Membrane Based Delivery
Devices such as the Norplant™ or the Vitrasert® are capable of pseudo-zero order delivery for periods of many months. The linearity of the drug release is achieved through the use of semi-permeable coatings. Water from tissue fluid diffuses through the membrane and dissolves the drug pellet, thereby creating a saturated solution inside the membrane. The drug in solution diffuses along a concentration gradient back through the membrane. Because the inside solution is saturated until the drug pellet is almost completely dissolved, and since the concentration outside the membrane is very low and relatively constant (sink conditions), the concentration difference between the inside and the outside of the membrane (and therefore the drug delivery rate) remains relatively constant for the majority of the duration of the drug delivery period. However, these devices require surgical implantation and are not suitable for most pharmaceutical indications because of dose size or frequency requirements.
On the other hand, currently available polymer-based sustained release suspensions can be injected, but have their own set of problems – poor drug loading, initial burst and poor delivery profiles. In contrast, the Plexis™ technology can theoretically deliver a drug in a pseudo-zero fashion as long as the polymer coating is intact and as long as there is enough drug remaining to maintain a saturated solution inside the microcapsule. Large particle size relative to membrane thickness leads to two additional benefits. First, the drug loading is substantially increased. For a 50um diameter drug particle with a 3um thick polymer coating, the drug loading is 84%. This means that there is less polymer used. Secondly, burst effects or drug dumping in the initial period of delivery leading to very high initial levels are not seen.