Preparation and in-vitro evaluation of rifampin-loaded mesoporous silica nanoaggregates by an experimental design

The goal of this research is preparation, optimization and in-vitro evaluation of rifampinloaded silica nanoparticles in order to use in the pulmonary drug delivery. Nanoparticles are exhaled because of their small size. Preparation of nanoaggregates in a micron-size scale and re-dispersion of them after deposition in the lung is an approach to overcome this problem. We used this approach in our research. Rifampin was selected as a model lipophilic molecule since it was a well-documented and much used anti tuberculosis drug. A half factorial design was used to identify significant parameters of the spray drying process. The results showed that feed concentration, feed pH and the interaction between feed flow rate and gas atomizer flow rate had statistically significant effects on the particle size of nanoaggregates. The Box-Behnken design was employed to optimize the spray drying process. Finally, a quadratic equation which explains the relation between independent variables and aerodynamic diameter of nanoaggregates was obtained. Rifampin-loaded silica nanoaggregates underwent different in-vitro tests including: SEM, Aerosol performance and drug release. The in-vitro drug release was investigated with buffer phosphate [pH=7.4]. Regarding the drug release study, a triphasic pattern of release was observed. The rifampin-loaded silica nanoaggregates were capable of releasing 90% drug content after 24 h in combination patterns of release. The prepared rifampin-loaded nanoaggregates seem to have a potential to be used in a pulmonary drug delivery

effect of PEG molecular weights on dissolution behavior of simvastatin in solid dispersions

The purpose of the present study was to investigate the effect of polyethylene glycol [PEG] molecular weights [6000, 12000 and 20000] as solid dispersion [SD] carriers on the dissolution behavior of simvastatin. SDs with various drugs: carrier ratios were prepared by solvent method and evaluated for dissolution rate. Differential scanning calorimetry [DSC], X-ray diffraction [XRD], infrared spectroscopy and solubility studies were also performed on the optimum SD formulation. Samples prepared with all three types of PEG showed improved drug dissolution compared to intact drug and corresponding physical mixtures. Meanwhile, the best result was obtained by PEG 12000 with drug: carrier ratio of 1:7 which showed a 3-fold increase in dissolution rate compared to the intact drug. Based on DSC and XRD, no crystalline change occurred during the sample preparation. Solubility studies revealed that increasing the PEG molecular weight resulted in higher phase solubility of drug. In addition, saturated solubility of the optimum SD was significantly higher than that of intact drug and the related physical mixture [24.83, 8.74 and 8.88 microg/mL, respectively] that could be due to the decreased particle size and aggregation. The results confirmed the influence of PEG molecular weight on drug dissolution rate from solid dispersion systems

Dissolution rate enhancement of clarithromycin using ternary ground mixtures: nanocrystal formation

Clarithromycin [CLA], a broad-spectrum macrolide, is a poorly soluble drug with dissolution rate limited absorption. The aim of this investigation was to prepare CLA nanoparticles from a ternary ground mixture in the presence of sodium lauryl sulfate [SLS] and poly vinyl pyrrolidone [PVP] as co-grinding water-soluble compounds, in order to improve the drug dissolution rate. Different weight ratios of CLA: SLS: PVP were ground in a dry process by planetary ball mill using different grinding ball size. Following the dissolution rate study, physical properties of the best dissolved co-ground formulation was studied. The accelerated stability studies were also conducted on the co-ground formulation. The results revealed that the dissolution rate of ternary ground mixtures was much higher than that of the intact drug [p < 0.001]. Decreasing the grinding ball size and weight with the same rotation speed resulted in particles with decreased dissolution. On the other hand, increasing the PVP concentration in the formulations reduced the drug dissolution. Dissolution efficiencies [DE[10] and DE[10] for the best dissolved formulation, which consisted of the equal ratio of each co-ground component, were 8.7 and 5 folds higher than the untreated CLA, respectively. This formulation formed nanocrystals with enhanced solubility after dispersing in water. X-ray diffraction, differential scanning calorimetry and infrared spectrophotometry confirmed no chemical interaction and phase transition during the process. Accelerated stability studies confirmed that the co-ground mixture almost remained unchanged in terms of dissolution rate, drug assay and particle size after exposing in stability conditions for three months

Prolonged release matrix tablet of pyridostigmine bromide: Formulation and optimization using statistical methods

The aim of this study was to design and optimize a prolonged release matrix formulation of pyridostigmine bromide, an effective drug in myasthenia gravis and poisoning with nerve gas, using hydrophilic - hydrophobic polymers via D-optimal experimental design. HPMC and carnauba wax as retarding agents as well as tricalcium phosphate were used in matrix formulation and considered as independent variables. Tablets were prepared by wet granulation technique and the percentage of drug released at 1 [Y[1]], 4 [Y[2]] and 8 [Y[3]] hours were considered as dependent variables [responses] in this investigation. These experimental responses were best fitted for the cubic, cubic and linear models, respectively. The optimal formulation obtained in this study, consisted of 12.8% HPMC, 24.4% carnauba wax and 26.7% tricalcium phosphate, had a suitable prolonged release behavior followed by Higuchi model in which observed and predicted values were very close. The study revealed that D-optimal design could facilitate the optimization of prolonged release matrix tablet containing pyridostigmine bromide. Accelerated stability studies confirmed that the optimized formulation remains unchanged after exposing in stability conditions for six months