Blank Formulation Research Articles

Effects of New Btk-Based Formulations BLB1 and Lip on Aquatic Non-Target Organisms.

Integrated pest management based on the use of biopesticides is largely applied. Experimental bioassays are critical to assess biopesticide biosafety at the ecotoxicological level. In this study, we investigated the effects of the new Bacillus thuringiensis subsp. kurstaki (Btk)-formulated-based biopesticides BLB1 and Lip, efficiently tested in field assays (IPM-4-CITRUS EC project no. 734921) on two aquatic non-target organisms, precisely the water flea Daphnia magna and the bioluminescent bacteria Aliivibrio fischeri. Acute toxicity studies, carried out in a comparative manner with Delfin® as the reference bioproduct and the lactose-based Blank formulation, show that no significant toxicity was observed up to 1 g/L. Our results indicated that BLB1- and Lip-formulated new bioproducts are far less toxic than the Delfin® reference bioproduct.

Benefits of combining supersaturating and solubilizing formulations – Is two better than one?

A variety of enabling formulations has been developed to address poor oral drug absorption caused by insufficient dissolution in the gastrointestinal tract. As the in vivo performance of these formulations is a result of a complex interplay between dissolution, digestion and permeation, development of suitable in vitro assays that captures these phenomena are called for. The enabling-absorption (ENA) device, consisting of a donor and receiver chamber separated by a semipermeable membrane, has successfully been used to study the performance of lipid-based formulations. In this work, the ENA device was prepared with two different setups (a Caco-2 cell monolayer and an artificial lipid membrane) to study the performance of a lipid-based formulation (LBF), an amorphous solid dispersion (ASD) and the potential benefit of combining the two formulation strategies. An in vivo pharmacokinetic study in rats was performed to evaluate the in vitro-in vivo correlation. In the ENA, high drug concentrations in the donor chamber did not translate to a high mass transfer, which was particularly evident for the ASD as compared to the LBF. The solubility of the polymer used in the ASD was strongly affected by pH-shifts in vitro, and the ph_dependence resulted in poor in vivo performance of the formulation. The dissolution was however increased in vitro when the ASD was combined with a blank lipid-based formulation. This beneficial effect was also observed in vivo, where the drug exposure of the ASD increased significantly when the ASD was co-administered with the blank LBF. To conclude, the in vitro model managed to capture solubility limitations and strategies to overcome these for one of the formulations studied. The correlation between the in vivo exposure of the drug exposure and AUC in the ENA was good for the non pH-sensitive formulations. The deconvoluted pharmacokinetic data indicated that the receiver chamber was a better predictor for the in vivo performance of the drug, however both chambers provided valuable insights to the observed outcome in vivo. This shows that the advanced in vitro setting used herein successfully could explain absorption differences of highly complex formulations.

Nintedanib and miR-29b co-loaded lipoplexes in idiopathic pulmonary fibrosis: formulation, characterization, and in vitro evaluation

Objective This study was aimed to develop a cationic lipoplex formulation loaded with Nintedanib and miR-29b (LP-NIN-miR) as an alternative approach in the combination therapy of idiopathic pulmonary dibrosis (IPF) by proving its additive anti-fibrotic therapeutic effects through in vitro lung fibrosis model. Significance This is the first research article reported that the LP-NIN-MIR formulations in the treatment of IPF. Methods To optimize cationic liposomes (LPs), quality by design (QbD) approach was carried out. Optimized blank LP formulation was prepared with DOTAP, CHOL, DOPE, and DSPE-mPEG 2000 at the molar ratio of 10:10:1:1. Nintedanib loaded LP (LPs-NIN) were produced by microfluidization method and were incubated with miR-29b at room temperature for 30 min to obtain LP-NIN-miR. To evaluate the cellular uptake of LP-NIN-miR, NIH/3T3 cells were treated with 20 ng.mL-1 transforming growth factor-β1 (TGF-β1) for 96 h to establish the in vitro IPF model and incubated with LP-NIN-miR for 48 h. Results The hydrodynamic diameter, polydispersity index (PDI), and zeta potential of the LP-NIN-miR were 87.3 ± 0.9 nm, 0.184 ± 0.003, and +24 ± 1 mV, respectively. The encapsulation efficiencies of Nintedanib and miR-29b were 99.8% ± 0.08% and 99.7% ± 1.2%, respectively. The results of the cytotoxicity study conducted with NIH/3T3 cells indicated that LP-NIN-miR is a safe delivery system. Conclusions The outcome of the transfection study proved the additive anti-fibrotic therapeutic effect of LP-NIN-miR and suggested that lipoplexes are effective delivery systems for drug and nucleic acid to the NIH/3T3 cells in the treatment of IPF.

