A major disadvantage of postoral delivery is that blood flow from the intestine leads into the portal vein which flows directly to the liver. This leads to the phenomenon of first pass clearance, in which drug is metabolized and/or excreted by the liver before it can reach the general circulation. Other routes of administration circumvent this direct flow to the liver and may have other specific advantages.

Sublingual or Buccal Administration:

Buccal or sublingual delivery is typically used for relatively potent drugs that are readily absorbed but undergo extensive first pass clearance. Specific dosage forms designed for the buccal cavity include sublingual tablets, buccal sprays, and buccal patches. These are not as readily accepted as postoral tablets but are still non-invasive and patient friendly.

Technically a dosage form for buccal administration has a quite high probability of success, and marketability and cost of goods would also be reasonable. Unfortunately the high probability of technical success could be a bit of a double-edged sword in that it could be used as the basis for an argument of obviousness by a patent examiner or someone challenging a patent in the future.

Oral Disintegrating Tablet:

Oral disintegrating tablets (ODTs) have been developed for ease of use since they do not require access to water and are suitable for patients who have trouble swallowing pills and capsules. Although these tablets are not typically intended to improve bioavailability, if a drug is absorbed rapidly enough, an ODT may act essentially as a buccal delivery dosage form.

Although the probability of technical success is lower for this approach than for specifically designed buccal dosage form, there are two substantial advantages. First, since ODTs are considered to be simply a different presentation for postoral delivery, any finding of improved bioavailability would be unexpected and would therefore constitute novel intellectual property. The second advantage is that unlike sublingual tablets, buccal sprays, and buccal patches, an ODT is considered to have a marketing advantage over standard postoral tablets and capsules.

Nasal Spray:

Another alternate delivery site is the nasal cavity. Currently, nasal sprays are used almost exclusively for local, rather than systemic, delivery, so there would be an inherent degree of novelty in a nasal spray formulation that would make an intellectual property platform easier to obtain. However, there are reasons why nasal sprays are not commonly used for systemic delivery, and these serve as impediments to this approach.

The primary obstacle to nasal delivery is patient friendliness and patient acceptance. Nasal sprays are inconvenient, are relatively difficult to use, and can cause local irritation. Furthermore, dosing can lack reproducibility due to the coordination required in activating the device while inhaling and the effects of nasal inflammation and mucus secretions. Another limitation of nasal sprays is that the amount of drug delivered is quite limited. A typical device delivers 50