Chitosan-coated diacerein nanosuspensions as a platform for enhancing bioavailability and lowering side effects: preparation, characterization, and ex vivo/in vivo evaluation

Abstract

Nanodrug delivery systems have been widely reviewed for their use in several drug formulations to improve bioavailability, sustain effect, and decrease side effects of many candidate drugs. The objective of this study was to evaluate the potential of chitosan (CS)-coated nanosuspensions to enhance bioavailability and reduce the diarrheal side effect of diacerein (DCN) after oral administration. DCN nanosuspensions (DNS) were prepared by sonoprecipitation technique using different stabilizers at three different concentrations. The selected DNS with optimum particle size (PS), polydispersity index (PDI), and Zeta potential (ZP) was coated with three different concentrations of CS-coated DNS (CS-DNS) and screened. In vitro dissolution was performed for the selected lyophilized formulae and compared with DCN powder in addition to the assessment of drug crystallinity via scanning electron microscopy, X-ray powder diffraction, and differential scanning calorimetry. Ex vivo drug permeability using noneverted rat intestine, intraluminal content, and mucoadhesion evaluation was studied for nominated formulae in comparison to DCN suspension. Moreover, in vivo study, pharmacokinetic parameters, and evaluation of diarrheal potential were conducted after oral administration of selected formulae. Polyvinyl pyrrolidone (PVP)-stabilized DNS showed a significant increase ( P ≤0.05) in PS and PDI as the stabilizer concentration increased. PVP-stabilized DNS with the lowest CS concentration was protected from aggregation by lyophilization with mannitol. A remarked enhancement in dissolution parameters was observed in the nanocrystals’ formulae. Morphological examination and X-ray diffraction confirmed drug crystallinity. The intermediate permeation parameters of CS-DNS-F10, lowest rhein-to-DCN ratio in intraluminal content along with the highest percentage of mucoadhesive, could serve as a sustaining profile of coated formula. CS-DNS-F10 showed a significantly higher C max of 0.74±0.15 µg/mL at a delayed T max of 3.60±0.55 hours with a relative bioavailability of 172.1% compared to DCN suspension. CS-coated nanosuspensions could serve as promising revenue to enhance bioavailability and reduce the diarrheal side effect of DCN after oral administration.

Development of orally disintegrating tablets containing solid dispersion of a poorly soluble drug for enhanced dissolution: In-vitro optimization/in-vivo evaluation

“…In addition, niosomes as well as, mixed niosomes were assigned for entrapping DCN as a model for poorly water soluble drug molecules, using different surfactant/cholesterol ratios [15]. Within the same context, DCN nano-suspensions were developed via sono-precipitation followed by chitosan coating [16].…”

Efficacy of adjunctive use of diacerein local delivery in the management of moderate chronic periodontitis: a double-blind randomized controlled trial

“…Diacerein is an anthraquinone derivative, originating from plants with anti-inflammatory and analgesic properties, however, it may cause uncomfortable GI irritation. The use of gel and other formulas can provide an easy, comfortable and efficient route of diacerein delivery to overcome GI undesirable reactions (29). In addition, all included participants were between 35-45 years of healthy-stable status which provide further persistent and endurance against any foreign materials including medications.…”

Novel rhein–phospholipid complex targeting skin diseases: development, in vitro, ex vivo, and in vivo studies

“…Despite the potential utility of RH as a pivotal candidate for treatment of various skin diseases, unfortunately its topical application is halted by its challenging physicochemical aspects and low dermal permeability [21]. Furthermore, RH manifested poor solubility in water concomitant with poor absorption which reduced its oral bioavailability (20-25%) [22] along with severe local gastric side effects causing diarrhea and hepatotoxicity which are considered the most relevant side effects restricting its oral application in clinic [23,24]. In particular, topical treatment has been regarded as the first line of therapy involving targeting the diseased site of skin, reducing systemic side effects, potentiating the treatment efficacy, and high patient compliance [25].…”