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peramivir, distilled water, starch, potassium iodate, sulphuric acid, (PT Merck Distilled

                   water will be purified before use with ELGA Water Purification System R15 supplied
                   with pump and tank (Elga Water System, UK). All other chemicals and solvents were of

                   analytical grade.


                   3.2    Formulation Development.

                          The formulation of Zanamivir will be using  Ionic Gelation technique. The core
                   coating material (sodium alginate) and the mucoadhesive polymers will be dissolved in

                   distilled  water  (32  ml)  to  form  a  homogeneous  polymer  solution.  Core  material
                   (Zanamivir)  will  be  added  to  the  polymer  solution  and  mixed  thoroughly  to  form  a

                   smooth viscous dispersion. The resulting dispersion will then add a thin stream to a 300

                   ml  of  arachis  oil  contained  in  a  500  ml  beaker  with  a  stirring  at  400  rpm  using  a
                   mechanical  stirrer.  The  stirring  will  be  continued  for  5  min  to  emulsify  the  added

                   dispersion as fine droplets. Calcium chloride (10%w/v) solution (40 ml) will then add
                   slowly while stirring for ionic gelation (or curing) reaction. Stirring will continue for 15

                   minutes to complete the curing reaction and to produce spherical microcapsules. Mixture
                   was then will be centrifuge and the product thus separated was washed repeatedly with

                   water and dried at 450 degrees for 12 h.

                   3.3    Preparation of solid lipid nanoparticles (SLNs)
                          Zanamivir-loaded SLNs will be prepared by a double emulsion (W/O/W) solvent

                   evaporation method as described previously (Cao et al., 2011). The inner aqueous phase
                   (10 mg/mL) will be prepared by dissolving drug in distilled water. The oil phase will be

                   prepared by dissolving glyceryl monostearate (12%, w/v) and soybean lecithin (4%, w/v)

                   in dichloromethane. 0.2 mL of the inner aqueous phase will be mixed with 1mL of the oil
                   phase and then subjected to an ultrasonic probe at 200 W for 60 s to obtain the primary

                   W/O emulsion. The double (W/O/W) emulsion will be formed after the addition of 4mL
                   of 1.0 % PVA solution (or 1.5 % poloxamer 188 solution) to the primary W/O emulsion

                   followed by sonication at 200 W for 60 s. The resulting emulsion will be kept in an ice

                   bath under mechanical agitation at 700 rpm 5 h to remove the organic solvent to form
                   SLNs. The SLN powder will be prepared by lyophilization using 5.0 % (w/v) mannitol as

                   a supporting agent in order to facilitate X-ray diffraction and FT-IR investigations.


                   3.3    Characterization study
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