TOPICAL PHARMACEUTICALS

Integrated project development

GALENIC DEVELOPMENT

This phase foreseen the following activities:

> Pre-formulation development: the drug candidate/s is/are analyzed in terms of physical, chemical characteristics in order to identify the best excipients selection and the topical pharmaceutical form.

> Formulation design: APR is able to set up a range of hypothetical formulations based on its background to achieve the requested characteristics both in terms of release and in terms of chemical, physical, texture and taste aspect. Generally several possible formulations are taken into account during this phase in order to evaluate different prototypes that could give different results especially as it concerns the long terms stability both in terms of API degradation and in terms on stability of the vehicle base.

> Prototypes development: based on the pre-formulation development, formulation design and compatibility test, APR R&D team selects different formulation solutions based on its background united with the continuous research of innovation that permit us to find out the best formulation. The best topical form and its manufacturing method are set up on our laboratory equipment thinking at the successive technology transfer and the consequent scale up. All the manufacturing phases are under control also as it concerns the analytical aspect: in process control are managed by the analytical department laboratory which is at its complete service for a continuous and fast analytical support.

> Preliminary stability study: a preliminary stability study in stressed and/or ICH storage conditions can be performed on the hypothetical formulation, as adjunctive information before the selection of the formulation/s able to achieve the big laboratory batch/es production. Both the aspects characteristics and the degradation ones are evaluated during the study. The best conditions for the preliminary evaluations are defined case by case and they are established looking at each product and formulation and at further particular customers requests. In this phase, the analytical methods are set up and , in some case, validated according our internal procedures.

> Microbiological analysis: Microbial contamination of products is a matter of great importance. Frequently their water and other components content promote the growing of microorganism which often cause organoleptic and physicochemical alterations (offensive odours, changes in colour, viscosity, pH ...) or, in some case, the formation of substances potentially hazardous for the consumer. In order to detect this risk a pool of test are carried out according to pharmacopoeias and cosmetic organisations during all the estimated shelf life taking into account also the consumer use as source of contamination.