(T1030-09-51) Simplification Study of Feed System in HPMCAS Dry Coating

Purpose: Hypromellose acetate succinate (HPMCAS) can be used in dry coating system, in which we don`t need any solvent during the process. But in conventional dry coating system, it is complicated to prepare powder of HPMCAS and liquid mixture including plasticizer and feed separately. For improving the ease of handling, we could develop new method to feed one mixture as powder.

Methods: We prepared Theophylline powder, SmartEx^® (QD-100), L-HPC^® (LH-31) and PVA (PE-05JPS) mixture, added water, high shear mixed and conducted extrusion granulation. The wet granule was sorted to particle and dried in oven. Then, it was thrown in centrifugal rolling machine (CF-Granulator CF-360) and powder mixture of HPMCAS (Shin-Etsu AQOAT^®, AS-LF), Talc, solid plasticizer (PEG-4000: Macrogol^® 4000PS, Stearic acid: Kolliwax^® S Fine) and solid wetting agent (Propylene glycol monostearate (PGS): HOMOTEX PS-200V^® was fed to it while being warmed. After the dry coating, we continued the simple heating as curing stage in another 30 min. Dissolution profiles in simulated gastric fluid (pH 1.2) and intestinal fluid (pH 6.8) was evaluated in each coated granule.

Results: We changed coating agents and conditions in each trial to check the effect to the coating yield and enteric film property. Adding PGS could help the powder mixture to laminate on the pellet and dramatically improved the coating yield, which could achieve to 87% (Sample A-C). In addition, by increasing the heating temp., the acid resistance of the coating layer was improved, and we could also confirm that the heating temp. is important to form a denser film (Sample C-D). Mixing PEG-4000 (water soluble) and Stearic acid (water insoluble) in specific ratio could balance the well acid resistance in pH 1.2 and immediate release in JP2 (Sample E-G).

Conclusion: By selecting solid ingredients as plasticizer and wetting agent, we could establish new dry coating system without spraying. And we could confirm that coating agents and conditions can affect the productivity and dissolution property of the dry coating. Using this technique, we can achieve the higher productivity coating process in which we don`t need any time of liquid preparation or dryness and eco-friendly method which don`t need any organic solvent.

Table 1. Formulations and conditions of dry coating

Figure 1. Dissolution profile of samples (pH1.2)

Figure 2. Dissolution profile of samples (pH6.8)