Nanoencapsulated Thymus daenensis and Mentha piperita essential oil for bacterial and biofilm eradication using microfluidic technology.

The use of essential oil (EO) nanoemulsions is expanding to meet customer demand for all-natural antibacterial agents. Thymus daenensis (T) and Mentha piperita (M) EOs were employed to make nanoemulsions (TEO and MEO NE), using Tween 80/Span 80 as surfactant/cosurfactant and a high-speed homogenizer. The TEO and MEO NEs were then characterized in terms of particle size (121, 113 nm), surface charge (-11.2 and -12.6 mV), morphology, and stability over time. Then, the antibacterial activity of EOs and their nanoformulations against Escherichia coli (E. coli) were evaluated based on various residence times, and concentrations on a microfluidic chip. The release of cytoplasmic constituents was used to compare the antibacterial activity of bulk EOs and nanoformulations. After completing MIC, MBC, and time-killing assays, the inhibitory effect of nanoformulations on E. coli biofilm formation was examined. Remarkable intensification was observed by employing a microfluidic chip owing to high-contact surface area provision between nanoemulsions and bacteria. Once compared to the conventional method for 3 h operation, the bacterial activity was nearly completely inhibited in a 24-min residence time using nanoemulsions. After 6 min of treatment, the cell membrane began to rupture, indicating that nanoemulsions could improve the antibacterial activity of bulk essential oils.

Preparation and characterization of tamoxifen loaded silica and NH2 functionalized mesoporous silica nanoparticles as delivery systems against MCF-7 breast cancer cells.

Objectives: Controlled drug delivery using nanotechnology enhances drug targeting at the site of interest and prevents drug dispersal throughout the body. This study focused on loading a poorly water-soluble drug tamoxifen (TMX) into silica nanoparticles (SNPs) and amine-functionalized mesoporous silica nanoparticles (NH2-SBA-15). Materials and Methods: SNPs were prepared according to the Stöber method and functionalized with an amine group using 3-aminopropyl triethoxysilane (APTES) through a one-pot synthesis method to produce amine-functionalized mesoporous silica nanoparticles (NH2-SBA-15). Characterization of both nanoparticles was performed using FT-IR, FE-SEM, CHN analysis, porosity tests (BET), and dynamic light scattering (DLS). Results: The results showed an average particle size of 103.7 nm for SNPs and 225.9 nm for NH2-SBA-15. Based on the BET results, the pore size of NH2-SBA-15 was about 5.4 nm. In both silica nanoparticles, drug release at pH=5.7 was greater than that of pH=7.4. However, Tamoxifen-loaded NH2-SBA-15 (TMX@NH2-SBA-15) indicated the highest drug release in the acidic medium among TMX-loaded SNPs (TMX@SNPs), perhaps due to the high columbic repulsion in the functionalized NH2-SBA-15 nanoparticles. Regarding cytotoxicity results against MCF-7 breast cancer cell lines, both TMX@SNPs and TMX@NH2-SBA-15 nanoparticles exhibited greater cytotoxicity compared to the free TMX as a positive control. Although TMX@SNPs had a small size and high loading capacity, the cytotoxic effects were higher than those of TMX@NH2-SBA-15. Conclusion: Amine functionalization of SNPs can improve the potential activity of these nanoparticles for target therapy.

Chitosan decorated essential oil nanoemulsions for enhanced antibacterial activity using a microfluidic device and response surface methodology.

