Improvement of Physical Stability of Soft Gelatin Capsules by Film Coating

ABSTRACT

Purpose

Physical stability of certain soft gelatin capsules stored at high humidity and elevated temperature can be a concern. The purpose of this study is to improve the physical stability of soft gelatin capsules by film coating.

Materials

Soft gelatin capsules:

The medium chain triglyceride (MCT)-filled 20 Oblong placebo soft gelatin capsules were manufactured by Catalent Pharma Solutions, Somerset NJ.

Coating material:

Opadry® II and Opadry 200 were sourced from Colorcon.Eudragit® EPO Readymix was sourced from Evonik.

Experiment

Soft gelatin capsules were coated using the O’Hara LabcoatMX pan coater. Three different coating systems including: Opadry II (HPMC as major coating polymer), Opadry 200 (PVA as the major polymer and Eudragit EPO Ready-mix (Amino Methacrylate Copolymer as the major polymer) were evaluated. The coating parameters for the three different coating formulations are listed in Table 1. For each coating formulation, samples were taken at 1.5%, 3.0% and 5.0% weight gain level.

The coated capsules along with the uncoated placebo capsules were bulk packaged in HDPE bottles and stored at 40°C/75%RH for up to 3 months. The sample description is presented in Table 2. Ten additional softgel capsules of each sample were also bulk packaged and stored at the same condition for water uptake testing.Samples were taken at predetermined time points (initial, 2 weeks, 1 month, 2 months, 3 months) for evaluations.

t1 t2

Testing

Samples were tested for appearance, hardness, water uptake and disintegration at predetermined time points. Appearance was assessed visually. Images were taken by Kodak 7590 digital camera. Water uptake was calculated by the following equation:

Water uptake %= (Weight of ten capsules at the predetermined time point-original weight of ten capsules)/Original weight of 10 capsules The hardness and disintegration tests were performed using the Bareiss Durometer and Lab disintegration tester, respectively. Five capsules were used for hardness test and three capsules were used in disintegration test. The disintegration tests were performed in 0.01N HCl solution at 37 + 0.5°C.

RESULTS

Appearance Testing Results:

The images of softgel capsules at 3 months are presented in Figure 1. No physical changes were observed from the Opadry II and Opadry 200 coated capsules regardless of the weight gain levels at the end of 3 months (Figure 1a-1f). Uncoated softgels and Eudragit EPO coated softgels at all coating levels all showed agglomeration and deformation (Figure 1g-1j). The results suggest Opadry II and Opadry 200 may provide better physical protection to uncoated softgel capsules than Eudragit EPO. Even at very low coating level, the softgel capsules are still able to maintain their physical stability. Lower Eudragit EPO coating level did not provide sufficient physical protection to the softgel capsules under accelerated storage conditions. Higher coating level could postpone the agglomeration process and provide better protection to the softgel capsules.

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Water Uptake Results:

Water uptake profiles are shown in Figure 2. The data demonstrates a relationship between level of water absorption and coating material/ level. Generally speaking, coated softgels absorbed less water than uncoated softgels. For the same coating system, the more coating material was applied, the less water uptake was observed. Opadry II and Opadry 200 coated softgels showed significantly less water uptake compared to Eudragit EPO coated softgels. Even at 1.5% coating weight gain, Opadry II and Opadry 200 coated softgels showed <3.0% water uptake after 3 months whereas 5.0% Eudragit EPO coated softgels absorbed more than 4.0% water after 3 months. The difference of water uptake between Opadry II and Opadry 200 is negligible. The water update results are consistent with the appearance. It was found that 3.5% water uptake is a threshold for this batch of softgels. When the water uptake is above 3.5%, softgel capsules tend to agglomerate and deform.

f2

Hardness:

The average hardness data is presented in Table 3. The data shows a trend of decrease in hardness over time when the samples were stored at 40°C /75 %RH. Very low hardness may cause softgel deformation. The degree of hardness decrease is directly related the coating formulation and coating level. All the coated capsules had a higher hardness than uncoated capsules. For the same coating formulation, the higher coating level showed higher hardness at all the time points. The rate of hardness decrease is different for different coating systems, the rank of decrease rate is as follows: Eudragit EPO> Opadry 200> Opadry II.

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Disintegration Results:

The disintegration results are presented in Table 4. The disintegration time of all softgel samples ranges between 12 and 20 minutes. Similar disintegration times were observed over the 3 month time course. There is no significant effect of either coating system or coating level on disintegration time. This suggests there is no chemical or physical interaction between the shell of softgel capsule and the coating layer.

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CONCLUSIONS

Film coating is a very good approach to protect soft gelatin capsules under the accelerate storage condition. Both coating formulation and coating level play a critical role in physical stability of softgels. Opadry II and Opadry 200-based coating formulations showed better protection than Eudragit EPO formulation. Higher coating level could also be of benefit.

 

 

http://www.catalent.com



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