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

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 (AUC_0–24, AUC_0–∞ (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.

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Materials

Zolmitriptan (ZMP) was supplied as a gift from Pharmaceutical Industries, EIPICO (Cairo, Egypt). Span 20 (S20), Span 60 (S60), hydroxypropyl methyl cellulose E15 (HPMC) and cellulose membrane (cut off 12,000–14,000 Mw) were procured from Sigma Aldrich Chemical Co. (St. Louis, MO, USA). El-Nasr Pharmaceutical Chemicals Company (Cairo, Egypt) provided Tween 80 (T80) and triethanolamine (TEA). Pemulen^® TR-2 was a kind gift from Luna Pharmaceuticals (Cairo, Egypt). Glyceryl behenate (Compritol 888 ATO^®), linoleoyl polyoxyl-6 glycerides (Labrafil^® 2125), caprylocaproyl macrogol-8 glycerides (Labrasol^®) and glyceryl tricaprylate/caprate (Miglyol^® 812) were obtained as a gift from Gattefosse (St-Priest, France). Methanol was provided by Merck (Darmstadt, Germany).

Hassan, D.H.; Shohdy, J.N.; El-Setouhy, D.A.; El-Nabarawi, M.; Naguib, M.J. 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. Pharmaceutics 2022, 14, 1484.
https://doi.org/10.3390/pharmaceutics14071484