In this work, the antibacterial activity of Satureja Khuzestanica essential oil nanoemulsions improved by employing chitosan (ch/SKEO NE) against E. coli bacterium. The optimum ch/SKEO NE with mean droplet size of 68 nm was attained at 1.97, 1.23, and 0.10%w/w of surfactant, essential oil and chitosan, using Response Surface Methodology (RSM). Applying microfluidic platform, the ch/SKEO NE resulted in improved antibacterial activity owing to the modification of surface properties. The nanoemulsion samples showed a significant rupturing effect on the E. coli bacterial cell membrane which resulted in a rapid release of cellular contents. This action was remarkably intensified by executing microfluidic chip in parallel to the conventional method. Having treated the bacteria in the microfluidic chip for 5 min with a 8 µg/mL concentration of ch/SKEO NE, the bacterial integrity disrupted quickly, and the activity was totally lost in a 10-min period at 50 µglmL, while it took 5 h for a complete inhibition in the conventional method using the same concentration of ch/SKEO NE. It can be concluded that nanoemulsification of EOs using chitosan coating can intensify the interaction of nanodroplets with the bacterial membrane, especially within the microfluidic chips which provides high contact surface area.

Interaction of a natural compound nanoemulsion with Gram negative and Gram positive bacterial membrane; a mechanism based study using a microfluidic chip and DESI technique.

The antibacterial activity of a nanoemulsion prepared from Satureja Khusitanica essential oil against a Gram-negative (Escherichia coli) and a Gram-positive (Bacillus atrophaeus) bacteria evaluated using microfluidic and conventional techniques. The effect of different residence time and concentrations on the antibacterial activity of nanoemulsion was studied by measuring the release of protein, nucleic acids, potassium, and also recording the MIC, MBC and time killing assays. Remarkable intensification was observed by employing microfluidic chip regarding a high-contact surface area between nanodroplets and bacterial membrane. The MIC and MBC values for E. coli and B. atrophaeus in conventional method were 400 and 1600 µg mL-1, respectively, whereas these values reduced to 11 to 50 µg mL-1 using microfluidic system. B. atrophaeus seemed to be more resistant than E. coli to the nanoemulsion treatment, perhaps due to different cell wall structures. Bacterial cell wall changes were examined using a desorption electrospray ionization (DESI) technique. It was found that the structural changes were more imminent in Gram negative E. coli by detecting a number of released lipids including phosphatidyl glycerol and phosphatidyl ethanolamines. The DESI spectra of B. atrophaeus revealed no M/Z related lipid release. These findings may help providing novel nano based natural antibacterials.

A microfluidic chip for visual investigation of the interaction of nanoemulsion of Satureja Khuzistanica essential oil and a model gram-negative bacteria.

Nanotechnology has provided novel approaches against food born and pathogenic bacteria. Within the present study, the effects of pure and nanoemulsified essential oil derived from Satureja Khuzistanica essential oil (SKEO) on Escherichia coli (E. coli ATCC 25922) as a human pathogen has been studied using a microfluidic chip. The morphology and antibacterial activity of E. coli at disparate residence durations (from 2 to 30 min) and various nanoemulsified or pure essential oil concentrations (8.0-62.5 µg mL-1) and numerous nanoemulsion's droplet sizes from 32 to 124 nm, have been investigated in the microfluidic system. Also, the quantitative analysis including optical density, time killing assay, protein, nucleic acid and potassium release were employed to confirm the effects of bacterial inhibition taking advantage of the chip apparatus. It was revealed that the prepared nanoemulsion left a considerable destructive effect on E. coli bacterial membrane, confirmed by fast release of cytoplasmic elements including protein, nucleic acid and potassium. However, this process was remarkably intensified for both nanoemulsion and pure essential oil using the microfluidic chip versus the conventional methods. The results also revealed that after 4 min of bacterium treatment by 12.5 µg mL-1 nanoemulsion with 32 nm mean particle size, the bacterial membrane wall began to degrade rapidly, and bacterial activity was almost completely inhibited in a 20-min period. These findings may have implications in the similarly structured and phospholipid-encapsulated bacteria and viruses, like COVID-19.

Circumventing paclitaxel resistance in breast cancer cells using a nanoemulsion system and determining its efficacy via an impedance biosensor.

