Suppression of Related Substance in Tablets Containing Pressure-Sensitive Drugs with Elongated Microcrystalline Cellulose

This poster was presented at the PBP World Meeting in Vienna 2024 by Asahi-Kasei

INTRODUCTION

It is known that the pressure, friction, heat, etc. applied during compression molding of some drugs causes crystal distortion and destabilization.
When dealing with such kinds of substances, excipient selection is important.
In this study, we report the use of different types of MCCs (Ceolus PH, Ceolus KG) to investigate their applicability in tablets containing candesartan cilexetil (CC) as a model pressure-sensitive drug.

Figure 4. CC and its related substances.

Ceolus Microcrystalline cellulose (MCC)

Ceolus brings unique properties due to their particle shapes.

Figure 1. Map of CeolusTM Compactibility vs. Flowability. — Figure 1. Map of Ceolus Compactibility vs. Flowability.

Ceolus PH (standard grade)

Figure 2. SEM images of CeolusTM particles.

Ceolus KG

Ceolus KG is a highly compactible MCC with elongated particles.

Solves tableting issues
Insufficient hardness, sticking, capping, high friability

Figure 3. Experimental example of using CeolusTM KG. — Figure 3. Experimental example of using Ceolus KG.

EXPERIMENTS

Table 1. Properties of MCCs used in this study.

1) Mixing condition: PE bag, Mixing time: 3 min.

2) Tool: MODEL-1011 CREEP, AIKOH ENGINEERING
Tablet size: 200mg, 8mmΦ-30R
*Tableting was carried out under the static condition
(10 sec of creep holding time).
*Compression force was adjusted to obtain the tablet
hardness of 50 N that is practically required value.

3) Tool: Model LC-10ADVP, Shimadzu Corporation
*The tablets were dissolved in a mobile phase to a
drug concentration of 160 mg/L, then filtered through a
0.45 μm filter.
*The ratio of related compounds was quantified by the
peak area ratio of CC and its related-compounds.

RESULTS

CONCLUSION

The tableting pressure to obtain tablets of the same hardness could be decreased with applying elongated-shaped MCCs (KG-1000 and KG-802) compared to amorphous-shaped MCC (PH-102).

The lower the compression force was applied, the less the amount of related substance generated.

KG-1000 showed the least amount of related substance.

See the full poster on “Suppression of Related Substance” here

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Source: Lei, J., Zhang, X., Zhuo, Z., Zhu, K., Sun, P., and Fan, Q., Asahi Kasei, HPLC-UV simultaneous determination of candesartan cilexetil and hydrochlorothiazide in compound candesartan cilexetil tablets, Yaow u Fenxi Zazhi, 27 (4), 566-568 (2007), Japanese Patent Publication 2008-505935A, poster “Suppression of Related Substance”, PBP 14th World Meeting, 18 – 21 March 2024, Vienna

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excipients formulation