Engineering microbial cells with metal chelating hydroxylated unnatural amino acids for removable of synthetic pollutants from water.

Lead (Pb) is a well-known heavy metal and toxic synthetic industrial pollutant in the ecosystem and causes severe threats to living organisms. It is paramount to develop a sustainable microbial engineering approach to remove synthetic pollutants from the environment. Genetic code engineering is emerging as an important microbial engineering tool in biosciences to biosynthesis congener protein production beyond the canonical set of natural molecules and expand the chemistries of living cells.

Granulation techniques and technologies: recent progresses.

Granulation, the process of particle enlargement by agglomeration technique, is one of the most significant unit operations in the production of pharmaceutical dosage forms, mostly tablets and capsules. Granulation process transforms fine powders into free-flowing, dust-free granules that are easy to compress. Nevertheless, granulation poses numerous challenges due to high quality requirement of the formed granules in terms of content uniformity and physicochemical properties such as granule size, bulk density, porosity, hardness, moisture, compressibility, etc.

Enhanced oral bioavailability of paclitaxel by solid dispersion granulation.

The main objective of this study was to develop novel orally administrable tablets containing solid dispersion granules (SDG) of amorphous paclitaxel (PTX) prepared by fluid bed technology, and to evaluate its in vitro dissolution and in vivo pharmacokinetics (PK) in beagle dogs. The SDG were prepared using optimized composition by fluid bed technology, and characterized for solid-state properties. The release study of SDG tablet (SDG-T) in simulated gastric fluid showed a rapid release of PTX, reaching maximum dissolution within 20 min.

Zanamivir oral delivery: enhanced plasma and lung bioavailability in rats.

The objective of this study was to enhance the oral bioavailability (BA) of zanamivir (ZMR) by increasing its intestinal permeability using permeation enhancers (PE). Four different classes of PEs (Labrasol(®), sodium cholate, sodium caprate, hydroxypropyl β-cyclodextrin) were investigated for their ability to enhance the permeation of ZMR across Caco-2 cell monolayers. The flux and Papp of ZMR in the presence of sodium caprate (SC) was significantly higher than other PEs in comparison to control, and was selected for further investigation.

Sildenafil vaginal suppositories: preparation, characterization, in vitro and in vivo evaluation.

Aim: The main objective was to investigate the in vitro release profile/kinetics, and in vivo plasma pharmacokinetics (PK) and organ biodistribution (BD) of the prepared sildenafil vaginal suppositories (SVS).

Methods: Suppositories containing 25 mg of sildenafil were prepared by the cream melting technique using Witepsol H-15 as a suppository base. The suppositories were characterized for weight variation, content uniformity, hardness, disintegration time and crystallinity change.

Biofilm formation by Streptococcus pyogenes: modulation of exopolysaccharide by fluoroquinolone derivatives.

Biofilm formation by Streptococcus pyogenes has been demonstrated as a potentially important mechanism contributing to antibiotic treatment failure. S. pyogenes is the frequent cause of purulent infections in humans and also, it could play a significant role in recurrent and chronic infections.

New clopidogrel napadisilate salt and its solid dispersion with improved stability and bioequivalence to the commercial clopidogrel bisulphate salt in beagle dogs.

The purpose of this study was to develop a novel clopidogrel napadisilate-loaded solid dispersion with improved stability and bioequivalence to the clopidogrel bisulphate-loaded commercial product. Clopidogrel napadisilate prepared in this study appeared as a white crystalline powder unlike clopidogrel base. However, this salt did not improve the solubility of clopidogrel, even with improved stability compared to clopidogrel bisulphate.

Solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine for enhanced bioavailability of highly lipophilic bioactive carotenoid lutein.

The objectives of this study was to prepare solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine (PC), an endogenous phospholipid with excellent in vivo solubilization capacity, as oil phase for the delivery of bioactive carotenoid lutein, by spray drying the SNEDDS (liquid system) containing PC using colloidal silica (Aerosil® 200 VV Pharma) as the inert solid carrier, and to evaluate the enhanced bioavailability (BA) of lutein from S-SNEDDS. The droplet size analyses revealed droplet size of less than 100 nm. The solid state characterization of S-SNEDDS by SEM, DSC, and XRPD revealed the absence of crystalline lutein in the S-SNEDDS.

