Microparticles, microspheres, and microcapsules are widely used constituents of multiparticulate drug delivery systems, offering both therapeutic and technological advantages. Microparticles are generally in the 1–1000 µm size range, serve as multiunit drug delivery systems with well-defined physiological and pharmacokinetic benefits in order to improve the effectiveness, tolerability, and patient compliance. This paper reviews their evolution, significance, and formulation factors (excipients and procedures), as well as their most important practical applications (inhaled insulin, liposomal preparations). The article presents the most important structures of microparticles (microspheres, microcapsules, coated pellets, etc.), interpreted with microscopic images too. The most significant production processes (spray drying, extrusion, coacervation, freeze-drying, microfluidics), the drug release mechanisms, and the commonly used excipients, the characterization, and the novel drug delivery systems (microbubbles, microsponges), as well as the preparations used in therapy are discussed in detail.

Microparticles have unique benefits in the formulation of multiparticulate and multi-unit type pharmaceutical dosage forms allowing improved drug safety and efficacy with favorable pharmacokinetics and patient centricity. On the other hand, the above advantages are served by high and well reproducible quality attributes of the medicinal product where even flexible design and controlled processability offer success as well as possible longer product life-cycle for the manufacturers. Moreover, the specific demands of patients can be taken into account, including simplified dosing regimens, flexible dosage, drug combinations, palatability, and ease of swallowing. In the more than 70 years since the first modified-release formulation appeared on the market, many new formulations have been marketed and many publications have appeared in the literature. More unique and newer pharmaceutical technologies and excipients have become available for producing tailor-made particles with micrometer dimensions and beyond. All these have contributed to the fact that the sub-units (e.g. minitablets, pellets, microspheres) that make up a multiparticulate system can vary widely in composition and properties. Some units have mucoadhesive properties and others can float to contribute to a suitable release profile that can be designed for the multiparticulate formula as a whole. Nowadays, there are some available formulations on the market, which are able to release the active substance even for several months (3 or 6 months depending on the type of treatment). In this review, the latest developments in technologies that have been used for a long time are presented, as well as innovative solutions such as the applicability of 3D printing to produce subunits of multiparticulate systems. Furthermore, the diversity of multiparticulate systems, different routes of administration are also presented, touching the ones which are capable of carrying the active substance as well as the relevant, commercially available multiparticle-based medical devices. The versatility in size from 1 µm and multiplicity of formulation technologies promise a solid foundation for the future applications of dosage form design and development.

A significant proportion of pharmaceuticals are now considered multiparticulate systems. Modified-release drug delivery formulations can be designed with engineering precision, and patient-centric dosing can be accomplished relatively easily using multi-unit systems. In many cases, Multiple-Unit Pellet Systems (MUPS) are formulated on the basis of a neutral excipient core which may carry the layered drug surrounded also by functional coating. In the present summary, commonly used starter pellets are presented. The manuscript describes the main properties of the various nuclei related to their micro- and macrostructure. In the case of layered pellets formed based on different inert pellet cores, the drug release mechanism can be expected in detail. Finally, the authors would like to prove the industrial significance of inert cores by presenting some of the commercially available formulations.

α-Aminophosphonates are organophosphorus compounds with an obvious similarity with α-amino acids. Owing to their biological and pharmacological characteristics, they have attracted the attention of many medicinal chemists. α-Aminophosphonates are known to exhibit antiviral, antitumor, antimicrobial, antioxidant and antibacterial activities, which can all be important in pathological dermatological conditions. However, their ADMET properties are not well studied. The aim of the current study was to provide preliminary information about the skin penetration of three preselected α-aminophosphonates when applying them as topical cream formulations in static and dynamic diffusion chambers. The results indicate that aminophosphonate 1a, without any substituent in the para position, shows the best release from the formulation and the highest absorption through the excised skin. However, based on our previous study, the in vitro pharmacological potency was higher in the case of para-substituted molecules 1b and 1c. The particle size and rheological studies revealed that the 2% cream of aminophosphonate 1a was the most homogenous formulation. In conclusion, the most promising molecule was 1a, but further experiments are proposed to uncover the possible transporter interactions in the skin, optimize the topical formulations and improve PK/PD profiles in case of transdermal delivery.

Organ-on-a-chip technologies show exponential growth driven by the need to reduce the number of experimental animals and develop physiologically relevant human models for testing drugs. In vitro, microfluidic devices should be carefully designed and fabricated to provide reliable tools for modeling physiological or pathological conditions and assessing, for example, drug delivery through biological barriers. The aim of the current study was to optimize the utilization of three existing skin-on-a-chip microfluidic diffusion chambers with various designs. For this, different perfusion flow rates were compared using cellulose acetate membrane, polyester membrane, excised rat skin, and acellular alginate scaffold in the chips. These diffusion platforms were integrated into a single-channel microfluidic diffusion chamber, a multi-channel chamber, and the LiveBox2 system. The experimental results revealed that the 40 µL/min flow rate resulted in the highest diffusion of the hydrophilic model formulation (2% caffeine cream) in each system. The single-channel setup was used for further analysis by computational fluid dynamics simulation. The visualization of shear stress and fluid velocity within the microchannel and the presentation of caffeine progression with the perfusion fluid were consistent with the measured data. These findings contribute to the development and effective application of microfluidic systems for penetration testing.

Background/Objectives: To improve the therapeutic efficacy of albendazole (ABZ) for ileocolonic diseases, its low solubility at higher pH levels should be enhanced. Organic acids have been widely used as pH modifiers to improve the solubility of weakly basic drugs. To achieve an adequate effect of the acidic microenvironmental pH during the drug release, pH modifiers should not leach out from the formulation. In the present work, we aimed to demonstrate that 100% tartaric acid pellets (TAP) can be used as pH-modifier cores, providing an acidic microenvironmental pH to enhance the solubility of albendazole at a higher pH. Methods: This study develops multilayer-coated pellets using TAP as starter cores in a bottom-spray-configured fluidized bed apparatus. The drug-layered TAP were coated with time-dependent and pH-dependent layers. Results: The release of ABZ from tartaric acid-based coated pellets was enhanced compared to that from pellets with the same layering structure but with an inert core of sugar or microcrystalline cellulose (MCC). In vitro experiments showed that tartaric acid remained in the pellet core during the dissolution test at a pH 6.8 medium, which resulted in an enhanced release of albendazole at a higher pH. The application of a combination of time-dependent and pH-dependent polymers aimed not only to prevent the release of albendazole at lower pH levels but also to protect TAP from premature release from the formulation. Conclusions: The application of 100% ready-to-use tartaric acid pellets (TAP) with the applied combination of coatings enhanced the solubility of the weakly basic drug albendazole at higher intestinal pH.