Levocetirizine dihydrochloride is an effective antiallergenic drug applied mostly orally; however, developing a topical formulation for localized treatment could be beneficial. To achieve this, a modified formulation technique is necessary to enhance bioavailability efficiency and minimize possible side effects. Therefore, levocetirizine particles were prepared by immobilization on mesoporous silica material. Both the dihydrochloride form and its free base of levocetirizine were fixed on a silica-type Syloid support. Immobilization of the active ingredient levocetirizine in a free base form on a Syloid support by mixing in a dichloromethane solution provides better surface coverage (65.5%) than immobilization in the dihydrochloride form in water or methanol (24.5% for both). The successful binding of levocetirizine was confirmed by X-ray photoelectron spectroscopy and infrared measurements. The active ingredient in the form of hydrochloride is more likely to be in the pores, while the free base is bound to the surface in larger quantities. The time-dependent levocetirizine release showed that the liberation of the active ingredient from the Syloid is slower than the dissolution of the starting active ingredient itself, so it may be suitable for exerting a more reliable and prolonged local effect. A gel containing a Syloid-fixed levocetirizine free base was tested in vivo in a croton oil-induced ear edema mouse model. When compared to a reference gel, the half-dose formulation containing levocetirizine free base demonstrated a similar efficacy to Fenistil gel, indicating that the new formulation may offer superior effectiveness at lower doses.

Antihistamines such as levocetirizine dihydrochloride (LC) are commercially used in oral tablets and oral drops to reduce allergic symptoms. In this study, LC was nano-spray-dried using three mucoadhesive polymers and four cyclodextrin species to form composite powders for nasal administration. The product was composed of hydroxypropyl methylcellulose polymer, including LC as a zwitterion, after neutralization by NaOH, and XRD investigations verified its amorphous state. This and a sulfobutylated-beta-cyclodextrin sodium salt-containing sample showed crystal peaks due to NaCl content as products of the neutralization reaction in the solutions before drying. The average particle size of the spherical microparticles was between 2.42 and 3.44 µm, except for those containing a polyvinyl alcohol excipient, which were characterized by a medium diameter of 29.80 µm. The drug was completely and immediately liberated from all the samples at pH 5.6 and 32 °C; i.e., the carriers did not change the good dissolution behavior of LC. A permeability test was carried out by dipping the synthetic cellulose ester membrane in isopropyl myristate using modified horizontal diffusion cells. The spray-dried powder with β-cyclodextrin showed the highest permeability (188.37 µg/cm2/h), as this additive was the least hydrophilic. Products prepared with other cyclodextrins (randomly methylated-beta-cyclodextrin, sulfobutylated-beta-cyclodextrin sodium salt and (hydroxypropyl)-beta-cyclodextrin) showed similar or slightly higher penetration abilities than LC. Other polymer excipients resulted in lower penetration of the active agent than the pure LC.

Levocetirizine dihydrochloride active ingredient was microencapsulated using nano spray-drying technology for preparing microparticles containing topical gel against edema. Hydroxyl propyl methyl cellulose (HPMC) was used as a carrier polymer during spray drying. The active ingredient content of the nano spray-dried products was 52.81% (w/w) and 51.33% (w/w) for ex vivo and in vivo experiments, respectively, and the average particle size was 2.6 µm. X-ray diffraction analysis indicated an amorphous state of the active ingredient embedded in the amorphous matrix of the polymer. Dermal oil gels composed of Miglyol 812 gelated by Dermofeel viscolid included 5% (w/w) (for ex vivo) and 10% (w/w) (for in vivo) active ingredient without or with 0.05% (w/w) menthol penetration enhancer. Qualitative ex vivo penetration studies using a confocal Raman microscopic correlation mapping were executed on human abdominal skin. The results showed that the active ingredient was enriched in the epidermis and upper dermis layer of the skin using oleogel loaded with the nano spray-dried drug-HPMC composite. Menthol addition to the oleogel resulted in the concentration of levocetirizine in the dermis. In vivo tests were performed on a mouse model of croton oil-induced ear edema. Negative control and Fenistil-treated groups were compared using the prepared oil gels with and without menthol. Without penetration enhancer, 20 µL of our oil gel loaded with nano spray-dried levocetirizine dihydrochloride composite showed similar effectiveness to the same volume of Fenistil gel, while 5 µL menthol containing sample was sufficient to eliminate the skin irritation similarly to 20 µL Fenistil.

