improvement of fine powders through nano-coating

Majority of the pharmaceutical dosage forms are manufactured from powders as a starting material. The handling and processing problems in pharmaceutical manufacturing still revolves around unpredictable bulk behavior of powders in different manufacturing conditions. This work is an attempt to improve and study the particle properties and bulk behavior of some of the commonly known fine cohesive powders under varying humidity conditions through surface modification using nano-coating technique. The effect of surface modification on bulk behavior and surface characteristics of three pharmaceutical excipient powders viz. Avicel PH105, Lactochem fine powder and Corn starch was studied. Hydrophilic (Aerosil 200P) and hydrophobic (Aerosil R972) colloidal silicon-di-oxide were used as guest particles for dry coating (nano-coating). An overall improvement in the flow and packing (bulk density and compressibility) properties of all the three excipients were observed after nano-coating. The results also confirmed that the quality of nano-coating achieved is strongly influenced by surface morphology of powder particles. The effect of surface modification on wettability and surface energy characteristics of these pharmaceutical excipients were also studied. The results showed that wettability increases with increasing specific component of surface energy (?ssp) of particles and successfully demonstrated that surface wettability and energetics of powders can be modulated by varying the type and level of surface coating. Influence of relative humidity (RH) on the surface energy characteristics of fine cohesive powders (Corn starch, Avicel PH105 and Ibuprofen) and its relationship with powder flow variations was explored. The ?sd component of surface energy barely changed with RH variation, whereas the ?ssp component of surface energy increased with increasing RH for hydrophilic powders. It was proposed that the ?ssp component of surface energy can be used as an effective indicator for tracking flow behavior of fine powders under varying humid conditions. The present study also brought out the existence of different regimes of probable interparticle forces which dictate the bulk flow behavior of fine hydrophilic powder under humid conditions. Subsequently, the effect of RH on the bulk behavior of raw and surface modified corn starch powder was studied. Powder bulk behavior like flow and packing properties of uncoated and coated corn starch powder, surface modified using hydrophobic (Aerosil R972) nano-silica, were studied at different relative humidity conditions (30%-90% RH). It was found that flow and packing properties of uncoated powder deteriorated at elevated RH conditions, with prominent changes observed above 60% RH. However, surface modification using nano-coating of particles countered the detrimental effects of humidity on its bulk behavior by preventing capillary bridge formation owing to increased nanoscale roughness and subsequent modification of interparticle contacts. Also, the interparticle adhesion force developed in these powders, under varying humid conditions and applied consolidation stresses, was estimated using tensile strength determination approach. For uncoated powders, the results indicated that, at low consolidation and high RH, capillary force is the prevailing force contributing to the total interparticle adhesion in contrast to higher consolidation conditions where load induced contact force plays a dominant role. The study also identified a stable humidity zone (45-60% RH) for uncoated powder, where interparticle forces were minimal or stable. Further extension of this work involved identifying and investigating the RH dependent stick-slip regime of frictional behavior and its effect on flow properties of corn starch. The stick-slip friction of the particles under stress increased with the reduction in RH whereas it diminished with the increase in humidity. This frictional behavior was attributed to the alternate sticking of the contacts into the discretely or very thinly distributed moisture on the particle surface at lower RH. On the other hand, at higher RH levels, the presence of thick lubricating moisture film reduced the frictional forces between the particles and improved powder flow. Three different fluid film lubrication regimes viz. boundary, mixed and hydrodynamic regimes were identified for corn starch particles, within the studied RH range. Moreover, nano-coating led to alleviation of such frictional behavior at all RH levels.

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