Category: Formulation and Quality
Purpose: Kollicoat® Smartseal 100P is a newly developed spray dried powder of a methyl methacrylate and diethylaminoethyl methacrylate copolymer, designed to provide taste-masking and moisture protection. Kollicoat® Smartseal 100P is a ‘reverse enteric’ polymer that is insoluble in the saliva (pH 6.8-7.2) and dissolves quickly in the acidic environment of the stomach (< pH 5.5) for gastric instant release. The objective of this study is to evaluate the suitability of using Kollicoat® Smartseal 100P as a moisture protective coating polymer for soft gelatin capsules. Commercially available uncoated fish oil soft gelatin capsules were used as a model system in this study. Soft gelatin capsules absorb moisture and agglomerate on storage especially in high humidity conditions. The project focused on developing an optimized talc-free Kollicoat® Smartseal 100P formulation for soft gel coating using glycerol mono stearate (GMS) as an anti-tacking agent and most importantly assessing the degree of moisture protection that could be achieved by varying the coating levels and process conditions employed.
Methods: Coating suspension preparation:
Mixture 1: Dissolve the antioxidant (Butylated hydroxytoluene, BHT) in the plasticizer (Triethyl citrate, TEC) and melt the mixture using a water bath at 70 - 80o C. Then mix it with GMS and Polysorbate 80 until fully dissolved. Add 75 ml of hot water (~85o C) and emulsify the mixture using a high shear homogenizer at 3500 RPM for 10 minutes.
Mixture 2: Gradually add the Kollicoat® Smartseal 100P powder into succinic acid solution under stirring at 500 RPM for 30 minutes.
Add mixture 1 gradually into mixture 2. The coating suspension was continuously stirred for an additional 30 minutes and passed through a 300 µm (50 mesh) sieve before use. The compositions of the selected formulations are listed in Table 1.
Coating Process: Coating of soft gel capsules (700 g) was performed in a 12-inch O’HARA perforated coating pan. The coating parameters is listed in Table 2.
Moisture absorption evaluation: Fifteen uncoated and coated capsules with various coating weight gains were placed in open glass dishes in a glass desiccator, maintaining a 75% relative humidity at room temperature. Moisture absorption was assessed by the capsule weight changes at the 2-week time point. Flowability tests were conducted at the same time by pouring the capsules out of dishes.
Results: In the first two formulations (F1 and F2), polysorbate 80 was included in addition to GMS. The coating process was very smooth, but the soft gels tended to stick onto the coating pan during the curing step, indicating the glass transition temperature (Tg) of the coated film was too low. Therefore, polysorbate 80 was eliminated from other formulations. The Kollicoat® Smartseal100P coating formulations were further optimized by changing the ratios amongst polymer, plasticizer and anti-tacking agent, and only the best formulation was listed in Table 1 (F6). The GMS/TEC combination worked very well for the preparation of Kollicoat® Smartseal 100P coating formulations. The coating process was smooth, and no tackiness was observed during the coating/curing process. The cured capsules exhibited a translucent shiny surface, which prevents the tackiness during storage.
Figure 1 shows the moisture absorption of the uncoated and coated fish oil capsules that were incubated in 75% relative humidity at room temperature for 2 weeks. It is seen that the uncoated fish oil capsules absorbed 4.6 % moisture. After being coated with the Kollicoat® Smartseal100P, the capsules absorbed much less moisture in the same condition. At the coating levels of 4% and 10%, the moisture absorptions in 2 weeks were 3.2% and 2.2%, respectively. The moisture absorption reached a plateau at ~ 1.5% when the coating levels were over 16%. Flowability tests indicate that the plasticizer and GMS helped improve the flowability.
Conclusion: The newly developed polymer, Kollicoat® Smartseal 100P was coated onto soft gelatin fish oil capsules, which can form a moisture barrier and significantly reduce moisture uptake during storage. The coating process was very stable and reproducible. The final in-process curing step enhanced the capsule flowability and shiny surface. The moisture protection effect increases with increasing the coating level. Kollicoat® Smartseal 100P may find more applications for other dosage forms containing moisture-sensitive actives.