N-phenylbenzamide (N-PBA) was synthesized with the solvent-pair mixtures (1:1 v/v) containing hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) to investigate the replacement/limitation of ...hazardous dipolar aprotic solvents in amide drug synthesis. Pure solvents: dimethylformamide (DMF), dichloromethane (DCM), acetonitrile (ACN), acetone (Ace), tetrahydrofuran (THF), ethyl acetate (EtAc), dimethyl sulfoxide (DMSO), and mixed solvents: H2O-THF, H2O-DMSO, H2O-Ace, H2O-DMF, H2O–EtOH, H2O-IPA, EtOH-DMF, EtOH-DMSO were selected based on Kamlet-Taft (KT) parameters, GSK 2016 health-safety scores. Syntheses were carried out with an amide coupling system at 25 °C to evaluate the reaction yield observed with high-performance liquid chromatography (HPLC). The percent yield of 72.68 ± 0.35 (H2O-THF), 71.24 ± 1.93 (H2O-Ace), 80.27 ± 1.67 (EtOH-DMF), 67.27 ± 0.64 (EtOH-DMSO), 65.38 ± 1.55 (H2O-IPA) were found by adjusting the pH 10.8 in solvent mixtures for synthesis. A ninefold increase in the N-PBA yield was obtained by adjusting the pH 10.8 in mixed solvents. Besides, (77.12 ± 1.66, DMSO), and (92.44 ± 0.82, DMF) %yields in N-PBA were found using pure solvents. The aforementioned findings indicate that safe solvent mixtures can be utilized in amide drug synthesis to avoid/limit hazardous dipolar aprotic solvents.
Display omitted
Acetaminophen (ACMP) was synthesized in mixed-solvents (H2O-acetone, H2O-dimethyl sulfoxide, H2O-isopropyl alcohol) for purposes of eliminating hazardous dipolar aprotic solvents. The H2O-acetone ...solvent-pair gave synthesized ACMP yields of 79.2%. Synthesized ACMP samples were encapsulated using solution enhanced dispersion by supercritical CO2 (SEDS) at 150 bar, 45 °C, 1.5 mL/min feed flow rate (30 mg ACMP/mL in mixed-solvent), CO2 flow rate of 15 L/min (1 bar, 25 °C) in which suitable products could not be formed with PEG-4000 excipient at ACMP:PEG ratios of 1:1 with mixed-solvents, however, with ethyl cellulose (EC) excipient at ACMP:EC ratios of 1:1 and ethanol-acetone mixed-solvent (x:y, v/v, x = 1–9, y = 9–1), encapsulated products could be formed over the full range of mixed-solvent compositions. ACMP encapsulated fine particles had purities as high as 99.9% demonstrating that SEDS with safe mixed-solvents can broaden methods available for encapsulating pharmaceuticals.
Display omitted
•Chemical synthesis of acetaminophen (ACMP, >79% yield) with water:acetone mixtures.•ACMP particle encapsulation with SEDS: PEG-4000 fails; ethyl cellulose (EC) succeeds.•ACMP reliably encapsulated with EC using SEDS - ethanol:acetone mixed-solvents.•Encapsulation yields > 80% for SEDS using ethanol:acetone (1:1) (v/v) mixed-solvents.•Ethyl cellulose encapsulated acetaminophen particles (258 nm) had ~100% purity.
•Phaleria macrocarpa is widely used as a remedy to reduce blood glucose levels.•GC–MS is a distinctive method dominating the metabolomics research area.•Chemometric analysis can be applied to resolve ...large data sets.
