Release Of Moxifloxacin Research Articles

Extended release and enhanced bioavailability of moxifloxacin conjugated with hydrophilic cellulose ethers

Macromolecular prodrugs (MPDs) of moxifloxacin were fabricated based on hydroxypropylcellulose (HPC) and hydroxyethylcellulose (HEC). UV/Vis spectrophotometry was employed to determine covalently loaded drug content (DC) of each conjugate. The degree of substitution (DS) of moxifloxacin attained ranged from 0.27 to 0.38 (HPC) and 0.19 to 0.26 (HEC) per anhydroglucose unit (AGU), respectively. Transmission electron microscopic analyses showed that HPC–moxifloxacin conjugates self-assembled into nanowires of ∼30nm diameters while HEC–moxifloxacin conjugates self-assembled into nanoparticles of 150–350nm. In vitro drug release studies revealed that 15 and 49% moxifloxacin release occurred from the HPC–moxifloxacin conjugate after 6h at pH 1.2 and 7.4, respectively. Similarly, moxifloxacin release from HEC–moxifloxacin conjugates was 15 and 39% at pH 1.2 and 7.4, respectively. Bioavailability and pharmacokinetic studies in rabbits showed that both HPC- and HEC-conjugates exhibited significantly enhanced moxifloxacin plasma half-life, over 24h, confirming sustained release and enhanced bioavailability (AUC 2.0–2.1 times higher) of moxifloxacin.

Release of Ciprofloxacin and Moxifloxacin From Daily Disposable Contact Lenses From an In Vitro Eye Model.

To analyze the release of two fluoroquinolones, ciprofloxacin and moxifloxacin, from conventional hydrogel (CH) and silicone hydrogel (SH) daily disposable contact lenses (CLs), comparing release from a fixed-volume vial and a novel in vitro eye model. Four CH CLs (nelfilcon A, omafilcon A, etafilcon A, ocufilcon B) and three SH CLs (somofilcon A, narafilcon A, delefilcon A) were used. The lenses were incubated in drug solutions for 24 hours. After the incubation period, the lenses were placed in two release conditions: (1) a vial containing 4.8 mL PBS for 24 hours and (2) an in vitro eye model with a flow rate at 4.8 mL over 24 hours. Release in the vial for both drugs was rapid, reaching a plateau between 15 minutes and 2 hours for all lenses. In contrast, under physiological flow conditions, a constant and slow release was observed over 24 hours. The amounts of ciprofloxacin released from the lenses ranged between 49.6 ± 0.7 and 62.8 ± 0.3 μg per lens in the vial, and between 35.0 ± 7.0 and 109.0 ± 5.0 μg per lens in the eye model. Moxifloxacin release ranged from 24.0 ± 4.0 to 226.0 ± 2.0 μg per lens for the vial, and between 13.0 ± 2.0 and 151.0 ± 10.0 μg per lens in the eye model. In both systems and for both drugs, HEMA-based CLs released more drugs than other materials. The parameters of the release system, in particular the volume and flow rate, have a significant influence on measured release profiles. Under physiological flow, release profiles are significantly slower and constant when compared with release in a vial.

Moxifloxacin in situ gelling microparticles–bioadhesive delivery system

Antibiotic use for ocular treatments has been largely limited by poor local bioavailability with conventional eyedrops formulations. Here, we developed a controlled delivery system composed of moxifloxacin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulated in a chondroitin sulfate-based, two-component bioadhesive hydrogel. Using a simple and fast electrohydrodynamic spray drying (electrospraying) technique, surfactant-free moxifloxacin-loaded microparticles were fabricated with diameters on the order of 1μm. A mixed solvent system of methanol/dichloromethane (MeOH/DCM) was employed to prepare the microparticles for the electrospraying processing. Extended release of moxifloxacin using a series of MeOH/DCM mixed solvents was accomplished over 10 days with release concentrations higher than the minimum inhibitory concentration (MIC). In contrast, moxifloxacin loaded directly in hydrogels was released rapidly within 24h. We observed a decrease of the drug release rate from the microparticles when using an increased percentage of methanol in the mixed solvent from 10% to 30% (v/v), which can be explained by the mixed solvent system providing a driving force to form a gradient of the drug concentrations inside the microparticles. In addition, the delivery system developed in this study, which incorporates a bioadhesive to localize drug release by in situ gelling, may potentially integrate antibiotic prophylaxis and wound healing in the eye.

Chitosan microspheres for intrapulmonary administration of moxifloxacin: Interaction with biomembrane models and in vitro permeation studies

Chitosan microspheres loaded moxifloxacin were prepared to obtain sustained release of the drug after intrapulmonary administration. The microspheres were produced by the spray-drying method using glutaraldehyde as the crosslinking agent. The particles were spherical with a smooth but distorted surface morphology and were of small size, ranging from 2.5 to 6.0 μm, thus suitable for inhalation. In vitro release studies showed a significant burst effect for all crosslinked systems, followed by a prolonged moxifloxacin release, particularly in the presence of the highest glutaraldehyde concentration. Lipid vesicles made of dipalmitoylphosphatidylcholine (DPPC) were used as an in vitro biomembrane model to evaluate the influence of chitosan microspheres on the interaction of moxifloxacin with biological membranes. Differential scanning calorimetry was used as a simple and non-invasive technique of analysis. Moxifloxacin freely permeates through DPPC liposomes, interacting with the hydrophobic zone of the bilayers (lowering of the Δ H value and loss of the cooperativity of the main transition peak). Uncrosslinked microspheres rapidly swelled and dissolved releasing free chitosan that was able to interact with liposomes (increase of Δ H value), probably altering the biomembrane permeability to the drug. Crosslinked microspheres did not show this property. Pulmonary absorption of moxifloxacin-loaded chitosan microspheres was evaluated compared to the free drug. A monolayer of Calu-3 human bronchial epithelial cells mounted on Franz diffusion cells was used as an in vitro bronchial epithelium model. Microspheres retard the absorption of moxifloxacin and within 6 h the cumulative amount of permeated drug was about 18%, 11% and 7% (w/w) for free moxifloxacin, moxifloxacin-loaded crosslinked and moxifloxacin-loaded uncrosslinked microspheres, respectively.