Development of emulgel formulation from Markhamia tomentosa leaf extract: Characterization and in vitro antimicrobial activity against skin isolates

Objectives: Skin infections are mild to severe infections often treated with antimicrobial agents. There is an increase in resistance to antimicrobial agents necessitating the search for new medicines. This study developed an emulgel formulation of Markhamia tomentosa leaf extract and evaluated its antimicrobial activity against skin isolates. Materials and Methods: A successive extraction of M. tomentosa leaves in five solvents – n-hexane, dichloromethane, ethyl acetate, ethanol, and distilled water was carried out. The activity of the extracts against skin isolates of Staphylococcus aureus, Staphylococcus epidermidis, and Bacillus subtilis was carried out. The distilled water extract was formulated into emulgel, characterized, and evaluated for antimicrobial activity. Results: The n-hexane and dichloromethane extracts of M. tomentosa were inactive against all organisms at concentrations used. The ethanol extract was active against S. aureus and S. epidermidis at 200 mg/mL. The ethyl acetate and distilled water extracts were active against S. epidermidis and B. subtilis at 100 and 50 mg/mL, respectively. All emulgel formulations of distilled water extract of M. tomentosa leaves were brown, smooth, and easy to spread on the skin and had a pH of 4.73–5.55. The formulation containing the distilled water extract was more viscous (7784cP) than the blank formulation (6328cP). The formulation was active against S. epidermidis. Conclusion: The distilled water extract of M. tomentosa leaves was the most active against S. epidermidis and B. subtilis. Its emulgel formulation had desirable physicochemical properties for application to the skin. Further studies can be carried out toward its development for the treatment of skin infection caused by organisms investigated.

Oral fast dissolving films for co-administration of breviscapine and matrine: Formulation optimization and in vitro characterization

Oral fast dissolving films (OFDFs) are popular dosage forms for enhanced oral absorption of active ingredients without experiencing gastrointestinal interference or first-pass metabolism. The primary challenge in OFDF design is balancing drug loading capacity with film properties, particularly for poorly soluble drugs. In the present work, an OFDF formulation containing co-amorphous mixture was successfully designed for co-administration of two natural products at a drug content of 14%. Breviscapine and matrine are commonly used for cardiovascular and cerebrovascular related diseases, but their clinical application was limited by low bioavailability, short biological half-life, and instability problems. Their co-administration as a compound remedy requires a novel product too enhance drug dissolution and patient compliance. A 33 Box-Behnken design was used to generate OFDF preparations by solvent casting method. The optimized blank film formulation, comprising 57.40% HPMC E50, 14.01% PEG 400 and 5.35% L-HPC, demonstrated a rapid disintegration in 18 s. XRD and FTIR analysis on drug-loaded films revealed good compatibility of drugs and polymers, and amorphous state of films with co-precipitates. The films were evaluated for morphology, folding endurance, disintegration time and in vitro BRE dissolution. Drugs incorporation extended the disintegration time of blank films, yet remained under 30 s. The co-amorphous mixture of BRE and MAT in films exhibited a faster BRE dissolution rate compared to the physical mixture. In conclusion, a compound OFDF formulation featuring a co-amorphous mixture of BRE and MAT offers an efficient strategy for hydrophobic drug delivery at high dose.

Integration of an LPAR1 Antagonist into Liposomes Enhances Their Internalization and Tumor Accumulation in an Animal Model of Human Metastatic Breast Cancer.

