Disintegrating pellets with improved dissolution/release performances

Purpose. The use of beta-cyclodextrin (betaCD) was previously proposed to overcome the matrix-like behaviour related with the lack of disintegration of pellets based on microcrystalline cellulose (MCC) as the spheronizing agent. The aim of the present work was to assess the influence of the solubility, disintegrating properties and ability to form interaction compounds of betaCD on the dissolution performances of such pellets. For this purpose, the effect of differing amounts of betaCD on the dissolution of a poorly soluble model drug (ibuprofen) from pellets containing 20% w/w of MCC, and the replacement of betaCD with soluble fillers (lactose, sorbitol) or disintegrants (Ludiflash®, Polyplasdone® XL, RxCipient® FM1000 and Explotab®) were evaluated. Methods. Pellets were prepared by mixing (turbula, 10 min), wet granulation (300 g of powder blend and distilled water in sufficient amounts to achieve the proper mass consistence for extrusion), extrusion through a radial screen extruder (NICA, type E4, Sweden; hole diameter 1.0 mm, screen thickness 1.25 mm, feeding speed 90 rpm, agitator speed 60 rpm), spheronization (NICA, type S2-450; plate rotation speed 800 rpm, 3 min), drying in oven (40°C, 24h). Pellets were characterized in terms of size, shape, friability, mechanical resistance, disintegration and dissolution performances. Disintegration tests (sample 50 mg) were carried out in a pharmacopeial apparatus provided with a 125 micron porous membrane placed at the bottom of the basket-rack assembly, with and without discs. Dissolution tests were carried out in a USP 30 paddle apparatus (1000 ml distilled water with 0.5% sodium lauryl sulphate, 37±0.5˚C, 100 rpm). Drug concentration was determined by spectrophotometer. Results. The ability of betaCD to improve the disintegration performance of pellets and promote ibuprofen dissolution was confirmed. Generally, soluble fillers and disintegrants irrespective of the inherent disintegration mechanism showed a lower impact on drug dissolution with respect to betaCD. Conclusion. The overall results indicated that an enhanced drug apparent solubility may play a major role in the performance of betaCDbased pellets. Furthermore, the use of betaCD was confirmed to be an effective formulation strategy to improve the functionality of pellets containing MCC as the spheronizing agent.