Advances in particle science and technology

An ideal drug delivery system (dds) should be capable of delivering the drug with the desired therapeutic effect. John Staniforth* explains how systems can be improved

Drug delivery technology platforms can present novel, high performance solutions to obtaining optimal product efficacy and patient compliance in a more cost-effective manner.

These high performance systems can be designed to enable better 'life-cycle management' opportunities for pharmaceutical companies, as well as better treatment outcomes and greater satisfaction for patients.

Vectura, a fast growing drug delivery company, specialises in applying its world-class expertise in particle science and engineering to a broad range of novel drug delivery technologies.

PowderHale

Efficient pulmonary delivery is highly desirable but not easily achieved. Direct administration of β2 agonists and steroids, which revolutionised the treatment of asthma, used a range of inefficient dds, delivering a variable and small dose fraction to the target site. It is now recognised that an improvement in both the efficiency and the reproducibility of delivery can widen the application, giving either improved local treatment or, more significantly, systemic activity.

Although systemic delivery applies particularly to administration of proteins and peptides, where the ability to invent new molecules has outrun the capacity to deliver them by routes other than injection, there are other simpler molecules that could benefit from a rapid onset of action which follows alveolar deposition, reduced first-pass or other metabolism and chemical degradation in the gastro-intestinal environment.

Achieving reproducible and efficient deep lung penetration demands a dry powder inhaler (dpi) starting point and requires an exquisite balance between the design of drug and 'inactive' particle surfaces and the device dynamics.

A lot of attention has been given to engineering more efficient metering systems and airways turbulence, and also to creating drug particles with the most appropriate aerodynamic size and shape, for example using supercritical fluid processing.

Left at this point, neither ultra-fine drug particles nor efficient devices give an adequately functional aerosol system. Further performance improvements through advanced formulation design have resulted in New physicoChemical Entities (NpCEs), capable of inter-particle force control and modulation of the surface dynamics of amorphous-crystalline island domains at the critical air-drug-substrate interfaces.

Together, especially using a formulation-integrated dpi product development, these improvements create a viable opportunity to deliver systemically acting drugs via the pulmonary route, as well as providing a more effective drug delivery platform for the new asthma and chronic obstructive pulmonary disease therapies.

A secondary but increasingly important requirement to achieving reproducibly efficient alveolar penetration is to modulate drug absorption. Formulation improvements, which can be applied to achieve these aims, include controlling the rate of drug diffusion to and across the pulmonary mucosa; bioenhanced mucosal absorption; and protection from recognition by the reticulo-endothelial system following absorption.

Pulmonary delivery of drugs is now a major opportunity created by integrated application of particle engineered drug, carrier and force control agents with high efficiency active dpi systems and any bio-modulating formulation agents. Formulation integrated dpi systems now offer the prospect of improving dose reproducibility and lung penetration, with the potential for reducing dose size and frequency, in a patient-friendly dds.

Accustar

This oral drug delivery device and formulation technology is designed for those patients who have difficulties or dislike swallowing traditional tablets and capsules. Accustar is based on the application of particle and device engineering expertise from dpi systems to oral delivery. Research is developing a portable, inexpensive multi-dose device that will accurately deliver a metered dose of drug into the mouth in a way that is convenient and pleasant for the patient to take.

The device is designed to be used with a broad range of low-excipient drug formulations, including fast dissolving, taste-masked, immediate and controlled release formulations, and should be easy to operate.

The novel formulations have no diluent/binder/disintegrant excipient payload, which means that the delivered powder mass is much less than conventional or chewable tablets, capsules, sachets etc. This in turn provides a much greater flexibility in terms of available mass for improving mouthfeel, taste-masking and functional requirements.

It is envisaged that such a delivery approach will compete effectively with the new 'dissolve in the mouth' formulations that are targeted at the large percentage of patients who have problems swallowing tablets and capsules.

Most modern medicines, with the exception of semi-solid transdermal preparations such as creams, ointments, gels and pastes, are used in a unit dose form, where an accurate pre-metered dose of drug is delivered to the body in a reproducible way.

The aim of the Pandermal project is to develop a series of cost-effective, unit dosage form presentations for topical use. These include a unit dosage form produced using a modification of established tablet production methods and a novel device/formulation system for accurate metering and convenient low contact application.

The formulations also reduce the dependence on undesirable preservative systems commonly used in conventional formulations. It is expected that Pandermal systems will meet the needs of the medical profession for a more accurate means of dosing drugs onto the skin, thereby eliminating many of the side-effects of potent drugs.

Maxsol

As an increasing number of novel compounds coming out of drug discovery programmes are insoluble, especially since the introduction of combinatorial chemistry techniques, these effectively insoluble new molecules present a significant oral pharmacokinetic challenge.

As a result, there is a growing demand for technologies that can ensure that a clinically significant and reproducible proportion of each dose does get into the bloodstream following oral delivery.

The technology is directed at maximising the dissolution characteristics and bio-availability of poorly soluble drugs by the generation of highly active nano-scale and pico-scale surfaces of drug particles contained on inert bio-compatible inorganic or organic constructs of known pharmaceutically approved materials.

These have high surface areas, produced using novel nano-fabrication techniques and with excellent secondary processing characteristics.

Gencontab

This technology has the potential to release a once daily dose of drug throughout the whole gastrointestinal tract and is being developed with an aim of providing unique release modulation suitable for both low and high dose drugs.

Oral controlled release medicines developed using this new technology have the potential to improve patient compliance through enhanced convenience, reduced dosing and minimised incidence of side effects.

Conclusion

Currently available oral controlled-release systems tend to be premium-priced compared with immediate-release formulations, often because of the need to use either relatively expensive inert processing materials or more complex manufacturing methods.

The new drug delivery technology, which is being developed in collaboration with Ranbaxy BV, uses cost efficient materials and processes and will further help in reducing the overall cost of therapy for chronic diseases.