Adriano Marim de Oliveira

Nano Spray Drying as an Innovative Technology for Encapsulating Hydrophilic Active Pharmaceutical Ingredients (API)

The vibrating mesh spray technology implemented in the Nano Spray Dryer B-90 was evaluated for drug delivery applications by spray drying solutions containing different functional polymers to structure the respective encapsulating matrices (Arabic gum, cashew nut gum, sodium alginate, sodium carboxymethyl cellulose and Eudragit RS100) and a specific model drug to be encapsulated (vitamin B12). A systematic study investigated the influence of feeding liquid stream properties such as viscosity, conductivity and surface tension respectively on particle size distribution, specific surface area and morphological aspects. The encapsulating efficiency and the release kinetics of the different systems were evaluated considering in-vitro experiments characterized by different pH conditions that respectively simulate the gastric (acid) and enteric conditions (alkaline). The performance of each formulation was evaluated by considering the intrinsic properties of the materials used and also the spray dryer operating conditions.

Rifampicin Nanoprecipitation using Flow Focusing Microfluidic Device

We present the nanoprecipitation of rifampicin performed in a microfluidic device as a means to reduce the particle size and enhance the dissolution rate. The microfluidic device was microfabricated in glass substrate with a 45° flow-focusing geometry. The dimensions of the central and side channels are 100 µm and 110 µm in width, respectively, and 85 µm in depth. We analyze the influence of different parameters in the rifampicin particles size, such as: rifampicin concentration, the presence of surfactant, the total fluid flow and solvent to anti-solvent flow rate ratio. The processed rifampicin was evaluated not only in terms of size, but also morphology, crystallinity, thermal characteristics and dissolution rate. We produce particle sizes in a controlled manner with sizes ranging from 100 nm to 1.2 µm. The particles present an amorphous profile and enhanced dissolution rate as compared to commercial raw rifampicin. These results are promising and have enabled us to better understand the rifampicin self-assembly process in microfluidic device .

Production of Nanofibers by Electrospinning Technology: Overview and Application in Cosmetics

This chapter relates to the techniques to produce polymer nanofibers and specifically discusses one of those techniques which has been recently investigated, namely Electrospinning. An overview of this technology is described, considering the work trend based on nanofiber and electrospinning publication in scientific paper and patents. Moreover, issues regarding the main process control parameters, applications of polymer nanofibers and the appropriate characterization of these nanofibers or mats are presented. Applications in cosmetic field are outlined, as well as the future perspective of the electrospinning technology in cosmetic application.

Synthesis and characterization of thermo-responsive particles of poly(hydroxybutirate-co-hydroxyvalerate)-b-poly(N-isopropylacrylamide)

A new kind of thermo-responsive particles were prepared by the self-assembly technique, comprising poly(hydroxyvalerate-co-hydroxybutirate)-b-poly(N-isopropylacrylamide)/ (PHBHV-b-PNIPAAm) block copolymers. The hydrophilic part PNIPAAm was synthesized by Reversible Addition- Fragmentation chain Transfer (RAFT) polymerization. Particles with core-shell morphology were obtained with hydrophilic outer shells and hydrophobic inner cores. Dexametasone acetate (DexAc) was used as a model drug with an encapsulation efficiency of 77%. The release of DexAc in aqueous solution was strongly dependent on temperature, suggesting that PHBHV-b-PNIPAAm particles can be used as a thermo-responsive carrier material with external control in a drug release system.

The effect of ozone gas sterilization on the properties and cell compatibility of electrospun polycaprolactone scaffolds

Abstract The growing area of tissue engineering has the potential to alleviate the shortage of tissues and organs for transplantation, and electrospun biomaterial scaffolds are extremely promising devices for translating engineered tissues into a clinical setting. However, to be utilized in this capacity, these medical devices need to be sterile. Traditional methods of sterilization are not always suitable for biomaterials, especially as many commonly used biomedical polymers are sensitive to chemical-, thermal- or radiation-induced damage. Therefore, the objective of this study was to evaluate the suitability of ozone gas for sterilizing electrospun scaffolds of polycaprolactone (PCL), a polymer widely utilized in tissue engineering and regenerative medicine applications, by evaluating if scaffolds composed of either nanofibres or microfibres were differently affected by the sterilization method. The sterility, morphology, mechanical properties, physicochemical properties, and response of cells to nanofibrous and microfibrous PCL scaffolds were assessed after ozone gas sterilization. The sterilization process successfully sterilized the scaffolds and preserved most of their initial attributes, except for mechanical properties. However, although the scaffolds became weaker after sterilization, they were still robust enough to use as tissue engineering scaffolds and this treatment increased the proliferation of L929 fibroblasts while maintaining cell viability, suggesting that ozone gas treatment may be a suitable technique for the sterilization of polymer scaffolds which are significantly damaged by other methods.