One of the best strategies to circumvent drug resistance is the employment of nanocarriers. For the current study, we have employed a nanoemulsion formulation of paclitaxel (PTX) to bypass drug resistance in the MDA-MB-231 cell line and impedance sensing biosensors to determine the exact time that PTX-NE induced apoptosis. Our MTT results demonstrated that PTX treatment could not reduce MDA-MB-231 cell viability to IC50 even after three days. However, the employment of the reagent TPGS (inhibitor of drug resistance) combined with paclitaxel could partially obviate PTX resistance. Next, the nanoemulsion form of PTX (PTX-NE) was fabricated employing the essential oil of the Satureja khuzestanica plant and was characterized using DLS and TEM methods. Our data showed that after 72 hours, PTX-NE at 250 nM concentration could induce a 50% reduction in cell viability. Moreover, annexin/PI and cell cycle analysis confirmed the apoptotic effect of PTX-NE on cancer cells. Lastly, we measured the impedance of MDA-MB-231 cells treated with the free and nanoemulsion forms of PTX. A significant decrease in the mean impedance of PTX-NE treated cells could be observed after 40 hours. To conclude, we have demonstrated here that PTX-NE could circumvent resistance and induce apoptosis in PTX-resistant breast cancer cells, which could be inferred from their impedance measurement.

Novel PEGylated derivatives of α-tocopherol for nanocarrier formulations; synthesis, characterization and in vitro cytotoxicity against MCF-7 breast cancer cells.

Despite numerous beneficial therapeutic effects namely antioxidant and anti-inflammatory activity, Vitamin E has limited clinical applications due to its low water solubility. Throughout the present work, α-tocopherol's new PEGylated derivatives alongside with polyethylene glycol 300 (α-1TPGT300), 400 (α-TPGT400), and 1000 (α-TPGT1000) were synthesized. A 1,2,3-triazole ring was utilized as a linker for the attachment of alpha tocopherol to the PEGs through a click reaction. The purified derivatives were characterized by the means of 1H NMR, 13C NMR, mass spectroscopy, UV-vis and FT-IR methods. Synthesized derivatives' capacity to produce self-assembly nanoparticles was evaluated employing the critical micelle concentration (CMC) values. The stability of the micelles was studied by size analysis. In vitro cytotoxicity of the products was investigated using MTT assay against MCF-7 breast cancer cells. The IC50 value for TPGT1000 after 24 h treatment was 15.0 ± 1.8 µM, whereas no significant cytotoxicity effect was observed following the treatment of MCF-7 cells by TPGT300, 400. The present study showed that polymeric micelle TPGT1000 possessed better physicochemical and biological properties including relatively lower CMC value, higher stability in FBS environment in addition to higher cytotoxicity against MCF-7 breast cancer cells compared to the lower molecular weight PEGylated derivatives. These results confirmed that increasing PEG chain length left a positive effect on the polymeric micelle properties and also improved the cytotoxicity effect of new PEGylated vitamin E derivatives.

Antibacterial hydroxypropyl methyl cellulose edible films containing nanoemulsions of Thymus daenensis essential oil for food packaging.

Edible films containing essential oils (EO) as natural antibacterial agents are promising systems for food preservation. In this work, nanoemulsions of Thymus daenensis EO (wild; F1 and cultivated; F2) were loaded in hydroxyl propyl methyl cellulose (HPMC) films and the effect of different parameters (polymer, plasticizer, and EO concentration) on the film properties were analyzed and optimized. Prepared HPMC films were characterized in terms of EO loading, morphology, mechanical properties, and the antibacterial activity. The results of SEM showed uniform incorporation of nanoemulsions into the edible film. Investigation of the mechanical properties of two edible films revealed a plasticizing effect of T. daenensis EO on the films. Also, edible films had noticeable antimicrobial activity against selected microorganisms, i.e. 47.0±2.5mm and 22.6±0.5mm zone of inhibition against S. aureus for films containing F1 and F2, respectively. Incorporation of nanoemulsions into the HPMC films can be used for active food preservation.

Ultrasonic nanoemulsification of food grade trans-cinnamaldehyde: 1,8-Cineol and investigation of the mechanism of antibacterial activity.

