Novel Formulation of Chlorhexidine Spheres and Sustained Release with Multilayered Encapsulation.
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This work demonstrates the synthesis of new chlorhexidine polymorphs with controlled morphology and symmetry, which were used as a template for layer-by-layer (LbL) encapsulation. LbL self-assembly of oppositely charged polyelectrolytes onto the drug surface was used in the current work, as an efficient method to produce a carrier with high drug content, improved drug solubility and sustained release. Coprecipitation of the chlorhexidine polymorphs was performed using chlorhexidine diacetate and calcium chloride solutions. Porous interconnected chlorhexidine spheres were produced by tuning the concentration of calcium chloride. The size of these drug colloids could be further controlled from 5.6 μm to over 20 μm (diameter) by adjusting the coprecipitation temperature. The chlorhexidine content in the spheres was determined to be as high as 90%. These particles were further stabilized by depositing 3.5 bilayers of poly(allylamine hydrochloride) (PAH) and polystyrenesulfonate (PSS) on the surface. In vitro release kinetics of chlorhexidine capsules showed that the multilayer shells could prolong the release, which was further demonstrated by characterizing the remaining chlorhexidine capsules with SEM and confocal microscopy. The new chlorhexidine polymorph and LbL coating has created novel chlorhexidine formulations. Further modification to the chlorhexidine polymorph structure is possible to achieve both sustained and stimuli responsive release, which will enhance its clinical performance in medicine and dentistry.