Enhanced bioavailability and retinal accumulation of lutein from self-emulsifying phospholipid suspension (SEPS).

Ability of any formulation to keep the drug in solubilized form in vivo is essential for bioavailability (BA) enhancement rather than the solubility of drug in the formulation vehicle/matrix itself. Besides, utilization of an excess amount of surfactants/co-surfactants to solubilize the drug in the lipid formulation poses potential pharmaceutical as well as health problems. To address this problem, self-emulsifying phospholipid suspension (SEPS) consisting of high amount of phospholipid (an endogenous lipid with efficient in vivo emulsification capability) and relatively low amount of surfactant/co-surfactant has been proposed to enhance the bioavailability (BA) of lutein.

Preparation and evaluation of Cremophor-free paclitaxel solid dispersion by a supercritical antisolvent process.

Objectives: To avoid the major adverse effects induced by Cremophor EL formulated in the commercial paclitaxel products of Taxol.

Methods: An injectable paclitaxel solid dispersion free of Cremophor was prepared by a supercritical antisolvent process and then was fully characterized and investigated with regard to its short-term and long-term stability. Pharmacokinetics in rats was also evaluated compared with the commercial product.

Physicochemical stability, pharmacokinetic, and biodistribution evaluation of paclitaxel solid dispersion prepared using supercritical antisolvent process.

Aim: To investigate the physicochemical stability, pharmacokinetics (PK), and biodistribution of paclitaxel (PTX) from paclitaxel solid dispersion (PSD) prepared by supercritical antisolvent (SAS) process.

Methods: Physicochemical stability was performed in accelerated (40°C 70 ± 5% RH) and stress (60°C) storage conditions for a period of 6 months and 4 weeks, respectively. PK and biodistribution studies were performed in rats following i.

Antitumor efficacy of solid dispersion of paclitaxel prepared by supercritical antisolvent process in human mammary tumor xenografts.

The efficacy of intravenous chemotherapy for breast cancer has been improving with newer agents. However, the fractional improvements in breast cancer progression-free survival were quite modest and these small gains are obtained at the cost of significant toxicity. To address this problem, paclitaxel solid dispersion (PSD), a Cremophor EL-free formulation prepared by supercritical antisolvent process using hydrophilic polymers as carrier, was developed to avoid Cremophor EL-associated toxicities in Taxol(®).

Synthesis and in vitro antimicrobial evaluation of novel fluoroquinolone derivatives.

A series of 1-ethyl-6,8-difluoro-4-oxo-7(4-aryl piperazin-1-yl) 1,4-dihydro-quinoline-3-carboxylic acid derivatives (6a-f) and 1-ethyl-6,8-difluoro-4-oxo-7(4-piperidin-1-yl) 1,4-dihydro-quinoline-3-carboxylic acid derivatives (7a-e) were synthesized and evaluated for antibacterial and antifungal activities. The antimicrobial activities of the compounds were assessed by the microbroth dilution technique. The compounds were also evaluated for antifungal activity against Candida albicans (ATCC 90028) and Cryptococcous neoformans (ATCC 14116) pathogens.

Novel self-nanoemulsifying drug delivery system for enhanced solubility and dissolution of lutein.

Self-nanoemulsifying drug delivery system (SNEDDS) containing oil (Phosal 53 MCT), surfactant (Labrasol), and cosurfactant (Transcutol-HP or Lutrol-E400) was prepared to enhance solubility and dissolution of lutein. Ternary phase diagram of the SNEDDS was constructed to identify the self-emulsifying regions following which the percentage of oil, surfactant, and cosurfactant in the SNEDDS were optimized in terms of emulsification time and mean emulsion droplet size. The optimized SNEDDS consists of 25% oil, 60% surfactant, and 15% cosurfactant.

Physicochemical characterization and skin permeation of liposome formulations containing clindamycin phosphate.

This study was undertaken to evaluate the physicochemical properties and skin permeation of liposome formulations containing clindamycin phosphate (CP), especially when charge was imparted to the liposome. Five different liposome formulations were prepared using Phospholipon 85G (PL) and cholesterol (CH) by conventional lipid film hydration technique. Molar ratio of CH to PL was varied in the range of 0.

