Matteo d’Amore

Intensifying the microencapsulation process: ultrasonic atomization as an innovative approach.

In this review, new approaches to the microencapsulation processes, widely used in the manufacturing of pharmaceutical products, are discussed focusing the attention on the emerging ultrasonic atomization technique. Fundamentals and novel aspects are presented, and advantages of ultrasonic atomization in terms of intensification and low energy requests are emphasized.

Piroxicam loaded alginate beads obtained by prilling/microwave tandem technique: Morphology and drug release

This paper presents a tandem technique, based on the combination of prilling and microwave (MW) assisted treatments, to produce biodegradable alginate carriers of piroxicam with different drug controlled release behaviours. Results showed that alginate/piroxicam beads demonstrated high encapsulation efficiency and very narrow dimensional distribution. Beads dried by MW retained shape and size distribution of the hydrated particles while drying rate was strongly increased compared to convective drying processes. Moreover, different MW irradiation regimes promoted interactions between the drug and alginate matrix, affected drug polymorphism as well as inner and surface matrix structure leading to different piroxicam release profiles. High level MW irradiation led to beads with highly porous and swellable matrix able to release piroxicam in few minutes in the intestine while convective drying produced gastro-resistant beads that exhibit sustained piroxicam release (total release in 5.5h) in intestinal environment. On these results the tandem technique prilling/MW irradiation appears to be promising to obtain alginate carrier with tailored NSAIDs release depending on drug characteristics and MW irradiation.

A combined technique based on prilling and microwave assisted treatments for the production of ketoprofen controlled release dosage forms

In this study the feasibility of joining prilling and microwave (MW) assisted treatments as combined technique to produce controlled release alginate beads was tested. Beads were produced by prilling (laminar jet break-up) using different polymer concentrations and loaded with ketoprofen, a slightly soluble non-steroidal anti-inflammatory BCS class II drug characterized by low melting point. MW assisted treatments applied using different irradiating conditions were performed as drying/curing step. The effect of formulation conditions and process variables on drying kinetics, particle micromeritics, shape, surface and inner characteristics of the matrix as well as drug loading and drug release behaviour was studied (USP pH change method). The properties of MW dried particles were compared to those dehydrated by convective methods (room conditions and tray oven 105°C). Results showed that MW dried ketoprofen loaded beads were obtained in a very narrow dimensional range retaining shape and size distribution of the hydrates particles. Compared to the traditional drying methods, MW treatments were able to strongly increase drying rate of the hydrated beads achieving faster and controllable dehydration kinetics. Moreover, different regimes of irradiation affected structural properties of the particles such as matrix porosity as well as the solid state of the loaded drug. DSC, X-ray and FTIR analyses indicated complex chemical interactions between the drug and polymer matrix induced by MW, related with the regime of irradiation, that contributes to the differences in release profiles. In fact, MW treatments under different time and irradiating regimes are able to modulate drug release from alginate beads; high levels of irradiation led to beads suitable for immediate release oral dosage forms whereas the lowest regime of irradiation led to beads that achieved a prolonged/sustained release of the drug till 8h in simulated intestinal medium. This study showed that prilling in combination with microwave treatments is a useful and simple tandem technique to prepare dextran-based dried beads.

A general code to predict the drug release kinetics from different shaped matrices.

This work deals with the modeling of drug release from solid pharmaceutical systems (matrices) for oral delivery. The attention was paid to the behavior of matrices made of hydrogels and drug, and the modeling was devoted to reproduce all the relevant phenomena (water up-take, gel swelling, diffusivity increase, drug diffusion and polymer erosion). Thus, the transient mass balances (for both drug and water), with the proper initial and boundary conditions were written, and a generalized numerical code was formulated; it is able to describe several geometries (slab, sphere, infinite and finite cylinders; this latter was done by an approximation which reduces the 2D problem to an 1D scheme). The main phenomena observed in drug delivery from hydrogel-based matrix, i.e. polymer swelling and erosion, were taken into account. The code was validated by comparison with analytical solutions, available for some simplified situation, and then it was tested with some experimental data taken from literature.

