Central Composite Optimization of Glycerosomes for the Enhanced Oral Bioavailability and Brain Delivery of Quetiapine Fumarate

Abstract

This study aimed to formulate and statistically optimize glycerosomal formulations of Quetiapine fumarate (QTF) to increase its oral bioavailability and enhance its brain delivery. The study was designed using a Central composite rotatable design using Design-Expert® software. The independent variables in the study were glycerol % w/v and cholesterol % w/v, while the dependent variables were vesicle size (VS), zeta potential (ZP), and entrapment efficiency percent (EE%). The numerical optimization process resulted in an optimum formula composed of 29.645 (w/v%) glycerol, 0.8 (w/v%) cholesterol, and 5 (w/v%) lecithin. It showed a vesicle size of 290.4 nm, zeta potential of −34.58, and entrapment efficiency of 80.85%. The optimum formula was further characterized for DSC, XRD, TEM, in-vitro release, the effect of aging, and pharmacokinetic study. DSC thermogram confirmed the compatibility of the drug with the ingredients. XRD revealed the encapsulation of the drug in the glycerosomal nanovesicles. TEM image revealed spherical vesicles with no aggregates. Additionally, it showed enhanced drug release when compared to a drug suspension and also exhibited good stability for one month. Moreover, it showed higher brain Cmax, AUC0–24, and AUC0–∞ and plasma AUC0–24 and AUC0–∞ in comparison to drug suspension. It showed brain and plasma bioavailability enhancement of 153.15 and 179.85%, respectively, compared to the drug suspension. So, the optimum glycerosomal formula may be regarded as a promising carrier to enhance the oral bioavailability and brain delivery of Quetiapine fumarate.

Fabrication and Assessment of Orodispersible Tablets Loaded with Cubosomes for the Improved Anticancer Activity of Simvastatin against the MDA-MB-231 Breast Cancer Cell Line

“…The supernatant containing the free SIM was filtered, properly diluted, and quantified for SIM concentration using an ultraviolet (UV) spectrophotometer (Shimadzu UV-1800, Kyoto, Japan) at a predetermined λmax (238 nm). The EE% was computed using the following equation: [ 20 , 37 , 38 ] EE% = (TD − FD)/TD × 100 where EE% is the entrapment efficiency percentage, TD is the total amount of drug, and FD is the free amount of drug in the supernatant.…”

Development and optimization of kaempferol loaded ethosomes using Box–Behnken statistical design: In vitro and ex‐vivo assessments

“…The amounts of ethanol (C) and lipid (B) had a significant impact on the vesicle's size. 20 It was discovered that the quadratic fit the VS data well ( p-value of .0001). The adjusted R 2 (.9477), as shown in Table 4, agreed with the predicted R 2 (.6650).…”

“…The impact of PDI on formulation factors was studied using a linear polynomial equation for entrapment PDI. 20 PDI Y 2 ð Þ¼ 0:4353…”

“…In accordance with the correlation equation's positive sign of their coefficients, it was shown that a lowering of ethanol concentration and a rise in lipid concentration both significantly increased the PDI. 20,27,32 3.1. depicted in Table 2, may be the reason of decreased ZP. In the formulation with 300 mg of lipid, the ZP of various ethosome formulations ranged from À17.69 ± 0.12 to À34.98 ± 0.4 mV.…”

Editorial—Current Insights on Lipid-Based Nanosystems

“…Randa Mohammed Zaki et al [ 15 ] developed a new generation of liposomes containing a high concentration of glycerol, which were called glycerosomes. In this study, the central composite rotatable design was used to optimize an oral formulation of quetiapine fumarate-loaded glycerosomes that showed highly improved brain and plasma drug bioavailability, when compared to an oral drug suspension.…”