Theoretical and experimental studies of vibrational spectra and thermal analysis of 2-nitroaniline and its cation.

The FTIR spectrum of 2-nitroaniline was recorded in the regions 4000-400 cm(-1). The optimized molecular geometry, bond orders, atomic charges, harmonic vibrational wave numbers and intensities of vibrational bands of 2-nitroaniline and its cation were calculated at DFT levels invoking two different basis sets 6-31G and 6-31+G using Gaussian 03W program. The X-ray geometry and FTIR vibrational frequencies were compared with the results of DFT calculations.

Formulation and in vitro assessment of minoxidil niosomes for enhanced skin delivery.

Niosomes have been reported as a possible approach to improve the low skin penetration and bioavailability characteristics shown by conventional topical vehicle for minoxidil. Niosomes formed from polyoxyethylene alkyl ethers (Brij) or sorbitan monoesters (Span) with cholesterol molar ratios of 0, 1 and 1.5 were prepared with varying drug amount 20-50mg using thin film-hydration method.

Skin penetration and retention of L-ascorbic acid 2-phosphate using multilamellar vesicles.

Transdermal formulation of L-ascorbic acid 2-phosphate magnesium salt (A2P) was prepared using multilamellar vesicles (MLV). A2P was either physically mixed with or entrapped into three different MLVs of neutral, cationic, and anionic liposome vesicles. For the preparation of neutral MLVs, phosphatidylcholine (PC) and cholesterol (CH) were used.

The effect of coenzyme Q10 on the pharmacokinetic parameters of theophylline.

Interaction of a drug with other drugs and dietary supplements is becoming an emerging issue for patients and health insurance authorities due to awareness of adverse drug event. In this study, we examined the effects of coenzyme Q10 (CoQ10), one of the most popular dietary supplements, on the pharmacokinetic parameters of theophylline in rats. The pharmacokinetic parameters of theophylline changed significantly when the drug was administered after five consecutive days of pretreatment with CoQ10.

Mixed micellar nanoparticle of amphotericin B and poly styrene-block-poly ethylene oxide reduces nephrotoxicity but retains antifungal activity.

Mixed micellar nanoparticle consisting of amphotericin B (AmB) and poly styrene-block-poly ethylene oxide (PS-block-PEO) was prepared by high pressure homogenizer. Nephrotoxicity of the nanoparticle was investigated along with antifungal activity and self-aggregation status of the drug in the nanoparticle. Nephrotoxicity was markedly reduced when AmB was intravenously administered to rats as mixed micellar nanoparticle with PS-block-PEO in terms of transmission electron microscopy of tubular cells and creatinine clearance.

The effect of 1-furan-2-yl-3-pyridine-2-yl-propenone on pharmacokinetic parameters of warfarin.

1-Furan-2-yl-3-pyridine-2-yl-propenone (FPP-3) is an investigatory drug which has a dual inhibitory action on cyclooxygenase (COX) and 5-lipoxygenase (5-LOX). We examined its effect on the pharmacokinetics of warfarin. Three consecutive days of pretreatment with 17 mg/kg of FPP-3 had no significant effect on the pharmacokinetic parameters of warfarin when orally administered to rats.

The effect of 1-furan-2-yl-3-pyridine-2-yl-propenone on pharmacokinetic parameters of theophylline.

The pharmacokinetic parameters of theophylline in rats did not change significantly when the drug was intravenously administered after three consecutive days of pretreatment with 17 mg/kg, orally, of 1-furan-2-yl-3-pyridine-2-yl-propenone (FPP-3), an investigatory drug having dual inhibitory action on cyclooxygenase (COX) and 5-lipoxygenase (5-LOX). However, significant changes were found in the pharmacokinetic parameters of the drug at doses of 34 mg/kg and more of FPP-3. Results of cytochrome P450 activity test indicated that the alteration in pharmacokinetic parameters of the drug appears to be due to the inhibitory effect of FPP-3 on cytochrome P450 1A which is responsible for the metabolism of theophylline.