Phaleria macrocarpa is a medicinal plant widely available in Malaysia. The plant parts have been traditionally used as an antidiabetic remedy. This study aimed to identify the putative inhibitors of the α-glucosidase enzyme from P. macrocarpa using a gas chromatography-mass spectrometry (GC–MS)-based metabolomics approach and further subjected them to in silico molecular docking analysis to elucidate the possible mechanism of action. This study assessed the inhibitory potential of P. macrocarpa fruit extracts (aqueous, 20 %, 40 %, 60 %, 80 %, and 100 % ethanol) against the α-glucosidase enzyme using GC–MS and chemometric analysis. Orthogonal partial least squares (OPLS) combined with GC–MS analysis were applied to correlate the inhibition of enzyme activity to the metabolites profile of P. macrocarpa. All the potential inhibitors identified were further docked to the yeast (Saccharomyces cerevisiae) protein crystal structure (PDB3A4A). The generated score scatter plot of OPLS showed a recognizable separation of all the extracts into six different clusters. GC–MS, incorporated with multivariate data analysis techniques, was used to identify significant chemical markers. Methyl α-d-glucopyranoside, squalene, palmitic acid, myo-inositol and isoquinoline metabolites were identified as putative inhibitors against α-glucosidase activity from P. macrocarpa. In conclusion, the GC–MS-based metabolomics approach identified potential chemical markers of P. macrocarpa that could be utilized in the development of herbal based medicine.
Background
Traditional medicine mainly of herbal origin is widely used all around the world. Heavy metal contamination in such products is frequently reported. Accumulation of heavy metals in the ...human body leads to various health hazards. Thus, precise determination for such contaminants is required for safety assurance. Sample preparation is a significant step in spectroscopic analysis to achieve reliable and accurate results. Wet digestion methods are basically used for the dissolution of herbal product samples prior to elemental analysis.
Methods
This study has been designed to evaluate the efficiency of three acid digestion methods using different solvents. Five samples were digested with three different acid digestion methods namely method A (a combination of nitric-perchloric acids HNO
3
–HClO
4
in a ratio 2:1), method B (only nitric acid HNO
3
), and method C (a mixture of nitric-hydrochloric acids HNO
3
–HCl in a ratio 1:3), to recommend the most efficient digestion method that gains the highest analyte recovery. The analysis of arsenic (As), cadmium (Cd), lead (Pb), nickel (Ni), zinc (Zn), and iron (Fe) was conducted using various techniques of atomic absorption spectrometry (AAS).
Results
The statistical analysis revealed that method C which represented the combination of nitric-hydrochloric acids HNO
3
–HCl in a ratio 1:3 was the most efficient digestion method for herbal product samples as it had given a significant high recovery (
p
< 0.05) for all metals compared to method A and method B. Accuracy of the proposed method was evaluated by the analysis of standard reference material (SRM) 1515 Apple Leaves from the National Institute of Standards and Technology (NIST) which presented good recoveries for all metals ranging from 94.5 to 108 %.
Conclusion
Method C provides highest recovery for all the analytes under investigation using AAS in herbal medicine samples.
Graphical Abstract:
Comparison of different sample prepartion for AAS analysis of herbal samples
Memantine hydrochloride is commonly prescribed for Alzheimer's disease and vascular dementia. However, the drug is only available in tablet form, a dosage form which is difficult for geriatrics to ...swallow. This problem is especially difficult for those patients diagnosed with Alzheimer's. This study was therefore aimed to develop and characterize an oral disintegrating film containing memantine hydrochloride using different types and concentrations of polymers. Using the solvent casting method, twelve formulations were developed, which involved manipulations on the type and concentration of the polymer. Afterwards, six formulations were selected to undergo characterization tests. These tests evaluated the films' tensile strength, Young's Modulus, percent elongation, folding endurance, disintegration and dissolution time, content uniformity, moisture loss, and moisture uptake. Polymers such as polyvinyl alcohol, hydroxypropyl methylcellulose, polyvinyl pyrrolidone, and pullulan gum were respectively incorporated at different concentrations. The study found that only hydroxypropyl methylcellulose and polyvinyl alcohol formulations developed into acceptable oral disintegrating films. Formulation E (hydroxypropyl methylcellulose 50-mg/film), which exhibited optimal mechanical strength, fast disintegration and dissolution, and excellent content uniformity, was identified as the best formula. Although polyvinyl alcohol showed higher mechanical strength, hydroxypropyl methylcellulose films were better at fulfilling the optimal characteristics of an oral disintegrating film. The study showed that the mechanical strength increased proportionally to the polymer concentration in the polyvinyl alcohol film. However, for the hydroxypropyl methylcellulose film, the mechanical strength increased only when hydroxypropyl methylcellulose's concentration was increased from a 40-mg/film to a 50-mg/film but decreased with a 60-mg/film. To summarize, orally disintegrating films containing memantine hydrochloride was developed, characterized, and reasoned to have high potential to be marketed and to increase medication compliance among geriatrics suffering from Alzheimer's disease.