Lysophosphatidic acid receptor 1 (LPAR1) is elevated in breast cancer. The deregulation of LPAR1, including the function and level of expression, is linked to cancer initiation, progression, and metastasis. LPAR1 antagonists, AM095 or Ki16425, may be effective therapeutic molecules, yet their limited water solubility hinders in vivo delivery. In this study, we report on the synthesis of two liposomal formulations incorporating AM095 or Ki16425, embedded within the lipid bilayer, as targeted nanocarriers for metastatic breast cancer (MBC). The data show that the Ki16425 liposomal formulation exhibited a 50% increase in internalization by MBC mouse epithelial cells (4T1) and a 100% increase in tumor accumulation in a mouse model of MBC compared with that of a blank liposomal formulation (control). At the same time, normal mouse epithelial cells (EpH-4Ev) internalized the Ki16425 liposomal formulation 25% lesser than the control formulation. Molecular dynamics simulations show that the integration of AM095 or Ki16425 modified the physical and mechanical properties of the lipid bilayer, making it more flexible in these liposomal formulations compared with liposomes without drug. The incorporation of an LPAR1 antagonist within a liposomal drug delivery system represents a viable therapeutic approach for targeting the LPA-LPAR1 axis, which may hinder the progression of MBC.

The effect of Al/oxidizers interfacial structure on the mechanical properties of composite propellants

In this paper, the mechanical properties of a typical four-component composite solid propellants with various designed Al/oxidizer interfaces have been studied. The Al/oxidizer interfacial control is mainly realized by using the core-shell composites AP@Al and Al@RDX with different particle sizes, where Al powder was coated with a thin layer of polydopamine (PDA) as the binding sites, so that the oxidizers could crystalize on it during a rapid spray granulation process. The stress-strain curves of the above propellants at different temperatures and different tensile rates have been obtained. The dependence of the loss factor on temperature was studied by using a dynamic thermomechanical analysis (DMA). It has been shown that the fracture elongation of the interfacial modified propellants can reach 51.81% at room temperature, which is 127.3% higher than that of the blank formulation under the same formulation. Moreover, the temperature and strain rate sensitivity of interfacial controlled HTPB propellants is much less than that of traditional ones. The microstructure of these propellants at the crack sites was investigated by scanning electron microscopy (SEM) supported with micro-area in-situ tensile CT scanning technology, to clarify their damage and failure mechanisms.

Antioxidant and Antiangiogenic Effect of Homoleptic Palladium (II) Carboxamide Complex Loaded Chitosan Modified PLGA Nanoparticles: In vitro Evaluation and In vivo Chick Embryo Chorioallantoic Membrane (CAM) Assay

Background: Angiogenesis is a natural and complex mechanism that is regulated by biomolecules formed by the body. Medicinal inorganic chemistry is increasing in popularity due to metal-based compounds, offering significant chances and possibilities for building novel anti-cancer medicines with promising anti-angiogenic effects. Objective: This study aimed to examine the successful results obtained from treatments with nanoparticle formulations of active drug substances. Methods: The nanoprecipitation/solvent displacement approach, with some changes, was used to make PLGA-based NPs. Results: The particle size obtained in the blank formulation was 82.4–473.9 nm, while the particle size in the API-loaded NPs was 193.2–678.0 nm. Among the formulations, NP-950-P, NP-390-P, and NP-350-CSP2 were found to have significant antioxidant potentials with IC50 values of 3.025, 5.198, and 7.4242 µg.mL-1, respectively, when compared to Vit C. According to the microscopic evaluations, NP-950-P (including Pd(PyCrbx)2Cl2 as 50 µg.pellet-1) and NP-950-CSP2 (including Pd(PyCrbx)2Cl2 as 50 µg.pellet-1) showed strong anti-angiogenic effect whereas the other NP formulations showed weak anti-angiogenic effect when compared with the positive control (±)-Thalidomide at the concentration of 50 µg.pellet-1. Conclusion: When the results were examined, it was found that nanoscale drug carrier systems were prepared, and high antioxidant activity and anti-angiogenesis activity were detected, especially in nanoparticles prepared with 950. As per our knowledge, it is the first study in this field that will bring a new perspective to cancer treatment.

