(M1230-02-14) The Influence of Coating Parameters on Transparency of Semi-permeable Membrane Coating of Push-Pull Osmotic Pump Tablets

Purpose: Cellulose acetate (CA) is commonly used as a semi-permeable membrane coating on osmotic pump tablets to control drug release rate. The transparency of the semi-permeable membrane coating of CA on the push-pull osmotic pump tablets is very important for identification of the drug layer and the push layer during laser drilling, so that the drug release orifice would be drilled on the correct side of tablets. In the process of semi-permeable film coating, the film may become opaque if the coating parameters are not used in their optimized ranges. The purpose of this study was to evaluate the effect of different coating parameters on the transparency of a semi-permeable membrane coating (Opadry® CA) on push-pull osmotic pump tablets.

Methods: Design of experiment (DoE）was used to carry out the random customized experimental design and 12 experiments were obtained, including one central point. Spray gun to bed distance, atomizing air pressure, pattern air pressure and pan speed were fixed in the study. Variables included: inlet temperature (30-60℃), inlet air volume (50-70 m3/h), liquid spray rate (10-30 g/min), coating weight gain (3-5%) and environmental humidity (57-80%). The product bed temperatures in different experiments were collected for further analysis. Push-pull osmotic pump tablets were replaced by placebo tablets coated with brown Opadry and further coated with Opadry CA according to the DoE conditions. The brown placebo tablets without Opadry CA coating were chosen as reference for color difference analysis. Coated tablets from different experiments were measured by Datacolor 600 spectrophotometer to get delta E (DE) values in order to quantify the transparency of the semi-permeable membrane. Then all data were analyzed by DOE software to find out the key parameters influencing film opacity. The tablets from different experiments were cut in half and cross sections of the film coat were examined using scanning electronic microscopy (SEM) to observe any structural differences of the film under different coating conditions.

Results: The results showed that liquid spray rate, inlet temperature and their interaction significantly influenced the transparency of semi-permeable membrane. Product bed temperature and its interaction with inlet air humidity were also significant factors for film opacity. SEM images showed that the film structure of Opadry CA was different when coating parameters were changed.

Conclusion: Two main reasons may explain CA membrane opacity: spray drying and solvent (acetone) evaporation in the presence of water when the bed temperature is close to dew point, and water condenses on the surface of the tablets. In this case, altering the coating parameters such as decreasing the spraying speed, increasing the inlet air temperature, increasing coating temperature or decreasing the coating environment humidity can also be useful to solve film whitening problems.

References: 1. Martin L, et al. Investigation of Critical Process Parameters for Coating Push-Pull Osmotic Pump Tablets with Opadry CA. AAPS Annual Meeting and Exposition, 2012.
2. Martin L, et al. Investigation of Cellulose Acetate Polymer Viscosity and Coating Solution Concentration on Performance of Push-Pull Osmotic Pump (PPOP) Tablets. CRS 39th Annual Meeting and Exposition of Controlled Release Society, 2012.

Fig.1 Appearances of the Placebo Tablets and the Semi-permeable Membrane-coated Tablets

Fig.2 Influence of Coating parameter on DE Value