Carboxymethylation of Locust Bean Gum: Application in Interpenetrating Polymer Network Microspheres for Controlled Drug Delivery

For hydrophilic modification, the sodium carboxymethyl ether of locust bean gum was developed by Williamson synthesis using monochloroacetic acid as the etherifying agent. The modification reaction was optimized in terms of concentration of monochloroacetic acid and sodium hydroxide. The modified gum was evaluated for its degree of substitution, elemental analysis, viscosity, swelling, and contact angle. The etherification of locust bean gum was further confirmed by FTIR, ¹³C NMR, DSC, and XRD techniques. Acute oral toxicity and biodegradability studies showed that the modified gum was safe enough for internal use. This carboxymethylated gum with poly­(vinyl alcohol) was utilized to prepare the interpenetrating polymer network microspheres of buflomedil hydrochloride for controlled drug delivery. The microspheres were evaluated for their drug entrapment efficiency, swelling, and particle size. The microspheres were further characterized by FTIR, ¹³C NMR, and XRD techniques. The in vitro release study of microspheres showed retarded drug release up to 12 h

Ligand-Assisted Acyl Migration in Au-Catalyzed Isomerization of Propargylic Ester to Diketone: A DFT Study

Gold-catalyzed isomerization of propargylic ester to a diketone derivative is a fascinating example for the generation of the C–C bond in organoaurate chemistry as it is one of the few reactions that exploit the nucleophilicity of organoaurates to a migrating acyl group. The proposed mechanistic pathway, involving the formation of a four-membered intermediate, has never been substantiated by any theoretical or experimental evidence. Detailed theoretical calculation suggests that the formation of an alkylideneoxoniumcyclobutene intermediate is highly unlikely. Instead, an acyl migration, assisted by the chlorine ligand in the square planar geometry of metal complex offers an alternative mechanism that can justify the reasonable activation barrier and the associated stereochemical feature involved in the reaction. The initial mandatory steps of the catalytic process such as allene formation (af) and rotamerization of allene-bound gold complex (ra) are found to be quite facile. However, the final step, acyl migration (am), that takes place through the formation of an intermediate with C–Cl bond, acts as the rate-determining step of the reaction. The mechanism also justifies the lack of sufficient activity of Au­(I) salt to catalyze the isomerization process

Solubility Enhancement of Ezetimibe by a Cocrystal Engineering Technique

The present study illustrates the formation and characterization of three different cocrystals of ezetimibe using methyl paraben as a coformer, employing three different processes, namely, solution crystallization, liquid assisted grinding, and reaction crystallization. Thermal analysis by differential scanning calorimetry (DSC) and thermogravimetric analysis were used as a primary analytical tool, followed by spectroscopic and crystallographic study as a confirmatory analytical tool. Equilibrium aqueous solubility studies were performed for all cocrystals taking ezetimibe as the control. The ideal solubility of drug and cocrystals was also calculated using data obtained from DSC (heat of fusion, Δ<i>H</i>, and transition melting temperature, <i>T</i>_m). The equilibrium aqueous solubility of ezetimibe was enhanced by about 2-fold in the case of cocrystal prepared by solution crystallization. Cocrystals prepared via reaction crystallization showed solubility that was almost the same as that of pure ezetimibe. The dissolution profile of all cocrystals, with pure ezetimibe as a control, was studied for 2 h in defined biorelevant media. Cocrystal II, prepared by a liquid assisted grinding method, showed significant improvement in solubility at 45 and 120 min, indicating a good dissolution profile. The study demonstrates that pharmaceutical cocrystallization of ezetimibe with methyl paraben can be a possible and potential alternative and effective approach for improving its solubility

Stimulus-Responsive, Biodegradable, Biocompatible, Covalently Cross-Linked Hydrogel Based on Dextrin and Poly(<i>N</i>‑isopropylacrylamide) for in Vitro/in Vivo Controlled Drug Release

A novel stimulus-sensitive covalently cross-linked hydrogel derived from dextrin, <i>N</i>-isopropylacrylamide, and <i>N</i>,<i>N</i>′-methylene bis­(acrylamide) (c-Dxt/pNIPAm), has been synthesized via Michael type addition reaction for controlled drug release application. The chemical structure of c-Dxt/pNIPAm has been confirmed through Fourier transform infrared (FTIR) spectroscopy and ¹H and ¹³C NMR spectral analyses. The surface morphology of the hydrogel has been studied by field emission scanning electron microscopic (FE-SEM) and environmental scanning electron microscopic (E-SEM) analyses. The stimulus responsiveness of the hydrogel was studied through equilibrium swelling in various pH media at 25 and 37 °C. Rheological study was performed to measure the gel strength and gelation time. Noncytotoxicity of c-Dxt/pNIPAm hydrogel has been studied using human mesenchymal stem cells (hMSCs). The biodegradability of c-Dxt/pNIPAm was confirmed using hen egg lysozyme. The in vitro and in vivo release studies of ornidazole and ciprofloxacin imply that c-Dxt/pNIPAm delivers both drugs in a controlled way and would be an excellent alternative for a dual drug carrier. The FTIR, powder X-ray diffraction (XRD), and UV–vis–near infrared (NIR) spectra along with the computational study predict that the drugs remain in the matrix through physical interaction. A stability study signifies that the drugs (ornidazole ∼97% and ciprofloxacin ∼98%) are stable in the tablet formulations for up to 3 months

In Situ Silver Nanowire Deposited Cross-Linked Carboxymethyl Cellulose: A Potential Transdermal Anticancer Drug Carrier

Recently, a novel biopolymeric nanocomposite hydrogel comprised of in situ formed silver nanowires (AgNWs) deposited chemically cross-linked carboxymethyl cellulose (CMC) has been developed, which demonstrates superior efficacy as anticancer drug-curcumin carrier. The cross-linked polymer has been prepared by grafting poly [2-(methacryloyloxy) ethyl trimethylammonium chloride] on CMC using diethylene glycol dimethacrylate cross-linker. The nanocomposite hydrogel has the capability to encapsulate both hydrophobic/hydrophilic transdermal drugs. With variation in reaction conditions/parameters, several composite materials have been synthesized and depending on lower swelling/higher cross-linking and greater gel strength, an optimized grade of nanocomposite hydrogel has been selected. The developed nanocomposite hydrogel is characterized with FTIR/NMR spectra, FESEM/XRD/TGA/AFM/XPS analyses, and UV–visible spectroscopy. Rheological study has been performed to enlighten the gel strength of the composite material. The synthesized nanocomposite hydrogel is biodegradable and nontoxic to mesenchymal stem cells (hMSCs). In vitro release of curcumin suggests that in situ incorporation of AgNWs on cross-linked CMC enhanced the penetration power of nanocomposite hydrogel and released the drug in sustained way (∼62% for curcumin released in 4 days). Ex vivo rat skin permeation study confirms that the drug from both the cross-linked and nanocomposite hydrogel was permeable through the rat skin in controlled fashion. Additionally the curcumin loaded composite hydrogel can efficiently kill the MG 63 cancer cells, which has been confirmed by apoptosis study and therefore, probably be a suitable carrier for curcumin delivery toward cancer cells