(T1430-10-59) Enhanced Versatility of a Novel Coating Methods of Fine Particles for Time-Saving

Tuesday, October 22, 2024

2:30 PM – 3:30 PM MT

Presenting Author(s)

AS

Ayaka Sato, MS

Staff Member
Freund Corporation
Hamamatsu-shi, Shizuoka, Japan

Main Author(s)

AS

Ayaka Sato, MS

Staff Member
Freund Corporation
Hamamatsu-shi, Shizuoka, Japan

Co-Author(s)

KA

Keisuke Ai, MS

Staff Member
Freund Corporation
Hamamatsu-shi, Shizuoka, Japan
IT

Ikuo Tanai, MS

Senior Research Scientist
Freund Corporation
Hamamatsu-shi, Shizuoka, Japan
YM

Yasuaki Morimoto, MS

Manager
Freund Corporation
Hamamatsu-shi, Shizuoka, Japan

Purpose: In the previous study, we introduced a new powder layering technology as a time-saving method to solve the issue of the enormous amount of time required for fine particle coating. In the past, we selected Acetaminophen (APAP), which is a water-soluble API, as the API to be layered.
In this study, we used Ethenzamide (EZ), which is soluble in water, as a model API to confirm the versatility of the powder layering method.

Methods: For API layering, NONPAREIL-MM (80) (NP-MM(80)) with an average particle diameter of about 80 µm (Mannitol-MCC spherical pellets) was used as the core particles. We selected EZ, which is less soluble in water, as a model API. EZ 30% layered pellets were prepared by putting NP-MM(80) into a high shear granulator (GM-MULTI) and the mixed powder of EZ 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 API-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 (Figure1). In addition, assuming that there is API that is more difficult to layer, we tried adding mannitol powder as a water-soluble excipient or spraying it during API layering.

Results: Powder layering was possible with poorly water soluble EZ, under the same conditions as APAP, and the time for 30% layering was 21 minutes. Polymer layering was also possible for the API-layerd pellets, and the time required for polymer layering was 26 minutes, and a total of 83 minutes including the curing time in the granulator. Regarding the dissolution rate, the API-layered pellets increased in the early stages of dissolution, whereas the dissolution rate of the polymer-layered pellets 1 minute after the start of dissolution was 3.0%, which was less than 10% to be confirmed sufficient masking. Furthermore, the API content of the API-layered pellets prepared by powder layering was 98.4%, and the API content of the API-layered pellets was further increased by adding water-soluble excipients (Powder form: 100.6%, Liquid form: 99.1%).

Conclusion: The novel coating method introduced in the previous study is a solution to the issue of the time required for fine particle coating. In order to apply this to a wider range of API, we focused on the water solubility of the API and conducted an investigation. As a result, we confirmed that layering is possible even with API that is less soluble in water. Moreover, the addition of water-soluble excipients is expected to improve the layering efficiency of the API. Since there were no problems with the API content or dissolution rate of the functional pellets prepared in this coating methods, we suppose that powder layering using a high shear granulator may be a more versatile method for solving the issues of fine particle coating.

Figure 1: Schematic of API and polymer layering