Recent Patents on Nanotechnology - Online First

Nanosuspension has emerged as an effective, lucrative, and unequalled approach for efficiently elevating the dissolution and bioavailability of aqueous soluble drugs. Diverse challenges persist within this domain, demanding further comprehensive investigation and exploration.

This study aims to design, develop, optimise formulation and process variables, and characterise the stabilised aqueous dissolvable nanosuspension using chlorthalidone as a BCS class-IV drug.

Nanosuspensions of the chlorthalidone drug were prepared using a combination of top-down and bottom-up approaches. Various polymers such as Pluronic L-64, F-68, F-127, and Synperonic F-108 were used as stabilisers in this research. All important processes and formulation variables, such as ultrasonication intensity and time, the concentration of the drug, organic solvent, and stabilisers that may critically influence the characteristics of the nanosuspensions, were optimised. Formulation screening was performed using the optimisation of process and formulation variables, and the optimised nanosuspension formulation was assessed for particle size, PDI, surface charge, morphology, in vitro drug release, and stability.

To select an optimised nanosuspension formulation, the effects of formulation and process variables were investigated. These variables critically influence the development of a stabilised nanosuspension. The outcomes revealed that the nanosuspension formulation containing pluronic F-68 as a stabiliser in 0.6% w/v concentration and the drug in 4 mg/ml concentration were optimized. The particle size and zeta potential of the optimised preparation were 110 nm and -27.5 mV, respectively. The in-vitro drug release of chlorthalidone drug from the optimised nanoformulation was increased up to 3-fold, approximately (88% in 90 min) compared with pure chlorthalidone drug (27% in 90 min) because of the decrease in particle size. Moreover, stability studies indicated that the crafted nanoformulation was stable at cold (4°C) as well as normal room temperature (25°C) for six months.

From the obtained results, it was concluded that the combination of top-down and bottom-up approaches employed for the fabrication of oral nanosuspension is a remunerative and lucrative approach to successfully resolve the perplexities associated with the dissolution rate of poorly aqueous soluble BCS class-IV drug moieties such as chlorthalidone.

Ambrisentan is a new endothelin receptor antagonist extensively used to manage pulmonary or pulmonary arterial hypertension.

The therapeutic efficacy of Ambrisentan is limited due to its reduced solubility, higher log P (3.4), and thus less bioavailability. The recent investigation was concentrated on the improvement of solubility, and bioavailability of Ambrisentan for the therapy of hypertension via solid lipid nanoparticles (SLN) administered orally.

XRD evaluated the compatibility of Ambrisentan with lipids with FTIR, DSC, and crystalline nature. The SLN was developed by High-pressure homogenization method. The Glyceryl monostearate and Tween 80 indicated the highest solubility, hence selected. The optimization was performed with Box-Behnken Design considering the concentration of GMS (X1), Tween 80 (X2), stirring speed (X3) as independent factors and particle size (Y1), entrapment efficiency (Y2) as dependent factors. The Patents on the SLN are Indian 202321053691, U.S. Patent, 10,973,798B2, U.S. Patent 10,251,960B2, U.S. Patent 2021/0069121A1 and U.S. Patent 2022/0151945A1.

The optimized batch F1 showed particle size (130 nm), ZP (-18.9 mV), and entrapment efficiency (85.73%). The dual release pattern (prompt and sustained) was achieved with the SLN-loaded Ambrisentan for about 24 hours. The lyophilized sample was subjected to SEM, which also revealed a spherical shape of a colloidal dispersion with a particle size of 126 nm. Hence, the F1 batch is highly recommended for solid oral delivery and also for the pilot-plant scale-up.

A marked improvement in the solubility and dissolution of Ambrisentan was attained with the SLN. Moreover, the sustained delivery via the oral route enabled the patient's comfort, compliance, and therapeutic efficacy.