Context: one of the major challenges to drug development today is poor solubility, as estimated 40% of all newly developed drugs are poorly soluble or insoluble in water.
Objective: The aim of this study was to prepare and characterize amorphous nanoparticles of cefixime to enhance water Solubility and oral bioavailability of this drug.
Method: Nanoparticles were prepared by the application ultrasonication method. The 32 factorial design was applied for the optimization of process variables. The factors involve solvent to antisolvent ratio, surfactant concentration and response selected were particle size and % release.
Results: The particle size and zeta potential of optimized batch of amorphous nanoparticles were found to be 206nm and 58.2 mV, respectively. In vitro dissolution rate of cefixime increased significantly by reducing particle size. In vivo test shows that relative bioavailability of amorphous nanoparticles was improved 3.91 and 7.55 fold as compared to marketed formulation and pure drug respectively. Antimicrobial efficacy studies reveal that there was increased zone of inhibition, indicating that solubility of cefixime was improved due to increased surface area.
Conclusion: Thus, from experimental study it can be concluded, cefixime bioavailability can be improved by amorphous nanoparticles which needs to be further proved in human beings.
Keywords: Cefixime, nanoparticles, Ultrasonication, Solvent Antisolvent, Bioavailability.
Nanoparticles are known to improve dissolution rate and bioavailability of poorly water-soluble drugs[1-5] owing to increased surface area available for dissolution, as described by the Noyes–Whitney equation . Nanoparticles are generally obtained by ‘top–down’ process which relies on mechanical attrition . However, it is energy-intensive, time-consuming and shows some disadvantages in practice such as the introduction of impurities, inadequate control of particle size and electrostatic effects. In the last decade, ‘bottom–up’ techniques like supercritical fluid technology and anti-solvent precipitation have been widely investigated to obtain nanoparticles [6-8]. Anti-solvent precipitation is an effective way to prepare micro or nano-size drug particles. In this method, briefly, the drug is first dissolved in the solvent, and then the drug solution is quickly introduced into the anti-solvent. Precipitation occurs immediately by rapid desolvation of the drug . Aqueous solutions containing some stabilizers, such as polymers and surfactants, are commonly used as the anti-solvent. Polymers, such as hydroxypropyl methylcellulose (HPMC) and methylcellulose (MC) , and Povidone (PVP) , can form strong hydrogen bonds with the drugs, which can be adsorbed on the hydrophobic particle surface, inhibiting the crystal growth of the drugs. However, there are some basic problems associated with common anti-solvent precipitation techniques, i.e. it is difficult to maintain the size of...