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