Co-Processed Excipient for Direct Compression Designed for Orally Disintegrating Tablets

Introduction

Developing orally disintegrating tablets (ODTs) is a worldwide trend. In recent years, new excipients and excipient blends have enabled manufacturers to produce ODTs using conventional equipment, ie, blenders and tablet presses. One such product is GRANFILLER-D, a co-processed excipient for direct compression ODTs. ODTs with GRANFILLER-D provide:

-Well-balanced properties between tablet hardness and disintegration time
-High-dosing capacity of active pharmaceutical ingredients (APIs)
-Good content uniformity of APIs

Powder Properties & Basic Characteristics

GRANFILLER-D includes four excipients listed in the USP, EP, and JP: mannitol, crospovidone, carmellose, and microcrystalline cellulose. These are co-processed using a unique water-based granulation method. Two grades of GRANFILLER-D with different median particle sizes are supplied: GNF-D211 has particles of 100 µm, and GNF-D215 has particles of 140 µm (Table 1). In addition, GRANFILLER-D (grade GNF-D211) has a US Master File and is used in marketed drug products mainly in Japan.

To make ODTs with GRANFILLER-D, one or more APIs, flavoring agent, sweetener, and a lubricant are blended and then compressed on a standard tablet press. The ODTs show satisfactory formability and rapid disintegration without addition of binders or disintegrants. This co-processed excipient significantly simplifies the formulation and manufacturing process of ODTs.

Characteristic Disintegrating Mode

ODTs using GRANFILLER-D have extremely rapid disintegration. In traditional ODTs, porous tablets are prepared with low compression force to ensure a water absorption route. However, in OTDs composed of GRANFILLER-D, the granule particles themselves function as the water absorption route.

The manner in which ODTs using GRANFILLER-D disintegrate differs from that of conventional ODTs. As ODTs that use conventional excipients disintegrate, they divide into block-like pieces. In contrast, when ODTs using GRANFILLER-D disintegrate, they exhibit a cream-like consistency, which improves mouth-feel (Figure 1).

Figure 1. Cream-like state in disintegration process

Balance Between Tablet Hardness & Disintegration Time

GRANFILLER-D allows the application of high compression forces. Even when compressed to a higher hardness range, tablets made using GRANFILLER-D maintain their short disintegration times. This superior hardness-disintegration property enables formulators to incorporate a wider variety of APIs into ODTs (Figure 2).

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High-Dosing Capacity

GRANFILLER-D also accepts high content of API while maintaining high hardness and rapid disintegration. Due to this high dosing capacity, GRANFILLER-D also provides the flexibility to formulate controlled-release tablets, mask bitter tastes, and stabilize APIs. Even if an API accounts for 30 to 70% of a tablet weight, trial ODTs made with GRANFILLER-D exhibit satisfactory hardness (greater than 40 to 50 N) and rapid disintegration (less than 20 to 30 seconds). This result suggests that the particles of GRANFILLER-D function as water absorption routes regardless of tablet porosity and the amount of API. Even when the ODTs contained poorly water-soluble APIs (eg, ethenzamide and acetaminophen), they exhibited excellent hardness-disintegration properties at a content of 50% to 70% (Figure 3).

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Flowability, Mixing Characteristics & Content Uniformity

The particles of many direct-compression excipients are spherical or nearly spherical and therefore have very high flowability. GRANFILLER-D particles, however, are non-spherical and irregularly shaped; the angle of repose is about 40 degrees , which exceeds the 30 degrees that is typical of ODT excipients whose particles are more spherical. GRANFILLER-D nonetheless has sufficient dynamic flowability for practical use and can be tabletted on presses equipped with force-fed and open feeders. In one case, a 38-station tablet press equipped with a force-fed feeder was used. It showed stable compression force, with a coefficient of variation (CV) of 3.6% when tableting GNF-D211 and a CV of 3.5% when GNF-D215 was used. The tablet weight CVs were 0.44% for GNF-D211 and 0.63% for GNF-D215. The values held steady even at a press speed of 100 rpm.

It is well known that blending improves when the sizes of the particles in the excipient and API are equivalent. Yet GRANFILLER-D blends well with APIs whose particles are smaller than those of the excipient due to their non-spherical, irregular shape (Figure 4). This was demonstrated by testing the content uniformity of ODTs containing just 1% of ibuprofen. Four samples of ibuprofen, each with a different median particle diameter (135, 34, 14, and 7 µm) were blended with GRANFILLER-D GNF-D215. The CVs of the API content in the resulting ODTs were 2.4%, 2.8%, 2.0%, and 3.3%, respectively.

DAICEL CORPORATION
Pharma Solutions, New Business Development
1-8-23, Konan, Minato-ku, Tokyo, 108-0075, Japan
T: +81-3-6711-8169, FAX: +81-3-6711-8168
W: https://daicel-excipients.com/
Contact: daicel-excipients@jp.daicel.com

Disclaimer
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