The processes behind drug loading and release in porous drug delivery systems.

Porous materials are ubiquitous and exhibit properties suitable for depositing therapeutic compounds. Drug loading in porous materials can protect the drug, control its release rate, and improve its solubility. However, to achieve such outcomes from porous delivery systems, effective incorporation of the drug in the internal porosity of the carrier must be guaranteed. Mechanistic knowledge of the factors influencing drug loading and release from porous carriers allows rational design of formulations by selecting a suitable carrier for each application. Much of this knowledge exists in research areas other than drug delivery. Thus, a comprehensive overview of this topic from the drug delivery aspect is warranted. This review aims to identify the loading processes and carrier characteristics influencing the drug delivery outcome with porous materials. Additionally, the kinetics of drug release from porous materials are elucidated, and the common approaches to mathematical modeling of these processes are outlined.

Loading of Porous Functionalized Calcium Carbonate Microparticles: Distribution Analysis with Focused Ion Beam Electron Microscopy and Mercury Porosimetry.

Accurate analysis of intraparticle distribution of substances within porous drug carriers is important to optimize loading and subsequent processing. Mercury intrusion porosimetry, a common technique used for characterization of porous materials, assumes cylindrical pore geometry, which may lead to misinterpretation. Therefore, imaging techniques such as focused ion beam scanning electron microscopy (FIB-SEM) help to better interpret these results. The purpose of this study was to investigate the differences between mercury intrusion and scanning electron microscopy and to identify the limitations of each method. Porous microparticles, functionalized calcium carbonate, were loaded with bovine serum albumin and dipalmitoylphosphatidylcholine (DPPC) by solvent evaporation and results of the pore size distribution obtained by both methods were compared. The internal structure of the novel pharmaceutical excipient, functionalized calcium carbonate, was revealed for the first time. Our results demonstrated that image analysis provides a closer representation of the material distribution since it was possible to discriminate between blocked and filled pores. The physical nature of the loaded substances is critical for the deposition within the pores of functionalized calcium carbonate. We conclude, that a combination of mercury intrusion porosimetry and focused ion beam scanning electron microscopy allows for a reliable analysis of sub-micron porous structures of particulate drug carriers.

Mucoadhesive microparticles for local treatment of gastrointestinal diseases.

Mucoadhesive microparticles formulated in a capsule and delivered to the gastrointestinal tract might be useful for local drug delivery. However, swelling and agglomeration of hydrophilic polymers in the gastrointestinal milieu can have a negative influence on particle retention of mucoadhesive microparticles. In this work, we investigated the impact of dry-coating with nano-sized hydrophilic fumed silica on dispersibility and particle retention of mucoadhesive microparticles. As a model for local treatment of gastrointestinal diseases, antibiotic therapy of Clostridium difficile infections with metronidazole was selected. For particle preparation, we used a two-step fluidized-bed method based on drug loading of porous microcarriers and subsequent outer coating with the mucoadhesive polymer chitosan. The prepared microparticles were analysed for drug content, and further characterized by thermal analysis, X-ray diffraction, and scanning electron microscopy. The optimal molecular weight and content of chitosan were selected by measuring particle retention on porcine colonic mucosa under dynamic flow conditions. Mucoadhesive microparticles coated with 5% (weight of chitosan coating/total weight of particles) of low molecular weight chitosan showed good in vitro particle retention, and were used for the investigation of dispersibility enhancement. By increasing the amount of silica, the dissolution rate measured in the USPIV apparatus was increased, which was an indirect indication for improved dispersibility due to increased surface area. Importantly, mucoadhesion was not impaired up to a silica concentration of 5% (w/w). In summary, mucoadhesive microparticles with sustained-release characteristics over several hours were manufactured at pilot scale, and dry-coating with silica nanoparticles has shown to improve the dispersibility, which is essential for better particle distribution along the intestinal mucosa in humans. Therefore, this advanced drug delivery concept bears great potential, in particular for local treatment of gastrointestinal diseases.