Formulation design and characterization of a non-ionic surfactant based vesicular system for the sustained delivery of a new chondroprotective agent

Abstract

Diacerein is used for symptomatic relief and cartilage regeneration in osteoarthritis. Due to gastrointestinal side effects, poor aqueous solubility and low bioavailability, its clinical usage has been restricted. The objective of the present study was to enhance its dissolution profile and to attain sustained release by designing a novel delivery system based on niosomes. Five niosomal formulations (F 1 -F 5 ) with nonionic surfactant (sorbitan monostearate) and cholesterol in varying ratios of 5:5, 6:4, 7:3, 8:2 and 9:1 were developed by the reverse-phase evaporation technique. The size and polydispersivity index (PDI) were found in the range of 0.608 µm to 1.010 µm and 0.409 to 0.781, respectively. Scanning electron microscopy (SEM) of the selected formulation (F 3 ) revealed spherical vesicles, and 79.8% entrapment was achieved with F 3 (7:3). Dissolution studies using the dialysis method showed sustained release behaviour for all formulations. The optimized surfactant-to-cholesterol concentration (7:3) in formulation F 3 sustained the drug-release time (T 50% ) up to 10 hours. Kinetic modelling exhibited a zero-order release (R 2 =0.9834) and the release exponent 'n' of the Korsmayer-Peppas model (n=0.90) confirmed non-fickian and anomalous release. The results of this study suggest that diacerein can be successfully entrapped into niosomes using sorbitan monostearate and that these niosomes have the potential to deliver diacerein efficiently at the absorption site. Uniterms:Chondroprotective. Diacerein/dissolution profile. Diacerein/sustained release. Niosomes. Sorbitan monostearate. Reverse-phase evaporation.A diacereína é usada para o alívio sintomático e para a regeneração da cartilagem na osteoartrite. Devido aos efeitos adversos gastrointestinais, baixa solubilidade aquosa e biodisponibilidade, o seu uso clínico tem sido restrito. O objetivo do presente estudo foi melhorar o perfil de dissolução deste fármaco e obter liberação prolongada através do planejamento de um novo sistema de liberação designado de niossoma. Cinco formulações distintas de niossomas (F 1 a F 5 ) contendo tensoativos não iônicos (monoestearato de sorbitano) e colesterol, em diferentes proporções, de 5:5, 6:4, 7:3, 8:2 e 9:1, foram desenvolvidas através da técnica de evaporacão de fase reversa. Os tamanhos e índices de polidispersibilidade (PDI) obtidos variam entre 0,608 e 1,01 µm e entre 0,409 e 0,7781, respectivamente. Imagens de microscopia electrônica de varrimento (SEM) da formulação selecionada (F 3 ) revelaram vesículas esféricas. Obteve-se encapsulação de 79,8% com a formulação F 3 (7:3). Estudos de dissolução usando o método de diálise demonstraram padrão de liberacão prolongada para todas as formulações. A proporção de tensoativo e colesterol (7:3) na formulacão F 3 prolongou o tempo de liberação do fármaco (T50%) até 10 horas. Estudos de modelação cinética demonstraram ordem de liberacão zero (R 2 =0,9834) e o expoente de liberação "n" do modelo de Korsmayer-Peppas (n=0.90) confirmou a liberação não-fickiana e anômala....

RETRACTED: Intranasal Niosomal In Situ Gel as a Promising Approach for Enhancing Flibanserin Bioavailability and Brain Delivery: In Vitro Optimization and Ex Vivo/In Vivo Evaluation

“…This effect could be credited to the relatively low HLB value of Span ® 85 employed in this study. The low HLB value could result in reduced surface energy, leading to less water uptake in the core, and consequently, reduced size [ 38 ]. The reduced size could also be explained by the possible formation of a micellar structure at higher surfactant concentrations, which is comparatively smaller in size [ 11 ].…”

RETRACTED: Application of Nanopharmaceutics for Flibanserin Brain Delivery Augmentation Via the Nasal Route

“…This observation could be explained on the basis of the increased hydrophobicity of the surfactant with reduced HLB values. Increased surfactant hydrophobicity could lead to reduction of surface energy and low water uptake into the vesicle core, resulting in reduction of the vesicle size [38,[45][46][47]. The boosted FLB permeation from optimized FLB TRF gel could be attributed to the synergistic advantages of TRFs and the nanosized system.…”

Fabrication of novel elastosomes for boosting the transdermal delivery of diacerein: statistical optimization, ex-vivo permeation, in-vivo skin deposition and pharmacokinetic assessment compared to oral formulation

“…A dialysis method was selected for determination of the release profiles of DCN from the prepared elastosomes (Khan et al., 2015 ). Cellulose dialysis membrane of molecular weight cutoff 12,000–14,000 Da (Spectrum Laboratories Inc., Rancho Dominguez, CA) was soaked in double-distilled water overnight before use for the experiment.…”