Scaling up of Rifampicin Nanoprecipitation Process in Microfluidic Devices

Microfluidic devices have become an important tool to produce micro and nanoparticles. However, the operation ranges of these systems are still a challenge when we think of large scale industrial applications. In this work we present two microfluidic devices for scaling up a nanoprecipitation process. The microfluidic systems are microfabricated in glass substrates and the flow distribution are done through reservoirs and a branching system, with four outputs in each device. In these systems we can operate in mL/min range and it is possible to have a yield up to ten times higher than a single channel system. We use the devices in a rifampicin nanoprecipitation process, obtaining nanoparticles in a range of 250 nm. As expected, parameters such as total flow rate and ratio between phases are determinant in the final mean particle size. Each output of our devices produces homogenous results and we can see that these results can be improved to obtain nanoparticles in larger volumes.

3D FOCALIZATION MICROFLUIDIC DEVICE BUILT WITH LTCC TECHNOLOGY FOR NANOPARTICLE GENERATION USING NANOPRECIPITATION ROUTE

Nanoprecipitation is a nanonization technique used for nanoparticle generation. Several fields, like pharmacology and fine chemistry, make use of such technique. Typically are used a bulky batch mechanical processes rendering high polydispersity index of generated nanoparticles, poorly particle size reproducibility and energy wasting. LTCC-based microsystem technologies allow the implementation of different unitary operations for chemical process, making it an enabling technology for the miniaturization of chemical processes. In fact, recently LTCC microfluidic reactors have been used to produce micro and nanoparticles with excellent control of size distribution and morphology. The present work provides a report on the performance of a 3D LTCC flow focusing Microfluidic device designed to fabricate polymeric nanocapsules for Hydrocortisone drug encapsulation, using nanoprecipitation route. Monodisperse Hydrocortisone nanocapsules were obtained with sizes (Tp) from 188.9 nm to 459.1 nm with polydispersity ...

Fab on a Package: LTCC Microfluidic Devices Applied to Chemical Process Miniaturization

Microfluidics has brought diverse advantages to chemical processes, allowing higher control of reactions and economy of reagents and energy. Low temperature co-fired ceramics (LTCC) have additional advantages as material for fabrication of microfluidic devices, such as high compatibility with chemical reagents with typical average surface roughness of 0.3154 μm, easy scaling, and microfabrication. The conjugation of LTCC technology with microfluidics allows the development of micrometric-sized channels and reactors exploiting the advantages of fast and controlled mixing and heat transfer processes, essential for the synthesis and surface functionalization of nanoparticles. Since the chemical process area is evolving toward miniaturization and continuous flow processing, we verify that microfluidic devices based on LTCC technology have a relevant role in implementing several chemical processes. The present work reviews various LTCC microfluidic devices, developed in our laboratory, applied to chemical process miniaturization, with different geometries to implement processes such as ionic gelation, emulsification, nanoprecipitation, solvent extraction, nanoparticle synthesis and functionalization, and emulsion-diffusion/solvent extraction process. All fabricated microfluidics structures can operate in a flow range of mL/min, indicating that LTCC technology provides a means to enhance micro- and nanoparticle production yield.

LTCC 3D MICROMIXERS FOR NON-MISCIBLE FLUIDS MICROEMULSION GENERATION

Abstract The present work shows a ceramics microfluidic device for non-miscible fluids microemulsion generation using 3D serpentine micromixers. The technology used for device fabrication was Low Temperature Cofired Ceramics (LTCC) which allows us for complex, high temperature and pressure resistant 3D microfluidic devices. The proposed device aims to obtain microemulsion with controlled drop size, low dispersion index and high production volumes using Top-Down approach. Previous simulation work had showed 3D serpentine as one of the best structures for rapid mixing due the chaotic advection generated on every 90 deg direction change. This effect, when mixing two fluids as oil and water leads to streamlines pinching-off making possible drop generation. We have used this effect on our device. For the experimental section, it was fabricated a 3D serpentine mixer microfluidic device with working region suitable for variable total flow rate. For certain value of total flow rate, the microemulsion showed highe...

LTCC MICROREACTORS APPLICATION IN A MICROFLUIDIC INTEGRATED SYSTEM FOR HYDROPHOBIC DRUG ENCAPSULATION IN POLYMERIC NANO/MICROPARTICLES

Nanotechnology develops methods and processes for Drug Delivery Systems (DDS) based on the fabrication of polymeric nano/microparticles with encapsulated drug that can be applied for maximize therapeutic activity and minimizes undesirable effects. However, these processes entail several conditions to operate efficiently. They present high sensibility to changes in temperature, flow rate, pressure, and chemical solution composition. An optimal configuration of these parameters is required to guarantee stable particle production. For these reasons, integration of technological devices like sensors, actuators, microfluidic devices and control systems is essential to increase particle production performance. The proposal of this work is to develop an integrated monitored and controlled system using LTCC (Low Temperature Co-Fired Ceramic) microreactors to generate polymeric nano/microparticles for encapsulation of hydrocortisone drug with PCL and Pluronic polymers. The microfluidic integrated system is develop...