Tripling the Bioavailability of Rosuvastatin Calcium Through Development and Optimization of an In-Situ Forming Nanovesicular System

Abstract

In situ forming nanovesicular systems (IFNs) were prepared and optimized to improve Rosuvastatin calcium (RC) oral bioavailability through increasing its solubility and dissolution rate. The IFN was composed of Tween® 80 (T80), cetyl alcohol (CA), in addition to mannitol or Aerosil 200. A single simple step was adopted for preparation, then the prepared formulations were investigated by analyzing their particle size (PS), polydispersity index (PDI), Zeta potential (ZP), entrapment efficiency (EE), and flowability properties. D-optimal design was applied to choose the optimized formulations. The maximum desirability values were 0.754 and 0.478 for the optimized formulations containing 0.05 g CA, 0.18 g T80, and 0.5 g mannitol (OFM) or Aerosil (OFA), respectively. In vitro drug release from the optimized formulations showed a significantly faster dissolution rate when compared to the market product. In vivo performance of the optimized formulations in rabbits was investigated after filling them into enteric-coated capsules. Ultimately, OFA formulation achieved a 3 times increase in RC oral bioavailability in comparison with the market product, supporting the hypothesis of considering IFNs as promising nanocarriers able to boost the bioavailability of BCS class II drugs.

Simultaneous Optimization of Oral and Transdermal Nanovesicles for Bioavailability Enhancement of Ivabradine Hydrochloride

“… 71 Their optimized formula entrapped ≈ 32.8% of the drug with an increase in bioavailability that reached 2.53 folds in comparison to buspirone solution. This could be attributed to the avoidance of the hepatic 1st pass effect through enhancing the lymphatic uptake as previously reported by Elsayed et al and Baek et al 16 , 72 A similar bioavailability enhancement (185.22%) was observed upon transdermal application of the nanovesicular gel. This might be referred to the small nanovesicular size (< 300 nm) and the presence of PL and SP as surfactants that could solubilize intercellular lipids and increase the fluidity of the stratum corneum layer, in addition to disrupting corneocytes because of the possible interaction with keratin filaments.…”

“…These nanovesicles could be able to increase the extent of drug absorption after oral administration through bypassing the hepatic uptake and metabolism due to their built-in lipophilicity and small particle size. 15 , 16 Moreover, the developed nanovesicles were embedded in a gel and then topically applied to ensure their abilities to enhance the transdermal permeation of ivabradine depending on the utilized surfactants that could act as potential permeation enhancers. 17 , 18 The excipients used to develop the nanovesicles are significantly cheaper than polylactic co-glycolic acid and D-α-tocopherol polyethylene glycol 1000 succinate used in a previous study.…”

Formulation and Development of Oral Fast-Dissolving Films Loaded with Nanosuspension to Augment Paroxetine Bioavailability: In Vitro Characterization, Ex Vivo Permeation, and Pharmacokinetic Evaluation in Healthy Human Volunteers

“…Finally, the chosen optimized OFDF was characterized by comparing its observed and predicted responses to ensure the model performance accuracy. Each film was weighed individually, utilizing an electronic balance (type AX200, Shimadzu corp., Kyoto, Japan) [22]. Each test was repeated three times.…”

“…PX content was detected utilizing a UV spectrophotometer (UV-1700; Shimadzu, Kyoto, Japan) at 294.3 nm [3]. PX average content ± SD was determined using the following equation [22]:…”

Effective asymmetric preparation of (R)-1-[3-(trifluoromethyl)phenyl]ethanol with recombinant E. coli whole cells in an aqueous Tween-20/natural deep eutectic solvent solution

“…These limitations can be alleviated to a certain extent by introducing proper surfactant into the reaction medium. The effect of surfactants in the biotransformation process might be attributed to their ability to form micellar systems with hydrophobic substrates (Cortes-Clerget et al 2019 ; Elsayed et al 2019 ; Santos et al 2016 ). The hydrophobic compound is distributed to the hydrophobic center of the surfactant micelle, thus the concentration of the substrate/product in the aqueous solution drops below inhibitory content, consequently increasing the water solubility of hydrophobic compound (Su et al 2010 ).…”