Purpose: Softgels are an attractive method of delivering a wide range of APIs to the human body. Due to the liquid/semisolid nature, potent, advanced, and functional softgel fills can be employed to address many challenging topics facing the pharmaceutical industry. However, the ability to modify release of softgels, when compared to solid oral doses (tablets) is not yet adequate. While enteric coatings are being widely utilized, the production of sustained release softgels is in its relative infancy. The soft, flexible, and permeable nature of the gelatin capsule makes coating a challenge both from a formulation and from a processing perspective. In this work, a novel coating formulation using Kollicoat® SR 30 D, a polyvinyl acetate based dispersion, is utilized for simple and efficient coating of commercial softgels. Furthermore, novel imagery techniques are utilized in order to understand mechanistically how the coating works on a softgel.
Methods: 1 gram, Omacor® omega 3 fatty acid capsules were utilized in this study to test and evaluate parameters and formulations capable of effectively producing a sustained release coating. Sustained release coating formulations were prepared utilizing a blend of Kollicoat® SR 30D, a polyvinyl acetate based 30% dispersion, Kollicoat® IR, a polyvinyl alcohol coplolymer as an instant release coating and pore former, triethyl citrate as a plasticizer and purified water for dilution. Various solids concentrations, coating weights, and processing parameters (Inlet Air temperature, exhaust air temperature, pan rotation speed, and spray rate) were tested on the Manesty XL Lab:01 pan coater. Batches were produced in 12 kg batches to closely mimic commercial coating mixing conditions. Standard USP II dissolution apparatus were utilized to test sustained release coatings in both low pH conditions of the stomach as well as 6.8 pH of the GI tract. Additional tests and analysis were performed using the Sirius® SDi2 in both visible and UV.
Results: In this study, it was found that for proper preparation and coating of a sustained release softgel, both the formulation and the manufacturing conditions are critical to performance. It was found specifically that a coating formulation of 15% w/w weight gain was required in order to achieve a homogeneous and adequate coating of the softgels to gain a sustained release effect. Furthermore, a blend of a minimum 30% Kollicoat® IR was required in the formulation in order to have an adequate release of drug over an 8 hour window. On the processing side, mixing in the pan was determined to be critical to adequate coating, while maintaining a relatively cool bed temperature of 36°C maximum to minimize the “spray drying” effect of the polymer coating. Mechanistic and visual studies of the resulting release indicate that the instant release coating (Kollicoat® IR) erodes first forming pores, which allow fluid to enter and begin dissolving the gelatin. Unlike traditional tablets, this is an additional mechanism required in order to begin release from the softgel, thus sufficiently more pore former needed to be used in order to facilitate diffusion of the gelatin, and later API.
Conclusion: Producing sustained release softgel formulations is possible through careful design of the coating formulation and care of the processing conditions. It was found in this work that utilizing a 30% blend of pore forming, Kollicoat® IR combined with Kollicoat® SR 30D produced adequate sustained release coatings of softgels in a traditional pan coater.