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  • Title: Incidence of drying on microstructure and drug release profiles from tablets of MCC-lactose-Carbopol and MCC-dicalcium phosphate-Carbopol pellets.
    Author: Gómez-Carracedo A, Souto C, Marti Nez-Pacheco R, Concheiro A, Gómez-Amoza JL.
    Journal: Eur J Pharm Biopharm; 2008 Jun; 69(2):675-85. PubMed ID: 18248805.
    Abstract:
    The influence of intragranular excipients (lactose or dicalcium phosphate) and the drying procedure and conditions (oven-drying and freeze-drying after freezing at -30 or -196 degrees C) on the properties of tablets of MCC-Carbopol pellets was evaluated. The drying procedure caused remarkable differences in pellet size and porosity (freeze-dried pellets were 3-fold more porous than those oven dried). Theophylline release from pellets was completed in less than 30 min and followed first-order kinetics, with a rate closely related to the intragranular porosity. The total porosity of the tablets (5-10%) was conditioned by the compression force (10-20 N), the drying procedure applied to the pellets and the coexcipient nature. Their intergranular porosity ranged inversely to the initial porosity of pellets due to the greater deformability of the most porous ones. A wide range of theophylline release rates were achieved depending on the drying procedure; tablets prepared from freeze-dried pellets sustained the release for 3h. Most profiles showed a bimodal kinetics with an initial zero-order release (while the tablets did not completely disintegrate) that changed, after a certain time, to a first-order kinetics. The intergranular porosity determined drug release rate up to disintegration. Then, the release kinetics became first-order and the rate constant, which was conditioned by the intragranular porosity, showed a complex dependence on the drying procedure, the compression force, and the nature of coexcipient. In sum, the modulation of drug release profiles from tablets of MCC-Carbopol pellets through an adequate control of the effects of the coexcipient nature, the drying procedure of pellets, and the compression force on the inter- and intragranular porosity opens interesting possibilities to control the release of hydrosoluble drugs.
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