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Six aminoethyl and aminobutyl esters of ketorolac containing 1-methylpiperazine (MPE and MPB), N-acetylpiperazine (APE and APB) or morpholine (ME and MB), were synthesized and their hydrolysis kinetics were studied. The hydrolysis was studied at pH 1 to 9 (for MPE, APE and ME) and pH 1 to 8 (for MPB, APB and MB) in aqueous phosphate buffer (0.16 M) with ionic strength (0.5 M) at 37°C. Calculation of k(obs), construction of the pH-rate profiles and determination of the rate equations were performed using KaleidaGraph® 4.1. The hydrolysis displays pseudo-first order kinetics and the pH-rate profiles shows that the aminobutyl esters, MPE, APB and MB, are the most stable. The hydrolysis of the ethyl esters MPE, APE and ME, depending on the pH, is either fast and catalyzed by the hydroxide anion or slow and uncatalyzed for the diprotonated, monoprotonated and nonprotonated forms. The hydrolysis of the butyl esters showed a similar profile, albeit it was also catalyzed by hydronium cation. In addition, the hydroxide anion is 105 more effective in catalyzing the hydrolysis than the hydronium cation. The hydrolysis pattern of the aminoethyl esters is affected by the number and pKa of its basic nitrogen atoms. The monobasic APE and ME, show a similar hydrolysis pattern that is different than the dibasic MPE. The length of the side chain and the pKa of the basic nitrogen atoms in the aminoethyl moiety affect the mechanism of hydrolysis as the extent of protonation at a given pH is directly related to the pKa.
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Anti-Inflamatórios não Esteroides/química , Inibidores de Ciclo-Oxigenase/química , Ésteres/química , Cetorolaco/análogos & derivados , Pró-Fármacos/química , Anti-Inflamatórios não Esteroides/síntese química , Catálise , Inibidores de Ciclo-Oxigenase/síntese química , Estabilidade de Medicamentos , Ésteres/síntese química , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Hidrólise , Hidróxidos/química , Cetorolaco/química , Cinética , Modelos Moleculares , Estrutura Molecular , Morfolinas/química , Oniocompostos/química , Piperazinas/química , Pró-Fármacos/síntese química , PrótonsRESUMO
BACKGROUND: With the expansion in pharmacy education in Saudi Arabia, there is a pressing need to maintain quality assurance in pharmacy programs using several tools. The progress test is a formative assessment tool that can serve to provide information to all stakeholders. This study evaluated the results of a unified progress test that was shared among 15 colleges of pharmacy. METHODS: The progress test was composed of 100 MCQs where 30% of which cover basic pharmaceutical sciences and 70% cover pharmacy practice. The questions were collected from all the 15 colleges of pharmacy participated in the test. The test was administered online to all undergraduate students in the professional programs of these colleges. RESULTS: The overall attendance rate was 80% from the total number of students enrolled in the participating colleges. Mean scores of students in basic pharmaceutical sciences were relatively higher than in pharmacy practice. The assessment results of the students in the unified program learning outcomes among colleges were higher in the domains of knowledge and skills compared to competence domain. There was a significant increment in the mean scores of the students as they progress through the years of the professional program. No correlation was found between the mean scores in the test and the cumulative grade point average (cGPA) of all students regardless of their level. CONCLUSION: The results indicated growth and maintenance of the gained knowledge and skills by the students as they progress through the years of the professional program with consistency in the results among the participating colleges. Sharing a unified test was effective as a valuable tool for the colleges of pharmacy for the purposes of benchmarking and improving the curricula. In addition, it could serve to evaluate learning of students and harmonize knowledge and skills gained by students at different institutions.
