Evaluation of Plant-Based Silver Nanoparticles for Antioxidant Activity and Promising Wound-Healing Applications.

The current research focuses on the green synthesis of silver nanoparticles (AgNPs) using a polar extract of taro corms and the evaluation of its antioxidant properties and wound-healing applications. Taro corm extract (100 mL) was treated with a 5 mM AgNO3 solution (100 mL) at room temperature for the formation of AgNPs, and a color change was observed. The surface plasmon resonance (SPR) peaks in their UV-visible spectra appeared at a range of 438-445 nm. Fourier transform infrared, scanning electron microscopy, energy-dispersive X-ray, dynamic light scattering, and X-ray diffraction were used for the characterization of the taro corms extract-mediated AgNPs (TCE-AgNPs). The synthesized AgNPs were crystalline and spherical, with an average size of 244.9-272.2 nm with a polydispersity index of 0.530 and zeta potential of -18.8 mV, respectively. The antibacterial potential of TCE-AgNPs was tested, and the inhibition zones detected against Cronobacter sakazakii, Pseudomonas aeruginosa, Listeria monocytogenes, and Enterococcus faecalis were 28, 26, 18, and 13 mm, respectively. Furthermore, the antioxidant activity of TCE-AgNPs showed significant radical-scavenging activity compared to the standard used. Collagen content data collected from regenerated tissue and higher collagen content indicated rapid wound healing compared to others, which was seen in a group treated with TCE-AgNP film bandages.

Influence of Quercetin Pretreatment on Pharmacokinetics of Warfarin in Rats.

BACKGROUND: Warfarin (WAR) is an anticoagulant with a narrow therapeutic index and is principally metabolized by CYP3A4 and CYP2C9 enzymes. The inhibitors of these enzymes may alter the systemic exposure to WAR. Quercetin (QUE), a bioflavonoid, may modify the bioavailability of drugs used concurrently by inhibiting CYP3A4, CYP2C8, CYP2C9, CYP1A2, and Pglycoprotein (P-gp). OBJECTIVE: The current study scrutinized the influence of QUE on WAR pharmacokinetics in rats. METHOD: QUE was orally administered to animals for 14 consecutive days, followed by WAR as a single oral dose on the 15th day in the pre-treatment group. The co-administration group received a single dose of QUE and WAR concomitantly. Only carboxymethylcellulose (CMC) 0.5% was administered as a vehicle to control group. RESULTS: In the pre-treated group, WAR's Cmax was increased by 30.43%, AUC0-∞ by 62.94%, and t1/2 by 10.54%, while Cl decreased by 41.35%, relative to control. In co-administered animals, WAR's Cmax increased by 10.98%, AUC0-∞ by 20.20%, and t1/2 by 8.87%, while Cl declined by 16.40%. CONCLUSION: QUE alters the pharmacokinetics of WAR, warranting possibly WAR dose adjustment after confirmatory clinical investigations, specifically in patients with thrombotic disorders and a pre-treatment history of QUE or its product.

Design of Multilayered 2D Nanomaterial Composite Structures for EMI Shielding Analysis.

It is still very challenging to effectively design nanocomposite microstructures with significantly improved electromagnetic interference shielding effectiveness (EMI SE). Herein, we developed a facile method for fabrication of molybdenum disulfide/graphene nanoplatelets (MoS2/GNPs) nanocomposites, in which GNPs are utilized as highly effective electrical transport materials, while MoS2 resolves the agglomeration problem of GNPs. GNPs also serve as an efficient cluster of electrical transport systems and dampen the incoming electromagnetic wave. Two types of samples are synthesized and compared in context of EMI SE values: physically mixed composite and layered samples. The sandwiched MoS2 between GNP layers showed an EMI SE of ∼24 dB, which was an almost 14% improvement relative to MoS2/GNPs nanocomposites exhibiting an EMI SE value of ∼21 dB, both containing 0.5 wt % GNPs. This work provides a new strategy for the design of multifunctional nanocomposites using the simple low-cost vacuum filtration method for EMI shielding for future applications.

