solution or drug suspension out of the

The IntelliCap system is a unique R&D tool for the

reservoir. Mechanical energy was generated inside thetargeted

capsule through electrolysis, if a 27 MHz hightract.TheIntelliCap incorporates a microprocessor,

frequency field was in resonance with the receiverbattery, pH sensor, temperature sensor, RF wirelessinside the capsule. Two different miniaturizedtransceiver,

oscillatory circuits were constructed, which act as theConstruction of the capsule in two main subunits: thereceivers in the capsules.Tramadol was used inelectronics body and the drug reservoir. With thisrelease experiments as a model drug. Delayed andmodular design, the drug comes into contact only withpulsed release profiles were obtained. A computer-the reservoir, which is made from inert polymer

controlled system was constructed, in which thematerials. To enable the capsule to release drug with

programmed release profiles are compared with theflexible profiles over time, the drug payload is in theactual release of the drug. [44]form of a liquid (solution, suspension, or gel).The

C. Magnetically controlled capsuleIntelliCap capsule communicates via a wireless

The two main components of the system aretransceiver to an external control unit worn by theconventional looking gelatin capsules that contain atest subject. IntelliCap technology features real-timetiny magnet and an external magnet that can precisely

wireless data recording, plus wireless remote control

172

deliveryfluid

Journal of Advanced Pharmacy Education & Researchon X-ray following

of

drugs

pump,

and

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radio

within

drug

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Mrs. Harsha Kathpalia et al.: Recent trends in Hard Gelatin capsule delivery Systemof dose delivery, giving researchers the ability to It can be used to quickly design and complete amonitor the capsule's progress through the GI tract

study in either a preclinical (animal model) or

and direct the delivery profile. The capsule measuresclinical setting.

pH and temperature nominally every 10 seconds and It allows the release profile to be explored,

reports the data immediately for display on a control

altered, and adapted quickly to determine up-

station computer. [46]frontApplication [46]committing resources for solid dosage form

 It provides a fast, cost-effective, and convenient

optimalreleaseprofile(i.e.,

beforedevelopment).

means for the controlled release of drugs to
specific sites in the GI tract.
Table 1: Comparison of advantages and disadvantages of HGC and SGC

Advantages

Disadvantages

Soft gelatin capsule (SGC) High Accuracy/precision and hermeticallysealed Reduced dustiness in manufacturing process Reduced gastric irritancy
 Costly to produce product manufacturer is contracted out to alimited number of speciality houses
 Intimate contact between the shell and contents
hence stability is a concern
 Mixed fills not adaptable

Hard gelatin capsule (HGC)
 Rapid drug release Unique mixed fills possible
 Good barriers to atmospheric oxygen Not suitable for bulky materials andstrongly
hygroscopic drugs
 Maintenance of proper shell moisture content
essential, therefore storage at 45-65% RH required Cross-linking can affect hard gelatin capsules

Table 2: Comparison between gelatin capsule and vegetarian capsuleGelatin capsule
Bovine skin, cow and pig
For non vegetarian population
Moisture content (13-15%)
Cross linking of gelatin with aldehyde
Allergy due to cow and bovine productNot for kidney and liver disease patientNot for moisture sensitive and hygroscopic ingredient
Preservative needed
BSE (mad cow disease) andTSE (Transmissible spongiform encephalopathy) to humans

Vegetarian capsule
Plant source like pine tree bark gum
For vegetarian population
Low moisture content (2-7%)
No cross linking
No allergy in patient
For kidney and liver disease patient
Ideal for moisture sensitive and hygroscopic ingredient
No need of preservative
Do not contain GMO (Genetically Modified Organisms)

Table 3: HPMC capsule shell manufacturers
Capsule shell brand name

Manufacturer

Quali –V
V cap
Embo Caps-Vg
VegiCaps
Natural Plant Capsule

Shionogi Qualicaps
Capsugel (A division of Pfizer)
Suheunge Capsule Co.Ltd.
R.P. Scherer Technologies
Zhejiang LinFeng Capsules Co. Ltd.

