Enhanced bioavailability of danazol nanosuspensions by wet milling and high-pressure homogenization

Abstract

Introduction:The majority of drugs obtained through synthesis and development show poor aqueous solubility and dissolution velocity, resulting in reduced bioavailability of drugs. Most of these problems arise from formulation-related performance issues, and an efficient way to overcome these obstacles and to increase dissolution velocity is to reduce the particle size of drug substances to form drug nanosuspensions.Materials and Methods:Danazol nanosuspensions were prepared by wet milling (WM) and high-pressure homogenization (HPH) methods. The nanosuspensions obtained using these fabrication methods were analyzed for their particle size, surface charge, and the crystallinity of the product was assessed by X-ray diffraction (XRD) and differential scanning calorimetry techniques. To determine in vitro and in vivo performances of the prepared nanosuspensions, dissolution velocity, and bioavailability studies were performed.Results:Particle size and zeta potential analysis showed the formation of nanosized particles with a negative charge on the surface. XRD depicted the nanocrystalline nature of danazol with low diffraction intensities. With increased surface area and saturation solubility, the nanosuspensions showed enhanced dissolution velocity and oral bioavailability in rats when compared to the bulk danazol suspension.Conclusions:The results suggest that the preparation of nanosuspensions by WM or HPH is a promising approach to formulate new drugs or to reformulate existing drugs with poorly water-soluble properties.

The Evaluation of Drug Delivery Nanocarrier Development and Pharmacological Briefing for Metabolic-Associated Fatty Liver Disease (MAFLD): An Update

“…Silybin-nanosuspension and micelles that improved the low oral absorption and bioavailability of silybin are examples of such instances. [ 279 , 280 ], as well as Schisandra extract loaded in liposome-encapsulated with β-cyclodextrin [ 281 ]. Natural polyphenol compounds are a major current trend in the development of MAFLD therapy [ 282 , 283 , 284 , 285 , 286 , 287 ] and have a strong presence worldwide in many traditional diets, mainly Mediterranean diets [ 288 ], and common Chinese dietary herbs [ 289 ].…”

Preparation and Pharmacokinetic Characterization of an Anti-Virulence Compound Nanosuspensions

“…Nanosuspension is defined as the colloidal dispersion of nanosized drug particles (100–1000 nm) in an aqueous vehicle such as water, aqueous solution or non-aqueous media stabilized with surfactants or polymeric stabilizers [ 28 ]. Nanosuspension technology is a promising approach for addressing poor-solubility problems and has many advantages including: (1) enhanced dissolution rate and oral bioavailability compared with raw drugs or coarse suspensions [ 31 , 32 ]; (2) high drug payload (e.g., 20–30% concentrated nanosuspensions produced via wet milling method, and up to 90% nanocrystal powder-loaded tablets) is available with benefits to high-dosing situations [ 33 , 34 ]; (3) nanoparticles contain almost 100% pure drug with low content of irritant excipients (e.g., surfactant and/or co-solvents) that reduces excipient-induced toxicity and improves drug safety [ 35 ]; (4) diverse dosage forms such as tablets, pellets, nanosuspensions, suppositories and hydrogels are available giving flexibility for various administration routes such as intravenous (IV) [ 36 ], intramuscular [ 37 ], oral [ 38 ], ocular [ 39 ], and nebulization [ 40 ].…”