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INTRODUCTION: The COVID-19 pandemic imposed dramatic changes on educational practices worldwide. Many universities and schools have moved into the delivery of their courses and educational programs utilizing fully electronic online modes. This study aims to evaluate the pharmacy student distance online learning experience during the COVID-19 pandemic. METHODS: A cross-sectional survey was utilized where a 3-domain survey questionnaire focused on preparedness, attitude and barriers was distributed to students at the time of conclusion of the semester. Each domain consists of multiple questions that made up a score that reflects their preparedness, attitude as well as barriers relevant to distance online learning experience. The survey was voluntarily, and all data were collected and recorded via google forms with maintaining anonymity. RESULTS: The response rate was about 75% (n = 309). The results' analysis revealed no gender differences in any of these domains. However, there were some variable responses among different educational levels. The average preparedness score was 32.8 ± 7.2 (Max 45), the average attitude score was 66.8 ± 16.6 (Max 105), and the average barrier score was 43.6 ± 12.0 (Max 75). There was statistical significance difference in both preparedness score and attitude scores between different professional years (P-value <.05). However, there was no difference in barrier scores among all professional years. The results indicated that about 61.4% of the students agreed on that college of pharmacy was well-prepared and ready for the online education during the emerging COVID-19 pandemic with complete transition into online education. The results also indicated that 49.2% of the students showed positive attitude toward the provided online learning. The results indicated that about 34% of the students identify some barriers toward the provided online learning. Finally, there were strong association between the need for training on how to receive online courses and preparedness and barriers scores. DISCUSSION AND CONCLUSION: E-learning experience pose challenges and presents opportunities during emergency situations. The need for training for students and faculty was highly associated with the preparedness and barriers domains rather than the infrastructure or computer literacy, so the school can improve their experience by addressing these needs.
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PURPOSE: The aim of this work is to optimize a polyethylene glycolated (PEGylated) polymer-lipid hybrid nanoparticulate system for the delivery of anastrozole (ANS) to enhance its biopharmaceutical attributes and overall efficacy. METHODS: ANS loaded PEGylated polymer-lipid hybrid nanoparticles (PLNPs) were prepared by a direct emulsification solvent evaporation method. The physical incorporation of PEG was optimized using variable ratios. The produced particles were evaluated to discern their particle size and shape, zeta-potential, entrapment efficiency, and physical stability. The drug-release profiles were studied, and the kinetic model was analyzed. The anticancer activity of the ANS PLNPs on estrogen-positive breast cancer cell lines was determined using flow cytometry. RESULTS: The prepared ANS-PLNPs showed particle sizes in the range of 193.6 ± 2.9 to 218.2 ± 1.9 nm, with good particle size uniformity (i.e., poly-dispersity index of around 0.1). Furthermore, they exhibited relatively low zeta-potential values ranging from -0.50 ± 0.52 to 6.01 ± 4.74. The transmission electron microscopy images showed spherical shape of ANS-PLNPs and the compliance with the sizes were revealed by light scattering. The differential scanning calorimetry DSC patterns of the ANS PLNPs revealed a disappearance of the characteristic sharp melting peak of pure ANS, supporting the incorporation of the drug into the polymeric matrices of the nanoparticles. Flow cytometry showed the apoptosis of MCF-7 cell lines in the presence of ANS-PLNPs. CONCLUSION: PEGylated polymeric nanoparticles presented a stable encapsulated system with which to incorporate an anticancer drug (ANS) with a high percentage of entrapment efficiency (around 80%), good size uniformity, and induction of apoptosis in MCF-7 cells.
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BACKGROUND: Vaso-occlusive crisis (VOC) is one of the acute complications of sickle-cell disease (SCD). Treatment mainly relies on hydration and pain control by analgesics. The specific aim of this study was to assess potential health outcomes within the first 72 h of admission between intermittent and patient-controlled analgesia (PCA) by opioids among VOC patients. METHODS: A retrospective chart review study was conducted to determine SCD patients with VOC. Using the hospital electronic system, the following data were collected: patient's age, gender, blood pressure, heart rate, respiratory rate, oxygen saturation, and pain score on admission and daily for 3 days as well as the cumulative opioid analgesic dose for 72 h which is reported as morphine equivalent. RESULTS: One hundred and seventeen patients were screened over a period of 5 years. Of those, 99 (84.6%) met the study inclusion criteria, and 18 patients (15.4%) were excluded from the study. During the first 72 h of admission, a significant reduction in pain score was observed in patients on intermittent intravenous (IV) administration compared to those in the PCA group (P < 0.0004) where the mean pain scores were 3 and 5, respectively. The total amount of morphine administered over 72 h of admission was significantly higher in PCA group (777 ± 175 mg) as compared to the intermittent IV administration group (149 ± 74 mg) (P < 0.000003). Clinically significant hypotension or respiratory depression was not observed in both groups over the 72 h of admission. CONCLUSION: During the first 72 h of admission, intermittent IV administration of morphine was more effective than PCA infusion in pain control.
