Chewing Over API Challenges

Cafosa's excipient Health in Gum is a mix of ingredients to which APIs can be added. How are APIs added to create a novel dosage form?

Marc RibeTraditionally, medicated chewing gum has been formulated and manufactured using hot mixing and extrusion procedures, which involve specific equipment that most pharmaceutical companies are not familiar with. Moreover, the use of heat in this process prevents many APIs from being considered because of their sensitivity to high temperature levels.

Our Health in Gum is a homogeneous powder excipient produced using proprietary technology. It is a combination of gum base, softeners and polyols that enables formulation and dry mixing with the API to produce chewing gums by direct compression. Medicated chewing gum is an interesting option for pharmaceutical companies looking to differentiate themselves by introducing products that are more attractive to consumers, but that possess the same efficacy as other dosage forms. In particular, the technology is useful to look at in light of the fact that many people dislike swallowing tablets or other medicines.

Chewing gum is also a convenient drug delivery form because it does not require water intake. In addition, it offers some well-known inherent benefits for oral health, or as a stress or weight management aid, and can be combined with the therapeutic action of an active ingredient to give great performance and improve compliance for consumers.

Importantly for pharma companies, medicated chewing gum is an accepted dosage form in current Pharmacopoeias and the ingredients are compliant with different monographs.

How are common API problems, such as taste masking and solubility, affected by using chewing gum?

Most active ingredients have a bitter and unpleasant taste and in the case of chewing gum, taste masking is of great concern because the residence time in the mouth is much longer (20–30 min) compared with other dosage forms.

However, similar strategies seen in other oral dosage forms can be used; combining flavours and intensive sweeteners has been successful in some cases, while other solutions may require ion exchange resins or complexing agents (e.g., cyclodextrins).

API solubility can be influential in the dissolution rate from the chewing gum matrix. We know that highly soluble APIs are released completely and much faster than slightly or poorly soluble APIs, which require longer chewing times. In some cases, only a percentage of the total drug content is made available. Again, we believe that solubility enhancers used in other dosage forms can be used to good effect in medicated gum to promote higher dissolution of poorly soluble actives. At our company, we’ve worked with poorly-soluble APIs and found that, in some cases, the gum should be chewed for 30 minutes or more to get a 50% release of the APIs. This isn’t like the sustained release of a normal tablet, which can take 3–4 hours in the digestive tract.

For pharmaceutical manufacturers, what are the benefits of packaging APIs in this way? What types of APIs in particular would benefit from being incorporated into chewing gum?

The advantages are that pharmaceutical companies do not have to invest in extra chewing gum equipment in their facilities because our product range uses standard direct compression technology. Chewing gum stability is also very good because the humidity content of the powder is low — much lower than traditional chewing gum made by extrusion. In particular, APIs that are heat and humidity sensitive are good candidates for formulation into medicated gum.

What are the specific manufacturing challenges associated with incorporating APIs and chewing gum?

We still have a few challenges to overcome with the technology. The main challenge is increasing the potential dose content of a given API in medicated chewing gum. Given that a chewing gum dosage form must have a minimum gum base content to be chewable, this limits the total API content to a maximum of approximately 200 mg in a total chewing gum piece of 1-1.2 g. However, we expect to be able to increase this minimum in the coming 1–2 years with new versions of the excipient.

What kind of future do you predict for this technology? Do you think uptake in the pharma industry will increase or will it always remain a niche dosage form?

We are pretty sure that more pharma companies will adopt this technology as a way to differentiate their product range in the current competitive landscape. New drug delivery systems are also gaining greater importance as a way to improve consumers´ compliance and preferences. Health in Gum is a good way to achieve this.

Today, chewing gum is still perceived as a confectionary pleasure by consumers, but its visibility as an attractive, high-valued drug delivery system is increasing. Major successes have been seen in the nicotine replacement therapy gum market, and several new products have also been developed in diverse categories such as analgesics, digestive, cough and cold medicines, and antiallergics. New gum medications in weight management, energy supply or oral care categories are also beginning to appear in pharmacies.

One issue to consider with medicated chewing gum is over consumption. Medicated chewing gum is a medicine and must be considered as such. This is reinforced with packaging, for instance, which is much more medical and contains a leaflet.

Theses successes make me really optimistic that medicated chewing gum will progressively leave its current niche category to become a solid drug delivery system in the coming years. Gum technology has evolved very much in the recent years and we are very confident that these breakthroughs can be transferred into the pharma industry.