Dermal flurbiprofen nanosuspensions: Optimization with design of experiment approach and in vitro evaluation.

Flurbiprofen (FB) is the one of the non-steroidal anti-inflammatory drugs (NSAIDs) which has low water solubility and dissolution. Nanosuspensions are promising drug delivery systems consisting pure drug particles to overcome poor water solubility issues. Recently, design of experiment (DoE) approaches have often been used to develop new formulations include nanosuspensions. The main objective of this study was to prepare FB nanosuspensions in existence of Plantacare 2000 (PL) as stabilizer using DoE approach to evaluate the critical formulation attributes (CFAs) and critical process parameters (CPPs). Particle size, particle size distribution and zeta potential values were selected as dependent variables and FB%, FB: PL and homogenization cycles were independent variables. Both 23 and 33 factorial designs were used to achieve optimum nanosuspension formulation. The final nanosuspension was freeze-dried and then crystalline state, morphological and thermal properties were investigated using X-ray diffraction, scanning electron microscopy and differential scanning calorimetry, respectively. The saturation solubility studies of nanosuspensions were conducted in comparison with the coarse powder and the physical mixture. The in vitro permeation of nanosuspension and FB solution were determined through dialysis membrane and rat skin. The particle size, polydispersity index and zeta potential values were found to range 665 nm-700 nm, 0.200-0.300 and approximately -30 mV, respectively. Nanosuspensions were obtained with spherical shape and no polymorphic or crystalline state change were observed. The saturation solubility of FB was 5.3 fold increased in nanosuspension formulation. Permeability of FB nanosuspension was higher than FB solution in rat skin. It was concluded that the DoE approach is a useful tool to prepare FB nanosuspensions and nanosuspensions benefit to improve water solubility and dermal permeation of Biopharmaceutical Classification System (BCS) Class II drugs.

New perspective to develop memantine orally disintegrating tablet formulations: SeDeM expert system.

Nowadays pharmaceutical industries and regulatory authorities suggest new approaches such as Quality by Design principles to reduce experiments of formulation studies, improve product quality, save cost and time. SeDeM Expert System is a predictive approach for the preformulation studies and it provides information about suitability of API for direct compression by evaluating 12 parameters. The system also allows selecting appropriate excipients by determining same parameters to improve compressibility of API. The objective of this study was to develop direct compressed memantine orally disintegrating tablets using SeDeM Expert System. Memantine was found to have poor flow and compressibility properties. Three different direct compressibility and super disintegrating agents (Ludiflash®, Ludipress® and Parteck®) were used to improve compressibility of memantine and according to SeDeM diagrams, Parteck® was selected for final formulation. Memantine direct compressed tablets showed proper friability, hardness and thickness. The disintegration time of the tables were found below 15 s which was suitable for ODTs. It was found that SeDeM Expert System was easy to use and application of this method provided to develop memantine direct compressed ODT formulation was successful.