Formulation and characterization of orodispersible film containing diltiazem hydrochloride with taste masked effects.

Orodispersible film (ODF) is a better alternate to oral disintegrating tablets owing to its ease in application and subsequent patient compliance. This study investigates an improvement in physico-mechanical properties and palatability of Diltiazem Hydrochloride (DTZ) by formulating ODF employing solvent casting method. DTZ, used in the treatment of angina and hypertension, undergoes extensive presystemic metabolism and gives an incomplete bioavailability of 35-40%. DTZ also manifests a very bitter taste and after taste. DTZ was formulated into films using different polymer concentrations of Hydroxypropyl methylcellulose ethocel5 and Carboxymethyl cellulose and plasticizer levels of Propylene glycol and Glycerin to screen appropriate polymer-plasticizer combination. Optimized film disintegrated in 10.0±1.53 sec and appeared to be clear and smooth and almost 100% of the drug release was achieved within 4min from the ODF. Film revealed a good mechanical strength with folding endurance of >260, tensile strength of 1.36±0.11 N/mm2 and % elongation of 15.47±0.47%. FTIR and DSC showed compatibility between the drug and polymer. Film demonstrated a slightly sweet taste and after taste as well as an acceptability by the human volunteers. In conclusion DTZ was successfully formulated into film with improved physical properties and taste and could be beneficial to patients with cardiovascular disorders.

Solubility and dissolution rate enhancement of ibuprofen by cyclodextrin based carbonate nanosponges.

In the present study nanotechnology approach, i.e., a cyclodextrin (CD) based carbonate nanosponge was used to improve the solubility and dissolution of ibuprofen. Solvent and ultrasound assisted methods were used to prepare nanosponges using two CDs (ß-CD and 2-hydroxypropyl-ß-CD (2HP-ß-CD)) and a cross-linker (CL) diphenyl carbonate (DPC) in varying molar ratios. Nanosponges were investigated for their solubilizing efficiency and phase solubility studies. Structural analysis by Fourier transform infrared (FTIR) and powder X-ray diffraction (PXRD), thermo-analytical characterization by differential scanning calorimetry (DCS), morphology by scanning electron microscopy (SEM). In-vitro drug release followed by in-vivo analgesic and anti-inflammatory studies were performed. 2HP-ß-CD based nanosponges (molar ratio 0.01:0.04) prepared by ultrasound assisted method showed the highest solubilizing efficiency (i.e., 4.28 folds). Stability constant values showed that all complexes were stable. Inclusion complexes of drug was confirmed by PXRD and DSC. SEM images showed porous structures confirming the formation of cross-linked network. Particle size was in the range of 296.8±64 to 611.7±32nm. In-vitro release studies showed enhanced dissolution profile from nanosponge formulation (~94% from I11) as compared to the pure drug (~45% Ibuprofen) in 120min. Significant (p<0.05) extent of pain inhibition and anti-inflammatory activity was observed for nanosponge formulation when compared with the pure drug. CD based carbonate nanosponges with better solubility, enhanced release profile, improved analgesic and anti-inflammatory activity were successfully formulated for ibuprofen.

Formulation and Evaluation of a Clove Oil-Encapsulated Nanofiber Formulation for Effective Wound-Healing.

Wound-healing is complicated process that is affected by many factors, especially bacterial infiltration at the site and not only the need for the regeneration of damaged tissues but also the requirement for antibacterial, anti-inflammatory, and analgesic activity at the injured site. The objective of the present study was to develop and evaluate the natural essential oil-containing nanofiber (NF) mat with enhanced antibacterial activity, regenerative, non-cytotoxic, and wound-healing potential. Clove essential oil (CEO) encapsulated in chitosan and poly-ethylene oxide (PEO) polymers to form NFs and their morphology was analyzed using scanning electron microscopy (SEM) that confirmed the finest NFs prepared with a diameter of 154 ± 35 nm. The successful incorporation of CEO was characterized by Fourier transform infra-red spectroscopy (FTIR) and X-ray diffractometry (XRD). The 87.6 ± 13.1% encapsulation efficiency and 8.9 ± 0.98% loading of CEO was observed. A total of 79% release of CEO was observed in acidic pH 5.5 with 117% high degree of swelling. The prepared NF mat showed good antibacterial activity against Staphylococcus aureus and Escherichia coli and non-cytotoxic behavior against human fibroblast cell lines and showed good wound-healing potential.