Measurements of non-uniform water content in hydroxypropyl-methyl-cellulose based matrices via texture analysis

The use of hydrogels in the preparation of controlled release pharmaceutical forms is extensively diffused. The main feature of these polymers is their ability to swell forming a gel layer when they enter in contact with fluids. Once the gel layer is formed, the drug contained in the matrix can easily diffuse ensuring a controlled release from the tablet. Measurement of water content within a hydrating matrix based on hydrogels is a key topic in the study of pharmaceutical solid dosage forms. The aim of this work is to evaluate the water content of swollen matrices composed by HPMC and theophylline both in axial and in radial direction, as a function of time, using a texture analysis. A relationship between water content and slope of the force-penetration curves has been obtained using a simplified system in which the water uptake is allowed only in radial direction, obtaining thus partially hydrated matrices with the water content varying only along the radial direction. Once the relationship has been validated, it has been applied in a more complex system in which the polymer swelling takes place in both axial and radial direction. Thus, using the texture analysis it has been possible to determine the water in each position within the hydrated matrices.

Analysis of Size Correlations for Microdroplets Produced by Ultrasonic Atomization

Microencapsulation techniques are widely applied in the field of pharmaceutical production to control drugs release in time and in physiological environments. Ultrasonic-assisted atomization is a new technique to produce microencapsulated systems by a mechanical approach. Interest in this technique is due to the advantages evidenceable (low level of mechanical stress in materials, reduced energy request, reduced apparatuses size) when comparing it to more conventional techniques. In this paper, the groundwork of atomization is introduced, the role of relevant parameters in ultrasonic atomization mechanism is discussed, and correlations to predict droplets size starting from process parameters and material properties are presented and tested.

Measurements of water content in hydroxypropyl-methyl-cellulose based hydrogels via texture analysis

In this work, a fast and accurate method to evaluate the water content in a cellulose derivative-based matrix subjected to controlled hydration was proposed and tuned. The method is based on the evaluation of the work of penetration required in the needle compression test. The work of penetration was successfully related to the hydrogel water content, assayed by a gravimetric technique. Moreover, a fitting model was proposed to correlate the two variables (the water content and the work of penetration). The availability of a reliable tool is useful both in the quantification of the water uptake phenomena, both in the management of the testing processes of novel pharmaceutical solid dosage forms.

In vitro dissolution of pH sensitive microparticles for colon-specific drug delivery

Objective: The objective of this work is to prepare oral dosage systems based on enteric materials in order to verify their possible use as Colon-Specific Drug Delivery Systems (CSDDSs). Methodology: In particular, three different copolymers of methyl-methacrylate (MMA) - acrylic acid (AA) are synthesized with increasing percentage of MMA (from 70% to 73%) and they are used to produce microparticles by the double-emulsion solvent evaporation method. The microparticles, loaded using theophylline as model drug, are then tested for drug release under varying pH to reproduce what happens in the human GI tract. Results: All the investigated systems have shown an effective pH sensitiveness: they show a good gastro-resistance, releasing the model drug only at higher pH, small intestine or colon, depending on the kind of used copolymer. Conclusion: The results confirm the usefulness of both the materials and the methods proposed in this study for colon-specific delivery applications.

Relevance of dielectric properties in microwave assisted processes

Microwaves are electromagnetic radiation with wavelength ranging from 1 mm to 1 m in free space with a frequency from 300 GHz to 300 MHz, respectively. International agreements regulate the use of the different parts of the spectrum; the frequencies 915 MHz and 2.45 GHz are the most common among those dedicated to power applications for industrial, scientific and medical purposes (Metaxas & Meredith, 1983).

In Vitro Simulation of Human Digestion: Chemical and Mechanical Behavior

The drug release pattern from an orally administrated pharmaceutical dosage form can be significantly affected by simultaneous food intake and drug administration due to the changes in the gastrointestinal physiology, in particular because of the pH profile evolution and of the mixing conditions. In this work, the release from a commercial diclofenac tablet subjected to the pH conditions experienced by the gastrointestinal tract in fed conditions was analyzed and then compared with the release pattern obtained using a conventional dissolution method. The tablets behaved differently because of the partial dissolution of the coating due to high pH values in the first stage of the dissolution method, which takes into account the fed-state conditions. Tablets composed of a homemade enteric polymer loaded with diclofenac overcame this drawback. Moreover, an in vitro device mimicking peristaltic contractions in the stomach was proposed, and the release pattern from commercial tablets was compared with that obtained under conventional dissolution conditions. The release pattern was strongly influenced by the hydrodynamics. The two experimental setups (pH and peristalsis simulations) demonstrate that a gastrointestinal reproduction closer to the real physiology is necessary to achieve an accurate and reliable prediction of the behavior of pharmaceuticals.