Drug permeation through a swollen cross-linked amylose starch membrane

Cross-linkedhigh amylose starch (CLA) is a pharmaceutical excipient used in direct compression for the preparation of controlled-release tablets and implants. In this work, the permeation properties of different model compounds through CLA membranes were examined. The membranes were prepared by compression in an instrumented eccentric machine, and then hydrated in aqueous buffers for 36 h. The apparent permeability (P app ) of the membranes was measured according to the 'lag-time' model by the diffusion-cell technique. The partition coefficient (K) was determined separately, and the diffusion coefficient (D g ) was then calculated using P app and K. The effects of compression force, CLA particle size, membrane thickness, additional excipients such as hydroxypropylmethyl cellulose (HPMC), magnesium stearate (MgSt) or colloidal silicon dioxide (CSD), and pH of the diffusion medium were evaluated. The permeation of rhodamine B in CLA was slightly influenced by compression force, particle size and the presence of HPMC (10%) or CSD (0.25 and 0.5%). The addition of MgSt (0.25 and 0.5%) significantly increased both P app and D g , while K was not affected. P app and D g decreased with membrane thickness. This was presumably caused by a loss of membrane homogeneity when thickness increased. Finally, an empirical relationship between D g , water solubility (S w ) and molecular weight (M w ) was established with model compounds possessing different S w and M w .