Modified release of pharmaceutical dosage forms

De Zordi, Nicola

Modified release of pharmaceutical dosage forms

De Zordi, Nicola

2012-03-26

http://hdl.handle.net/10077/7733

Doctoral Thesis

Contributor(s)

Kikic, Ireneo

Abstract

During these three years, the research was focused on the preparation of pharmaceutical solid oral dosage forms with the aim to improve the dissolution behaviors and bioavailability of poor soluble drugs, or preparing sustained release systems for water-soluble drugs. In order to improve the bioavailability of poor soluble drugs, we adopted two strategies: 1) the micronization of the drug to increase their surface area, 2) preparing solid dispersions (SDs) using hydrophilic carrier. As known in the SDs the drug is dispersed or solubilized in an inert excipient or matrix where the active ingredient could exist in finely crystalline or amorphous state. When the system is exposed to aqueous media, the carrier dissolved and the drug is released as a very fine colloidal particles. This greatly reduction in particles size and the following surface area increase, results in an improvement of the dissolution rate. In addition to bioavailability enhancement, SDs systems were also directed towards the development of extender-release dosage forms using lipophilic carriers. For both the formulative approaches, we investigated the application of microwave (MW) and supercritical fluids (SCF) as preparative methods. In particular, MW ware employed for the preparation of solid dispersion either for immediate or sustained release of drugs, while SCF were investigated for the micronization and preparation of solid with the aim to prepare immediate release systems. Moreover, were investigated the thermodynamic aspect involved in the drug processing developing mathematical approaches able to predict the best operative conditions. Beside the preparation of these systems the physicochemical characterization of the compounds were investigated in order to understand the influence of the above technologies on the solid state of the materials. The goal of these behaviors was investigated trough the dissolution profile. From the obtained results these two technologies can be considered innovative and promising way to design particles.