Since its inception hard gelatin capsules have remained a highly popular pharmaceutical dosage form principally due to its ease of manufacturing and rapid disintegration in gastric lumen providing quick therapeutic action. However, this rapid dissolution of hard gelatin capsules is not desired for acid sensitive drugs, drugs causing irritation to gastric lining and those intended to treat intestinal diseases. Of late, enteric coated hard gelatin capsules have been gaining popularity due to their ability to protect acid-sensitive drugs from gastric fluids. The enteric coating in the capsules helps them remain intact in the stomach and release in the intestine.
Typically, enteric coating is composed of film forming polymers, plasticizers, anti-adhesion agents, colorants, dispersion agents and other additives. Coating can be applied using organic solvents, aqueous-organic emulsions, aqueous solutions or aqueous polymer dispersions. The different methods that are used for coating range from pan coating to fluidized bed coating, electrostatic coating and also hot melt coating. So as to achieve maximum coating efficiency, it is necessary to optimise process variables such as air temperature, suspension feed rate, air flow rate, load of capsules in the bed, suspension viscosity and coating duration. Some of the manufacturing challenges faced during enteric coating of hard gelatin capsules along with possible remedies have been discussed below.
Coagulation of coating blend: Compared to organic solutions, aqueous dispersions/solutions are more prone to foam formation due to the presence of high-speed stirrers, sensitivity to temperature and electrolytes that have direct implications on their rheological properties. These factors may result in precipitation or coagulation of polymeric particles which cannot be redispersed further. This can be avoided by addition of 0.5% anti-foaming agent (such as simethicone), optimizing stirring speed and temperature of the coating blend and most importantly using it promptly after formulating.
Blocked spray jets: High inlet air temperatures above the polymer glass transition temperature may lead to coagulation of polymer blend. Aggregated or coagulated polymer particles result in partial or complete blockage of spray nozzles resulting in non-uniform coating. This issue can be greatly resolved by passing the blend through a fine sieve (0.1 – 0.25 mm mesh size) before initiating the coating process.
Sticking: It is possible for coated capsules to stick to one other during storage that can damage the formed film. The use of anti-adhesion agents is highly recommended here which can solve this issue to a great extent, although it may compromise the transparency of the capsule.
Orange peel effect: Enteric film coating using organic solvents leads to orange peel effect due to the imperfect adhesion of enteric coat onto the smooth capsule surface which gives little anchorage. This can be prevented by pre-coating the capsules with 5% hypromellose (HPMC) or polyvinyl alcohol (PVA) and increasing the plasticizer content in the coating solution
Softening: Coating capsules with aqueous spray formulations often leads to softening, swelling, and sticking of capsule shell. This can also be prevented by pre-coating the capsules with low density polymers.
Brittle film: If the coating forms a thin brittle film, chances of it breaking away from the capsule are high. This will then cause the capsule to lose its enteric integrity.
Here, the content of both polymer as well as the plasticizer will need to be increased to build more flexibility to the film.
Change of appearance: Color and glossy appearance of hard gelatin capsules can be affected due to enteric coating. It is important to take this into consideration while performing pre-formulation studies and carefully choose the film ingredients.
Oliveira, H. V. A., M. P. G. Peixoto, and L. A. Tacon. “Enteric coating of hard gelatin capsules by the spouted bed process.” Journal of Applied Pharmaceutical Science 3.8 (2013): 57.
Thoma, Karl, and Karoline Bechtold. Enteric coated hard gelatin capsules. Capsugel Library, 1992.
Mounica, P., S. Pavani, and P. Mounica Rani. “A REVIEW ON RECENT ADVANCES IN ENTERIC COATING AND ENTERIC POLYMERS.” (2017).