· Accommodates a wide variety of compounds filled as a semi-solid, liquid, gel or paste. · Can be used to improve bioavailability by delivering drug in solution or other absorption enhancing media. Disadvantages of softgels · Requires special manufacturing equipment.
· Stability concerns with highly water soluble compounds, and compounds susceptible to hydrolysis. · Limited choices of excipients/carriers compatible with the gelatin. Outer shell of softgels The outer shell is composed of a gelatin or potato starch matrix. 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.
not kosher) gelatin may be overcome by piscine (fish) gelatin. Plasticizer - Glycerin and Sorbitol Special are the two most common plasticizers. 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. Optional Ingredients – Approved colors and flavors. 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®. Types of inner fill materials There are three primary types of inner fill materials. · Oils such as soybean oil and Miglyol 812 (neutral oil, triglycerides of medium chain fatty acids). · Other solvents: Any other solvent which doesn't degrade or solubilize the gelatin shell, i.e., dimethyl isosorbide, surfactants, diethylene glycol monoethly ether. · Optional Ingredients: * Water or alcohol: up to 10% w/w, if needed for solubility. * Glycerin: 1 to 4% w/w to retard the migration of the glycerin out of the shell into the fill. * Polyvinylpyrrolidone: Up to 10% w/w used in combination with PEG, can increase drug solubility, and also improve stability by inhibiting drug recrystallization. · Suspensions can accommodate about 30% solids before viscosity and filling become a problem. · Suspensions can be heated up to 35ºC to decrease viscosity during the filling process. · Suspended solids must be smaller than 80 mesh -- mill or homogenize before filling to prevent needles from clogging during filling. * Oily mixtures: 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 non-dispersible plug. 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 variability. * Polyethylene glycol: PEG 800 -1000 for semi-solid fills. * Glycerides: Glycerides of long chain fatty acids (e.g. Surfactant: Sorbitan derivatives such as polysorbate 80 or lecithin.
For 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. Incompatibilities · 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). ranitidine) or undergo polymorphic conversion (e.g. · 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. Soft Gelatin Encapsulation Processes and Equipment. 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 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 gram.