Escinosome thermosensitive gel optimizes efficacy of CAI-CORM in a rat model of rheumatoid arthritis.

Rheumatoid arthritis is among the most common disabling diseases associated with chronic inflammation. The efficacy of the current therapeutic strategies is limited; therefore, new pharmacological agents and formulation approaches are urgently needed. In this work, we developed a thermosensitive gel incorporating escinosomes, innovative nanovesicles made of escin, stabilized with 10% of tween 20 and loaded with a Carbonic Anhydrase Inhibitor (CAI) bearing a Carbon Monoxide Releasing Moiety (CORM) (i.e., CAI-CORM 1), previously synthesized by some of the authors as a new potent pain-relieving agent. The light scattering analysis of the developed formulation showed optimal physical parameters, while the chromatographic analysis allowed the quantification of the encapsulation efficiency (90.1 ± 5.91 and 91.6 ± 8.46 for CAI-CORM 1 and escin, respectively). The thermosensitive gel, formulated using 23% w/v of poloxamer 407, had a sol-gel transition time of 40 s and good syringeability. Its stability in simulated synovial fluid (SSF) was morphologically evaluated by electron microscopy. Nanovesicles were physically stable in contact with the medium for two weeks, maintaining their original dimensions and spherical shape. The viscosity increased by about 30- to 100-fold with the temperature change from 25 °C to 37 °C. The gel erosion in SSF occurred within 9 h (88.2 ± 0.743%), and the drug's passive diffusion from escinosomes lasted 72 h, allowing a potential sustained therapeutic effect. The efficacy of a single intra-articular injection of the gel containing escinosomes loaded with CAI-CORM 1 (3 mg/mL; 30 μL, CAI-CORM 1 formulation) and the gel containing unloaded escinosomes (30 μL, blank formulation) was evaluated in a rat model of Complete Freund's Adjuvant (CFA)-induced rheumatoid arthritis. CAI-CORM 1 formulation was assessed to counteract mechanical hyperalgesia, spontaneous pain, and motor impairments on days 7 and 14 after treatment. The histological evaluation of the joints stressed the improvement of several morphological parameters in CFA + CAI-CORM 1 formulation-treated rats. In conclusion, the hybrid molecule CAI-CORM 1 formulated in escinosome-based thermosensitive gel could represent a new valid approach for managing rheumatoid arthritis.

Investigating Key Molecular Descriptors Affecting Particle Size: A Predictive Exemplary Approach for Self-Emulsifying System.

The self-nano/microemulsifying drug delivery system is one of the well-established techniques for enhancing the solubility of poorly water-soluble drug molecules. The ratio of oil:surfactant:cosolvent plays a key role in globule size on dispersion into water, but there is very limited information on how a drug molecule affects the size. The rationale of this project was to illustrate the correlation between the particle size of nanoemulsion droplets and molecular descriptors of a drug. In the study, a self-nanoemulsifying preconcentrate containing drug with medium chain triglycerides (oil), dimethylacetamide (DMA, cosolvent), and Kolliphor EL (surfactant) was prepared for 40 drug molecules with diverse physicochemical properties. The self-nanoemulsifying preconcentrate was dispersed in water, and dynamic light scattering particle size was analyzed. A majority of drugs showed a significant increase in globule size compared to blank formulation, while few drugs showed a stark reduction in globule size. It is interesting to understand the attributes of molecules driving the self-emulsification and the diameter of nanoglobules. A systematic correlation of resultant particle size with 1D, 2D, and 3D molecular descriptors (overall more than 700 descriptors) was carried out for the data set using the PaDEL tool kit. The data compilation, curation, and analysis were performed using the SIMCA14 software. In the process of molecular descriptors screening, thereafter curation, 50 descriptors were selected using the genetic algorithm screening. The PLS-DA statistical method was employed for conversion of data into binomial systems. Final group of 5 descriptors: SpMiSpMin2_Bhe, RNCS, TDB9i, JG17, and ETA_Shape showed the correlation with particle size and classifying the drug molecules facilitating increase or decrease in particle size.

