Influence of Superdisintegrants on the Rate of Drug Dissolution from Oral Solid Dosage Forms

The authors examine common superdisintegrants (i.e., crospovidone Type A, crospovidone Type B, croscarmellose sodium, and sodium starch glycolate) with a set of poorly soluble drug actives and evaluate in vitro drug dissolution.
Apr 01, 2009

Table I
Dissolution is essential for a drug to be absorbed through the biological membranes into systemic circulation for therapeutic efficacy. Conventional tablet formulations generally require rapid disintegration to aid drug dissolution. Superdisintegrants are added to oral solid dosage formulations to facilitate disintegration. Commonly used superdisintegrants such as crospovidone, croscarmellose sodium, and sodium starch glycolate are highly efficient at low concentration levels (2–5 w/w%) in the tablet formulation at facilitating the rate and extent of tablet disintegration. The correlation between tablet disintegration and drug dissolution, however, is not always observable (1–3).

Table II
One recent study, for example, evaluated the respective effects of crospovidone, croscarmellose sodium, and sodium starch glycolate on the dissolution behavior of eight cationic drugs from a model direct-compression tablet formulation with 2% w/w superdisintegrant (4). No significant differences were observed in the disintegration times of the tablets. However, the study did show that crospovidone demonstrated a more rapid dissolution rate than the other superdisintegrants for the cationic drugs studied, irrespective of the drug's aqueous solubility.

Table III
The dissolution studies were performed for each drug in the compendial media for the drug. Crospovidone provided the fastest dissolution in the compendial media for seven of the eight drugs. Because crospovidone is nonionic, ionic interaction between this superdisintegrant and the cationic drug was impossible. In contrast, croscarmellose sodium and sodium starch glycolate are both anionic, and these superdisintegrants could potentially interact with cationic drug actives and slow their dissolution. As a result of these observations, the authors recommended formulation screening of superdisintegrants during excipient selection to minimize dissolution retardation resulting from any drug–excipient interaction.

Table IV
More than 60% of new drugs currently in development today are considered poorly soluble, as are nearly half of the drugs whose patents will expire in the next 10 years. Selecting formulation ingredients that enhance the dissolution of poorly soluble drugs has therefore become 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. Water-soluble drugs provide rapid and high-level drug release. However, other ingredients in the formulation of poorly soluble drugs, including the disintegrant, must play a key role in determining the finished formulation's drug-dissolution characteristics. With that in mind, this study was conducted to explore the impact of superdisintegrant selection on the rate of dissolution of poorly soluble drugs.