Table 4: Manufacturers of Pullulan capsule shell
Brand name

Manufacturer

NP CapsCapsugel Health Care Ltd.

Daula

Pharma (Nanjing) Co.Ltd.

Guangsheng

Shanxi Gaungsheng Medicinal Capsule Co.Ltd

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Table 5: Examples of pellets filled in capsule shell
Drug

Types of pellet capsulated

Pyridylmethylsulfinyl-benzimidazoles

Rapid release pellet

Duloxetine hydrochloride

Sustained release pellets

Nifedipine

Controlled release pellets

EsomeprazoleEnteric coated controlled release pellets

Table 6: Product formulated as liquid filled capsules
Active Drug

Brand name

Manufacturer

Danthron

Co-Danthroner

NAPP Pharmaceutical,U.K.

Captopril

Captopril- R

Daiichi Sankyo India PharmaPvt.Ltd.

Isotretinoin

Claravis

Teva pharmaceutical Industries Ltd.

Mebevarine

Mebevarine

Mylan Laboratories Limited,India

Table 7: Formulation of semi solid in capsule
Drug
Amprenavir
Cyclosporine
Saquinavir
Ritonavir

Trade name
Agenerase

Formulation compostiond- α -Tocopherylpolyethylene glycol 1000 succinate , PEG-400, propylene glycol

Fortovasae

Corn oil, mono-diglyceride, cremophore RH40 , Ethanol,
α -tocopherol, propylene glycol
Medium chain mono-diglyceride, Povidone , α-tocopherol

KaletraOleic acid, propylene glycol, cremophor EL

NeoralFigure 1: Banding technology
CONCLUSION

patient compliance, product recognition and productIn recent years, the interest in using hard gelatindifferentiation. The demand for plant-based capsules

capsules in developing and manufacturing medicines

will grow as customers look for performance, quality

has increased considerably. This is most probably due

and lifestyle fit. The unique features of non-animal

to rapid advances in hard gelatin capsule dosage form.

capsules offer distinct advantages in manufacturing

The choice available in terms of capsule type, theease, marketing, global certification, dissolution

range of sizes, the capsule's attractive appearance andprofiles, delivery of specific ingredients and more. For

printing directly onto the capsule, ensure better

multiple-units, hard gelatin capsules are the ideal

174

Journal of Advanced Pharmacy Education & Research

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Vol 4

Issue 2

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formulation in hard gelatin capsules offer new

5:185-188.

opportunities

forﬁllingliquidandsemi-solid

4.

Costs: Tablets versus Capsules. Pharmaceuticalformulations in them, as a rapid and easy sealing
technology is now available and the capital outlay isreasonable. Formulation in liquid dosage form

Technology Europe 1998; 5:17-26.
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Augsburger L.L. Modern Pharmaceutics. In: Banker
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Loyed

V.A.,

Nicholas

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HowardC.A.

release characteristics can be developed using semi-

Pharmaceutical Dosage Forms and Drug Delivery

solid formulation. The combination of liquid-filled

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7.

Churchill Livingstone. Elsevier Philadelphia; 515-

Encap’s ENCODE colonic coating technology) where
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powder filled capsules or tablets could be a major

538.
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the

pharmaceuticalindustry.

With

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10.

Doshi R., Patel P., Patel M., Patel K.R., Patel N.M. A

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release development and for compounds in which

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Solid

http://kinam.com/lectures/363/3.capsules%20text.

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Aulton E.M. A Hand Book of Aulton’s Pharmaceutics.

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How to cite this article: Harsha Kathpalia*, Komal
Sharma, Gaurav Doshi; Recent trends in Hard Gelatin
capsule delivery System; J. Adv. Pharm. Edu. & Res.
2014: 4(2): 165-177.
Source of Support: Nil, Conflict of Interest: Nil

Drug Delivery & Development. Drug development
and delivery. 2013;13 Suppl 3:24.

Journal of Advanced Pharmacy Education & Research

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Issue 2177