Amelioration of physicochemical, pharmaceutical, and pharmacokinetic properties of lornoxicam by cocrystallization with a novel coformer.

OBJECTIVE: The present study was aimed to prepare and characterize new cocrystals of lornoxicam (LORX), a BCS class II drug employing 1,3-dimethyl urea (DMU) as a coformer to improve physicochemical, pharmaceutical, and pharmacokinetic performance. METHODS: A screening study was conducted by employing three techniques viz. neat grinding, liquid-assisted grinding (LAG), and solvent evaporation (SE) using different drug-coformer molar ratios (1:1, 1:2, and 1:3). Samples were characterized by DSC, PXRD, ATR-FTIR, SEM, intrinsic dissolution rate (IDR) studies, compressional studies, and pharmacokinetic studies. In vitro dissolution and stability studies (25 °C/60%RH and 40 °C/75%RH for three months) were carried out for cocrystal tablets. RESULTS: LAG and SE were found successful in ratio 1:3 and IDR showed approximately 28- and 19-fold increase, respectively in 0.1 N HCl (pH 1.2) and buffer (pH 7.4) as compared to pure LORX. The cocrystal exhibited good tabletability and was ∼2.5 times that of LORX at 6000 Psi. Dissolution profiles of tablets of cocrystal increased (56% and 100% at pH 1.2 and 7.4, respectively in contrast to those of physical mixture (PhyMix) (∼35% and ∼10%) and pure LORX (∼17% and ∼7%) within 60 min. The Cmax and AUC0-∞ for the selected cocrystal were significantly increased (p < 0.05) which was 2.4 and 2.5 times, respectively, that of LORX in a single dose oral pharmacokinetic study executed in rabbits. Tablets of cocrystal were found stable at both conditions. CONCLUSION: The study indicates that cocrystallization with DMU can concomitantly improve tabletability, dissolution rate, and in vivo performance of dissolution limited drug LORX.

Physicomechanical, stability, and pharmacokinetic evaluation of aceclofenac dimethyl urea cocrystals.

Poor physicomechanical properties and limited aqueous solubility restrict the bioavailability of aceclofenac when given orally. To improve its above properties, aceclofenac (ACE) was cocrystallized with dimethyl urea (DMU) in 1:2 molar ratio by dry and solvent assisted grinding. The cocrystals were characterized by ATR-FTIR, DSC, and PXRD, and their surface morphology was studied by SEM. There was enhancement in intrinsic dissolution rate (IDR) (~eight- and ~fivefold in cocrystals prepared by solvent assisted grinding (SAG) and solid state grinding (SSG), respectively, in 0.1 N HCl, pH 1.2) and similarly (~3.42-fold and ~1.20-fold in phosphate buffer, pH 7.4) as compared to pure drug. Additionally, mechanical properties were assessed by tabletability curves. The tensile strength of ACE was < 1 MPa in contrast to the cocrystal tensile strength (3.5 MPa) which was ~1.98 times higher at 6000 psi. The tablet formulation of cocrystal by direct compression displayed enhanced dissolution profile (~36% in 0.1 N HCl, pH 1.2, and ~100% in phosphate buffer, pH 7.4) in comparison to physical mixture (~ 30% and ~ 80%) and ACE (~18% and ~50%) after 60 min, respectively. Stability studies of cocrystal tablets for 3 months indicated a stable formulation. Pharmacokinetic studies were performed by using rabbit model. The AUC0-∞ (37.87±1.3 µgh/ml) and Cmax (6.94±2.94 µg/ml) of the selected cocrystal C1 prepared by SAG were significantly enhanced (p < 0.05) and were ~3.43 and ~1.63-fold higher than that of ACE. In conclusion, new cocrystal of ACE-DMU was successfully prepared with improved tabletability, in vitro and in vivo properties.