Using ultrasonic technology, trans-cinnamaldehyde as a natural antibacterial compound was used to prepare nano size emulsions to increase its bioavailability and therefore bactericidal action. Nanoemulsions containing trans-cinnamaldehyde as an active agent and 1,8 cineol as co additive oil (Ostwald ripening inhibitor) were formulated using probe sonicator. Three different determining factors, namely time of sonication, surfactant to oil ratio and type of emulsifier (Tween 80 and Tween 20) were investigated to enhance the stability profile. In addition, the effect of changes in the particle size and emulsifier on the antibacterial activity against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus were examined using agar dilution method. Then, the effect of optimized formulation on the membrane fluidity and cell constituent release, were investigated by analysis of membrane lipids using GC-MS and IR spectrometry, respectively. The data showed that a 15min sonication of the formulation containing Tween 80 as emulsifier with surfactant to oil ratio of 2:1 (w/w) resulted in a significant stability for 6months with considerably small particle size of 27.76±0.37nm. Furthermore, the nanoemulsion showed great antibacterial activity and could reduce the minimum inhibitory concentration (MIC) from 8 to 1mg/mL against E. coli and S. aureus, and from 16 to 2mg/mL against P. aeruginosa. Interestingly, E. coli's membrane fluidity increased dramatically after treatment with the optimum nanoemulsion (T804). This study revealed that nanoemulsion of trans-cinnamaldehyde and 1,8 cineol has substantial antibacterial activity against selected microorganisms.

Superior antibacterial activity of nanoemulsion of Thymus daenensis essential oil against E. coli.

Natural preservatives are being extensively investigated for their potential industrial applications in foods and other products. In this work, an essential oil (Thymus daenensis) was formulated as a water-dispersible nanoemulsion (diameter=143nm) using high-intensity ultrasound. The antibacterial activity of the essential oil in both pure and nanoemulsion forms was measured against an important food-borne pathogen bacterium, Escherichia coli. Antibacterial activity was determined by measuring the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The antibacterial activity of the essential oil against E. coli was enhanced considerably when it was converted into a nanoemulsion, which was attributed to easier access of the essential oils to the bacterial cells. The mechanism of antibacterial activity was investigated by measuring potassium, protein, and nucleic acid leakage from the cells, and electron microscopy. Evaluation of the kinetics of microbial deactivation showed that the nanoemulsion killed all the bacteria in about 5min, whereas only a 1-log reduction was observed for pure essential oil. The nanoemulsion appeared to amplify the antibacterial activity of essential oils against E. coli by increasing their ability to disrupt cell membrane integrity.

Reduction of date microbial load with ozone.

BACKGROUND: Date is one of the foodstuffs that are produced in tropical areas and used worldwide. Conventionally, methyl bromide and phosphine are used for date disinfection. The toxic side effects of these usual disinfectants have led food scientists to consider safer agents such as ozone for disinfection, because food safety is a top priority. The present study was performed to investigate the possibility of replacing common conventional disinfectants with ozone for date disinfection and microbial load reduction. MATERIALS AND METHODS: In this experimental study, date samples were ozonized for 3 and 5 hours with 5 and 10 g/h concentrations and packed. Ozonized samples were divided into two groups and kept in an incubator which was maintained at 25°C and 40°C for 9 months. During this period, every 3 month, microbial load (bacteria, mold, and yeast) were examined in ozonized and non-ozonized samples. RESULTS: This study showed that ozonization with 5 g/h for 3 hours, 5 g/h for 5 hours, 10 g/h for 3 hours, and 10 g/h for 5 hours leads to about 25%, 25%, 53%, and 46% reduction in date mold and yeast load and about 6%, 9%, 76%, and 74.7% reduction in date bacterial load at baseline phase, respectively. Appropriate concentration and duration of ozonization for microbial load reduction were 10 g/h and 3 hours. CONCLUSION: Date ozonization is an appropriate method for microbial load reduction and leads to an increase in the shelf life of dates.

Determination of Cefixime by a Validated Stability-Indicating HPLC Method and Identification of its Related Substances by LC-MS/MS Studies.

