The influence of superdisintegrant choice on the rate of drug dissolution

Sep 01, 2009
Volume 21, Issue 9

This article is an adaptation of an article published in Pharmaceutical Technology, April 2009. The full version can be accessed at:

(Todd Pearson/Getty Images)
Dissolution of a drug is essential for its absorption through the biological membranes into systemic circulation and, thus, for therapeutic efficacy. To aid dissolution, conventional tablet formulations generally require rapid disintegration, which can be facilitated by the addition of superdisintegrants. Commonly used superdisintegrants, such as crospovidone, croscarmellose sodium and sodium starch glycolate, are highly efficient at low concentration levels (2–5 w/w%) in tablet formulations at facilitating the rate and extent of tablet disintegration. However, the correlation between tablet disintegration and drug dissolution is not always observable.1–3

More than 60% of new drugs in development — along with nearly half the drugs coming off patent in the next 10 years — are poorly soluble, and selecting formulation ingredients that enhance dissolution is increasingly important to achieve therapeutic efficacy. Once a tablet disintegrates, the solubility properties of the drug, either alone or assisted by other formulation ingredients, determine the drug's subsequent dissolution rate and extent of release.

The solubility properties of water-soluble drugs result in rapid and high-level drug release, but with poorly soluble drugs, other ingredients in the formulation, including the disintegrant, play a key role in determining the drug dissolution characteristics exhibited by the finished formulation.

With that in mind, a study was conducted to explore the impact of superdisintegrant selection on the dissolution rate of poorly soluble drugs.

Chemical and physical properties

Crospovidone, croscarmellose sodium and sodium starch glycolate are superdisintegrants widely used to accelerate the rate of disintegration in oral solid dosage forms. Although these materials are used to provide the same function within the formulation, they differ in their chemical structure, particle morphology and powder properties.

Croscarmellose sodium is the sodium salt of a cross linked, partly O (carboxymethylated) cellulose, while sodium starch glycolate is the sodium salt of a carboxymethyl ether of starch or of a cross linked carboxymethyl ether of starch.4 Both are sodium salts and are anionic. In addition, their polymer backbones are composed mostly of glucose repeat units.

In contrast, crospovidone is an insoluble, cross-linked homopolymer of N vinyl 2 pyrrolidone and is nonionic. Chemically, the repeat structure of crospovidone is similar to N methylpyrrolidone (NMP), a water miscible, polar aprotic solvent with high interfacial activity used as a solubilizer in many applications.

Table 1: Comparison of physical properties of common superdisintegrants.
When examined under a scanning electron microscope, croscarmellose sodium particles have a fibrous, nonporous structure; sodium starch glycolate particles are spherical and nonporous; and crospovidone particles (Type A and Type B) appear highly porous and granular (Table 1).

As outlined in the European Pharmacopoeia, crospovidone is available in different particle sizes, with crospovidone Type B having a smaller average particle size than crospovidone Type A. Although they differ in particle size, both types have similar particle morphology. In Table 1, a comparison of typical average particle size and surface area, determined by a Malvern Mastersizer (Malvern Instruments, UK) and BET gas adsorption, respectively, of the superdisintegrants shows crospovidone Type B to have the smallest particle size with highest surface area. The high surface area further increases interfacial activity, which can aid drug dissolution. Thus, the unique, chemical structure and powder properties of crospovidone Type B may improve the dissolution of poorly soluble drugs.

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