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Stable Indomethacin Dispersions in Water from Drug, Ethanol, Cationic Lipid and Carboxymethyl-Cellulose

[ Vol. 4 , Issue. 2 ]


Eliete G. Lima, Luciano R. Gomes and Ana M. Carmona-Ribeiro   Pages 126 - 135 ( 10 )


Background: The problem of formulating hydrophobic drugs in aqueous solutions is addressed from the point of view of nanotechnology. Nanoparticles (NPs) can incorporate high drug-to-carrier molar ratios with optimal drug dispersion and colloidal stabilization in water solution, especially when a biocompatible and hydrophilic polymer acts as an outer stabilizing layer. The hydrophobic drug indomethacin (IN) and the cationic lipid dioctadecyldimethylammonium bromide (DODAB) are soluble in ethanol (ET) and this property is useful to formulate the drug.

Objective: This work aims at optimal colloidal stability for aqueous IN dispersions employing IN/DODAB ethanolic solutions dispersed in water solutions of carboxy-methyl-cellulose (CMC).

Method: Photographs, dynamic light scattering for sizing, zeta-potential and polydispersity analysis are determined as a function of time for one week and scanning electron microscopy (SEM) for dried dispersions.

Results: Over a range of (CMC), NPs with good colloidal stability and absence of sedimentation were obtained both over a low or high (CMC) for (IN): (DODAB) around 1. Only around zero of zeta -potential there is precipitation with poor colloidal stabilization. The data point out a remarkable colloidal stability for IN/ET/DODAB/CMC NPs over a range of (CMC) (0.01-1 mg/mL). ET harmonizes lipid and drug imparting a good colloidal stability over the long run. The self-assembled NPs obtained in aqueous solution disassemble upon drying with appearance of fibers and aggregates reminiscent of NPs that occurred in water.

Conclusion: The co-solubilization /nanoprecipitation process is a powerful strategy to disperse hydrophobic drugs as nanoparticles in water solution of biocompatible hydrophilic polymers.


Anti-inflammatory nonsteroidal drugs, dioctadecyldimethylammonium bromide, ethanol, carboxymethylcellulose, dynamic light scattering, colloidal stabilization, nanoparticles.


Departmento de Bioquímica, Instituto de Química, Universidade de São Paulo, P.O. Box: 26077, 05513970, São Paulo, Brazil.

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