Application of Chitosan-Based Gels in Pharmaceuticals - Chitosan Based Hydrogels: Functions and Applications - page 318

sieve with a suitable mesh size to get microparticles. The microparticles are washed with
a 0.1 N NaOH solution to remove the unreacted excess glutaraldehyde and dried overnight
in an oven at 40°C. Clozapine is incorporated into CS before cross-linking with entrapment
efficiency up to 98.9%. This method is devoid of tedious procedures, and can be scaled up
easily. Microparticles are irregular in shape, with the average particle sizes in the range of
5 4 3 - 6 9 8 μm. The in vitro release is extended up to 12 h, while the in vivo studies indicated
a slow release of clozapine.
7.2.2 Methods of Preparing Films based on Chitosan
A chitosan solution (50 mM acetic acid), prepared allowing for the content of water and
ash, was filtered through a sterile 0.22 μm filter. Then 200 μL aliquots were layered
over 1 cm 2 dishes. The solvent was allowed to evaporate in an open plate inside a ster-
ile laminar flow hood overnight at room temperature. Gelated films were treated with
phosphate buffer (0.25 M), pH 7.0. Afterwards, the films were extensively washed with
phosphate-buffered saline (PBS).
7.2.3 Methods of Preparation of Mass gels based on Chitosan
7.2.3.1 Cross-Linking
Chitosan was dissolved in distilled water with 50 mM acetic acid, and other additives
(such as polyvinyl alcohol, polyethylene glycol, carboxymethyl cellulose, sodium alginate,
etc.) solutions were added into the chitosan solution with stirring. Afterwards, the stable
solution was cross-linked by using an appropriate cross-linking agent such as glutaralde-
hyde to harden the mass gels. The resultant mixture was dipped in distilled water for 3
days at 10°C to completely remove the unreacted cross-linking agent.
7.2.3.2 Freeze/Thawing Process
Chitosan and other additive solutions were prepared by dissolving chitosan in distilled
water in an autoclave at 121°C for 1 h. Solutions were stirred till they cooled to room tem-
perature to prevent aggregation of polymers. Air bubbles were removed by resting the
solution at room temperature. The solutions were cast into Perspex molds that were 1.5 mm
in thickness. Then they were physically cross-linked by five freeze/thawing cycles, which
consisted of freezing at −20°C for 12 h and thawing at room temperature (21°C) for 12 h.
The hydrogels were further submerged in a constantly stirred coagulation bath (7.5%
KOH and 1 M Na 2 SO 4 ) for 1 h. After removing from the coagulation bath, the resulting
hydrogels were washed several times with distilled water [16].
7.2.4 Methods of Preparation of Thermosensitive In Situ gels based on Chitosan
The chitosan solution was obtained by dissolving 400 mg of chitosan (medium viscosity,
75-80% deacetylated) in 18 mL of 0.1 M acetic acid solution prepared in PBS. Then 150 mg
of glycerol phosphate was dissolved in 1 mL of PBS. And then a glycerol phosphate solu-
tion was carefully added dropwise to the chitosan solution. The final liquid solution was
clear and homogeneous. The solution was filtered through a 0.22 mm membrane filter. The
pH value of the final solution before heating was 7.15 [17].