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The aim of this study was to prepare fast-dissolving tablets of meloxicam after its complexation with ß-cyclodextrin (ß-CD) and to investigate the effect of using different superdisintegrants on the disintegration and release of meloxicam from the tablets. A complex of meloxicam with ß-CD was prepared by spray drying and then compressed in the form of tablets utilizing the direct compression technique. Three superdisintegrants were employed at various levels - sodium starch glycolate, croscarmellose sodium, and crospovidone. Co-spray dried micro-crystalline cellulose and mannitol (Avicel HFE-102) were used as diluents in the tablets. Prior to compression, the pre-compression parameters showed satisfactory flow properties. Post-compression parameters showed that all tablet formulations had acceptable mechanical properties. Wetting and disintegration times were prolonged by increasing the level of sodium starch glycolate in the tablets. This was attributed to the formation of a viscous gel layer around the tablets by sodium starch glycolate whereas this effect was not observed with croscarmellose sodium and crospovidone. Dissolution studies showed fast release of meloxicam except in tablets containing a high level of sodium starch glycolate. Complexation of meloxicam with ß-CD significantly improved the solubility of the drug and improved the mechanical properties of tablets produced by direct compression.
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Anti-Inflamatórios não Esteroides/administração & dosagem , Excipientes/química , Tiazinas/administração & dosagem , Tiazóis/administração & dosagem , beta-Ciclodextrinas/química , Anti-Inflamatórios não Esteroides/química , Carboximetilcelulose Sódica/química , Celulose/química , Manitol/química , Meloxicam , Povidona/química , Solubilidade , Amido/análogos & derivados , Amido/química , Comprimidos , Tiazinas/química , Tiazóis/química , Fatores de TempoRESUMO
The specific aim of this work was to prepare mucoadhesive patches containing tetracycline hydrochloride and carvacrol in an attempt to develop a novel oral drug delivery system for the treatment of mouth infections. The bilayered patches were prepared using ethyl cellulose as a backing layer and carbopol 934 as a matrix mucoadhesive layer. Patches were prepared with different loading amounts of tetracycline hydrochloride and carvacrol. The antimicrobial activity was assessed for the prepared patches using the disc-diffusion method against the yeast Candida albicans and five bacterial strains, including Pseudomonas aeruginosa, Escherichia coli, Bacillus cereus, Staphylococcus aureus, and Bacillus bronchispti. In this work, we highlighted the possibility of occurrence of a synergistic action between carvacrol and tetracycline. The best formulation was selected based on microbiological tests, drug release, ex-vivo mucoadhesive performance, and swelling index. Physical characteristics of the selected formulations were determined. These included pH, patch thickness, weight uniformity, content uniformity, folding endurance, and patch stability.
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Two polymorphs and three solvates of fluconazole were isolated and characterized by x-ray powder diffractometry, IR spectroscopy, differential scanning calorimetry (DSC), thermogravimetry, and their dissolution rates. The different forms were prepared by crystallization of the original powder in different solvents at different cooling rates. X-ray diffraction patterns of the five solid modifications exhibited substantial differences in both the intensity and position of the peaks. FTIR spectra of the five different solid-state modifications also exhibited differences in the peaks' positions and intensities. DSC thermogram of anhydrate form I showed a single melting point at 139.2 degrees C. Anhydrate form II showed two endothermic peaks at 136.5 and 139.2 degrees C and one exothermic peak in between. The DSC thermogram of acetone 1/4 solvate exhibited two endothermic peaks at 75.5 and 139.2 degrees C. Benzene 1/7 solvate exhibited two endothermic peaks at 131.5 and 138.8 degrees C. Hydrate E exhibited two endothermic peaks at 102.7 and 139.2 degrees C. The DSC thermogram of anhydrate form II showed that this form is sensitive to the application of a mechanical force. The solubility study showed that anhydrate form II and acetone 1/4 solvate have higher solubilities than anhydrate form I while benzene 1/7 solvate and monohydrate have lower solubilities than anhydrate form I. The intrinsic dissolution study confirmed these results.