About Soft Gelatin Capsules:
|1] What is a softgel?
A softgel (a.k.a., a soft gelatin capsule) is
a solid capsule (outer shell) surrounding a liquid or semi-solid center
(inner fill). An active
ingredient can be incorporated into the outer shell, the inner
fill, or both.
|2) Advantages of
|Ease of Use
||Easy to swallow, no taste, unit dose delivery,
||Wide variety of colors, shapes, and sizes.
Accommodates a wide variety of compounds filled as a semi-solid,
liquid, gel or paste.
Immediate or delayed drug delivery.
Can be used to improve
bioavailability by delivering drug in
solution or other absorption enhancing media.
Disadvantages of softgels:
Requires special manufacturing
Stability concerns with highly
water soluble compounds, and compounds susceptible to hydrolysis
choices of excipients/carriers compatible with the gelatin
The outer shell is composed of a gelatin or potato
Gelatin matrix consists of gelatin, plasticizer,
solvent and optional ingredients such as flavors and colorants.
Gelatin - bovine, porcine, or piscine
(fish) origin. Comes in a variety of bloom strengths, the higher
the bloom strength, the more resilient the gel. Most oil based
fills are encapsulated using a bloom strength of 150. When
polyethylene (PEG) based fills are used, a higher bloom strength
is generally used.
limitations of bovine (i.e. bovine-related diseases) and porcine
(i.e. not kosher) gelatin may be overcome by piscine (fish)
Glycerin and Sorbitol
Special are the two most common plasticizers. Glycerin is
generally used with oil based fills. Sorbitol Special is used
with PEG based fills. Sorbitol is not soluble in PEG and
therefore will not leach out of the shell into the PEG based
fill like Glycerin would. Sorbitol Special is formulated to inhibit sorbitol from crystallizing out in the
gelatin shell. Do not substitute Sorbitol for Sorbitol Special.
Solvent - Water
|Potato starch matrix
|This is a smooth, transparent substance resembling gelatin,
which is neutral in taste and color, easily digestible and of
plant origin, and therefore, the concerns of certain bovine
related diseases are not an issue, and they offer a gelatin
free alternative for vegetarians and vegans. Currently,
available from Swiss Caps under the name Vegagels«. |
There are three primary types of inner fill materials:
especially oily liquids
Fills: Active dissolved in a carrier
such as soybean oil and Miglyol 812 (neutral oil, triglycerides
of medium chain fatty acids)
Glycols: especially PEG 400 -600
solvents: Any other solvent which doesn't degrade or solubilize
the gelatin shell, i.e., dimethyl isosorbide, surfactants,
diethylene glycol monoethly ether
or alcohol: up to 10% w/w, if needed for solubility
1 to 4% w/w to retard the migration of the glycerin out of
the shell into the fill
Up to 10% w/w used in combination with PEG, can increase
drug solubility, and also improve stability by inhibiting
Fills: Active dispersed in a carrier
can accommondate about 30% solids before viscosity and
filling become a problem
can be heated up to 35║C to decrease viscosity during the
solids must be smaller than 80 mesh -- mill or homogenize before filling to prevent needles from
clogging during filling.
Soybean Oil with beeswax (4-10% w/w) and lecithin (2-4%
w/w). The lecithin improves material flow, and imparts
some lubrication during filling. Add enough
beeswax to get a good suspension, but avoid creating a
Oil (e.g. Geloil« SC), a ready to use system composed
of soybean oil, a suspending agent, and a wetting agent.
Simplifies the manufacturing process, and avoids batch
to batch and supplier to supplier
800 -1000 for semi-solid fills
10,000 -100,000for solid fills
mixtures of the above.
Heat up to 35║C to make fluid enough for
of long chain fatty acids
(e.g. Gelucire« 33/01). Hydrophobic with surfactant
sorbitan derivatives such as polysorbate 80 or lecithin.
hydrophobic drugs dissolved or dispersed in an oily
matrix, a surfactant of HLB 10 will increase the dispersibility of the product in
aqueous fluids and also may improve bioavailability.
|Avoid aldehydes which can lead to cross linking (pellicle
formation) of the gelatin, and poor dissolution of the gelatin
capsule in water. This may be overcome by adding enzymes to the
dissolution media, (see FDA Guidelines)|
|Drugs sensitive to water can degrade (e.g. ranitidine) or undergo
polymorphic conversion (e.g. terazosin). |
|Compounds (especially those of high water solubility) can migrate
from the fill into the shell or get trapped in a hydrophobic matrix
resulting in poor dissolution and loss of bioavailability. |
Suppliers of Gelatin:
Gallard-Schlesinger Ind., Garden City, NY
Leiner Davis Gelatin,
OC Lugo (gelatin of piscine origin), New York,
Penta Manufacturing Co., Livingston, NJ
Rousselot, Waukesha, WI
Need a supplier?
Submit in Excipients
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7) Soft Gelatin Encapsulation Processes and
Rotary Die process
Two ribbons of gelatin are fed continuously into a rotating die assembly
and are simultaneously formed into the two halves of a capsule. The ribbons
converge adjacent to a fill injector. The fill injector is actuated by a pump
which measures and dispenses the appropriate volume of fill material into the
capsules. The filled capsules are subsequently sealed as the die assembly
rotates. This process permits accurate and reproducible fill uniformity.
Pump heads are available for fill weights as low as 100 mg. For oral dosage
forms, the fill weight ranges from 100 mg up to about 1
The following should be monitored/controlled:
|Seal or seam width|
Following encapsulation, the capsules undergo drying in a tumble drying
tunnel with an elevated temperature and a large volume of forced air. From the
drying tunnel, the capsules are transferred onto trays and placed into a low
humidity drying room.
The following should be monitored:
|Capsule hardness |
Drying is a dynamic process, and the goal is to have the gelatin shell
return to it's equilibrium moisture content in the range of 6 - 8%.
fills dry faster than PEG fills, and typically reach a shell moisture content
of 6 to 8% within 24 hours.
If water migrates into the fill, it needs to migrate back out or at lease
be in equilibrium with the moisture content of the shell for good
stability. This is more typical of the PEG fills. These can take 7 to 10 days
to reach acceptable moisture levels, and may still contain up to 10% water after drying.
Equipment Suppliers for Soft Gelatin Encapsulation:
Caps Plus Technologies, Phoenix, AZ
Chatsworth Machine Co., Chatsworth, CA
GIC Engineering, Tampa, FL
Pharmagel Engineering, Berkhamsted, Hertfordshire, UK
Contract Soft Gelatin Encapsulation Services
Banner Pharmacaps Inc., High Point, NC
Goldcaps, Miami, FL
K-International Equipment, Cottage Grove, OR
Pharmagel Engineering, Berkhamsted, Hertfordshire, UK
RP Scherer, Tampa, FL
Rexall Sundown, Boca Raton, FL
Softgel Formulators, Inc.
Swisscaps, Miami, FL
Softgel Drug Delivery and Development Services
Banner Pharmacaps, Inc., High Point, NC
Softgel Consulting Services
Softgelex, Valencia, CA
Gelatin Recovery Services
A.B.T., Dresher, PA
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