Cefixime is an important cephalosporin antibiotic that easily decomposes and releases different related substances in preparation and storage steps. The objective of the current study was to develop a simple, precise, and accurate isocratic liquid chromatography (LC) method for the determination of cefixime in the presence of its related substances generated from thermal stress in the bulk drug. The chromatographic conditions were comprised of a reversed-phase C18 column (4.6 × 250 mm, 5 µm) with a mobile phase composed of water: acetonitrile (85:15 v/v, with 0.5% formic acid) and ultraviolet detection (UV). Some thermal degradation products were identified using a proposed liquid chromatography-mass spectrometry method. Five peaks (A, B, C, D, and E impurities based on British Pharmacopoeia) were known and a few unknown peaks appeared in the thermal stress solution of cefixime. The linear regression analysis data for the calibration plot of the LC-UV method showed a good linear relationship in the concentration range 0.9-1000.0 µg mL(-1). The recovery of the optimized method was between 94.6 and 98.4% and the inter- and intra-day relative standard deviations were less than 3.3%. The obtained results shown in the LC-UV proposed method can be conveniently used in a quality control laboratory for routine analysis of cefixime for the assay and related substances, as well as for the evaluation of stability samples of bulk drugs.

A Case of Multiple Endocrine Neoplasia Type 2B and Gangliomatosis of Gastrointestinal Tract.

Multiple endocrine neoplasia type 2 (MEN2) is a rare familial syndrome caused by mutations in the RET protooncogene and it is transmitted as an autosomal dominant trait. The underlying problem for all the MEN syndromes is failure of a tumour suppressor gene. The genetic defect in MEN2 is on chromosome 10 (10q11.2) and has also been identified both for MEN2A and MEN2B. The reported patient is an 18-year-old girl presented with long-term diarrhea and enterocutaneous fistula. Her thyroid nodules, marfanoid habitus and bumpy lips, were also highly suggestive for MEN2B.

Survival after In-Hospital Cardiopulmonary Resuscitation in a Major Referral Center during 2001-2008.

Despite efforts to save more people suffering from in-hospital cardiac arrest, rates of survival after in-hospital cardiopulmonary resuscitation (CPR) are no better today than they were more than a decade ago. This study was undertaken to assess the demographics, clinical parameters and outcomes of patients undergoing CPR by the code blue team at our center during 2001 to 2008. Data were collected retrospectively from adult patients (n=2262) who underwent CPR. Clinical outcomes of interest were survival at the end of CPR and survival at discharge from the hospital. Factors associated with survival were evaluated using binomial and tests. Of the patients included (n=2262), 741 patients (32.8%) had successful CPR. The number of male patients requiring CPR was more than females in need of the procedure. The majority of patients requiring CPR were older than 60 years (56.4±17.9). The number of successful CPR cases in long-day shift (7:00 to 19:00) was more than that in the night shift (19:00 to 7:00). Furthermore, 413 (18.4%) cases were resuscitated on holidays and 1849 (81.7%) on the working days. The duration of CPR was 10 min or less in 710 (31.4%) cases. Cardiopulmonary resuscitations which lasted less than 10 minutes were associated with better outcomes. The findings of the present study indicate that some manageable factors including the duration of CPR, working shift, working day (holiday or non-holiday) could affect the CPR outcomes. The findings might also be taken as evidence to suggest that the allocation of more personnel in each shift especially in night shifts and holidays, planning to increase the personnel's CPR skills, and decreasing the waste time would result in the improvement of CPR outcome.

Survival after in-hospital cardiopulmonary resuscitation in a major referral center.