Due to the great potential of biocompatible cucurbit[7]uril (CB7) and 4-sulfonatocalix[4]arene (SCX4) macrocycles in drug delivery, the confinement of the pharmaceutically important metronidazole as an ionizable model drug has been systematically studied in these cavitands. Absorption and fluorescence spectroscopic measurements gave 1.9 × 105 M−1 and 1.0 × 104 M−1 as the association constants of the protonated metronidazole inclusion in CB7 and SCX4, whereas the unprotonated guests had values more than one order of magnitude lower, respectively. The preferential binding of the protonated metronidazole resulted in 1.91 pH unit pKa diminution upon encapsulation in CB7, but the complexation with SCX4 led to a pKa decrease of only 0.82 pH unit. The produced protonated metronidazole–SCX4 complex induced nanoparticle formation with protonated chitosan by supramolecular crosslinking of the polysaccharide chains. The properties of the aqueous nanoparticle solutions and the micron-sized solid composite produced therefrom by nano spray drying were unraveled. The results of the present work may find application in the rational design of tailor-made self-assembled drug carrier systems.

In this study metronidazole drug was encapsulated by hydroxypropyl methylcellulose and polyvinylpyrrolidone polymers from solutions using nano spray drying technology. The influence of the process parameters and formulation variables were investigated on product morhology and structure, production yield and entrapment efficiency. The use of surface active admixtures (polyvinyl alcohol, Tween-80 and Pluronic F68) increased the product yield substantially. The entrapped metronidazole was partially in crystalline and amorphous state in both amorphous polymers as confirmed by DSC and powder X-ray diffraction measurements. In the composites with hydroxypropyl methylcellulose the degree of crystallinity was between 50.2 and 81.0%, and with polyvinylpyrrolidone between 35.0 and 50.0% (with respect to the drug content). Melting point decrease phenomena was observed by differ-ential scanning calorimetry between bulk metronidazole and spray dried products. Peak broadening was indicated by powder X-ray diffraction measurements, which could be the result of formation of small drug crystallites. The TEM images showed beside the larger crystals (200-400 nm) a fraction of smaller crystals (20-50 nm in diameter), which are in good correlation with the calculated coherent scattering domain sizes of 19-87 nm based on X-ray data. The drug-polymer composites produced by nano spray drying process were identified as crystalline-amorphous nanostructured micronized solid dispersions. (c) 2021 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.

Valsartan is an antihypertensive drug used primarily orally, however, due to its hydrophobic nature it has got low bio-availability thus requiring higher dosage/frequency and causing more side effects. The aim of our work was to prepare valsartan-loaded nanoparticles by using ethyl cellulose and poly(methyl methacrylate) polymers which can be administered orally and to investigate the preparation conditions and their significance as potential drug carriers for valsartan delivery by in vitro release studies. Ethyl cellulose and poly(methyl methacrylate) polymers were used for the preparation of nanoparticles by single emulsion-solvent evaporation technique. The formation of drug-loaded nanoparticles was designed by experimental design for size and encapsulation efficiency, in addition the prepared nanosuspensions were nano spray dried in order to gain a powder form that is easy to handle and store. Both of the nano spray dried formulations had an amorphous structure in contrast to the pure drug according to differential scanning calorimetry and X-ray diffraction analysis, which can be advantageous in drug absorption. The originally processed ethyl cellulose-valsartan nanoparticles increased the solubility of the drug in the model intestinal medium, while poly(methyl methacrylate)-valsartan nanoparticles enabled substantially prolonged drug release. The release kinetics of both types of nanoparticles could be described by the Weibull model.