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Clinical Aspects

Fertin Pharma has over the years gained significant experience in the complex clinical aspects relating to medical chewing gum and registration of medical chewing gum.

Local effect

Systemic effects of active substances released from chewing gum can be achieved in two ways; either by swallowing or via buccal absorption through the oral mucosa. Chewing gum promotes buccal absorption by releasing active substances at carefully-controlled rates to give extended exposure in the oral cavity. Buccal absorption is of particular interest, as it avoids first-pass hepatic metabolism of the active substance.

Active substances that are absorbed through the buccal mucosa pass via the jugular veins directly to the systemic circulation. Due to the rich vascular supply of the buccal mucosa, measurable concentrations of active substance may be present in the blood after only a few minutes of chewing, making fast onset of action likely. Furthermore, hepatic first-pass metabolism and degradation in the gastrointestinal tract is avoided with buccal absorption. This also allows for an increase in bioavailability.

The buccal absorption of nicotine has been studied extensively. It is therefore a good example of buccal absorption through the use of chewing gum as a drug delivery system. A study carried out into the pharmacokinetics of nicotine chewing gum indicated that some nicotine was not absorbed buccally, but was swallowed and underwent first-pass metabolism (ref.1).
It was estimated that approximately 80% of nicotine released from the chewing gum was absorbed buccally. Even though the percentage swallowed for a 4 mg formulation was higher than that of a 2 mg formulation, the delivered systemic dose was only 50% higher after intake of the 4 mg formulation. A similar result was recorded when administering nicotine in a sublingual tablet, Though incorrect use of the sublingual tablet lead to variations in bioavailability (ref.2).

Different delivery forms employing buccal absorption have been compared in a study using a model substance.   The study looked at local kinetic parameters after administration of lozenges, chewing gum, and sublingual tablets containing the model substance. Six healthy males were included in the crossover study. The disappearance half-life from the oral cavity (T½) was longest for sublingual tablets, followed by chewing gum and then lozenges. The AUC values obtained from the activity-time curves in the oral cavity followed the same pattern: highest for sublingual tablets, followed by chewing gum and then lozenges – all differences were statistically significant. In the discussion, the authors comment on other problems relating to correct placement of the sublingual tablet and the resulting differences in bioavailability.

With any chewing gum formulation, part of the active substance will be swallowed along with the saliva and absorbed through the GI tract. This process is comparable to absorption from conventional tablets. However, as the active substance released from chewing gum is dissolved in saliva, it is readily accessible for absorption. This also means that the processes of disintegration and dissolution are bypassed.

References