Formulation development, process optimization and characterization of dermal etodolac nanosuspensions

Drug application from skin is a suitable route for local or systemic effect. However poor solubility of drug candidates limits drug application through skin. Nanosuspensions are promising approach to increase solubility of lipophilic compounds and hence dermal penetration. They can be defined as nano-sized drug particles prepared with minimum quantity stabilizer. The objective of this study was to prepare etodolac (ETD), the NSAID drug compound which is Biopharmaceutical Classification System (BCS) Class II drug with low solubility and high permeability, nanosuspensions using wet ball grinding method. PVP was used as stabilizer. The Box-Benkhen design was created randomly to perform the experiments. Diameter of grinding beads (0.1, 0.5, 1 mm), grinding time (1, 2.5, 4 h) and grinding speed (200, 400, 600 rpm) were selected as independent variables. Particle size (PS), particle size distribution (PDI) and zeta potential (ZP) values were analyzed as dependent variables. Nanosuspensions were lyophilized and DSC was performed to determine melting points of samples. The XRD patterns of ETD and nanosuspensions were collected to evaluate possible changes of crystallinity. The PS, PDI and ZP values were found, 210.1 ± 2.3 nm, 0.098 ± 0.012, -15.3 ± 0.4 mV, respectively.  SEM images were also proved that PS values were obtained approximately 200 nm. Uniform and spherical particles were observed. DSC and XRD results showed that, the structure of ETD was not changed during preparation process. ETD nanosuspensions were prepared using wet ball grinding method successfully. Box-Benkhen design to develop nanosuspension formulation was found effective approach to improve final product quality while reducing the number of experiments.

Author(s): Alptug Karakucuk

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