Review: Emerging role of nanosuspensions for drug delivery and stability

: Poor aqueous solubility of some of the drug molecules are of a major concern, which can be emerged in the nano-suspension for better delivery. Coming up to the nanoparticles, it enhances the bioavailability along with the aqueous solubility of the drug which is accomplished by increasing the active surface area of the drug. The gained attention of the nanosuspension is due to its stabilization facility which is done by polymers such as polyethylene glycol (PEG) having a particular size range of 10-100 nm. Hence, to our notice, these nanoparticles have the capacity of binding in the targeted parts with a very low damage to the healthy tissues. These are seen to be prepared by various methods such as media milling, high pressure homogenization, and emulsification along with melt emulsification. Apart it can also be seen that surface modification and solidification have been used to add specific properties to the advanced therapies as post-processing techniques. These days, it is very evident that the drugs are water insoluble and thus have a poor bioavailability which have been developed from the drug delivery programmes and in order to combat this obstacle, nanotechnology have been found to be of specific interest. In order to elevate the bioavailability by increasing the dissolution rate, the methodology of reduction of the associated drug particles into its subsequent submicron range is incorporated. For oral and non-oral administration, these nanosuspensions formulations are used for delivering of the drugs.

Optimization of Performance Variables of Exemestane Nanosuspension Using Box-Behnken Design to Improve Dissolution and Oral Bioavailability

Purpose: Present investigation was aimed to fabricate nanocrystal of exemestane, an anticancer drug with poor dissolution properties and oral bioavailability. Methods: Influence of various process parameters on the formulation of exemestane nanosuspension using media milling technique were investigated in the trial batches. Box-Behnken design was applied with independent variables identified in the preliminary studies, viz. X1-Milling time, X2-Amount of stabilizer and X3-Amount of milling agent. In vitro dissolution and in vivo studies were carried out. Solid state characterization (PXRD, SEM, and DSC) studies demonstrated physical changes in drug due to nano-crystallization. Accelerated stability studies of optimized formulation were carried out. Results: Individual process attributes exhibited significant effect on the average particle size of exemestane nanosuspension. Dissolution studies revealed enhancement in drug release rate as compared to pure exemestane powder. The in vivo pharmacokinetic parameters of exemestane nanosuspension showed significant improvement in Cmax and AUC0-t, about 283.85% and 271.63% respectively suggesting amelioration in oral bioavailability by 2.7-fold as compared to pure exemestane. Accelerated stability studies of the optimized formulation suggested stability of the nanocrystals for at least sixmonth period. Conclusion: Nanocrystals prepared by media milling technique were successful in improving the poor dissolution properties and oral bioavailability of exemestane.

Nanosuspensions and Microneedles Roller as a Combined Approach to Enhance Diclofenac Topical Bioavailability

Topical application of the anti-inflammatory drug diclofenac (DCF) reduces the severity of systemic unwanted effects compared to its oral administration. A number of transdermal formulations are available on the market and routinely used in clinical and home-care settings. However, the amount of DCF delivered across the skin remains limited and often insufficient, thus making the oral route still necessary for achieving sufficient drug concentration at the inflamed site. In attempting to improve the transdermal penetration, we explored the combined use of DCF nanosuspensions with a microneedle roller. Firstly, DCF nanosuspensions were prepared by a top-down media milling method and characterized by spectroscopic, thermal and electron microscopy analyses. Secondly, the pore-forming action of microneedle rollers on skin specimens (ex vivo) was described by imaging at different scales. Finally, DCF nanosuspensions were applied on newborn pig skin (in vitro) in combination with microneedles roller treatment, assessing the DCF penetration and distribution in the different skin layers. The relative contribution of microneedle length, nanosuspension stabilizer and application sequence could be identified by systemically varying these parameters.

Study of homogenization on media milling time in preparation of irbesartan nanosuspension and optimization using design of experiments (DoE)

Background The present investigation aimed at preparing nanosuspension of irbesartan to improve its dissolution. Dissolution enhancement of irbesartan can improve the oral bioavailability. Here, it was also studied how media milling time can be reduced by subjecting irbesartan to prior homogenization and then media milling. Results First, homogenization of irbesartan was carried out in the presence of poloxamer 407 at 6000 rpm for 2 h. Final nanosuspension preparation was done by media milling with zirconium dioxide beads. Here, the amount of poloxamer 407 and zirconium dioxide beads was studied as statistical independent variables. Response surface plot analysis and desirability function were applied to the selected optimized batch. The prepared batches were subjected to evaluation for zeta potential value, mean particle size, PDI, dissolution study, and stability study. Target particle size was less than 500 nm, and in vitro dissolution in 10 min was more than 80%. Zeta potential value was ~ 27 mV for optimized nanosuspension. Desirability of 0.941 was achieved. Checkpoint batch was prepared and evaluated to confirm the validity of mathematical model. Accelerated stability study was performed on the optimized batch at 40 ± 2 °C/75 ± 5% RH for 6 months. Conclusion The results confirmed the stability of formulation at accelerated stability conditions. Using presuspension prepared by homogenization, media milling time primarily reduced from 24–28 h to 18 h. Future perspective is to study other factors in combination method in discrete.