The amlodipine besylate tablet is one of the most highly prescribed medicines to manage hypertension in the geriatric population. However, the difficulty of swallowing tablets due to problems like ...dysphagia, fear of choking, and odynophagia has been identified as one of the contributing factors to non-compliance among geriatrics. Due to the swallowing factor among geriatrics, this study was conducted to compare two compounding methods of orally disintegrating films, namely solvent casting and spray casting, to produce an orally disintegrating film containing amlodipine besylate. Different polymers were used to develop the orally disintegrating films, and the formulations were subjected to validation tests such as thickness, folding endurance, tensile strength, percentage of elongation, Young's modulus, disintegration, and dissolution. Chemicals like hydroxypropyl methylcellulose, carboxymethyl cellulose, glycerin, mannitol, sodium lauryl sulfate, citric acid, peppermint oil, and a coloring agent were used to formulate the orally disintegrating films. In addition, orally disintegrating films were prepared using the solvent casting and the spraying method. An increase in the polymer's concentration resulted in the formation of a greater mechanical strength. After a comparison between the hydroxypropyl methylcellulose and the carboxymethyl cellulose as film-forming agents, it was discovered that hydroxypropyl methylcellulose had greater mechanical film properties than carboxymethyl cellulose, except for the folding endurance. Moreover, hydroxypropyl methylcellulose was shown to have a better disintegration time, which was in the range of 30 minutes to 90 minutes, with a drug release of 95% to 100%, while carboxymethyl cellulose disintegrated at 6 minutes to 15 minutes with a drug release of 60% to 75%. On the other hand, both the solvent casting and spraying methods produced an evenly matched orally disintegrating film quality. Orally disintegrating films containing amlodipine besylate were developed and characterized. It was concluded that these orally disintegrating films have a great potential in the market and a profound ability in the reduction of geriatric non-compliance to antihypertensive drugs.
Orally disintegrating tablets, which were originally developed in the pharmaceutical field to improve the compliance of patients who had difficulty swallowing tablets, have become a preferable choice ...in solid dosage forms since it brings advantages to the patients and consumers in the healthcare system. Among the advantages of this novel dosage form are a faster onset of action, improved bioavailability, and the ease of administration as it can be taken without water. However, there are still some limitations of orally disintegrating tablets that need to be overcome, including a lack of mechanical strength, an unpleasant taste of the drug in the mouth, and a stability issue due to its hygroscopicity nature. This objective of this study was to identify the composition of co-processed excipients comprising of mannitol, microcrystalline cellulose, xylitol, and crospovidone or croscarmellose sodium in order to formulate orally disintegrating tablets containing memantine hydrochloride. This study was carried out in two stages. Firstly, orally disintegrating tablets containing memantine hydrochloride with 6 different formulations, which differed in the percentage of crospovidone or croscarmellose sodium, were formulated and manufactured. Secondly, the orally disintegrating tablets obtained were evaluated through pre- and post-compression tests based on the standard for orally disintegrating tablets. Formulation 3, which consisted of 10% xylitol, 10% mannitol, 72% microcrystalline cellulose, and 8% crospovidone, was chosen as the optimum formulation for the co-processed excipient since it was the fastest disintegration process among all the formulations in the study. In addition, Formulation 3 also showed the acceptable and satisfying results in other evaluation tests such as - weight variation test, hardness test, and friability test. The co-processed excipient comprising of 10% xylitol, 10% mannitol, 72% microcrystalline cellulose, and 8% crospovidone, which is characterized by improved functionalities such as a fast disintegration process, plays a crucial role in the application of orally disintegrating tablets.
PDF