Ultrasonic Extraction of Phenolic Compounds from Eggplant Peel and Formulation of Eggplant Peel Extract-Enriched Ice-Cream

In this study, ultrasound-assisted extraction (UAE) was used for the extraction of bioactive compounds from eggplant peels (EPP) and conditions were optimized by using response surface methodology (RSM). Methanol concentrations (60%, 70%, and 80%), time (30 min, 45 min, and 60 min), and temperature (30°C, 45°C, and 60°C) were selected as independent extraction parameters, whereas total anthocyanin content (TAC), DPPH inhibition, and total phenolic content (TPC) were response variables. The optimal extraction was at 45°C for 45 min of extraction time with 70% solvent which corresponded to TAC, TPC, and DPPH inhibition values of 7.94 mg/g, 7.03 mg GAE/g, and 94.8%, respectively. The optimized EPP extract was chemically characterized by a Fourier-transform infrared spectrometer (FTIR), high-performance liquid chromatography (HPLC), and a gas chromatography mass spectrometer (GCMS). The optimized extract was further evaluated for antioxidant and anticancer potential. For antioxidant and anticancer potential, the corresponding IC50 values of the EPP extract were 243.2 μg/ml and 1.52–1.99 mg/ml, respectively. Furthermore, the EPP extract significantly inhibited the migratory ability of cancer cells in a dose-dependent manner. Major components identified in the EPP extract were chlorogenic acid (261.76 mg/kg), benzoic acid (184.41 mg/kg), syringic acid (78.48 mg/kg), p-coumaric acid (49.59 mg/kg), cinnamic acid (32.17 mg/kg), quercetin (5.24 mg/kg), sinapic acid (5.14 mg/kg), and gallic acid (4.34 mg/kg). The EPP extract-enriched ice-cream showed high antioxidant potential and consumer acceptability than the blank ice-cream formulation. The EPP extract, due to its antioxidant and anticancer potential, can be used in the formulation of functional food products.

Xylityl Sesquicaprylate Efficacy as an Antiseptic Ingredient for Oral Care Products (Mouthwash): An In Vitro Screening Investigation against Eight Microorganisms.

For dental caries and periodontal diseases initiated by dental plaque (as bacterial communities) and to inhibit the growth of oral pathogenic bacteria, oral care products containing antiseptic active ingredients are highly recommended, nonetheless, side effects of such actives are a concern (teeth discoloration/staining and taste perception, for example). In this context, we challenged xylityl sesquicaprylate, an antiseptic compound from natural resources, as an active ingredient to be used in an alcohol-free mouthwash formulation. The xylityl sesquicaprylate sample was compared to a respective blank mouthwash formulation and one containing triclosan. The in vitro efficacy was screened by the time-kill assay against eight microorganisms. The xylityl sesquicaprylate-containing mouthwash (0.45% w/w) presented a particularly interesting profile of efficacy against Actinomyces viscosus, Fusobacterium nucleatum, Porphyromonas gingivalis, and Tannerella forsythia, with results of greater magnitude to reduce the log10 of those microorganisms in comparison with the triclosan sample.

Development and Evaluation of an Antimicrobial Formulation Containing Rosmarinus officinalis.

Rosmarinus officinalis belongs to the Lamiaceae family, and its constituents show antioxidant, anti-inflammatory, antidepressant, antinociceptive, and antibacterial properties. The aim of this study was to develop a topical formulation with R. officinalis extract that had antimicrobial and antioxidant activity. Maceration, infusion, Soxhlet, and ultrasound were used to produce rosemary extracts, which were submitted to antioxidant, compound quantification, cell viability, and antimicrobial assays. Infusion and Soxhlet showed better results in the DPPH assay. During compound quantification, infusion showed promising metabolite extraction in phenolic compounds and tannins, although maceration was able to extract more flavonoids. The infusion and ultrasound extracts affected more strains of skin bacteria in the disk diffusion assays. In the minimum inhibitory concentration assay, the infusion extract showed results against S. aureus, S. oralis, and P. aeruginosa, while ultrasound showed effects against those three bacteria and E. coli. The infusion extract was chosen to be incorporated into a green emulsion. The infusion extract promoted lower spreadability and appropriated the texture, and the blank formulation showed high levels of acceptance among the volunteers. According to the results, the rosemary extract showed promising antioxidant and antimicrobial activity, and the developed formulations containing this extract were stable for over 90 days and had acceptable characteristics, suggesting its potential use as a phytocosmetic. This paper reports the first attempt to produce an oil-in-water emulsion using only natural excipients and rosemary extract, which is a promising novelty, as similar products cannot be found on the market or in the scientific literature.

