Development of mirtazapine loaded solid lipid nanoparticles for topical delivery: Optimization, characterization and cytotoxicity evaluation

• Published in: International journal of pharmaceutics Vol. 586; p. 119439
• Main Authors: Kaur, Randeep, Sharma, Nisha, Tikoo, Kulbhushan, Sinha, V.R.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.08.2020
• Subjects: Administration, Cutaneous; Animals; Antidepressive Agents - administration & dosage; Antidepressive Agents - pharmacokinetics; Antidepressive Agents - toxicity; Box-Behnken design; Cell Line; Cytotoxicity; Drug Delivery Systems; Drug Liberation; Drug Stability; Drug Storage; Humans; Lipids - chemistry; Mirtazapine; Mirtazapine - administration & dosage; Mirtazapine - pharmacokinetics; Mirtazapine - toxicity; Nanoparticles; Particle Size; Pruritus; Pruritus - drug therapy; Rats; Rats, Wistar; Skin Absorption; Solid lipid nanoparticles; Temperature; Topical; Mirtazapine; Cytotoxicity; Topical; Pruritus; Box-Behnken design; Solid lipid nanoparticles
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2020.119439

[Display omitted] Mirtazapine, an antidepressant drug has been proved to exert antipruritic effect upon oral administration in numerous clinical trial studies. The objective of the current study was to develop mirtazapine loaded solid lipid nanoparticles (SLNs) and evaluate its potential as a topical drug delivery system for management of pruritus. Mirtazapine loaded SLNs were successfully developed and optimized applying Box-Behnken design. The optimized mirtazapine loaded SLNs were characterized for physicochemical parameters and morphology. The in vitro cytotoxicity and cellular uptake studies of optimized SLNs were performed in human epithelial A-431 cell line. Further, the optimized mirtazapine loaded SLNs dispersion was incorporated into gel and characterized for rheology and texture analysis. The particle size and PDI of optimized mirtazapine loaded was found to be 180.3 nm and 0.209 respectively. The cytotoxicity studies revealed the safety of mirtazapine loaded SLNs on topical administration. The developed gel showed pseudoplastic flow behavior and good textural profile. The in vitro drug release studies showed that the developed mirtazapine loaded SLNs dispersion and its gel followed Korsmeyer-Peppas model (R2 = 0.905) and Higuchi model (R2 = 0.928) respectively. The ex vivo drug permeation studies showed higher values for mean cumulative amount of drug released (548.25 ± 29.29 μg/cm2), permeation flux (45.10 ± 0.78 μg/cm2/h) and skin retention (11.33 ± 0.85%) of SLNs gel in comparison to pure drug gel. The stability studies indicate the stability of SLNs gel for three months at refrigerated and ambient temperatures. Therefore, abovementioned findings suggest that mirtazapine loaded SLNs could be a potential system for topical management of pruritus.