Preparation of Orally Disintegrating Tablet by Co-Spray Drying F-MELT® and Active Ingredients

Issue 26: AUG 2012

Preparation of Orally Disintegrating Tablet by Co-Spray Drying F-MELT® and Active Ingredients

Ref: Hitoshi Machimura¹, Japan Society of Pharmaceutical Machinery and Engineering, 20, 26-32 (2011)

1: Fuji Chemical Industry Co., Ltd.

INTRODUCTION
F-MELT® is a spray-dried excipient designed to manufacture Orally Disintegrating Tablet (ODT). ODT can easily be manufactured through direct compression by blending F-MELT® with active ingredient and lubricant. In certain cases where the formulation consists of cohesive fine particles, exhibits poor flowability and have high drug load, Co-Spray Dry (Co-SD) method is offered as a solution.

CASE STUDY 1. ODT design by Co-SD with F-MELT® and micronized Acetaminophen(AA)

Micronized AA (mean particle size of approximately 2 µm) was selected as a model drug, and was mixed with F-MELT® Type C to prepare slurry. Co-SD powder with drug content of 20%, 40%, and 60% were then prepared. SD was easily performed at all the drug concentration. The pre-mix powder for direct compression was prepared from micronized AA at high content while maintaining good flowability. The Co-SD powder was mixed with 0.4% of magnesium stearate (Mg-St) and tablets of 8 mm diameter and 200 mg in weight were produced using a rotary tableting machine. Tablets using the Co-SD powder could be compressed at considerably low compression force of 4-5 kN for all the AA content of 20%, 40%, and 60%.

Figure 1. Tablet characteristics of ODT prepared from Co-SD powder of F-MELT® and Acetaminophen

Figure 1. shows the tablet hardness and disintegration time of the ODT prepared by the Co-SD method. Good moldability and disintegratability were observed at all the drug load. Preparation of pre-mix powder for direct compression by Co-SD method was found beneficial for tablets containing high content of micronized active ingredient.

Stability tests for the ODT were conducted under open conditions at 25°C, 75%RH for one week. Figure 2. shows the tablet hardness before and after the stability test as well as hardness retention ratio. The initial hardness was 60-70 N, and a comparatively high hardness of at 45-65 N was maintained after stability test, achieving a 75-95% retention ratio.

Figure 2. Tablet hardness and retention rate of ODT prepared from Co-SD powder of F-MELT® and Acetaminophen

To optimize the ODT formulation and further improve the disintegration time, a disintegrant and additional filler were added to the Co-SD powder with AA content of 40%. (Table 1).

Table 1. Improvement in ODT performance by adding a disintegrant and filler

Granulation Method	Co-SD
F-MELT® Type C (wt%) Acetaminophen (wt%) (D50=12 μm) Co-SD (AA40%)	- - 75
Disintegrant	2.6
Other filler	22.0
Mg-St (wt%)	0.4
Molding pressure (kgf)	510-550
Tablet hardness (N)	56.8
Oral disintegration time (sec)	11.9
25˚C × 75%RH, Open for 1 week
Tablet hardness (N)	37.0
Hardness retention rate (%)	65.1
Oral disintegration time (sec)	11.7

Disintegration time after storage under open conditions was good without substantial change. The ODT produced from the Co-SD powder also showed better hardness retention ratio after stability test.

CASE STUDY 2. ODT design by Co-SD with F-MELT® and "Drug D"

"Drug D" (name undisclosed) was used as a model active ingredient that has fine particles (mean particle size of 13μm) and exhibits poor flowability. ODT formulation by Co-SD of F-MELT® Type C and "Drug D" was examined, and the effects on powder flowability, tablet disintegration time and mouth feel were investigated. Table 2 shows the tablet properties of ODT manufactured by Co-SD method.

The Co-SD powder mix containing 40% of "Drug D" and 60% of F-MELT® Type C exhibited very good flowability, and it was possible to mold tablets with significantly low compression force and weight variation. Also, the mouth feel was excellent.

Table 2. Tablet property evaluation using the Co-SD powder containing "Drug D"

Drug D (wt%)	40
Type C (wt%)	59.2
Flavor/Sweetener (wt%)	0.4
Mg-St (wt%)	0.4
Compression force (kgf)	450-480
Tablet hardness (N)	58.2
JP Disintegration time (Sec)	19.1
Oral disintegration time (sec)	25.1
Tablet weight variation (CV%)	0.36
Mouth feel (Mealy texture, etc)	Good
Flowability	Very Good

Drug D, mean particle size-12.6 µm (dry laser method)
Tablet parameters: 9 mm diameter, flat face bevel edge, 250 mg tablet; rotary tablet compression machine, 15 rpm; tablet hardness: 55-60 N; tabletting machine: HT-AP18SS-II, Hata Iron Works Co., Ltd.
Tablets compressed at a compression force of 400-500 kgf were sampled.

CONCLUSIONS

The two examples demonstrate that Co-SD of F-MELT® with active ingredients is an effective method to prepare ODT of formulations with cohesive fine particles, poor flowability and high drug load. The Co-SD powder can be easily made into a ODT tablet through direct compression.

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