AIM: This study was undertaken to assess the demographics, clinical parameters and outcomes of patients undergoing cardiopulmonary resuscitation (CPR), by the code blue team at our center to compare with other centers. MATERIALS AND METHODS: Data were collected retrospectively from all adult patients who underwent CPR at our hospital from 2007 to 2008. CPR was performed on 290 patients and it was given 313 times. Clinical outcomes of interest were survival at the end of CPR and survival at discharge from the hospital. Factors associated with survival were evaluated via binomial and chi square-tests. RESULTS: Of the 290 patients included, 95 patients (30.4%) had successful CPR. However, only 35 patients (12%) were alive at discharge. The majority requiring CPR were above 60 years of age (61.7%). Males required CPR more than females. There were 125 women (43.1%) and 165 males (56.9%) aged 3 to 78 (average 59.6) years. Majority (179) of the cases (61.7%) were above 60 years of age. Regarding the various wards, 54 cases (17.3%) were in the internal medicine ward, 63 cases (20.1%) in the surgery ward, 1 case (0.3%) in the clinic, 11 cases (3.5%) in the paraclinic, 116 cases (37.1%) in the emergency (ER), 55 cases (17.5%) in the Intensive Care Unit (ICU) and Coronary Care Unit (CCU), and 13 cases (4.2%) were in other wards. Cardiac massage was done in 133 cases (42.5%), defibrillation only via electroshock 3 cases (1%), and both were used in177 cases (56.5%). The ER had the most cases of CPR. Both cardiac massage and electroshock defibrillation were needed in most cases. CONCLUSION: In-hospital CPR for cardiopulmonary arrest was associated with 30.4% success at our center at the end of CPR but only 12% were alive at discharge. Duration of CPR >10 minutes was predictive of significantly decreased survival to discharge.

Preconcentration and determination of ultra-traces of platinum in human serum using the combined electrodeposition-electrothermal atomic absorption spectroscopy (ED-ETAAS) and chemometric method.

Platinum compounds, including cis-dichlorodiaminoplatinum(II) or cisplatin, are an important class of anti-cancer drugs, which should be carefully monitored in the biological fluids. In this study, electrodeposition coupled with electrothermal atomic absorption spectrometry (ETAAS) was used for determination of Pt concentration in the human serum samples. The chemometric techniques were also used to verify the probable interactions among the important and effective parameters in the atomization process. Using response surfaces obtained by two factorial design techniques, the experimental design was applied for three effective parameters namely ashing temperature, atomizing temperature and modifier concentration as effective parameters on the atomization of Pt. The in situ digestions of serum samples, as well as the separation of the ultra-traces of Pt from concomitant in these samples were performed by using the in situ electrodeposition (ED) technique prior to the measurement by ETAAS. Six plasma samples of a patient who was administered parenteral cisplatin were analyzed using the proposed ED-ETAAS technique. The results showed the pharmacokinetic parameters of cisplatin in serum in accordance to the well-established data. A relatively good reproducibility %RSD=2.44, low limit of detection LOD=2.54 microg/L and promising characteristic mass m(o)=91.30 pg were obtained using this technique.

Quality by design: optimization of a liquid filled pH-responsive macroparticles using Draper-Lin composite design.

In this study, pH responsive macroparticles incorporating peppermint oil (PO) were prepared using a simple emulsification/polymer precipitation technique. The formulations were examined for their properties and the desired quality was then achieved using a quality by design (QBD) approach. For this purpose, a Draper-Lin small composite design study was employed in order to investigate the effect of four independent variables, including the PO to water ratio, the concentration of pH sensitive polymer (hydroxypropyl methylcellulose phthalate), acid and plasticizer concentrations, on the encapsulation efficiency and PO loading. The analysis of variance showed that the polymer concentration was the most important variable on encapsulation efficiency (p < 0.05). The multiple regression analysis of the results led to equations that adequately described the influence of the independent variables on the selected responses. Furthermore, the desirability function was employed as an effective tool for transforming each response separately and encompassing all of these responses in an overall desirability function for global optimization of the encapsulation process. The optimized macroparticles were predicted to yield 93.4% encapsulation efficiency and 72.8% PO loading, which were remarkably close to the experimental values of 89.2% and 69.5%, consequently.

Determination of N-vinyl-2-pyrrolidone and N-methyl-2-pyrrolidone in drugs using polypyrrole-based headspace solid-phase microextraction and gas chromatography-nitrogen-phosphorous detection.

