Nasal Drug Delivery

FORMULATION DEVELOPMENT

Analytical method development

MedPharm can develop a suitable analytical method or use a method provided by the client.

MedPharm will ensure that the method is 'fit for purpose' in order to assay the drug concentration in the presence of any of the formulations.

(See Analytical Services)

Pre-formulation / Formulation development and optimisation

Two formulation routes can be explored for nasal drug delivery. The first comprises liquid formulations which can be solutions or suspensions of the drug, usually in an aqueous medium. The second option is to formulate the drug as a dry powder. This approach may be similar to the use of dry powders in inhalation devices; however the particle characteristics may have to be different for nasal delivery and will be explored in conjunction with a selected device.

A number of powder preparation methods can be investigated including:

• Milling
• Nanoisation
• Spray drying
• Freeze drying
• Coacervation
• Solvent precipitation
• Solvent Evaporation

MedPharm will identify a range of excipients which are suitable to achieve the formulation target, and we will then test compatibility of these excipients with the drug. Based on the results from the compatibility tests, simple formulations will be generated and assessed for macroscopic and microscopic appearance, aesthetics and short-term physical stability.

Candidates for the next stage of formulation development will then be selected in consultation with the client and laboratory scale batches of the selected formulations will be prepared.

Formulation optimisation – release and deposition testing

A crucial step in formulation development is to achieve optimum release of the drug from the matrix in an in-use situation. The formulation is a major factor for controlling extent and rate of drug release, and thus for maximising bioavailability.  MedPharm have an in-depth understanding of the mechanisms involved in controlling drug release from nasal formulations.

Drug release from the formulations will be determined using an established and validated in house method suitable to the formulation type. Powder formulations can be characterised for drug release using an adaptation of a method utilising conventional dissolution apparatus as listed in the British Pharmacopoeia. Liquid formulations can be characterised using Franz cells with a choice of a range of synthetic or excised membranes.

Mucociliary clearance

This in-vitro study examines the effect of the formulation on the cilostatic/ cilotoxic and mucociliary clearance of the frog palate. The mucociliary clearance data will also provide an indirect measure of the relative mucoadhesive properties of the microparticle formulations.

Laboratory scale stability studies

Stability indicating drug assays can be developed and stability testing (physical, chemical and microbiological) performed to ICH guidelines.

Packaging Material and Compatibility

Primary packaging material can be selected in agreement with the client and compatibility can be tested with the selected formulations.

Pre-clinical and clinical trials

MedPharm can supply GLP and/or GMP samples for pre-clinical and/or clinical investigation.