Rakesh Kumar Mahajan

One of the key strategy for enhancing the poor solubility and bioavailability of active pharmaceutical ingredients (APIs) is their conversion to ionic liquids (ILs) form, commonly referred to as API‐ILs. Herein, we report the synthesis and physiochemical investigation of two such API‐ILs based on the salicylate ion, namely benzalkonium salicylate (BzSal) and cetylpyridinium salicylate (CetPySal). To evaluate the pharmacological behaviour of these Sal‐ILs, theoretical studies viz. molecular docking and experimental studies viz . DPPH, FRAP and MIC assay were carried out. The Sal‐ILs have been found to possess antibacterial activity against Enterobacter aerogenes ( E. aerogenes ) , Klebsiella pneumoniae ( K. pneumoniae ), and Proteus vulgaris ( P.vulgaris ) as well as antioxidant potential against the target protein, i.e., NO‐synthase (PDB ID: 6NGJ). Further, as these Sal‐ILs were amphiphilic, so conductivity and UV‐visible measurements were employed to determine their aggregational characteristics both in the absence and presence of certain additives (Alcohols/Tweens). Lastly, the in vitro skin permeation studies have been performed using dialysis membrane, indicating at the higher permeability of Sal‐ILs in comparison to parent salicylic acid.

Numerous tests have been developed for early clinical detection of the novel coronavirus, COVID-19, including RT-PCR, rapid PCR, laminar flow tests, and large-scale decentralized screening of SARS-CoV-2 in a point-of-care format.

The nature of counter-ions governs the micellar and structural characteristics of surface-active ionic liquids (SAILs). Especially, the introduction of aromatic counter-ions significantly increases their surface adsorption and induces the formation of various type of aggregates like prolate ellipsoidal micelles, rod micelles, vesicles, etc. The present study reports the role of charge delocalization of two different aromatic counter-ions on the micellization behavior of their respective SAILs in aqueous medium. For this purpose we have synthesized two SAILs, namely, 1-tetradecyl-3-methylimidzolium phenolate [C14mim][PO] and 1-tetradecyl-3-methylimidzolium benzoate [C14mim][BZ]. The O-atom of phenolate (PO-) possesses negative charge which is delocalized on its phenyl ring. Conversely, the negative charge of benzoate (BZ-) is not delocalized on its phenyl ring. The more hydrophobic BZ- counter-ion increases the hydrophobic interactions and reduces the electrostatic repulsions more efficiently as compared PO- which results to the smaller critical micelle concentration (cmc) of [C14mim][BZ] than [C14mim][PO]. Interfacial properties obtained by using tensiometry reveals better surface-activity and absorption efficiency of [C14mim][BZ] as compared to [C14mim][[PO]. The increase of cmc and degree of counter-ion binding (β) with the rise of temperature for both SAILs have been provided by conductometry. The decrease in the polarity of pyrene micro-environment explains the higher compactness of [C14mim][BZ] aggregates than [C14mim][PO] by fluorimetry. The position of PO- and BZ is at the stern and palisade layer of C14mim+ aggregates, respectively located by 1H-NMR. The existence of prolate ellipsoidal micelles for both SAILs have been established by using small angle neutron scattering measurements. So, the interfacial and bulk properties of [C14mim][PO] lies somewhere in between the SAILs having perfect aromatic counterions, [C14mim][BZ] and the SAILs having regular inorganic counter-ions like Cl-, Br- etc.

Pluronics (tri-block copolymers) have a significant role in the pharmaceutical industry and are being used to enhance the solubility and delivery of hydrophobic drugs in different marketed formulations. However, instability and unsatisfactory drug-loading capacity are the major weak spots of these pluronic micelles. The present research work is designed to solve the existing issues by the solubilization study of hydrophobic drugs in different pluronic micelles at variable temperatures. The solubilization of the hydrophobic antiepileptic drug lamotrigine (LAM) in five different pluronic micelles viz. P84, P85, F127, F108, and F68 was studied at different temperatures, 37, 47, and 57 °C, using UV–visible spectroscopy. The solubilization of LAM in pluronic micelles increased with the increase in temperature. Small-angle neutron scattering (SANS) measurements were used to observe the morphological and structural changes taking place in pluronics by increasing the temperature. The SANS results showed the morphological changes of spherical P84 micelles to prolate ellipsoidal micelles at 57 °C due to remarkable increase in the aggregation number. This morphological conversion was further confirmed by the heat transfer method (HTM) and dynamic light scattering (DLS) measurements. DLS measurements confirmed that LAM-loaded micelles showed a greater hydrodynamic diameter (D_h) compared to unloaded micelles, assuring LAM solubilization in the pluronic micelles. The rate of controlled release of LAM from five different pluronic micelles was accessed by using different kinetic models to evaluate the in vitro release profile. This is the first report in which HTM measurements are established for the analysis of morphological changes in the thermoresponsive pluronic micelles in real time. The present work corroborates how we can control the drug-loading capacity, morphological structure of the drug carrier, as well as drug release by simply changing the temperature of pluronic micellar media.

The interactional and morphology behavior of mixed system embracing chlorpromazine hydrochloride (CPZ) drug and surface active biamphiphilic ionic liquids (BAILs); 1‐hexyl‐3‐methylimidazolium dodecylsulfate ([C ₆ mim][C ₁₂ OSO ₃ ]) and 1‐butyl‐3‐methylimidazolium octylsulfate ([C ₄ mim][C ₈ OSO ₃ ]) at pH 7 have been investigated to develop new strategies to use BAILs as carriers of pharmaceutical active compounds. UV‐vis absorption spectroscopy and cyclic voltammetry (CV) methods are used to shed light on the foremost interactions governing CPZ + BAILs mixtures. The higher value of binding constant ( K _a ) and Gibbs free energy change (Δ G ) for CPZ + [C ₆ mim][C ₁₂ OSO ₃ ] mixture, determined from absorbance measurements depict the existence of more attractive interactions than CPZ + [C ₄ mim][C ₈ OSO ₃ ]. The composition mediated self‐assembly of CPZ + BAIL mixed aggregates in bulk has been investigated by small angle neutron scattering (SANS), dynamic light scattering (DLS) and zeta potential measurements.

Here, we present how replacing the usual inorganic counter ion with a pharmaceutically active aromatic one can greatly affect the interfacial as well as bulk properties of ionic liquids (ILs). We have synthesized a series of novel drug-based ILs, namely, 1-alkyl-3-methylimidazolium diclofenate ([C_nmim][DF]; n = 6, 8, 10, 12, and 14) abbreviated as DF-ILs, wherein DF^– is a well-recognized analgesic and nonsteroidal anti-inflammatory drug. We show strong synergistic interactions between C_nmim⁺ and aromatic DF^– attributed to reduced electrostatic repulsions and increased hydrophobicity from their incorporation, reflecting a 300-fold smaller critical aggregation concentration than that of their Cl^– analogue [C_nmim][Cl]. Interfacial properties for such strongly associating systems are discussed and clearly established to have remarkably improved properties than those of their Cl^– analogues. The decreasing polarity of the cybotactic region of pyrene with increase in the chain length “n” indicates an increased extent of packing of cationic head groups in the Stern layer. DF^– ion seems to play a vital role in the formation of the resulting aggregates, as probed by small angle neutron scattering and transmission electron microscopy. The thermodynamical insights of the aggregation process have been studied using isothermal titration calorimetry and temperature-dependent conductivity experiments. Unilamellar vesicles are formed at extremely low concentration, and also it is the first report that puts into picture the formation of vesicles for [C₆mim][DF] with such a short chain.