Self-nanoemulsifying drug-delivery systems for potentiated anti-inflammatory activity of diacerein

Abstract

BackgroundEffective treatment of osteoarthritis necessitates both symptomatic relief and hindrance of joint degeneration progression. Non-steroidal anti-inflammatory drugs permit symptomatic relief only and can cause mucosal injury in the gut. Before absorption, diacerein (Dcn) is converted into rhein that counteracts cartilage degeneration without affecting prostaglandin production. Yet, low solubility and laxative action of unabsorbed rhein in the colon hindered its use. Thus, enhanced Dcn dissolution would allow absorption at the upper gut improving its bioavailability and possibly abolishing the laxative action.MethodsTherefore, self-nanoemulsifying drug delivery systems (SNEDDSs) with each of gelucire 44/14 (Glc) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) at different drug:carrier weight ratios of 1:1, 1:2, 1:4, 1:6, 1:8 and 1:10 were prepared by melt method and filled into hard gelatin capsules. The optimized binary systems were selected based on solid state characterization, scanning electron microscopy (SEM) and in vitro evaluation of the prepared SNEDDSs in comparison with their corresponding physical mixtures (PMs) and Dcn. The optimized systems were further examined with respect to their morphology, size distribution and ζ-potential. Moreover, the anti-inflammatory activity of the optimized systems against carrageenan-induced paw edema in rats was assessed through estimation of edema and edema inhibition percentages as well as histopathological examination and immunohistochemical localization of tumor necrosis factor-alpha (TNF-α) and caspase-3.ResultsSignificantly (P<0.05) enhanced in vitro drug release was recorded for SNEDDSs with either carrier when compared to Dcn and the corresponding PMs. SNEDDSs based on 1:10 Dcn:Glc and 1:8 Dcn:TPGS showed significantly (P<0.05) reduced edema and inflammation as well as expression of TNF-α and caspase-3 relative to positive control and Dcn pretreated groups.ConclusionThese SNEDDSs can be represented as potential oral drug delivery systems of Dcn for enhanced dissolution and anti-inflammatory activity against carrageenan-induced paw edema.

A Solid Ultra Fine Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) of Deferasirox for Improved Solubility: Optimization, Characterization, and In Vitro Cytotoxicity Studies

“…The n value indicates the characteristic of release mechanisms [ 37 ]. An n value higher than 1.0 which was calculated for all formulations implies that DFX release from S-SNEDDS formulations follows the Super case-II transport release mechanism, which refers to the erosion of the polymer chain and explains the initial burst release [ 38 ].…”

Preparation and Characterization of Self Nano-Emulsifying Drug Delivery System Loaded with Citraland Its Antiproliferative Effect on Colorectal Cells In Vitro

“…These mixtures are oil, surfactants, co-surfactants, and alsoan active drug compound that will produce oil-in-water emulsion into aqueous media by mild agitation. This will lead to the production of nano-particles SNEDDS approximately less than or equals to 200 nm in size [17,18,19,20].…”

Design and optimization of candesartan loaded self-nanoemulsifying drug delivery system for improving its dissolution rate and pharmacodynamic potential

“…Its smaller size results in greater interfacial surface area for assimilation of medicament and enhanced bioavailability. Hence, its smaller size may govern the effective discharge of (Eltobshi et al, 2018). The globule size of optimized formulations specifies that droplets of emulsion are in nanometric range (13.91 nm) with a PDI value less than 0.5 which indicates uniformity in the globule size distribution and zeta potential value of -0.32 mV as shown in Figure 8.…”