Transdermal delivery of duloxetine-sulfobutylether-β-cyclodextrin complex for effective management of depression

• Published in: International journal of pharmaceutics Vol. 594; p. 120129
• Main Authors: Kumar, Rajiv, Sinha, V.R., Dahiya, Lalita, Sarwal, Amita
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2021
• Subjects: Duloxetine; Enhancement ratio; Forced swim; Locomotor activity; Skin retention; DXT; DMSO; Kp; kDa; MDD; SBEβCD; SA; DS; SC; Enhancement ratio; βCD; Locomotor activity; Δδ; PBS; Eqn; FST; Skin retention; CMS; 1H NMR; Jss; μg; Duloxetine; ppm; ER; Q72; Forced swim; CS; PII; PEG; δ; MeOH; PE; PG; LAT; HPMC
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2020.120129

[Display omitted] •Spray dried complexation leads to more solubility, penetration/permeation.•HPMC based transdermal patches exhibit better permeation and retention in skin.•Pharmacodynamic activity in Wistar rats shows improved efficacy of drug via transdermal route compared to oral route.•Behavioural alterations are indicatives of changes of 5-HT and NE level after transdermal administration of DXT.•Pharmacokinetic studies in Wistar rats indicate enhanced absorption of DXT from optimized transdermal formulation. Aim of the study was to reduce the dose and dosing frequency of duloxetine HCl (DXT) by complexation with sulfobutylether-β-cyclodextrin (SBEβCD), an anionic cyclodextrin through permeation enhancement for more effective management of depression. Spray dried inclusion complexes of drug with SBEβCD were prepared and incorporated in medicated patches followed by their ex vivo permeation and skin retention studies. Then, in vivo efficacy and absorption of the drug from developed optimised patch was determined in Wistar rats by administering drug through oral route (free drug) and transdermal route (complexed drug). Swimming, immobility and climbing parameters in FST while ambulation and rearings parameters in LAT test were assessed. Addition of permeation enhancer (PE) increased drug permeation and the enhancement ratio (ER) was 3.05 and 1.67 for the patch having complexed DXT and spray dried sample of DXT in comparison to free DXT respectively. The amount of drug retained in skin and in optimized medicated patch after 72 h was relatively lower compared to the formulation having free DXT. Enhanced antidepressive activity was observed for complexed drug compared to free drug. We believe that spray dried complexation based transdermal patch can serve as potential innovative drug delivery system for DXT.