Drug Delivery
IONSYS for the treatment of acute post-operative pain. However, following identification of corro- sion in a system component of one lot of IONSYS, which could trigger self-activation of the system – a potentially lethal overdosing risk – the European Medicines Agency recommended suspension of the marketing authorisation for IONSYS in November 2008. Janssen-Cilag, the developer and marketer of IONSYS, subsequently withdrew IONSYS from all European markets. IONSYS was very much at the leading edge of innovation for a TDD system. Its on-demand, patient-involved pain-management concept had the opportunity to showcase what personalised pain treatment could be. Regrettably, prohibitive technical intricacy and overwhelming product quality challenges short- circuited, literally and figuratively, this once- promising prospect. However, during the past decade TDDs have
essentially remained static and there has been little change in the composition of the patch systems. Modifications have been mostly limited to refine- ments of the materials used. One reason might be that only certain specialised companies can manu- facture transdermal patches. Another reason is that only a limited number of drugs fit the molecular weight, lipophilicity and potency requirements for transdermal absorption.
Third-generation TDD The third generation of TDDs is poised to make significant impact on drug delivery because it tar- gets its effects to the stratum corneum. This target- ing enables stronger disruption of the stratum corneum barrier, and thereby more effective trans- dermal delivery. The third generation of TDDs use microneedles as a means of circumventing the stra- tum corneum. Limitations with respect to the molecular weight of the drug is not of concern with this form of microneedle-mediated TDD. For ther- apeutic protein and peptide delivery, while intra- dermal delivery may provide a more advantageous pharmacokinetic profile compared with subcuta- neous or intramuscular injections, other tangible patient benefits, such as easy self-administration, less perceived pain, enhanced safety and ambient temperature stability are correspondingly essential to make this a compelling product concept.
Developing TDD to treat migraine Migraine is a disabling neurological disease that involves recurrent attacks of moderate to severe head pain. It is one of the most disabling diseases in the world and is the leading cause of disability among all neurological disorders. Due to the sever-
Drug Discovery World Winter 2018/19
ity of migraine attacks, migraine treatments need to bring relief to patients quickly and safely. Recent advances in the development of TDD for treatment of migraine show promise.
Unmet need Migraine is the most common disease in the world affecting approximately 39 million people in the US and one billion worldwide. More than 90% of migraine sufferers are unable to work or function normally during a migraine due to severe head pain and associated neurological symptoms including nausea, vomiting and extreme sensitivity to light and sound. The transdermal route offers a large and varied
surface as well as ease of application. There are limitations for this type of delivery since molecules with molecular weight greater than 1kDa are unable to cross the stratum corneum. Triptans are first-line therapies for moderate to
severe migraine and come in several formula- tions, including oral pill, nasal spray and injec- tion. Each of these routes of administration have their own set of limitations. Oral pills, the most common way to treat migraine, are slowly absorbed by the body leading to delayed migraine symptom relief. Nasal sprays can offer faster relief but the nasal route has a limited sur- face area and the fast mucociliary clearance and drainage into the oesophagus can result in highly variable absorption. Although the drug is sprayed nasally, a signifi-
cant amount of drug is swallowed and then absorbed by the body, which can result in gastro- paresis, a common condition among those suffer- ing from migraine. The pulmonary route offers a large and highly-vascularised mucosal surface for drug absorption, but the accessibility with current- ly-available inhalers is limited and can additionally be compounded by variability from patient self- administration. Injection is the most effective deliv- ery route. However, drawbacks of this method include pain, stigma associated with administering injections in public and needle phobia. Research demonstrates that treating migraine is a
race against time. The faster a patient receives a drug, the more likely that patient is able to fully benefit from it. Although migraine is not life-threat- ening, it is severely debilitating and reduces the quality of life of those who suffer from this disease.
Innovation Though there are a number of treatment options available for patients suffering from migraine, there is still a high unmet need for additional
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