Pharmaceutical regulation and pseudo - generics

Dissertação de mestrado em Economia Industrial e da Empresa

Dissolution enhancement of active pharmaceutical ingredients by therapeutic deep eutectic systems

A therapeutic deep eutectic system (THEDES) is here defined as a deep eutectic solvent (DES) having an active pharmaceutical ingredient (API) as one of the components. In this work, THEDESs are proposed as enhanced transporters and delivery vehicles for bioactive molecules. THEDESs based on choline chloride (ChCl) or menthol conjugated with three different APIs, namely acetylsalicylic acid (AA), benzoic acid (BA) and phenylacetic acid (PA), were synthesized and characterized for thermal behaviour, structural features, dissolution rate and antibacterial activity. Differential scanning calorimetry and polarized optical microscopy showed that ChCl:PA (1:1), ChCl:AA (1:1), menthol:AA (3:1), menthol:BA (3:1), menthol:PA (2:1) and menthol:PA (3:1) were liquid at room temperature. Dissolution studies in PBS led to increased dissolution rates for the APIs when in the form of THEDES, compared to the API alone. The increase in dissolution rate was particularly noticeable for menthol-based THEDES. Antibacterial activity was assessed using both Gram-positive and Gram-negative model organisms. The results show that all the THEDESs retain the antibacterial activity of the API. Overall, our results highlight the great potential of THEDES as dissolution enhancers in the development of novel and more effective drug delivery systems.

PDMS encasing system for integrated lab-on-chip Ag/AgCl reference electrodes

Poly(dimethylsiloxane) (PDMS) is an organosilicon polymer widely used in the fabrication of microfluidic systems to integrate biochips. In this study, we propose the use of an adapted PDMS mould for the creation of a miniaturized, reusable, reference electrode for in-chip electrochemical measurements. Through its integrated microfluidic system it is possible to replenish internal buffer solutions, unclog critical junctions and treat the electrode’s surface, assuring a long term reuse of the same device. Planar Ag/AgCl reference electrodes were microfabricated over a passivated p-type Silicon Wafer. The PDMS mould, containing an integrated microfluidic system, was fabricated based on patterned SU-8 mould, which includes a lateral horizontal inlet access point. Surface oxidation was used for irreversible permanent bondage between flat surfaces. The final result was planar Ag/AgCl reference electrode with integrated microfluidic that allows for electrochemical analysis in biochips

Supercritical fluid and pharmaceutical applications. Part I: Process classification

The supercritical fluid technology has been target of many pharmaceuticals investigations in particles production for almost 35 years. This is due to the great advantages it offers over others technologies currently used for the same purpose. A brief history is presented, as well the classification of supercritical technology based on the role that the supercritical fluid (carbon dioxide) performs in the process.

Hierarchical modelling of timber reference properties using probabilistic methods: Maximum Likelihood Method, Bayesian Methods and Probability Networks

In recent decades, an increased interest has been evidenced in the research on multi-scale hierarchical modelling in the field of mechanics, and also in the field of wood products and timber engineering. One of the main motivations for hierar-chical modelling is to understand how properties, composition and structure at lower scale levels may influence and be used to predict the material properties on a macroscopic and structural engineering scale. This chapter presents the applicability of statistic and probabilistic methods, such as the Maximum Likelihood method and Bayesian methods, in the representation of timber’s mechanical properties and its inference accounting to prior information obtained in different importance scales. These methods allow to analyse distinct timber’s reference properties, such as density, bending stiffness and strength, and hierarchically consider information obtained through different non, semi or destructive tests. The basis and fundaments of the methods are described and also recommendations and limitations are discussed. The methods may be used in several contexts, however require an expert’s knowledge to assess the correct statistic fitting and define the correlation arrangement between properties.