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Nanocarrier Technologies for Enhancing the Solubility and Dissolution Rate of Api
Published in Debarshi Kar Mahapatra, Sanjay Kumar Bharti, Medicinal Chemistry with Pharmaceutical Product Development, 2019
Ashwini Deshpande, Tulshidas S. Patil
Diacerein, a BCS class II drug, was incorporated in lecithin-gold (LD-Au NPs) hybrid nanocarriers and its anti-inflammatory activity is proved against carrageenan-induced inflammation. The drug was loaded in lecithin NPs followed by coating with Au NPs, either by in-situ production or by employing pre-synthesized Au NPs. All LD-Au NPs depicted 2.5-fold enhancement in oral bioavailability by specifically releasing the drug at physiological pH of 7.4. The improved pharmacological efficacy of LD-Au NPs in terms of anti-inflammatory activity was demonstrated by suppressing inflammation at first phase. In case of acute toxicity studies, LD-Au NPs showed no hepatic damage, but the renal toxicity parameters were found to be close to the upper safety limits. It was hypothesized that along with the improved oral bioavailability and anti-inflammatory activity of hydrophobic drug, these LD-Au NPs might have potential applications in gold-based photothermal therapy as well as in tracing of inflammation at atherosclerotic and arthritic site [238].
Diacerein solid dispersion loaded tablets for minimization of drug adverse effects: statistical design, formulation, in vitro, and in vivo evaluation
Published in Pharmaceutical Development and Technology, 2021
Mohamed Ahmed Naseef Soliman, Howida Kamal Ibrahim, Samia Abd El-Kader Nour
Diacerein is a unique chondroprotective agent for the treatment of osteoarthritis. It is 4,5-diacetoxy-9,10-dioxy-9,10-dihydroanthracene-2-carboxylic acid (Jain et al. 2015; Naseef et al. 2018). Diacerein is entirely converted to rhein (the active metabolite) before reaching systemic circulation (Naseef et al. 2018). Rhein can act by selective downregulation of the synthesis of interleukin-1β, nitrous oxide, pro-inflammatory cytokines, and proteolytic enzymes which are the major factors promoting the breakdown of cartilage. Rhein also induces production of the main cartilage constituents such as proteoglycans and hyaluronic acid leading to regeneration of normal state (Jain et al. 2014; Parekh et al. 2017; Naseef et al. 2018). Unlike NSAIDS, rhein does not inhibit prostaglandin synthesis, so it has no gastrointestinal damaging effect (Eltobshi et al. 2018). Diacerein belongs to Biopharmaceutics Classification System class II drugs with high permeability and low aqueous solubility (Eltobshi et al. 2018). The acid/base hydrolysis of unabsorbed diacerein in the colon results in the formation of rhein molecules which cause the laxative effect of diacerein. Therefore, the low solubility and bioavailability of diacerein increase the possibilities of high rhein formation and accumulation in the colon that worsen its adverse effect (Naseef et al. 2018).
Development, optimisation, and evaluation of nanoencapsulated diacerein emulgel for potential use in osteoarthritis
Published in Journal of Microencapsulation, 2020
Bazla Siddiqui, Asim.ur. Rehman, Ihsan-Ul Haq, Nasir M. Ahmad, Naveed Ahmed
Diacerein (DCR) or diacetylrhein has gained much attention due to its improved disease-modifying anti-catabolic (Steinecker-Frohnwieser et al. 2017), anti-inflammatory and pro-anabolic actions (da Silva et al. 2017) on cartilage and synovial fluid of joints by producing inhibitory action on interleukin-1β (de Isla and Stoltz 2008). Moreover, DCR is associated with decreased off-target effects as compared to excruciating side effects associated with NSAIDs. European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) certified greater benefit to risk proportion of DCR in symptomatic treatment of OA and positioned it as the first line agent for the patients contraindicated for NSAIDs with carry-over effects up to several months after therapy has been discontinued (Pavelka et al. 2016). However the therapeutic effect of DCR is compromised owing to its poor aqueous properties and decreased oral bioavailability of 35–56% having a shorter half-life of 4 h. Further, the drug is mostly recommended orally as 40–50 mg bid creating non-compliance among OA patients following twice daily regimen for a sufficiently long time. Clinical acceptance of DCR was restricted owing to the presence of gastrointestinal adverse effects, such as hepatotoxicity and diarrhoea on chronic use (Panova and Jones 2015). Hence, there is a need to introduce a novel approach for obtaining greater therapeutic benefits from the drug avoiding systemic toxicity.
Pharmaceutical cocrystal: a game changing approach for the administration of old drugs in new crystalline form
Published in Drug Development and Industrial Pharmacy, 2020
Prabhakar S. Panzade, Giridhar R. Shendarkar
Chadha et al. have undertaken cocrystallization of diacerein with nicotinamide, nicotinamide, and theophylline as coformers to improve its biopharmaceutical parameters. Diacerein is an anti-arthritic drug and its activity is limited due to poor aqueous solubility and bioavailability. The cocrystals were developed by the liquid assisted grinding method in 1:1 ratio using the micro quantity of ethanol to facilitate cocrystal formation. The solubility and IDR of all the cocrystals were enhanced substantially than pure diacerein. Cocrystal of diacerein with nicotinamide exhibited the highest dissolution rate amongst all and intrinsic dissolution profile of drug and coformer was similar to pure drug. Evaluation of biopharmaceutical parameters in wistar rats indicates that Cmax and AUC of all the cocrystals were significantly improved than pure drug. Further, pharmacodynamic evaluation (anti-arthritic activity) of cocrystal in rats showed reduction in paw volume, paw withdrawal threshold and left joint diameter. This investigation indicated the potential of cocrystal to enhance the biopharmaceutical properties of drugs [83].