Sun Y M, Hsu S C, Lai J Y
Department of Chemical Engineering, Yuan Ze University, Chung-Li, Taoyuan, Taiwan, Republic of China.
Pharm Res. 2001 Mar;18(3):304-10. doi: 10.1023/a:1011098712693.
Ammonio methacrylate copolymer is a pharmaceutical excipient widely used as a coating material for encapsulation of pellet and tablet dosage forms. Because of the charged ammonio function groups within the polymer, ionic drugs may interact with the coating film while transporting through it. The kinetic swelling and drug permeation properties of the ammonio methacrylate copolymer membranes were studied to delineate the effect of ionic interaction between the ionic drugs and the membranes.
The pH and ionic strength of the solutions and the charged properties of drugs were varied to study the effects on the transport properties through the membranes. Ambroxol was chosen as a model cationic drug and aspirin as a model anionic drug.
The degree of membrane swelling in the drug-free solution decreases as the ionic strength increases but it is irrelevant to the pH. With the presence of ionic drugs, the degree of membrane swelling is affected by the drug species as well as the pH of the solutions in addition to the effect of ionic strength. The degree of swelling for a membrane in a solution containing aspirin is higher at a lower pH and ambroxol is lower at a lower pH. Aspirin experiences a three-stage permeation and ambroxol a two-stage one. The ion-exchange reaction between the anionic carboxylic groups in aspirin and the cationic ammonio groups in the membranes results in a slow permeation stage during the transient state. The pseudo steady-state permeability for each drug follows the trend as the degree of membrane swelling in the drug media at various pH and ionic strengths. However, it is much higher for aspirin than ambroxol although the degree of membrane swelling is higher in an ambroxol solution than that in an aspirin solution. The permeability of ambroxol through the membrane is largely reduced because of the Donnan exclusion effect.
The interaction between ionic drugs with the cationic groups in the membranes affects the ionic strength of the solutions and results in a pH-dependent degree of swelling. The ionic interaction also determines the drug permeation rates as well as the transient permeation behaviors.