Therapeutic Efficacy of Carvacrol-Loaded Nanoemulsion in a Mouse Model of Schistosomiasis.

Since praziquantel is the only drug available to treat schistosomiasis, a neglected parasitic disease that affects more than 240 million people worldwide, there is an urgent demand for new antischistosomal agents. Natural compound-loaded nanoparticles have recently emerged as a promising alternative for the treatment of schistosomiasis. Carvacrol is an antimicrobial monoterpene present in the essential oil extracted from several plants, especially oregano (Origanum vulgare). In this study, a carvacrol nanoemulsion (CVNE) was prepared, characterized, and administered orally (200 mg/kg) in a mouse infected with either immature (prepatent infection) or adult (patent infection) Schistosoma mansoni. For comparison, data obtained with an unloaded nanoemulsion (blank formulation), free carvacrol, and the drug of reference praziquantel are also presented. CVNE was more effective than free carvacrol in reducing the worm burden and egg production in both patent and prepatent infections. Favorably, CVNE had a high effect in terms of reducing the number of worms and eggs (85%–90%) compared with praziquantel (∼30%) in prepatent infection. In tandem, carvacrol-loaded nanoemulsion markedly improved antischistosomal activity, showing efficiency in reducing worm and egg burden, and thus it may be a promising delivery system for the treatment of schistosomiasis.

Formulation and Evaluation of Topical Linezolid Nanoemulsion for Open Incision Wound in Diabetic Animal Model.

The present study aimed to investigate the role of topical nanoemulsion of linezolid in attenuating diabetic wound by delivering the drug to the target tissue. The nanoemulsions (NEs) were prepared by high-pressure homogenization and subjected to thermodynamic stability, pH, droplet size, viscosity, surface charge, polydispersity index (PDI), entrapment efficiency, drug content, and in vitro drug release. All formulations were thermodynamically stable. The pH was in the range of 5 to 6. The viscosities of LZD-0, LZD-1, LZD-2, and LZD-3 were recorded as 68.75 ± 2.23 mPas, 69.56 ± 2.11 mPas, 96.45 ± 3.39 mPas, and 45.5 ± 1.12 mPas respectively. LZD-1 exhibited droplet size of 376.5 nm ± 0.98, surface charge - 22.5mV, and PDI 0.387. Drug content and entrapment efficiency of LZD-1 were found to be 93 ± 3.31 % and 72 ± 1.67 %, respectively. LZD-1 released 80 ± 2.87% of drug. Due to significant (P < 0.05) in vitro results, LZD-1 formulation was selected for in vivo evaluation. Diabetes was induced in Sprague-Dawley rats using intraperitoneal streptozotocin injection at dose of 50 mg/kg. Open-incision wounds were inflicted among all diabetic rats at dorsal shaved area. Randomly, all rats were divided into positive control (blank formulation), negative control (no formulation), and test group (LZD-1). Wound healing occurred in order of test group > positive control > negative control. Skin histology and tensile strength also revealed significant results. The study concluded that topical nanoemulsion of linezolid may open new horizon in treating diabetic wounds.

