Delivery orifice

Polymeric Expanded push compartment push compartment

Before operation During operation

Figure 8.38 Cross-section of the 'push-pull' osmotic pump for nifedipine.

Reproduced from A. Zaffaroni, Ann. N. Y. Acad. Sci., 618, 405 (1991).

osmotic pump (Oros or Osmet) the drug is mixed with a water-soluble core material. This core is surrounded by a water-insoluble semipermeable polymer membrane in which is drilled a small orifice. Water molecules can diffuse into the core through the outer membrane to form a concentrated solution inside. An osmotic gradient is set up across the semipermeable membrane with the result that drug is pushed out of the orifice (Fig. 8.37).

The core may be a water-soluble polymer, an inert salt or, as in the case of metoprolol fumarate,13 the drug itself, whose saturated solution has an osmotic pressure of 32.5 atm. The osmotic tablet of nifedipine is described in detail in Fig. 8.38, which shows the semipermeable cellulose acetate coating, the swellable hydrogel layer of polyoxyethylene glycol and hydroxypropylmethylcellulose (HPMC) and the drug chamber containing nifedipine in HPMC and PEG.

For simple osmotic systems the initial zero-order delivery rate (dm/dt) is given by dm A

Calculated and experimental release rates are shown in Fig. 8.39.

One problem is that of controlling the transit of the device down the gastrointestinal (GI) tract, as individual subjects vary considerably in GI transit times. If the system is designed to release drug over a period of 10 hours and total transit time in the gut is 5 hours, bioavailability will obviously be reduced.

Transdermal delivery systems

Several transdermal systems ostensibly dependent on rate-controlling membranes are available for the delivery of glyceryl trinitrate,

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