Development and Optimisation of Spironolactone Nanoparticles for Enhanced Dissolution Rates and Stability

Abstract

Abstract.Stable solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) formulations to enhance the dissolution rates of poorly soluble drug spironolactone (SP) were being developed. Probe ultra-sonication method was used to prepare SLNs and NLCs. All NLCs contained stearic acid (solid lipid carrier) and oleic acid (liquid lipid content), whereas, SLNs were prepared and optimised by using the solid lipid only. The particles were characterised in terms of particle size analysis, thermal behaviour, morphology, stability and in vitro release. The zeta sizer data revealed that the increase in the concentration of oleic acid in the formulations reduced the mean particle size and the zeta potential. The increase in concentration of oleic acid from 0 to 30% (w/w) resulted in a higher entrapment efficiency. All nanoparticles were almost spherically shaped with an average particle size of about ∼170 nm. The DSC traces revealed that the presence of oleic acid in the NLC formulations resulted in a shift in the melting endotherms to a higher temperature. This could be attributed to a good long-term stability of the nanoparticles. The stability results showed that the particle size remained smaller in NLC compared to that of SLN formulations after 6 months at various temperatures. The dissolution study showed about a 5.1-to 7.2-fold increase in the release of the drug in 2 h compared to the raw drug. Comparing all nanoparticle formulations indicated that the NLC composition with a ratio of 70:30 (solid:liquid lipid) is the most suitable formulation with desired drug dissolution rates, entrapment efficiency and physical stability.

Topical Treatment of Human Skin and Cultured Keratinocytes with High-Dose Spironolactone Reduces XPB Expression and Induces Toxicity

“…Our results shown here may therefore be somewhat artificial due to the vehicle employed in our work. Nonetheless, as research is underway at improving the delivery of SP into the skin (Abdel-Raouf et al 2021;Abdel-Raouf et al 2020;Biyashev et al 2020;Ilic et al 2021;Kelidari et al 2017;Kelidari et al 2016;Kelidari et al 2015;Salama et al 2019), we suggest that care may need to be taken to ensure that such approaches do not induce toxicity or cause a reduction in XPB protein expression, which could interfere with UV photoproduct removal and increase the risk of skin carcinogenesis.…”

“…Though SP has traditionally been used as an oral medication, there has been an interest in developing alternative formulations (Abdel-Raouf et al 2021;Abdel-Raouf et al 2020;Biyashev et al 2020;Ilic et al 2021;Kelidari et al 2017;Kelidari et al 2016;Kelidari et al 2015;Salama et al 2019) that can be applied topically on the skin for beneficial purposes and to avoid the systemic effects that usually limit its use to females (Bowman et al 2012). In addition, because glucocorticoids can induce skin atrophy and inhibit wound healing due to aberrant stimulation of mineralocorticoid receptors, SP and related MR antagonists have been employed in experimental studies in mouse models and human subjects to counteract some of the negative effects of glucocorticoids (Boix et al 2018;Maubec et al 2015;Nguyen et al 2016).…”

MTDH/AEG-1 downregulation using pristimerin-loaded nanoparticles inhibits Fanconi anemia proteins and increases sensitivity to platinum-based chemotherapy

“…Nanoparticles have been extensively utilized for delivering therapeutic and diagnostic agents. Nanoparticles offer a superior dissolution profile of their payload due to their unique size range that governs a vast increase in the exposed surface area to the dissolution medium [35]. Nanoparticles prepared from natural or synthetic polymers modify drug release and create a sustained or controlled release profile [36].…”

Investigative Study on Impact of Solid: Liquid Lipid Ratio and Stabilizer Amount on Some Characteristics of Nanostructure Lipid Carriers of Quetiapine Fumarate

“…[3][4][5][6][7] Also, greater solubility of the drug in liquid lipid as compared to solid lipid gives higher entrapment efficiency. [8][9][10] NLCs are also solid at room and body temperature but their melting point is lower than their corresponding SLNs [10][11][12] due to their disordered and imperfect crystalline structure. 13,14 In the present study an investigation of the impact of formulation variables like solid:liquid lipid ratio and stabilizer amount on some important NLC characteristics like percent Entrapment Efficiency (%EE), Particle Size (PS), Polydispersity Index (PDI) and Zeta Potential (ZP) was done.…”