New Gd(I)/Cs(III) complexes of benzil‐based thiocarbohydrazone macrocyclic ligand: Chemical synthesis, characterization, and study their biological effectiveness as antibacterial, antioxidant, and antiviral additives for polyurethane surface coating

AbstractGerms are transmitted in different ways and remain viable or infectious on metal, glass, wood, fabrics, and plastic surfaces for prolonged periods of time. Thus, sterilizing commonly handled everyday objects and public places with high contamination potential is a major global strategy to combat the spread of pathogenic microorganisms. Consequently, our response is development of durable surface‐active coating embedded with new Gd(I)/Cs(III) complexes that derived from condensation of thiocarbohydrazide and benzil precursors. Chemical structures of these complexes were elucidated by Fourier transform infrared (FTIR), electron impact ionization (EI‐MS), 1H nuclear magnetic resonance (NMR), elemental analysis, and scanning electron microscopy (SEM). Next, the well‐established complexes were physically mixed with wide‐range applicable polyurethane (PU) varnish as potential biocide agents. With laboratory scale, coating material was loaded into stainless steel and wood panels to evaluate the physical and mechanical properties. In comparison with the blank formulation, our additives enhanced the gloss levels of the developed PU from 75 to 80 gloss unit (GU), and the scratch hardness was increased to reach &gt;2 kg. Meanwhile, all the coated films passed the flexibility bend test and showed none flaking in mechanical adhesion test. Consequently, Gd(I) and Cs(III) metal complexes did not show any undesirable side effects on PU coating performance. Concerning biological screening, macrocyclic Gd(I) and Cs(III) complexes as well as the reformulated PU varnish were assayed for their antibacterial, antioxidant, and antiviral activities. Antibacterial activity of the developed PU was slightly increased than the individual treatments of Gd(I)/Cs(III) complexes by 1–2 mm, although the blank PU showed no obvious activity against all the tested bacterial strains. Antiviral overall results indicated that the Gd(I) and Cs(III) complexes demonstrated higher activity than the developed PU samples against ADeno‐7, CV‐B4, and HSV‐1 viruses in all modes of action, and hence these coordinated compounds could be promising virucidal agents with good biocompatibility.

Formulation, Development and Characterization of Sustained Release Formulation of Herbal Extracts

Aim: The aim of the present investigation is to design of sustained release dosage form of different extracts that will help in releasing only small quantities of drug over a prolonged period of time. Material and Methods: The different ingredients for formulations are given as in Table 1 below. The measured quantities of drug, HPMC, MCC and NaHCO3 were mixed thoroughly using a mortar and pistil. The granules were punched into tablets using direct compression technique. The blank formulation (or) placebo (HPMC+ MCC+NaHCO3) and polyherbal formulation were also tested using FTIR Spectrometer. The release rate kinetics of the formulations was analyzed and the data obtained were fitted into Zero order, First order, Higuchi model and Kozmeyer Peppas model. Results: The pre-formulation study results obtained on various parameters on granules were found satisfactory. The granules obtained for the batches (F1-F12) were satisfactory. No rat holing, capping or sticking was observed during the flow of granules from the hopper. The maximum weight variation of the tablets was±1.8%, which falls within the acceptable range of±5%, hence the tablets passed the weight variation test. Hardness for tablets of all batches was in the range of 4.92 to 5.35 kg/cm², which falls above the limit of not less than 3.0 kg/cm². The floating lag time ranged from 35 s to 50 s. From the Table 5, it was found that the formulation F11 has the minimum floating lag time of 35 s and maximum total floating time of 15 h with 100.12% drug content. Conclusion: The effect of ingredients in the polyherbal tablet was analyzed, where HPMC contributed as the floating matrix, MCC to increase the bulk density of the tablet and sodium bicarbonate to initiate the dissolution process.

Development of Eudragit® Nanoparticles for Intranasal Drug Delivery: Preliminary Technological and Toxicological Evaluation

Intranasal administration has assumed in the last years an increasing value as an alternative strategy for the systemic adsorption of drugs, as an alternative to oral and parenteral routes thanks to the high vascularized nasal mucosa. Nevertheless, different drug features may restrict its absorption through the nasal mucosa with an insufficient diffusion to the systemic circulation. Several technological strategies are under investigation to improve drug absorption during nasal formulation design and production. The use of bioadhesive polymers can be considered a valid approach to pursue the aforementioned goal. Based on this consideration, Eudragit® Retard RS100 and RL100 resins were selected as positively charged copolymers to prepare polymeric NPs with potential mucoadhesive properties suitable for intranasal application. NPs were produced by the Quasi-emulsion Solvent Evaporation (QESD) method and loaded with diclofenac acid (DIC) or its epolamine salt (DIEP). Preliminary investigations were performed to obtain the optimized blank formulation and drugs loaded NPs evaluating different parameters that can affect particles size and polydispersity. The optimized formulations unloaded and loaded with DIC and DIEP were further evaluated for their thermotropic behavior by differential scanning calorimetry. Mucoadhesive evaluation was assessed by measuring variation in zeta potential and by turbidimetric assay after incubation of particles with mucin in simulated nasal fluid (SNF) at 37 °C at different time points (0, 1 and 24 h) compared to the pure suspensions. Stability of DIC and DIEP loaded NPs was also evaluated in SNF to predict potential aggregation phenomena after nasal administration. Finally, in vivo experiments showed absence of toxicity on the nasal mucosa of mice.

