Purpose: Traditional two hard piece capsule shells are designed for immediate release and in order to provide gastric resistance or targeted release, capsules require further treatment, in the form of banding and enteric coating. DRcaps™ are HPMC based capsules and can help to protect capsule contents from the acidic environment in the stomach. For a liquid fill product, in order to prevent leaking of the liquid fill material from the gap and body join region, a sealing band around this area is required. In addition, there is a risk under the mechanical stress of in vitro dissolution testing, for the body and cap, to become separated. In order to effectively prevent the body-cap separation and the material leaking though the cap and body join, banding the capsules with an appropriate banding solution is a logical approach. Traditional HPMC and gelatin banding solutions do not exhibit appropriate acid resistance, therefore HPMCAS was investigated as an acid resistant banding solution.
Methods: DRcaps™ capsules were first filled with a liquid formulation consisting of 97% w/w Miglyol and 3% w/w Aerosil. The filled capsules were then banded with a variety of banding solutions, consisting of 14.2% w/w HPMCAS as the acid resistant polymer. The polymer was prepared with 0.7% w/w NH3 in a variety of ethanol to water ratios (100:0, 90:10, 80:20, 75, 25, 70:30, 60:40, 50:50). The capsules were banded using a bench scale bander and left to dry at room temperature. Capsules were then leak tested under vacuum (<- 20 mmHg) and the extent of capsule leaking was recorded. The banding region was assessed visually and band region capsule constriction was measured by microscopy, band constriction was also assessed on capsules with a 0:100 and 30:70 ethanol to water ratio. Finally capsule disintegration was assessed in 0.1 M HCl and capsules were monitored visually for signs of capsule elongation, separation and capsule breach.
Results: For each variation of the banding solution, approximately 400 capsules were filled and banded. On vacuum leak testing, the extent of capsule leaking increased when the water content of the banding solution was increased above an ethanol to water ratio of 70:30. Figure 1 shows unacceptable leakage rate at ethanol to water ratios of less than 60:40, with no leaking observed at 80:20 and 100:0. Band constriction increased with increasing water content, with high levels of constriction occurring with 70:30 water to ethanol, of approximately 11.5%. (Figure 2). Minimal constriction along with optimal visual band appearance was demonstrated with 80:20 ethanol to water. Disintegration testing in 0.1 M HCl was then performed on the prepared capsules and capsules with a 100:0, 60:40, 50:50 ethanol to water ratio, elongated during the test. Capsules with a 90:10, 80:20, 75:25 and 70:30 survived two hours in the acid test intact and without material breach.
Conclusion: An acid resistant HPMCAS banding solution was developed for DRcaps™ capsules. The dried band performance with respect to prevention of leaking of capsule contents, acid resistance during disintegration and visual appearance was influenced by the water to ethanol ratio in the band. Based on the results obtained banding solutions with 90:10, 80:20 and 70:30 ethanol to water ratio, were optimal for band performance.