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Biopharmaceutics classification systems based on the properties of solubility and permeability or the extension of metabolism are very important tools in the early stages of the development and regulatory stages of new products. However, until now, there was no clear understanding between the interplay among these classification systems. Therefore, the main objective of this work was to make a comparison of concepts of BCS and BDDCS to understand what are the key factors that allow for the integration of these biopharmaceutics classification systems. Also, the suitability of an in situ single-pass intestinal perfusion assay in rats (SPIP) development was assessed by us to determine the limit between high and low permeability following what the FDA BCS guidance suggests. An excellent correlation was found between the values of permeability obtained by applying SPIP assays and the extensions of the metabolism of the set of compounds studied in this work, with the exception of three compounds that showed disparity between their permeability coefficients ( Peff), obtained herein by SPIP, and their metabolism (acetazolamide, azithromycin, and efavirenz). Discrepancies allowed us to elucidate the interrelationship between BCS and BDDCS.

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This paper is focused on the synthesis of chitosan-coated polycaprolactone nanoparticles in microreactors and on the freeze-drying of the nanosuspension, to separate the particles from the liquid phase. Nanoparticles were produced in the confined impinging jets mixer (CIJM) and in the multi-inlet vortex mixer (MIVM), using the solvent displacement method, with acetone or tert-butanol (TBA) as polymer solvent. The study was initially carried out considering a feed flow rate of 80 ml min-1: using acetone, the mean particle size was lower (163 ±â€¯7 nm) and the Zeta potential was higher (31.4 ±â€¯37 mV) with the MIVM, with respect to the CIJM (265 ±â€¯31 nm and 9.8 ±â€¯2.4 mV, respectively). Slightly larger particles were obtained using TBA in the MIVM (mean diameter: 221 ±â€¯44 nm): in this case it is no longer required removing the solvent before the freeze-drying stage. The effect of the liquid flow rate was then investigated, confirming that the best results were obtained at 80 ml min-1. With respect to the freeze-drying process, the effect of lyoprotectants and of steric stabilizers on particle stability was investigated. Best results were obtained with 5% sucrose and 2.5% Poloxamer 388 (mean diameter: 306 ±â€¯8 nm); in all cases Zeta potential remained positive and larger than +30 mV. Preliminary results about the encapsulation of a test drug, ciprofloxacin, are also shown and discussed.

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AIM: This work aimed to design and characterize cross-linked hyaluronic acid-itaconic acid films loaded with acetazolamide-hydroxypropyl ß cyclodextrin-triethanolamine complexes. MATERIALS & METHODS: Films were cross-linked with itaconic acid and poly(ethyleneglycol)-diglycidylether. Biopharmaceutical properties were assessed by evaluating in vitro drug release rate, biocompatibility in a human corneal epithelial cell line, bioadhesiveness with pig gastric mucin, in vivo bioadhesion and efficacy. RESULTS: Showed good mechanical properties and oxygen permeability. Proliferation rate of corneal cells was affected by highest acetazolamide concentration. Bioadhesive interaction exhibited a water movement from pig mucin to the film; in vivo experiments showed strong bioadhesion for 8 h and hypotensive effect for almost 20 h. CONCLUSION: Experimental set showed promising performance and encouraged future studies to optimize formulation. [Formula: see text].

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This work is focused on the synthesis of polycaprolactone nanoparticles, coated with chitosan, in a confined impinging jet reactor using the solvent displacement method. The role of the various reacting species was investigated, evidencing that a biocompatible polymer, for example, polycaprolactone, is required to support chitosan to obtain a monomodal particle size distribution, with low particle diameters. A surfactant is required to reduce the nanoparticle size (down to a mean diameter of about 260 nm) and obtain a positive zeta potential (about +31 mV), perfectly suitable for pharmaceutical applications. Different surfactants were tested, and Poloxamer 388 appeared to be preferable to polyvinyl alcohol. The effect of the concentration of Poloxamer 388 (in the range 0.5-5 mg mL-1) and of chitosan (in the range 1.5-5 mg mL-1) on both the mean particle size and zeta potential was also investigated, evidencing that chitosan concentration has the strongest effect on both parameters. Finally, the effect of solvent evaporation, quenching and feed flow rate was investigated, showing that the evaporation stage does not affect particle characteristics, quenching is required to avoid particle aggregation, and a minimum liquid flow rate of 80 mL min-1 is required in the considered reactor to minimize the particle size.

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A protocol is developed to allow the accurate characterization of partition to lipid bilayers for solutes with low affinity, using isothermal titration calorimetry. The methodology proposed is suitable for studies using complex membranes, such as intact biomembranes or whole cells. In the method developed, the association is characterized at increasing solute concentrations. This allows the characterization of solute partition into unperturbed membranes, as well as effects induced by high solute concentrations. Most druglike molecules are expected to interact with low-to-moderate affinity with relevant cell membranes. This is due to both the need for a relatively high aqueous solubility of the drug and the poor binding properties of the cell membranes. The methodology is applied to characterize the interaction of antibiotic Rifampicin with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and with lipid bilayers representative of bacterial membranes.