Simultaneously Improving Mechanical, Formulation, and In Vivo Performance of Naproxen by Co-Crystallization.

Naproxen (NAP), an anti-inflammatory drug belonging to class II of Biopharmaceutic Classification System, has low aqueous solubility and dissolution rate which limit its oral bioavailability. The focus of this investigation was to assess the impact of co-crystallization in improving the physico-mechanical and in vivo performance of NAP. NAP was co-crystallized using nicotinamide as a co-former employing liquid-assisted grinding method and characterized by intrinsic dissolution rate, DSC, and PXRD. Prepared co-crystal exhibited improved physicochemical and mechanical properties. Mechanical behavior of NAP and developed co-crystal was analyzed by drawing tabletability curves. Over the entire range of used compaction pressure, NAP showed poor tensile strength (< 2 MPa) which resulted in lamination and capping in some tablets. In contrast, tensile strength of co-crystal gradually increased with pressure and was ~ 1.80 times that of NAP at 5000 psi. Intrinsic dissolution profile of co-crystal showed a more than five and twofold faster dissolution than NAP in 0.1 M HCl and phosphate buffer pH 7.4 at 37°C. In addition, formulation of co-crystal powder into tablets by direct compression demonstrated enhanced dissolution profiles (~ 43% in 0.1 M HCl and ~ 92% in phosphate buffer pH 7.4) in comparison to a marketed product, Neoprox (~ 25 and ~ 80%) after 60 min. In a single dose oral exposure study conducted in sheep, co-crystal showed more than 1.5-fold increase in AUC and Cmax. In conclusion, co-crystals of NAP illustrated better tabletability, in vitro and in vivo performance.

Development of paracetamol-caffeine co-crystals to improve compressional, formulation and in vivo performance.

Paracetamol, a frequently used antipyretic and analgesic drug, has poor compression moldability owing to its low plasticity. In this study, new co-crystals of paracetamol (PCM) with caffeine (as a co-former) were prepared and delineated. Co-crystals exhibited improved compaction and mechanical behavior. A screening study was performed by utilizing a number of methods namely dry grinding, liquid assisted grinding (LAG), solvent evaporation (SE), and anti-solvent addition using various weight ratios of starting materials. LAG and SE were found successful in the screening study. Powders at 1:1 and 2:1 weight ratio of PCM/CAF by LAG and SE, respectively, resulted in the formation of co-crystals. Samples were characterized by PXRD, DSC, and ATR-FTIR techniques. Compressional properties of PCM and developed co-crystals were analyzed by in-die heckle model. Mean yield pressure (Py), an inverse measure of plasticity, obtained from the heckle plots decreased significantly (p < .05) for co-crystals than pure drug. Intrinsic dissolution profile of co-crystals showed up to 2.84-fold faster dissolution than PCM and physical mixtures in phosphate buffer pH 6.8 at 37 °C. In addition, co-crystals formulated into tablets by direct compression method showed better mechanical properties like hardness and tensile strength. In vitro dissolution studies on tablets also showed enhanced dissolution profiles (∼90-97%) in comparison to the tablets of PCM prepared by direct compression (∼55%) and wet granulation (∼85%) methods. In a single dose sheep model study, co-crystals showed up to twofold increase in AUC and Cmax. A significant (p < .05) decrease in clearance as compared to pure drug was also recorded. In conclusion, new co-crystals of PCM were successfully prepared with improved tabletability in vitro and in vivo profile. Enhancement in AUC and Cmax of PCM by co-crystallization might suggest the dose reduction and avoidance of side effects.