(T1030-09-61) A Novel Method for Coating of Fine Particles to Time-Saving

Purpose: In the development of oral formulations for children, there is a demand for formulations that are easy to take without bitterness and grittiness in the mouth. One approach for improving medication adherence is masking bitterness by adding sweetener. Furthermore, physical masking (coating) is more effective for complete taste masking. However, it take a time to coat fine particles that do not give a gritty texture when taking medicine. To overcome this issue, we developed a coating method using a high shear granulator in a short time.

Methods: For drug layering, NONPAREIL-MM (NP-MM) with an average particle diameter of about 80 µm (Mannitol-MCC spherical pellets, under development) was used as the core particles. We selected Acetaminophen (APAP), which has a strong bitter taste, as a model drug. APAP 30% layering pellets were prepared by putting NP-MM into a high shear granulator (GM-MULTI) and the mixed powder of APAP and light silicic anhydride (AD-101) is powder-layered while spraying the Hydroxypropyl Cellulose (HPC-SSL) aqueous solution. For polymer layering, aminoalkyl methacrylate copolymer E (Eudragit, E PO) was chosen as the taste masking polymer. The drug layered pellets prepared above, the mixed powder of polymer, magnesium stearate, and AD-101 were put into a high shear granulator (GM-MULTI), and Triethyl Citrate (CITROFLEX 2(SC-60), TEC) aqueous solution was sprayed to prepare E PO 40% layered pellets(Fig.1).

Results: Using the developed coating method, it was possible to coat in about 1/10 the time for drug layering and about 1/8 the time for polymer layering, compared to conventional fluidized bed coating. In addition, although there was concern about the breakage of core particles during layering, no breakage was confirmed when NP-MM was used as the core. Furthermore, the yield was about 94% for APAP 30% layered pellets and about 96% for polymer layered pellets. The particle size distribution of the prepared APAP 30% layered pellets and polymer layering pellets shifted in the increasing direction as the coating progressed, and layering was completed without significant agglomeration and fine powder(Fig.2). The drug content of the prepared samples was 99.0% for APAP 30% layered pellets and 100.2% for polymer layered pellets. In addition, the dissolution rate of the polymer layered pellets after 1 minute was 10% or less, indicating sufficient taste masked coating. From the above, it was confirmed that the drug and polymer could be coated without loss even by powder layering in the agitating granulator.

Conclusion: In order to solve the issue of the time required for fine particle coating, we developed a novel coating method. As a result, it was confirmed that it is possible to significantly reduce the time required for layering by this method using a high shear granulator rather than the conventional coating method. Since no problems were observed in the yield, particle size distribution, drug content, and elution rate, we propose this coating method as a measure to solve the issues of fine particle coating.

Figure 1: Schematic of drug and polymer layering

Figure 2: Changes in particle size distribution