Microstructural and drug release properties of oven-dried and of slowly or fast frozen freeze-dried MCC-Carbopol ® pellets

Abstract

The influence of the procedure and conditions of drying (oven-drying and freeze-drying after slow or fast freezing) and of the CaCl 2 concentration in the wetting liquid on the physical characteristics and drug release behaviour of microcrystalline cellulose (MCC)-carbopol 40:60 pellets containing theophylline or ketoprofen has been evaluated. The microstructural, morphological and mechanical properties can be modulated, to a large extent, through the control of the drying step and the CaCl 2 proportion. The drying step determines the volumetric contraction of the pellets and, consequently, the porosity parameters. When freeze-drying is applied, the freezing conditions have a marked influence on total porosity and mean pore size of the pellets. Slowly frozen pellets present the lowest porosity but the pores are the greatest. Pore size appears as a critical factor for achieving controlled release; the greater the pores, the faster the entrance of water and, consequently, the drug release. Therefore, if freeze-drying is used to remove water from wet pellets, the control of the ice formation is essential to modulate the release profiles. The practical possibilities of such modulation are especially clear for a slightly-water soluble drug, such as ketoprofen.