Preservative-Free System (P.F.S.) in Nasal Drug Delivery
Nasal Drug Delivery Devices Nowadays a wide range of nasal devices are available to patients. Spray pumps are one of the most convenient and safest ways to deliver drugs because they are metering systems that dispense an accurate dose of drug and generate a controlled spray that covers efficiently the nasal mucosa. Thanks to recent technological advances spray pumps have expanded to non-preserved drug formulations which represent a new trend, particularly in Europe and Latin America. Preservative Free Systems (P.F.S.) Preservatives are commonly used in drug formulations and they are generally well tolerated when used in small amounts for occasional treatments. However in the case of nasal spray delivery, preservatives can be irritating to the patient mucosa causing some unpleasant itching, but more seriously can also slow down or even stop the mucociliary clearance which is an essential natural mechanism for the protection of the upper airways. Preservatives can also make the work of the formulation scientist more challenging by causing some stability/compatibility issues, and/or by modifying the smell and/or taste of the drug product. The German health authority (BfArM) recently published a risk assessment concerning the widely used preservative Benzalkonium Chloride (BKC). In Germany the package insert of a drug product must indicate that frequent administration of BKC irritates the nasal mucosa. To help formulation scientists reduce and eliminate preservatives from nasal spray formulations, drug delivery device manufacturers have successfully developed and marketed specific multidose spraying devices called Preservative Free Systems (P.F.S.). There are two main categories of technologies currently used for P.F.S. Fully sealed systems: This technology was developed by Valois Pharma. The pumps are non-vented which means contamination from the environment cannot enter the container- by design - and come into contact with the drug product. In addition specific actuators equipped with a mechanical tip seal prevents contamination of the formulation in the actuator between actuations Vented pumps equipped with a micro-filter: Several manufacturers are using this technology. These pumps are designed in such a way that the air is sterile-filtered at the inlet via the micro-filter. These pumps are also used in conjunction with specific self-sealing valves in the actuator tip. An alternative approach is to use a specific actuator with a bacterio-static material (generally silver derivatives or ions) that is released into the drug formulation in the actuator tip. The Future for P.F.S. Since non-preserved drug formulations for nasal sprays represent a major benefit both for patients and for formulation experts, there is room for creativity and improvements. The market has already started to shift towards P.F.S. not only for nasal decongestants and salines where it represents a significant market share in Europe but also for Rx drugs including those therapies for systemic delivery. The non-preserved approach is of particular interest in the case of chronic treatments such as allergic rhinitis or hormone therapies. For what concern devices, new generation of nasal dispensing systems have appeared recently such as the Pfeiffer Cartridge and the Valois Freepod™. Those devices were specifically designed for non preserved formulations and not adapted from conventional devices like the previous generations. This results in devices that are even more efficient in protecting the formulation, easier to fill and more patient friendly thanks to a wide choice of customizations to improve convenience and style. P.F.S. also represents a great opportunity for Life Cycle Management of existing Rx drug products which are threatened by generic versions. Reformulation of non-preserved versions of existing drugs can not only benefit the patients but also the pharmaceutical company who could receive further patent protection and enhance product differentiation on the market place.