John Fitzpatrick
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When it comes to immediate‑release tablet formulations, the choice of disintegrant can have a significant effect on the rate
and extent of drug dissolution. Once a tablet disintegrates, the characteristics of the API, either alone or assisted by other
formulation ingredients, determine the dissolution rate and extent of the API. Thus, the choice of superdisintegrant is important,
especially with poorly soluble APIs.
Not all superdisintegrants are the same
The three most common classes of superdisintegrants are: crospovidone, croscarmellose sodium and sodium starch glycolate.
In general, all of these provide rapid disintegration at low use levels in both wet and dry granulations and direct compression
tablet processes; however, the classes of disintegrants differ in chemistry and particle morphology. Crospovidone possesses
unique pyrrolidone chemistry and a highly porous particle morphology that results in high surface area. The high surface area
combined with unique chemistry results in high-interfacial activity that serves to enhance the dissolution of poorly soluble
drugs in a way that is not possible with other disintegrant technologies. Indeed, studies have shown that tablets containing
a poorly soluble API and crospovidone, Type B, have significantly faster dissolution rates compared with tablets formulated
with other superdisintegrants (1).
It has been widely reported that more than 60% of drugs in development and over 40% of recently launched drugs have issues
related to poor solubility, leading to long development times or cancellations. Before evaluating advanced techniques, such
as amorphous solid dispersions, more traditional approaches such as the influence of superdisintegrants on dissolution are
now being considered. The selection of a superdisintegrant and the use level plays a key role in determining the drug release
of finished formulations
Choosing an optimal superdisintegrant
It is important to consider the impact of the superdisintegrant with respect to the performance of the final dosage form.
As drug dissolution is essential for absorption by the body, formulators no longer select disintegrants based on the lowest
disintegration time because it is important to also consider the effect of the superdsintegrant on dissolution. Additionally,
the ionic nature of both the API and the superdisintegrants must also be considered. Anionic superdisintegrants, such as croscarmellose
sodium and sodium starch glycolate, can interact with cationic APIs and retard dissolution. Thus, nonionic superdistegrants
are preferred when working with cationic APIs. Formulators also consider the impact of the superdisintegrant on physical tablet
characteristics, such as tablet breaking force and friability. In today’s high-speed tablet presses, superdisintegrants that
provide tablets with high breaking force and low friability, while maintaining fast disintegration, are particularly important.
Oral disintegrating tablets (ODTs)
There are a growing number of oral disintegrating tablets (ODTs) and chewable tablets available on the market. These products
have increased in popularity because consumers—old and young—find them convenient and easy to use. In addition, pharmaceutical
companies have found an opportunity to extend product lifecycles or differentiate their products by offering these new dosage
forms. To achieve rapid disintegration in the mouth in a direct compression ODT formulation, the selection of superdisintegrant
and optimisation of use level is an important consideration. In a recent internal ISP survey of commercially marketed ODT
products, it was found that more than 60% of the products surveyed used a superdisintegrant. The most common superdisintegrant
listed in the ingredients was crospovidone.
New innovation
One recent innovation from ISP is the introduction of two new Grades of crospovidone that have lower specifications for peroxides
compared with other commercially available crospovidone products. These low peroxide levels are achieved by manufacturing,
drying, packaging and sealing the product under inert conditions to limit peroxide formation.
It is likely that the proliferation of blended/co-processed systems will continue, but the major innovations will be at the
polymer chemistry level. With a better understanding of the physico-chemical properties achievable via advanced polymer science,
improvements such as optimised particle morphology, cross-link density and purity will lead to new formulation and processing
approaches.
References
1. J. Balasubramaniam and T. Bee, Pharmaceutical Technology, Excipient suppl. s24–s14 (2009).
John Fitzpatrick is Global Director, Plasdone and Polyplasdone at ISP.