A headspace solid-phase microextraction and gas chromatography-nitrogen-phosphorous detection (HS-SPME-GC-NPD) method using polypyrrole (PPy) fibers has been introduced to determine two derivatives of pyrrolidone; N-vinyl-2-pyrrolidone (NVP) and N-methyl-2-pyrrolidone (NMP). Two types of PPy fibers, prepared using organic and aqueous media, were compared in terms of extraction efficiency and thermal stability. It was found that PPy film prepared using organic medium (i.e. acetonitrile) had higher extraction efficiency and more thermal stability compared to the film prepared in aqueous medium. To enhance the sensitivity of HS-SPME, the effects of pH, ionic strength, extraction time, extraction temperature and the headspace volume on the extraction efficiency were optimized. Using the results of this research, high sensitivity and selectivity had been achieved due to the combination of the high extraction efficiency of PPy film prepared in organic medium and the high sensitivity and selectivity of nitrogen-phosphorous detection. Linear range of the analytes was found to be between 1.0 and 1000 microg L(-1) with regression coefficients (R(2)) of 0.998 and 0.997 for NVP and NMP, consequently. Limits of detection (LODs) were 0.074 and 0.081 microg L(-1) for NVP and NMP, respectively. Relative standard deviation (R.S.D.) for five replications of analyses was found to be less than 6.0%. In real samples the mean recoveries were 94.81% and 94.15% for NVP and NMP, respectively. The results demonstrated the suitability of the HS-SPME technique for analyzing NVP and NMP in two different pharmaceutical matrices. In addition, the method was used for simultaneous detection of NVP, 2-pyrrolidone (2-Pyr), gamma-butyrolactone (GBL) and ethanolamine (EA) compounds.

Investigation of the solid state properties of amoxicillin trihydrate and the effect of powder pH.

The purpose of this research was to investigate some physicochemical and solid-state properties of amoxicillin trihydrate (AMT) with different powder pH within the pharmacopoeia-specified range. AMT batches prepared using Dane salt method with the pH values from 4.39 to 4.97 were subjected to further characterization studies. Optical and scanning electron microscopy showed that different batches of AMT powders were similar in crystal habit, but the length of the crystals increased as the pH increased. Further solid-state investigations using powder x-ray diffraction (PXRD) demonstrated the same PXRD pattern, but the intensity of the peaks raised by the powder pH, indicated increased crystallinity. Differential scanning calorimetry (DSC) studies further confirmed that as the powder pH increased, the crystallinity and, hence, thermal stability of AMT powders increased. Searching for the possible cause of the variations in the solid state properties, HPLC analysis showed that despite possessing the requirements of the United States Pharmacopoeia (USP) for purity/impurity profile, there was a direct relationship between the increase of the powder pH and the purity of AMT, and also decrease in the impurity I (alpha-Hydroxyphenylglycine) concentration in AMT powder. Recrystallization studies confirmed that the powder pH could be controlled by adjusting the pH of the crystallization.

A new solution for a chronic problem; aqueous enteric coating.

In this research, we have reconsidered the current enteric coating techniques and offered a new solution using both theoretical and practical approaches. This approach is based on the fact that salt formation can solubilize the pH-sensitive polymers in water. However, having applied the polymer solution onto the dosage form's surface, the polymer should be converted to the nonionized form for delayed release action. Ammonium hydrogen carbonate (AHC) is used as a buffering agent with dual actions of salting in and desalting the polymer. Following the application of the coating medium onto the dosage form's surface and drying, AHC dissociate completely to ammonia, carbon dioxide, and water converting the polymer to its nonionized form. FT-IR studies on free film samples further confirmed the proposed mechanism. A range of pH-sensitive polymers and other ingredients in water have been successfully applied at the surface of a model ASA tablets, using pan coating technique. According to the SEM observation, the coating layer is very dense and rigid, despite the fact that, the coated amount of the polymers is quit small. The enteric tablets maintain their shapes in acid medium and passed the USP dissolution test for DR ASA tablets.