sorbitan-monooleate and ethyl-cellulose

Microsponges drug delivery system (MDDC) was prepared by double emulsion-solvent-diffusion technique using rotor-stator homogenization. Quality by design (QbD) concept was implemented for the development of MDDC with potential to be incorporated into semisolid dosage form (gel). Quality target product profile (QTPP) and critical quality attributes (CQA) were defined and identified, accordingly. Critical material attributes (CMA) and Critical process parameters (CPP) were identified using quality risk management (QRM) tool, failure mode, effects and criticality analysis (FMECA). CMA and CPP were identified based on results obtained from principal component analysis (PCA-X&Y) and partial least squares (PLS) statistical analysis along with literature data, product and process knowledge and understanding. FMECA identified amount of ethylcellulose, chitosan, acetone, dichloromethane, span 80, tween 80 and water ratio in primary/multiple emulsions as CMA and rotation speed and stirrer type used for organic solvent removal as CPP. The relationship between identified CPP and particle size as CQA was described in the design space using design of experiments - one-factor response surface method. Obtained results from statistically designed experiments enabled establishment of mathematical models and equations that were used for detailed characterization of influence of identified CPP upon MDDC particle size and particle size distribution and their subsequent optimization.

Topics: Acetone; Cellulose; Drug Carriers; Drug Design; Hexoses; Hydrochloric Acid; Least-Squares Analysis; Methylene Chloride; Multivariate Analysis; Polysorbates; Principal Component Analysis

Fluconazole-loaded ethyl cellulose microspheres were prepared by alginate facilitated (water-in-oil)-in-water emulsion technology and the effects of various processing variables on the properties of microspheres were investigated. Scanning electron microscopy revealed spherical nature and smooth surface morphology of the microspheres except those prepared at higher concentration of emulsifiers and higher stirring speeds. The size of microspheres varied between 228 and 592 mum, and as high as 80% drug entrapment efficiency was obtained depending upon the processing variables. When compared up to 2 h, the drug release in pH 1.2 HCl solution was slower than in pH 7.4 phosphate buffer saline solution. However, this trend was reversed at high shear conditions. The microspheres provided extended drug release in alkaline dissolution medium and the drug release was found to be controlled by Fickian-diffusion mechanism. However, the mechanism shifted to anomalous diffusion at high shear rates and emulsifier concentrations. The aging of microspheres did not influence the drug release kinetics. However, the physical interaction between drug and excipients affected the drug dissolution behaviors. X-ray diffractometry (X-RD) and differential scanning calorimetry (DSC) analysis revealed amorphous nature of drug in the microspheres. Fourier transform infrared (FTIR) spectroscopy indicated stable character of fluconazole in the microspheres. The stability testing data also supported the stable nature of fluconazole in the microspheres. The fluconazole extracted from 80% drug-loaded formulation showed good in vitro antifungal activity against Candida albicans. Thus, proper control of the processing variables involved in this modified multiple emulsion technology could allow effective incorporation of slightly water soluble drugs into ethyl cellulose microspheres without affecting drug stability.

Topics: Alginates; Antifungal Agents; Calorimetry, Differential Scanning; Candida albicans; Cellulose; Chemistry, Pharmaceutical; Drug Carriers; Drug Compounding; Emulsions; Fluconazole; Hexoses; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; Microspheres; Particle Size; Solubility; Solvents; Spectroscopy, Fourier Transform Infrared; Surface-Active Agents; X-Ray Diffraction

This study reports the laboratory optimization for the preparation of sustained release amoxicillin (AMX) ethylcellulose microcapsules by an emulsion solvent evaporation process by adjusting the viscosity and concentration of ethylcellulose, ratio of amoxicillin to ethylcellulose, and concentration of emulsifier and pore inducer. When ethylcellulose with a viscosity of 45 mPa.s was used, almost no material stuck to the inside wall of the beaker and uniform microcapsules were prepared. The average diameter of microcapsules increased and yield and release rate decreased as the concentration of ethylcellulose increased from 1% to 8%. The release of amoxicillin from microcapsules was influenced by the ratio of the weight of drug to that of ethylcellulose and ratios of 2:1 and 4:1 were most suited for optimum amoxicillin release. The average diameter of microcapsules decreased and the release rate increased as the concentration of the emulsifier increased from 1.5% to 6.0%, however, the size distribution became significantly wider with the increase in the concentration of sorbitan monooleate. Addition of small amounts of a water-soluble agent sucrose improved the release of active ingredient from the microcapsule matrix without influencing the morphology and particulate properties of the microcapsules.

Topics: Absorption; Amoxicillin; Capsules; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Emulsions; Hexoses; Microscopy, Electron, Scanning; Particle Size; Solubility; Solvents; Surface-Active Agents; Time Factors; Viscosity

The effects of Tween 80 (polysorbate 80) and Span 80 (sorbitan monooleate) surfactants on release characteristics of clonidine hydrochloride from ethylcellulose 10 and 20 cps matrix films containing castor oil as a plasticizer were investigated. The release rates of drug from these films in water at 37 degrees C were found to increase with the addition of surfactant, which was highest for the film prepared from ethylcellulose 20 cps with Tween 80. The experimental values of the cumulative amount of drug released were found to conform to the solution matrix model. The calculated values of the cumulative amount of clonidine hydrochloride released using the experimentally determined diffusion coefficients were also found to be in good agreement with the observed values.

Topics: Algorithms; Castor Oil; Cellulose; Clonidine; Diffusion; Drug Carriers; Hexoses; Pharmaceutic Aids; Polysorbates; Solubility; Solutions; Surface-Active Agents