Development of ciprofloxacin-loaded poly(vinyl alcohol) dry powder formulations for lung delivery.

Polymeric microparticles are micro carriers for the sustained drug delivery of drugs in the lungs, used as alternatives to the use of established excipients. This study aims to develop and characterize inhalable ciprofloxacin (CPx)-loaded poly(vinyl alcohol) (PVA) microparticles by a single-step spray-drying procedure. The optimization of the processing parameters was achieved by an orthogonal design of the most relevant processing parameters (polymer concentration, feed rate and inlet temperature). The obtained spray-dried particles showed a drug encapsulation efficiency higher than 90%. Furthermore, PVA-CPx formulations, with drug contents up to 10 wt%, showed a morphology and size suitable for inhalation, with a sustained release profile over 24 h. Data from Fourier transformed infra-red spectroscopy and differential scanning calorimetry indicated absence of interaction between the polymer matrix and the drug. Aerodynamic assessment of PVA-CPx 10 wt% was determined by the next generation impactor (NGI), using spray-dried CPx as a control. The results showed improved values of mass median aerodynamic diameter (5.06±0.10µm) and a fine particle fraction (39.78±0.98%) when comparing with the CPx alone (5.33±0.39µm and 30.43±1.38%). This study highlights the potential of spray-dried PVA microparticles as drug carriers for lung local delivery of antibiotics.

Enhancement of the in vitro penetration of quercetin through pig skin by combined microneedles and lipid microparticles.

Silicon microneedle patches were investigated, alone or in combination with lipid microparticles (LMs), as a system to improve the in vitro skin penetration of the antioxidant flavonoid, quercetin. LMs loaded with quercetin were prepared by melt emulsification and sonication. The flavonoid content of LMs was 11.7±0.3% and their mean diameter and polydispersity index were 8.1 µm and 0.66, respectively. Emulsions containing quercetin, free or microencapsulated, were applied to untreated- or microneedle-treated pig skin mounted in Franz diffusion cells. The amount of flavonoid penetrated into the stratum corneum and viable epidermis were measured by HPLC, after validated tape-stripping and bead mill homogenization procedures, respectively. Compared to intact skin, a marked increase in quercetin levels permeated into the stratum corneum (from 1.19 ± 0.12 µg/cm(2) to 2.23 ± 0.54 µg/cm(2)) and viable epidermis (from 0.10 ± 0.01 µg/cm(2) to 0.56 ± 0.27 µg/cm(2)) was achieved when skin was treated with the flavonoid-loaded LMs in combination with microneedle arrays. Conversely, perforation of the cutaneous surface by microneedles did not produce any significant improvement in the skin penetration of non-encapsulated quercetin. The enhanced (5.5-fold) intra-epidermal delivery of quercetin attained by the LM/microneedle strategy described here, is particularly relevant since the main quercetin site of action is in the epidermis.