What Is Soft Capsule?
Research and Development
Our Company
Contact Us
Research, Development, and Manufacture of Investigational Drugs
Manual for Soft Capsule Development
Gelatin Alkalized gelatin and acidified gelatin are generally used. However, when there is a possibility that fill material may cause insolubility, succinated gelatin is used.
Plasticizer Adds elasticity to the capsule, thus preventing cracking. Concentrated glycerin and D-Sorbitol are mainly used.
Preservatives Ethyl paraben and propyl paraben are mainly used.
Titanium ovide Titanium oxide is added to light-sensitive compounds to prevent light penetration.
Colorants Colorants allow easy coloring to make capsules more distinguishable and appealing.
Crystallized gelatin Mixing with crystallized gelatin prevents capsules from sticking together or to a container, and also prevents delayed dissolution of the capsules.
Moisture content Moisture content of the capsule shells is reduced to 7 〜 9%. Generally, moisture content that is too low could lead to the tendency for cracking and too high a moisture content could cause problems such as sticking.
Coating Enteric coating enables absorption in the intestinal tract.
3.Fill Material
1 Drug substances that are naturally in an oil phase
2 Oil phase drug substances that are diluted with an oily base
3 Oil-soluble drug substances that are dissolved in an oily base
4 Water-soluble drug substances that are dissolved in an aqueous base (Macrogol 400)
5 Drug substances that are suspended in an oily base
Drug substances
1 High gas barrier properties of the capsule shell protect stability of drug substances against oxidation
2 Treatment of the capsule shell with titanium oxide for protection against light supports stability of drug substances.
3 Compounds that are active at trace amounts, such as alfacalcidol, can be injected uniformly on an μg scale.
4 Compounds that cannot be processed into tablet form due to their relatively low melting point can be filled as an oil phase without melting into a soft capsule.
5 Drug substances in oil phase or as suspensions lead to higher bioavailability.
6 Ability to formulate drug substances with strong odor or volatile compounds.
7 Higher cost efficiency by simplified manufacturing processes and high product quality due to accurate and precise encapsulation machinery.
Oily bases
Vegetable oils such as corn oil, soybean oil, sesame oil, cottonseed oil, safflower oil, wheat germ oil, and middle chain triglycerides have been widely used.
Oily bases used especially for pharmaceutical products are carefully selected based on multiple studies such as drug substance stability.
Aqueous bases
Macrogol 400 is used as an aqueous base. If a drug substance is water soluble, it is either solubilized in water first and mixed with Macrogol 400, or solubilized directly in Macrogol 400. Excess water could lead to problems after the encapsulation process. Drying process conditions must be adjusted accordingly when aqueous bases are used.
When a drug substance is solubilized in an oily base, it becomes clear. However, when a drug substance is insoluble in an oily base or its low solubility requires a large volume of solution, then it is treated as a suspension. Beeswax or surfactants are used as a suspension agent for oily bases, and Macrogol 4000 or 6000 is used when Macrogol 400 is the base.
Surfactants are not only used as a suspension agent, but also to enhance solubility and stability. In addition, as an effect on elution and absorption, surfactants are considered to be important in the designing of inner fill material formulation. Polysorbate, glycerin fatty acid esters, and hydrogenated castor oil are mainly used.
Compatibility for filling
Viscosity (Fluidity)
Clear Solublized Solution - 2000 mm2/s or less (viscosity rate)
Suspension Solution - 30000 mPa.s or less
  Suspension Particle
Particle Size - Solid material should pass through 100 mesh
  Permissive Range for Content Amount
Regular range is 50 to 2000mg; however, amounts beyond this range are also possible.
4.Sample Production
Sample production can be from as small a scale as a couple kilograms to the manufacture of investigational drugs by our Technical Research Laboratory. During sample production, capsule shell formulation, fill material formulation, and data collection at critical steps of the manufacturing process are performed. We design formulations customized to the drug substances provided by our customers.
5.Stability Testing

Stability testing is performed after the final stage of bottling, PTP, or pillow packaging. We also perform stability testing and elution testing upon request.

Copyright(c)2007 TOKAICAPSLE Co, .Ltd.All Rights Reserved.