Impact of cyclodextrin derivatives on systemic release of duloxetine HCl via buccal route. (2nd June 2020)

• Record Type: Journal Article
• Authors: Kumar, Rajiv; Sinha, V. R.; Dahiya, Lalita; Singh, Gurpal; Sarwal, Amita
• Is Part Of: Drug development and industrial pharmacy. Volume 46:Number 6(2020)
• Page Start: 931
• Page End: 945
• Publication Date: 2020-06-02
• Subjects: Complexation -- Carbopols -- buccal tablet -- permeation -- depression -- duloxetine; Pharmaceutical chemistry -- Periodicals; Pharmaceutical industry -- Periodicals; Drug Industry -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615.05
• DOI: 10.1080/03639045.2020.1764019
• Languages: English
• ISSNs: 0363-9045

Abstract

Abstract: Aim: The aim of this work was to develop buccoadhesive tablets for the systemic delivery of duloxetine HCl (DXT) using more soluble derivatives of β-cyclodextrin, i.e. hydroxypropyl-β-cyclodextrin (HPβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) and to investigate enhanced cellular uptake of inclusion complexed drug. Materials and methods: Freeze dried and spray dried complexes of both cyclodextrin derivatives with DXT (1:1 molar) were prepared and characterized with DSC, FTIR, and PXRD techniques. C971 and PC, on the basis of swelling behavior, erosion and in vitro residence time, were selected for further study at different levels (−1, 0, +1) to optimize the formulation in terms of enhanced drug release and ex vivo permeation. Results: SBEβCD based complexes show more aqueous solubility of DXT (0.782 and 0.958 mM) and more complexation efficiency compared to HPβCD at 25 °C and 37 °C, respectively. Apparent stability constant was reported to be higher (1109.94 and 1693.25 M −1 ) for DXT-SBEβCD at 25 °C and 37 °C, respectively, than the corresponding values for DXT-HPβCD systems. Enhanced cellular uptake using fibroblast cells was revealed for complexed drug compared to free drug . Conclusion: Both cyclodextrin derivatives are able to enhance drug release and permeation in vitro and ex vivo .