Compritol-Based Nanostrucutured Lipid Carriers (NLCs) for Augmentation of Zolmitriptan Bioavailability via the Transdermal Route: In Vitro Optimization, Ex Vivo Permeation, In Vivo Pharmacokinetic Study

Abstract

Migraine is a severe neurovascular disease manifested mainly as unilateral throbbing headaches. Triptans are agonists for serotonin receptors. Zolmitriptan (ZMP) is a biopharmaceutics classification system (BCS) class III medication with an absolute oral bioavailability of less than 40%. As a result, our research intended to increase ZMP bioavailability by developing transdermal nanostructured lipid carriers (NLCs). NLCs were prepared utilizing a combination of hot melt emulsification and high-speed stirring in a 32 full factorial design. The studied variables were liquid lipid type (X1) and surfactant type (X2). The developed NLCs were evaluated in terms of particle size (Y1, nm), polydispersity index (Y2, PDI), zeta potential (Y3, mV), entrapment efficacy (Y4, %) and amount released after 6 h (Q6h, Y5, %). At 1% Mygliol as liquid lipid component and 1% Span 20 as surfactant, the optimized formula (NLC9) showed a minimum particle size (138 ± 7.07 nm), minimum polydispersity index (0.39 ± 0.001), acceptable zeta potential (−22.1 ± 0.80), maximum entrapment efficiency (73 ± 0.10%) and maximum amount released after 6 h (83.22 ± 0.10%). The optimized formula was then incorporated into gel preparation (HPMC) to improve the system stability and ease of application. Then, the pharmacokinetic study was conducted on rabbits in a cross-over design. The calculated parameters showed a higher area under the curve (AUC0–24, AUC0–∞ (ng·h/mL)) of the developed ZMP-NLCs loaded gel, with a 1.76-fold increase in bioavailability in comparison to the orally administered marketed product (Zomig®). A histopathological examination revealed the safety of the developed nanoparticles. The declared results highlight the potential of utilizing the proposed NLCs for the transdermal delivery of ZMP to improve the drug bioavailability.

Cod liver oil nano-structured lipid carriers (Cod-NLCs) as a promising platform for nose to brain delivery: Preparation, in vitro optimization, ex vivo cytotoxicity & in vivo biodistribution utilizing radioiodinated zopiclone

“…This results in lower perfection of the matrix and forming an amorphous structure. Thus allows more drug loading and better encapsulation of either hydrophilic or hydrophobic drugs and less drug leaking from the matrix ( Hassan et al, 2022 ; Shirazi et al, 2021 ). On the other hand, SLNs yield a perfect crystalline lattice providing very small space for the encapsulation of drug molecules ( Katopodi and Detsi, 2021 ).…”

Kinetics and Thermodynamics of Adsorption for Aromatic Hydrocarbon Model Systems via a Coagulation Process with a Ferric Sulfate–Lime Softening System

“…The measured values could be any denomination between 0 and 1, where lower values indicate more homogenous dispersions than higher values. Usually, values < 0.5 are considered acceptable concerning the homogeneity of the prepared dispersions [ 30 ]. PNP flocs with lab water showed values for PDI higher than 0.5 (ferric sulfate PDI = 0.7 ± 0.1 and aluminum PDI = 0.8 ± 0.1).…”

Brain targeting of zolmitriptan via transdermal terpesomes: statistical optimization and in vivo biodistribution study by 99mTc radiolabeling technique

“…Figure 4 illustrated the DSC thermograms of pure ZT, PC, SDC, ZT-PC-SDC physical mixture and T6 lyophilized terpesomes. The crystallinity of ZT was evidenced by its specific sharp melting endothermic peak at 137.8 °C [ 7 , 20 ]. ZT’s melting peak disappeared in the thermogram of T6, indicating amorphization and successful entrapment of ZT inside the terpesomal vesicles [ 46 ].…”

“…High brain targeting efficiency (BTE% = 315%) of 99m Tc-ZT-T6 was revealed, which confirmed its successful capability in crossing the blood brain barrier (BBB), as well as higher distribution in brain compared to 99m Tc-ZT solution. This improvement could be correlated to various factors; (i) the lipid nature of the vesicular system enhancing its affinity in crossing the skin as well BBB either intact or fragmented [ 20 , 49 ] (ii) the augmented effects of terpene, ethanol and SDC in enhancing skin permeation [ 22 ], (iii) the small particle size, large surface area and elasticity allowing the intimate contact and penetration through the skin layers [ 23 ], and (iv) bypassing the hepatic first pass metabolism [ 46 , 50 ].…”

“…Previous studies explored the transdermal route of administration for enhancing the bioavailability of ZT via bypassing portal and liver metabolism through the development of various systems as nanostrucutured lipid carriers [ 20 ], niosomal emulgel [ 8 ], adhesive patch [ 21 ]. On the other hand, successful skin permeation of various drugs was achieved via terpesomes [ 22 – 25 ].…”