Soft gelatin capsules (SGC) are primarily a single unit oral dosage form consisting of a liquid, semi-liquid, semi solid fill enclosed by a one piece hermetically sealed elastic outer shell of gelatin.
They are formed, filled and sealed in one continuous operation, most preferably by the rotary die process. The majority of soft capsules are made from gelatin owing to the unique physical properties that it is an ideal material for the rotary die process. Originally developed in the 19th century to mask unpleasant taste and odor of drug substances, SGC has found many applications in recent times for pharmaceuticals, health, nutrition products, cosmetic application and even recreational products such as paint balls.
In the pharmaceutical field SGC as an oral dosage form are increasingly being chosen for strategic reasons, (1) easy to use, (2) easy to swallow, (3) no taste, (4) unit dose delivery, (5) tamper proof, (6) wide variety of colours, shape and size, (7) immediate or delayed drug delivery, (8) can be used to improve bioavailability by delivering drug in solution or other absorption enhancing media. It is well known, that many pharmaceutical active compounds intended for oral administration are poorly soluble in water, this hydrophobic property often makes difficult to formulate a drug so that it exhibits a satisfactory bio-availability profile in vivo. Poor bio-availability may lead to ineffective therapy, the need for higher dosing and/or undesirable side effects.
Over the years the drug formulation art has developed numerous oral delivery systems for hydrophobic drugs dispersed or dissolved in an oil which may sometimes contain a co-solvent. For such formulation, the oil appears to be an important component for promoting drug absorption. However, the administration of a drug in oil alone is not advantageous because of the poor miscibility of the oil with the aqueous environment of the GI tract. This poor miscibility can lead to variable gastric emptying, which in turn, produce variable absorption of drug from the small intestine.
Accordingly, in order to increase the dispersibility of the oil in aqueous fluids, it is the normal practice in the oil based pharmaceutical formulations to include a surfactant component. Lipophillic surfactant are capable of promoting some emulsification of the oil, but the resulting emulsion are normally too crude, in terms of size, to be useful. The hydrophillic surfactants are much superior with respect to forming oil in water (O/W) emulsion and can be used to produce fine, uniform emulsion, which are more likely to empty rapidly and uniformly from the stomach and coupled with a very large surface area will promote faster and more complete absorption. However, hydrophillic surfactants by themselves are often not sufficiently miscible with the oil component to ensure good homogenity and consequently the surfactant components of an oil based drug usually consist of a mixture of lipophillic and hydrophillic surfactants.
The most interesting advances recently have been made in the area of developing liquids, semi-liquids, hydrophilic formulation in a soft gelatin capsules to address bio-availability, decreased plasma variability and absorption enhancing techniques. The proper design for a specific SGC formulation requires the appropriate selection of shell and fill composition and the optimisation of the two, to allow for the efficient production of a chemically and physically stable product with desired bio-pharmaceutical properties.
Interestingly soft gelatin capsules fill formulation have changed over time from lipophillic to hydrophilic solution or suspension and recently to more complex self emulsifying systems. Basic lipophillic solutions or suspensions have been the traditional and most frequently used for the soft capsules fill formulations in the past. They have been applied successfully to formulate oily and lipophillic low melting point drugs such as vitamin A ,D & E drugs with unpleasant taste and/or odour such as the vitamins of B group, herbal extract, fish oil, drugs with critical stability i.e., oxygen and high sensitive drugs and low dose or highly potent drugs. The vehicle used for this purpose are lipiophillic liquids and semisolids. And the optional use of surfactants.
Fill material
The formulation of the fill is individually developed to fulfill the following;
o to optimize the chemical stability of the active compound.
oto improve bioavailability of the active com pound
oto allow for an efficient and safe filling process
o to acheive a physically stable capsule product
Final product stability is related to shell compatibility with fill material. For soft gelatin capsules filling operation, the technologically important factors to be born in mind are temperature, viscosity and surface activity of the fill material and in the case of suspensions the particle size of the suspended drugs (solids),liquids or combinations of liquids for encapsulation must possess a viscosity sufficient to be precisely dosed by displacement pump,(at a temperature of 35C or below),and may not show stinging to allow for a clean break from the dosing nozzle.
Owing to certain tolerance of the encapsulation equipment, suspended solids should have a particle size below 200 micron to ensure maximum homogeneity of the suspended particles in suspension. More over the surface active properties of the fill whether a solution or a suspension may not interfere with the formation of the seal. Soft gelatin capsule formulation strategies have to consider the specific shell/fill interaction that may occur during manufacturing: drying, and on storage and control their rate and extent to achieve stable product. Cross linking of gelatin leading to solubility problems of the shell is well known problem, associated with the encapsulation of drugs containing reactive groups such as aldehydes shall be kept in mind by the person concerned in the development of the new formulations of fill materials.
The shell of SGC is composed of gelatin, plasticizer or a combination of plasticizers, water preservatives, coloring and opacifying agents, flavoring and sweeteners as per the end use and requirements. The gelatin used for pharmaceuticals, health and nutrition, soft capsule products, are described by official pharmacopeias or are approved by the local authorities for physico-chemical specifications.
For soft capsules production, the pharmacopeial specification generally represent the minimum requirement, capsule manufacturer's specifications are more detailed and stringent with respect to the performance related physico-chemical properties of the gelatin. This is due to the fact that these parameters are critical for economic soft capsules production by the rotary dye process and for the quality of the final products.
Gelatin type and grade those are adequate for continuous commercial soft capsules production requires ability to set at a fast rate to formation of ribbon of defined thickness and reproducible microstructure and to produce films with a mechanical strength and elasticity sufficient to survive all the manipulations on the encapsulation machine i.e., to allow the wet films to be easily removed from the drum, to stretch during filling, to be sealed at temperature below the melting point of the film and to be dried quickly under ambient conditions to a specified capsule strength. Moreover the disintegration/dissolution time characteristics of the resulting capsules have to fulfill the pharmacopeial requirements
There are many types and grades of the gelatin available for soft capsules production. But the proper choice of the gelatin grade is related to technological issue, pricing, and end use.
The formulation of the gelatin will vary with product to product, depending upon the chemical and physical properties of the fill material, packing mode, storage conditions etc.
The plasticizers frequently used are glycerol, sorbitol, polyethylene glycol, propylene glycol etc. depending upon the fill material .An ideal plasticizer should interact with gelatin molecule in such a way that stabilises the three dimensional gel network structure and shall be physically embedded in the sol phase of the gel network to avoid bleeding.
(The author is with Softesule Pvt. Ltd., Mumbai)