Evaluating the effect of sodium alginate and sodium carboxymethylcellulose on pulmonary delivery of levofloxacin spray-dried microparticles.

BACKGROUND: Patients with cystic fibrosis commonly suffer from lung infections caused by Pseudomonas aeruginosa. Recently, the Levofloxacin (LVF) nebulizing solution (Quinsair®) has been prescribed for the antimicrobial management. The sustained-release (SR) dry powder formulation of LVF is a convenient alternative to Quinsair®. It has the potential to enhance patient convenience and decrease the likelihood of drug resistance over time. OBJECTIVE: In this paper, we set forth to formulate and evaluate the potential application of sodium alginate (SA) and sodium carboxymethylcellulose (SCMC) for sustained pulmonary delivery of LVF. METHODS: The spray-dried (SD) LVF microparticles were formulated using SCMC and SA along with L-leucine (Leu). The microparticles were analyzed in terms of particle size, morphology, x-ray diffraction (XRD), in-vitro drug release, and aerodynamic properties. Selected formulations were further proceeded to short-term stability test. RESULTS: The polymer-containing samples displayed process yield of 33.31%-39.67%, mean entrapment efficiency of 89% and volume size within the range of 2-5 µm. All the hydrogel microparticles were amorphous and exhibited rounded morphology with surface indentations. Formulations with a drug-to-excipient ratio of 50:50 and higher, showed a 24-h SR. The aerodynamic parameters were fine particle fraction and emitted dose percentage ranging between 46.21%-60.6% and 66.67%-87.75%, respectively. The short-term stability test revealed that the formulation with a 50:50 drug-to-excipient ratio, containing SA, demonstrated better physical stability. CONCLUSION: The selected formulation containing SA has the potential to extend the release duration. However, further enhancements are required to optimize its performance.

Comparison of 25-hydroxy vitamin D, calcium and alkaline phosphatase levels in epileptic and non-epileptic children.

OBJECTIVE: There is evidence for the existence of bone disease in epileptic patients. The goal of this study was the comparison of serum levels calcium, alkaline phosphatase (ALKP) and 25-hydroxyvitamin D in ambulatory epileptic children in order to evaluate the bone metabolism in epileptic patients. METHODS: In this prospective analytical study 48 ambulatory epileptic children who were treated by antiepileptic drugs for atleast 6 months as case group compared with 48 children who were age and gender matched as control group. Patients with any neurological deficits and other systemic diseases were excluded. Data was collected by questionnaire and analyzed by spss software version 18. RESULTS: Mean of calcium level in case and control groups was 9.91 ±0.675 and 10.08 ±0.331 mg/dl respectively, means of ALKP in case were 703 and 607.75 IU/L respectively. Only difference between the ALKP were significant. Calcium levels, ALKP and vitmain D in any of the two groups were not associated with age and a sex but ALKP level in patients was higher and it was statistically siginificant. Calcium levels, ALKP and vitamin D in patients with drug type, dosage and duration of treatment were irrelevant. CONCLUSION: The results of this study showed that calcium and vitamin D levels were in normal ranges in epileptic and control groups but ALKP levels were significantly higher in epileptic group which can be a valuable indicator of bone metabolism in these patients.

Spray freeze drying to solidify Nanosuspension of Cefixime into inhalable microparticles.

PURPOSE: Spray-freeze drying (SFD) incorporating diverse carbohydrates and leucine was employed to obtain dried nanosuspension of cefixime with improved dissolution profile, good dispersibility, and excellent inhalation performance. METHODS: Nanoprecipitation was utilized to prepare nanoparticles (NPs). Nanosuspensions of cefixime were solidified via SFD to access inhalable microparticles. The aerosolization efficiencies were evaluated through twin stage impinger (TSI). Laser light scattering and scanning electron microscopy (SEM) provided assistance to determine the particle size/size distribution and morphology, respectively. Amorphous/ crystalline states of materials were examined via differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Release profiles of candidate preparations were evaluated. RESULTS: The fine particle fraction (FPF) ranged from 18.96 ± 0.76 to 79.28 ± 0.45%. The highest value resulted from trehalose with NP/carrier ratio of 1:1 and leucine 20%. The particle size varied from 5.24 ± 0.97 to 10.17 ± 1.01 µm. The most and the least size distribution were achieved in mannitol and trehalose containing formulations, respectively. The majority of samples demonstrated ideally spherical morphology with diverse degrees of porosity and without needle-shaped structure. Percentages of release in F7 and F8 were 89.33 ± 0.88% and 93.54 ± 1.02%, respectively, via first 10 min. CONCLUSION: SFD of nanosuspensions can be established as a platform for the pulmonary delivery of poorly water-soluble molecules of cefixime. Trehalose and raffinose with a lower ratio of NP to the carrier and higher level of leucine could be introduced as favorable formulations for further respiratory delivery of cefixime.

Engineering of levodopa inhalable microparticles in combination with leucine and dipalmitoylphosphatidylcholine by spray drying technique.

The aim of this work was to study the effect of concomitant use of leucine and dipalmitoylphosphatidylcholine, in different ratios, on aerosolization performance of levodopa. Three-component formulations were selected based on a central composite design using percentages of leucine and dipalmitoylphosphatidylcholine as the independent variables. Particle size, surface roughness index, surface phosphorus and fine particle fraction were considered as dependent variables in the model. The spray dried samples were also characterized to determine their particle shape and solid state nature. levodopa was spray dried with 10-40% w/w of the excipients to prepare two- or three-component formulations. A crystalline nature was determined for levodopa in all samples spray dried from water:ethanol (30:70 v/v). Roughness in surface of the processed particles increased with increasing total concentration of the excipients, specially above 25% w/w. Analysis of phosphorus on the surface demonstrated that three-component formulations prepared with combination of 12.5% w/w leucine had the highest amount of dipalmitoylphosphatidylcholine in the surface, regardless of its percentage used in the initial feed. A combination of 12.43% w/w of leucine and 9.80% w/w of dipalmitoylphosphatidylcholine used in formulation exhibited the highest fine particle fraction (72.63%). It can be concluded that spray drying of levodopa with a suitable combination of both excipients leads to production of a three-component formulation of crystalline levodopa, with an aerosolization performance which is significantly higher than two-component formulations composed of the drug with either leucine or dipalmitoylphosphatidylcholine.