Gum: a friendly drug delivery system

L Maggi¹, L Segale¹, S.Conti¹, U Conte¹ and A Salini² discuss the use of chewing gum as a delivery system for nutraceuticals, drugs, food integrators and vitamin supplements.

Data from the Medicines Monitoring Unit (MEMO) at the University of Dundee indicates that only one third of patients are fully compliant with their drug prescriptions. One third are non-compliant while the re-maining third are considered completely non-compliant. The result is a $30bn annual cost to pharmaceutical companies from prescriptions and repeat prescriptions never filled and patients suffering in terms of loss of quality of life. From a patient's point-of-view, compliance tends to be more complicated for children or in people with swallowing disorders.

However, Flarer has developed a system that may alleviate some of these problems by introducing therapies in a chewing gum format. Such a dosage form offers a number of advantageous features: the drug is dissolved in the saliva, thereby increasing patient compliance; the drug is readily available for absoption and thus bioavailability increases; a discreet product means that it can be taken any way and at any time without the need for liquids to enable swallowing; the system can be used to act locally, for the treatment of oral cavity diseases, for instance; gastric mucosa will not suffer from direct contact with high concentrations of a solid state drug, thus reducing the risk of intolerance or erosion; possibility of administering lower dosages of active ingredient, thus reducing possible side effects; reduced likelihood of accidental overdose; if the gum is swallowed the mechanism of release, i.e. the saliva and chewing, is negated; and from a marketing view the method could revive old products such as vitamin C, which could be chewed as a person is training in the gym.

This new chewing gum entails a different production technology from the common industrial process, developed to prevent the gum-base heating/melting step and the consequent exposure of the active ingredient to high temperatures. The new '3TabGum' is obtained at room temperature by direct compression using conventional pharmaceutical equipment, and the resulting chewing gum consists of a gum core combined with two protective layers, mainly constituted by antiadhesive excipients, (see figure 1 and table 1). In this way, only the external antiadherent layers come into contact with the punches of the tableting machine and the sticking problems, generally encountered in direct compression, are solved.

drug uptake

The advantage of three layers is that different actives, even if incompatible with each other, can be filled in the same tablet simply by placing them in different layers. Furthermore, one active for immediate release can be placed in the external layers and an-other for prolonged release (30-40 minutes) in the internal layer.

3TabGums containing different model drugs were prepared and tested by a panel of volunteers to verify the drug release from the dosage form. Each person was asked to chew samples of tablet-gums for different time periods; the gum cuds were then cut into small pieces, frozen and ground to a fine powder, and the residual drug content was determined. The amount of drug released during mastication is obtained by subtracting the amount of the residual active ingredient present in the gum from the total content.

chewing time

Figure 2 shows the percentage of drug released as a function of mastication time from chewing gum containing sennosides, metoclopromide and ranitidine. The APIs are quickly released after a few minutes of mastication. Almost the 90% of the drug is delivered after a chewing time of 20 minutes: the mean chewing time of a gum being 36 minutes.1 No significant differ-ences in uptake can be seen between this time and those obtained after 30-40 minutes of chewing. In the case of chewing gums containing less soluble drugs, such as ketoprofen, acetylsalicylic acid, diclofenac, and paracetamol (figure 3), it is evident that the per-centage of the active delivered increases progressively as a function of the chewing time. The data indicates that after 40 minutes the medicament is almost totally delivered.

The new compression technology developed for the production of a three-layered medicated chewing gum provides good and advantageous results from a technological viewpoint. The application of external layers to a core containing the gum base makes it possible to produce chewing gum using direct compression.

Furthermore the therapeutic system discloses a good functionality and efficiency in term of release of the active.