An All-Round Excipient For Direct Compression

In the past, many efforts have been made to develop a single excipient that incorporates the properties of a binder, disintegrant and lubricant, and which can also be used for direct compression of an API. Using new co-processing technologies, the authors show that it is possible to formulate such an 'all-round' excipient.
Oct 01, 2010


WJONES/GETTY IMAGES.
A classical powder mixture for the direct compression of tablets contains at least a binder and a lubricant, as well as, in some cases, a disintegrant and a glidant. Magnesium stearate is usually used as a lubricant, but this dramatically limits the blending time of a powder mixture,1 and also decreases tablet hardness and retards disintegration time.2 Moreover, magnesium stearate is incompatible with many APIs, mainly because of the electrophilic character of the Mg2+ ion and the basic reaction of the material itself.3,4

In the past, many efforts have been made to develop a single excipient that incorporates binding, disintegrating and lubricating properties, but none of these attempts were successful because of the limitations linked to magnesium stearate. However, new approaches to this challenge have been made possible using more hydrophilic lubricants such as stearic acid, glycerin monostearate and sodium stearyl fumarate.5 Because all of these materials show a higher watersolubility than magnesium stearate, it is easier to coprocess them in aqueous systems. Such lubricants have been used in pharmaceutical technology for many years and the advantages over magnesium stearate are very well known.6


The authors say...
To reduce the number of additives in a formulation and to overcome the problems associated with magnesium stearate, we have developed a coprocessed excipient that acts as a binder, disintegrant, lubricant and a glidant — an 'allround' commercial excipient called the PROSOLV EASYtab. We tested this product both in the laboratory and under production conditions. Overall, we found that this new material gives a much higher tablet output, particularly in highspeed rotary presses. Even at high tabletting speeds, the content uniformity of the coprocessed excipient was better than that of the physical mixture.

Materials and methods

Both, the 'allround' excipient and the physical mixture are composed from a binder (microcrystalline cellulose; VIVAPUR, JRS Pharma), a glidant (colloidal silicon dioxide; Aerosil, Evonik ), a disintegrant (sodium starch glycolate; VIVASTAR, JRS Pharma) and a lubricant (sodium stearyl fumarate; PRUV, JRS Pharma).


Figure 1: Physical mixture of microcrystalline cellulose, colloidal silicone dioxide, sodium starch glycolate and sodium stearyl fumarate. The components differ in appearance and can be easily distinguished. It is obvious that this powder mixture may have segregation. (MCC = microcrystalline cellulose, SSG = sodium starch glycolate, CSD = colloidal silicon dioxide, Lub = lubricant)
Tablets were compressed using a Fette 2090i (Fette Compacting, Germany) highspeed rotary press for the highspeed compression trials. A Schleuniger Pharmatron 8M (Dr. Schleuniger Pharmatron, Switzerland) was used to test tablet hardness. Both, the physical mixture of all four components and the coprocessed 'all-round' material were tested using the Fette 2090i system.


Figure 2: The single all-rounder excipient. The particles look very homogenous. All components from the physical mixture are well integrated.
The use of co-processing technology — a synergistic consolidation of all excipients into one to develop powders for direct compression — is becoming increasingly popular. Coprocessed powders generally give superior properties, mainly in flowability, but also in tablet hardness compared with physical mixtures.7,8 As such, coprocessing was used to manufacture the 'all-round' excipient. The ingredients were co-processed with a coprocessing technology based on a fluidbed granulation, which makes the particles more homogenous and less prone to segregation. Figure 1 and Figure 2 show the appearance of the starting material and the finished excipient, respectively.

The 'all-round' excipient was co-processed to create a medium particle size of 100 µm. The specific surface area was 6.4 m2/g for the co-processed excipient and 3.6 m2/g for the physical blend of the four components. In all trials, paracetamol tablets were pressed with 300 mg weight to a diameter of 13 mm. Tablets from the co-processed excipient contained 60% paracetamol and 40% PROSOLV EASYtab; tablets from the physical mixture were composed of 60% paracetamol, 38.6% of microcrystalline cellulose, 0.8% of colloidal silicon dioxide, 0.4% of sodium starch glycolate and 0.2% of sodium stearyl fumarate.