Drug nanosuspensions offer a promising approach to improve bioavailability for poorly soluble drug candidates. Such formulations often necessitate the inclusion of an excipient to stabilize the drug nanoparticles. However, a rationale to choose the correct excipient for a given drug candidate remains unclear. To gain molecular insight into formulation design, this work first utilizes molecular dynamics simulation to computationally investigate drug-excipient interactions for a number of combinations that have been previously studied experimentally. We find that hydrophobic interactions drive excipient adsorption to drug nanoparticles, and that the fraction of polar surface area serves as a predictor for experimental measurements of nanosuspension stability. To test these ideas prospectively, we applied our model to an uncharacterized drug compound, GDC-0810. Our simulations predicted that salt forms of GDC-0810 would lead to more stable nanosuspensions than the neutral form; therefore, we tested the stability of salt GDC-0810 nanosuspensions and found that the salt form readily formed nanosuspensions even without excipient. To avoid computationally expensive simulations in the future, we extended our model by showing that simple, two-dimensional properties of the single drug molecule can be used to rationalize nanosuspension design without simulation. In all, our work demonstrates how computational tools can provide molecular insight into drug-excipient interactions, and aid in rational formulation design.

We have successfully developed curcumin nanosuspension aimed for oral delivery. The main purpose is to improve bioavailability through enhancing its solubility. The nanoparticles were stabilized using various stabilizers including polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), sodium carboxymethylcellulose (Na-CMC), d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS), and sodium dodecyl sulfate (SDS). The average diameter of particles, microscopic appearance, and sedimentation of each preparation was observed and compared. Each stabilizer demonstrated different degree of inhibition of particle aggregation under electrolyte-containing simulated gastrointestinal (GIT) fluid. Non-ionic stabilizers (PVA, PVP, and TPGS) has shown to preserve the nanosuspension stability against electrolytes. In contrast, strong ionic surfactants such as SDS were found to be very sensitive to electrolytes. The results can provide useful information for the formulators to choose the most suitable stabilizers by considering the nature of stabilizers and physiological characteristics of target site of the drug.

The aim of this study is to improve the therapeutic effectiveness of the sorafenib loaded polymeric nanoparticles, surface modified by the pluronic F-127 for the treatment of hepatocellular (HCC) and renal cell carcinomas (RCC). Poly Lactic co-glycolic acid (PLGA) was used to encapsulate sorafenib by simple modified solvent evaporation technique. The nanoparticles were prepared with different concentration of sorafenib and pluronic F-127 keeping PLGA concentration constant. There were no incompatibilities among the sorafenib, PLGA and pluronic F-127 showing that the integrity of polymer, stabilizer and drug remain the same under different conditions. The size of the coated and plain PLGA nanoparticles were ~140 ± 14.7 nm and ~ 200 ± 10.1 nm, respectively. The in-vitro release studies demonstrated that the PLGA controlled the release of sorafenib, avoiding the initial burst release. The effect of coated and plain nanoformulations was found out in squamous cell carcinoma cells. The results showed that surface modified nanoparticles treated hepatocellular and renal carcinoma in a better way as compared to plain PLGA nanoparticles and free dug by keeping the dose constant (20 mg/kg body weight).The targeted delivery of polymeric PLGA nanoparticles into squamous cell carcinoma was improved. The pharmacokinetic parameters have been improved significantly as compared to the reported nanoformulations.