Britannia: a nose for success in drug delivery

For years, it has been common wisdom in the pharmaceutical industry that delivery of drugs via the nose only really works if the compound can be presented in liquid form. One company begging to differ is Britannia Pharmaceuticals of the UK, which is breaking new ground with a dry powder technology that promises to expand the horizons of nasal drug delivery.

Dry powders have tended to be unsuitable for nasal delivery because they are often irritant and cause sneezing, making accurate dosing difficult, and suffer from irregular absorption patterns. Moreover, there is an association between this form of delivery and illicit drug use which has not helped persuade companies to invest in it.

Britannia's director of development, Alex Duckworth, believes the company has put together a technology which solves many of these issues. He told In-Pharmatechnologist.com​: "A nasal powder offers an excellent way of delivering medication in a highly-targeted, quickly-absorbed dose. It offers a rapid onset that is comparable to subcutaneous injection and much faster than oral dosing, and bioavailability that is also comparable to the sc route."​

Britannia began work on dry powders because it was seeking an alternative delivery system for apomorphine, a dopamine agonist sold by the firm as an sc injection (Apo-go) for late-stage Parkinson's disease. In a bid to overcome the need for regular injections, Britannia looked at nasal liquids, but found that apomorphine oxidised in solution to form irritant compounds. Turning to nasal powders, the company again encountered teething problems; stability was improved but the rate of absorption was not optimal.

Finally, the company hit upon a technique that resulted in good stability as well as good absorption. The proprietary process hinges on the use of lyophilisation (freeze-drying) and careful selection of excipients to create a powder in which there is a careful balance between the amorphous and crystalline forms of apomorphine. The aim is to reduce water absorption in order to improve tolerability and reduce particle clumping, and to achieve a uniform particle size (10-80 microns) that allows even dispersal through the nasal passages.

The result is a product which could offer the first realistic alternative to sc apomorphine for late-stage Parkinson's patients, something which Britannia intends to test in a Phase III clinical trial due to start in the next four to five months, according to Duckworth. This will involve 50-100 patients and will look at use of the drug in restoring motor function first thing in the morning. Many Parkinson's patients rely on oral levodopa for this, which can take up to an hour to work, vs 10-15 minutes with sc apomorphine; if the nasal powder form can match the sc route, this will be real benefit to patients.

Duckworth told In-Pharmatechnologist.com​ that sales of sc apomorphine currently run at around $15-$20 million in the UK, and he believes this market could expand to as much as $250-$300 million with an effective nasal formulation, particularly as this may encourage use of the drug in earlier stages of Parkinson's.

Most of Britannia's current $50 million turnover comes from distribution activities, with a minority portion coming from drug sales at present. Should the nasal powder form of apomorphine debut on schedule in 2004, the company believes it could enjoy a five- to six-fold increase in product revenues.

Britannia truly seems to have got into the dry-powder nasal delivery sector at its outset, with only a handful of companies operating in this area. Those that approach the sector from another angle - Denmark's Direct Haler, Norway's OptiNose, Bespak of the UK and Germany's Pfeiffer - are all developing devices that can deliver powdered medicines to the nose, a trend which bodes well for Britannia's investment in this area.

Meantime, Britannia is already working on new projects, including a dry powder formulation of dihydroergotamine for migraine, due to start Phase I studies shortly, and a low-dose formulation of nasal apomorphine that could compete with the likes of Pfizer's blockbuster medication Viagra (sildenafil) in the treatment of erectile dysfunction.