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

Single-Pot Semicontinuous Bench Scale Apparatus To Produce Microparticles

This work presents both the design of a novel process to produce microparticles with a shell−core structure and a bench scale apparatus purposely realized. The developed process was designed to respond to mandatory needs of process intensification. It involved the coupling of two emergent technologies: atomization assisted by ultrasonic energy and microwave heating. The former was used to atomize polymeric solutions; the latter was applied to stabilize the produced droplets by drying. Both operations were performed in the same vessel with the aim to have a single-pot process chamber and were carried out by a semicontinuous procedure. Basic design criteria and advantages of the ultrasonic−microwave coupled operations in the realized apparatus are presented and discussed. Results of testing and of operating runs to produce shell−core microparticles are also reported, emphasizing the main features of the produced particles

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

Synthesis and characterization of P(MMA-AA) copolymers for targeted oral drug delivery

This paper describes the development of pH-sensitive poly(methyl methacrylate-acrylic acid) copolymers for the enteric coating of pharmaceutical products for oral administration. To obtain the dissolution at the desired pH level, different pH-sensitive polymers are available on the market. Usually, for each desired dissolution pH, an ad hoc polymer is designed. Thus, different dissolution pH values could ask for completely different polymers. Instead, the materials proposed in this work are copolymers of the same two monomers, and the different dissolution pH was obtained by changing the volume fraction of the hydrophobic methyl methacrylate monomer to the hydrophilic acrylic acid monomer. Increasing the volumetric percentage of methyl methacrylate causes the polymer to dissolve at increasing pH, until the dissolution does not take place at all, and it is replaced by a slow swelling phenomenon. The copolymers obtained were characterized by differential scanning calorimetry, in order to evaluate their glass transition temperature, and these latter were related to %MMA. The molecular weights of the pure polymers (PAA, PMMA) were measured by intrinsic viscosity, to further validate the glass transition temperatures observed. The dissolution of the copolymers was carefully tested in buffer solutions for a dense set of pH values. A linear relationship between dissolution pH and volumetric percentage of methyl methacrylate was obtained from these measurements. As a result, for any physiological compartment, the copolymer which dissolves at the pH of interest can be easily synthesized. doi:10.1007/s00289-009-0040-

Pharmaceutical Applications of Biocompatible Polymer Blends ontaining Sodium Alginate

Biocompatible polymer blends, such as alginate blends, have a widespread use in pharmaceutical and medical applications due to their specific features, such as biodegradation, adhesiveness, and thermo- and pH sensitivity and that can be obtained from the mixture composition. In this work, the use of alginate blends was tested in a novel production methodology of therapeutic dosage forms based on polymeric chain reticulation phenomena induced by exposure to bivalent ions. Two kinds of sodium alginate were used to obtain gel films (structured films) in blends with Pluronic F127®. The blends were considered for applications in gel paving of drug-eluting stents. Sodium alginate was also used in shell–core particle production (structured particles) to obtain shell-barrier reducing drug release in the preparative steps (see wash operations). Both structures, films and particles, were obtained using Cu2+ and Ca2+ ions, respectively. Film/shell barrier properties were tested in dissolution experiments using vitamin B12 as an active molecule model. Experimental work demonstrated that the alginate composition is a crucial point in defining reticulated structures

An Engineering Point of View on the Use of the Hydrogels for Pharmaceutical and Biomedical Applications

In this chapter, the modern uses of hydrogels in pharmaceutical and biomedical applications are revised following an engineering point of view, i.e. focusing the attention on material properties and process conditions. The chapter discusses the applications following the increase in scale‐size. First, the nanoscale systems, i.e. hydrogel nanoparticles (HNPs), are analysed in terms of preparative approaches (polymerization methods and uses of preformed polymers) and with a brief mention of the future trends in the field. Secondly, systems based on hydrogel microparticles (HMPs) are examined following the same scheme (polymerization methods, uses of preformed polymers, a mention of novel and future trends). Thirdly, and last but not the least, the hydrogel‐based drug delivery systems (macroscopic HB‐DDSs) are presented, focusing in particular on tablets made of hydrogels, discussing the characterization methods and on the modelling approaches used to describe their behaviour. Other macroscopic systems are also discussed in brief. Even if the vastness of the field makes its discussion impossible in a single chapter, the presented material can be a good starting point to study the uses of hydrogels in pharmaceutical and biomedical sciences

An engineering approach to biomedical sciences: advanced strategies in drug delivery systems production

Development and optimization of novel production techniques for drug delivery systems are fundamental steps in the “from the bench to the bedside” process which is the base of translational medicine. In particular, in the current scenery where the need for reducing energy consumption, emissions, wastes and risks drives the development of sustainable processes, new pharmaceutical manufacturing does not constitute an exception. In this paper, concepts of process intensification are presented and their transposition in drug delivery systems production is discussed. Moreover, some examples on intensified techniques, for drug microencapsulation and granules drying, are reported

Droplet size prediction in the production of drug delivery microsystems by ultrasonic atomization

Microencapsulation processes of drugs or other functional molecules are of great interest in pharmaceutical production fields. Ultrasonic assisted atomization is a new technique to produce microencapsulated systems by mechanical approach. It seems to offer several advantages (low level of mechanical stress in materials, reduced energy request, reduced apparatuses size) with respect to more conventional techniques. In this paper the groundwork of atomization is briefly introduced and correlations to predict droplet size starting from process parameters and material properties are presented

Inside the Phenomenological Aspects of Wet Granulation: Role of Process Parameters

Granulation is a size-enlargement process by which small particles are bonded, by means of various techniques, in coherent and stable masses (granules), in which the original particles are still identifiable. In wet granulation processes, the powder particles are aggregated through the use of a liquid phase called binder. The main purposes of size-enlargement process of a powder or mixture of powders are to improve technological properties and/or to realize suitable forms of commercial products. A modern and rational approach in the production of granular structures with tailored features (in terms of size and size distribution, flowability, mechanical and release properties, etc.) requires a deep understanding of phenomena involved during granules formation. By this knowledge, suitable predictive tools can be developed with the aim to choose right process conditions to be used in developing new formulations by avoiding or reducing costs for new tests. In this chapter, after introductive notes on granulation process, the phenomenological aspects involved in the formation of the granules with respect to the main process parameters are presented by experimental demonstration. Possible mathematical approaches in the granulation process description are also presented and the one involving the population mass balances equations is detailed

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