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Transfection activity of layer-by-layer plasmid DNA/poly(ethylenimine) films deposited on PLGA microparticles
Authors:Kakade Sandeep  Manickam Devika Soundara  Handa Hitesh  Mao Guangzhao  Oupický David
Institution:CIMA LABS INC., Brooklyn Park, MN, USA.
Abstract:In this study, the dynamics of powder flow upon griseofulvin-self-emulsified drug delivery system (SEDDS) addition to silica and silicates and the effect of these adsorbents on drug release were investigated. SEDDS was adsorbed at SEDDS/adsorbent ratios from 0.25:1 to 3:1 on magnesium aluminum silicate 5 and 80 microm], calcium silicate 25 microm], and silicon dioxide 3.6, 20, and 300 microm]. Powder flow was evaluated using the powder rheometer and compared to angle of repose. Release of drug from a 1:1 SEDDS/adsorbent powder was determined by dissolution using USP Type 2 apparatus. Powder rheometer profiles indicated that effect of SEDDS on the flow behavior of the adsorbents could be correlated to stepwise or continuous growing behavior as observed in wet granulation process. However, due to their porous nature, adsorbents exhibited an initial lag phase during which no change in flow was observed. Dissolution of drug from adsorbed-SEDDS was found to be dependent on pore length and nucleation at the lipid/adsorbent interface. Increase in dissolution rate was observed with an increase in surface area and was independent of the chemical nature of the adsorbents. Therefore, in order to manufacture free flowing powder containing liquid SEDDS, special attention should be given to particle size, specific surface area, type and amount of adsorbent.
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