Pulmonary 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

MedPharm will investigate solubility and stability of the drug with a range of solvents and excipients commonly used for nebuliser fromulations. Based on the results from this study a solution will be chosen for the nebuliser experiments.

Nebulisation experiments

Although several formulation approaches can be taken, it is recommended that initially a simple solution for a jet nebuliser is developed and the spray plumes are analysed with a laser diffraction particle sizer.  This is the simplest, quickest and most cost effective formulation approach to take to allow a proof of concept study to determine if sufficient quantities of the API can be delivered to the lung.

Proof of concept pre-clinical study.

Prior to any further formulation work it is advisable to conduct an in-vivo pre-clinical proof of concept study to confirm the inhalation bioavailability of the API when delivered by nebuliser. MedPharm can manufacture the material for testing and give further advice on the study design if required.

Formulation development.

A. development of a pMDI solution formulations.

The solubility of the API in standard propellants with and without standard solubilisers will be investigated. If the drug can be solubilised lead formulations will be developed with a range of delivery devices and the influence of excipients on the particle size will be assessed using a Twin Stage Impinger or Anderson Cascade Impactor. If the drug can not be solubilised it must be further processed to produce suitable particles to be incorporated in to either a suspension pMDI or DPI.

B. development of a pMDI suspensions of DPI formulations.

MedPharm will undertake the preformulation and compatibility screening of the API with excipients and drying techniques (e.g. Spray Drying) involved in the preparation of dry powders.

MedPharm have developed numerous preformulation screening tools that expedite and rationalise the suspension pMDI formulation development process. Such techniques will be used to assess the performance of the devloped formulations prior to aerodynamic characterisation using inertial impaction.

Alternatively once a suitable dry powder has been identified it can be mixed with lactose of a suitable particle size to create a DPI formulation. Such formulations can then be characterised by techniques such as Twin Stage Impaction.

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.