Because development of an optimized method needs

Because the number of variables in SLN preparation is very high and the development of an optimized method needs many experiments, we useda series of screening tests by varying only one factor at a time to reduce thenumber of independent variables and experiments. Theresults of the screening tests indicated thatthis system was highly influenced by microemulsion temperature duringthe production. We set the temperature 5 0Cabove melting point of the lipid. A reductionof temperature can increase particle size.

On the other hand, the upper temperatures can decompose curcumin partly (31).The effect offour different lipids, glycerylmonosterate, cetyl palmitate, stearic acid and beeswax,was studied on particle size(nm),PDI and stability of SLNs (Table 2). Cetylpalmitate was chosen due to the smaller particle size and narrow sizedistribution and most stability of SLNs(32).The effect of probe sonication on size, PDI and %LE of Cur-SLNs wasstudied by varying amplitude and sonication time (Table 3). The best resultswere observed in 30% amplitude at 5 min of sonication time. Increased in sizeand PDI was observed when the amplitude of probe sonication increased to 40%. Applying higher amplitude or sonication time causes the formation ofunstable SLNs.

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This phenomenon is because of increasing particle size and PDI,which was the result of the destruction of surfactant coatings due to apply higherkinetic energy.In addition the influence of homogenization time, mechanical stirring intensity(rpm) and time of stirring on the particle size (nm) and PDI of SLNs have beeninvestigated. Then the mentioned parameters were fixed in 8min, 1000 rpm and 30min respectively. Homogenization was performed at 10000 rpm for five differenttime intervals (2, 5, 8 , 10 and 15  min).Decreased in size and PDI was observed when homogenization time increased from  2  to 8  min  while at 10 min  both size and PDI wereincreased.

Homogenization is  one  of the  important  strategies of  applying  kinetic energy in order to  achieve  lower size  and  PDI. Applying  high  kinetic energy  for  longer period of time  may  lead to  instability  of  thesystem.  This phenomenon is because of aggregation  and formation  of  larger particles.  Size  and PDI  were  higher at  2 and 5  min when  compared  to 8 min due to  insufficient homogenization. Therefore, anoptimum duration of homogenization will result in formation of stable particleswith uniform size distribution (Table 4)

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