Asenapine Maleate Loaded Solid Lipid Nanoparticles for Oral Delivery

Abstract

Asenapine maleate (ASM) is a new second-generation antipsychotic approved in August 2009 by U.S FDA for the acute treatment of schizophrenia and manic or mixed episodes associated with bipolar disorder in adults. It shows poor oral bioavailability of < 2% due to extensive first pass metabolism in liver. The present study was aimed at developing and characterizing solid lipid nanoparticles (SLNs) of ASM.SLNs were prepared by solvent injection method by employing Compritol ATO 888 as the lipid matrix and Poloxamer 188 as stabilizer. A 3 2 full factorial design was employed to study the influence of independent variables (amount of lipid and % surfactant) on dependent variables (particle size, and % entrapment efficiency). Optimized ASM-loaded SLNs were further studied for zeta potential, in vitro drug release and TEM. Nanoparticles were lyophilized to improve the physical stability and obtain free flowing powder. Mannitol was employed as a cryoprotectant. Lyophilized ASM-loaded SLNs were characterized using DSC and XRD. The optimized ASM-loaded SLNs exhibited mean particle size 318.5 ± 3.2 nm; polydispersity index of 0.255; zeta potential -29.75 ± (-0.92) mV; entrapment efficiency 53.13 ± 1.77 %; drug release extended up to 36 hours. TEM image exhibited spherical smooth surfaced nanoparticles. Accelerated stability studies of optimized ASM-loaded SLNs and Lyophilized ASM-loaded SLNs revealed its stability. The formulation developed shows reduction in dose and dosing frequency and thus reduces dose related side effects and improved patient compliance.

Validation of an RP-HPLC Method for the Determination of Asenapine Maleate in Dissolution Media and Application to Study In Vitro Release from Co-Crystals

“…Several methods indicating the stability of the drug in bulk and pharmaceutical formulations were also developed [18][19][20][21][22][23]. In preformulation studies, during the development of various dosage forms, several spectrophotometric [24][25][26][27][28] and HPLC [1,5,6,24,[29][30][31] methods were used to determine drug loading and study in vitro release. Most of these studies just mention the kind of method without giving details.…”

Asenapine Maleate-Loaded Nanostructured Lipid Carriers: Optimization and In Vitro , Ex Vivo and In Vivo Evaluations

“…Many studies have been conducted to develop different formulations of ASPM, including sublingual film [6], thermo-responsive in situ nasal gel containing ASPM-hydroxyl propyl βcyclodextrin inclusion complex [7], nanostructured lipid carriers of ASPM for intranasal delivery [8], solid lipid nanoparticles of ASPM for oral delivery [9,10]. Additionally, three patents are also available on intranasal [11], transdermal [12] and injectable [13] formulations of asenapine.…”