Effects of cis-Jasmone Treatment of Brassicas on Interactions With Myzus persicae Aphids and Their Parasitoid Diaeretiella rapae.

There is a need to develop new ways of protecting plants against aphid attack. Here, we investigated the effect of a plant defence activator, cis-jasmone (CJ), in a range of cultivars of Brassica napus, Brassica rapa and Brassica oleracea. Plants were sprayed with cis-jasmone or blank formulation and then tested with peach potato aphids (Myzus persicae Sulzer) (Hemiptera: Aphididae) and their parasitoid Diaeretiella rapae (M'Intosh) (Hymenoptera: Braconidae). CJ treated plants had significantly lower aphid settlement than control plants in a settlement bioassay. Conversely, in a foraging bioassay, D. rapae parasitoids spent a significantly longer time foraging on CJ treated plants. Our results reveal that CJ treatment makes plants less attractive to and less suitable for M. persicae but more attractive to D. rapae in a range of brassica cultivars. It is likely that these effects are due to changes in volatile emission indicating activation of defence and presence of conspecific competitors to aphids but presence of prey to parasitoids. Increases in volatile emission were found in CJ induced plants but varied with genotype. Among the synthetic volatile compounds that were induced in the headspace of CJ treated brassica cultivars, methyl isothiocyanate, methyl salicylate and cis-jasmone were most repellent to aphids. These results build on earlier studies in Arabidopsis and show that tritrophic interactions are influenced by CJ in a wide range of brassica germplasm. The implication is that CJ is a promising treatment that could be used in brassica crops as part of an integrated pest management system.

Comparative Pharmacokinetics of Enrofloxacin After SubcutaneousAdministration of a Novel in situ Gel Forming Preparation and aConventional Product to Rabbits

BACKGROUND: Frequent drug dosing and animal handling are usually required in conventional antimicrobial therapy but sustained release formulations can improve compliance. OBJECTIVES: This study aimed to evaluate the pharmacokinetic (PK) parameters of a novel sustained release enroflox-acin (ENR) hydrogel in comparison to a conventional ENR formulation in rabbit animal model. METHODS: A total of 20 rabbits were randomly divided into three groups and received a single dose of ENR or blank by subcutaneous (SC) injection as following: Group 1 (n=8) received ENR (10 mg/kg) using a conventional product (Enrovet®); Group 2 (n=8) received ENR (33.3 mg/kg) using a hydrogel formulation; and Group 3 or control group (n=4) received equal volumes of a blank hydrogel formulation. Blood samples were collected at different time points post-dosing. ENR concen-trations in plasma were estimated by high-performance liquid chromatographic (HPLC) method and PK parameters were calculated using a non-compartmental analysis. RESULTS: The ENR hydrogel released the drug in a sustained manner with mean residence time (MRT) of 78.4 ± 15.3 h, which was significantly more than that of the conventional formulation (7.39 ± 2.37 h, p <0.05). However, maximal plasma concentration (Cmax) for ENR hydrogel (1.41 ± 0.76 μg/mL) was significantly less than that of the conventional product (2.86 ± 0.79 μg/mL). The relative bioavailability (Frel) was not significantly different between the two formula-tions. CONCLUSIONS: The hydrogel formulation significantly increased the MRT of ENR. Hence, it could be a promising delivery system to prolong the pharmacological activity of ENR in animals and enhance compliance.