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1.
Water Environ Res ; 96(5): e11018, 2024 May.
Article in English | MEDLINE | ID: mdl-38712584

ABSTRACT

Applicable and low-cost ultrafiltration membranes based on waste polystyrene (WPS) blend and poly vinylidene fluoride (PVDF) were effectively cast on nonwoven support using phase inversion method. Analysis was done into how the WPS ratio affected the morphology and antifouling performance of the fabricated membranes. Cross flow filtration of pure water and various types of polluted aqueous solutions as the feed was used to assess the performance of the membranes. The morphology analysis shows that the WPS/PVDF membrane layer has completely changed from a spongy structure to a finger-like structure. In addition, the modified membrane with 50% WPS demonstrated that the trade-off between selectivity and permeability is met by a significant improvement in the rejection of the membrane with a reduction in permeate flux due to the addition of PVDF. With a water permeability of 50 LMH and 44 LMH, respectively, the optimized WPS-PVDF membrane with 50% WPS could reject 81% and 74% of Congo red dye (CR) and methylene blue dye (MB), respectively. The flux recovery ratio (FRR) reached to 88.2% by increasing PVDF concentration with 50% wt. Also, this membrane has the lowest irreversible fouling (Rir) value of 11.7% and lowest reversible fouling (Rr) value of 27.9%. The percent of cleaning efficiency reach to 71%, 90%, and 85% after eight cycles of humic acid (HA), CR, and MB filtration, respectively, for the modified PS-PVDF (50%-50%). However, higher PVDF values cause the membrane's pores to become clogged, increase the irreversible fouling, and decrease the cleaning efficiency. In addition to providing promising filtration results, the modified membrane is inexpensive because it was made from waste polystyrene, and as a result, it could be scaled up to treat colored wastewater produced by textile industries. PRACTITIONER POINTS: Recycling of plastic waste as an UF membrane for water/wastewater treatment was successfully prepared and investigated. Mechanical properties showed reasonable response with adding PVDF. The modified membrane with 50% PS demonstrated that the trade-off between selectivity and permeability is met by a significant improvement in the rejection.


Subject(s)
Coloring Agents , Fluorocarbon Polymers , Membranes, Artificial , Ultrafiltration , Water Pollutants, Chemical , Water Purification , Ultrafiltration/methods , Coloring Agents/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/isolation & purification , Water Purification/methods , Plastics/chemistry , Waste Disposal, Fluid/methods , Polyvinyls/chemistry , Permeability
2.
J Agric Food Chem ; 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38597922

ABSTRACT

Quinazoline compounds have gained significant attention in the fields of agriculture and chemistry due to their diverse activities. In this study, we focused on a series of quinazoline derivatives (4a-l). The objectives involved multiple aspects, including preparation, evaluation of their agricultural bioactivity against the maize aphid (Rhopalosiphum maidis), estimation of the structure-activity relationships (SAR), and conducting molecular docking analysis. The results of the agricultural bioactivities revealed that compound (4b) possesses the highest insecticidal activity, and the other compounds have good potential as insecticidal agents. We conducted the SARs and also molecular docking investigation to elucidate the binding modes and interactions of these compounds with target proteins relevant to the agricultural bioactivity. The docking results provided valuable information on the binding affinities and molecular interactions, aiding in the rationalization of the observed bioactivity trends. The enzyme, acetylcholinesterase (AChE), was docked with the 12 synthetic compounds (4a-l). Among these compounds, (4b), (4i), and (4e)exhibited the highest binding affinity, with docking scores (S) of -7.96, -7.83, and -7.73 kcal/mol, respectively. They were followed by compounds (4d) (S = -7.57 kcal/mol), (4c) (S = -7.53 kcal/mol), (4g) (S = -7.34 kcal/mol), (4f) (S = -7.23 kcal/mol), (4h) (S = -7.14 kcal/mol), (4k) (S = -6.61 kcal/mol), (4j) (S = -6.57 kcal/mol), (4a) (S = -6.28 kcal/mol), and finally (4l) (S = -6.01 kcal/mol). These compounds were shown to have a variety of binding interactions within the 2ACE active site, as evidenced by protein-ligand docking configurations. This study gives evidence that those compounds have AChE-inhibitory capabilities and, hence, may be used for AChE-targeting development. Also, the findings in this study highlight the potential of these compounds as agricultural agents and provide valuable insights for the design and development of some quinazoline derivatives with enhanced bioactivity for crop protection.

3.
J King Saud Univ Sci ; 35(4): 102628, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36908997

ABSTRACT

In the present work, we describe the extraction of a natural product namely 1,4,9,9-tetramethyloctahydro-4,7-(epoxymethano)azulen-5(1H)-one, and its structure was confirmed by single crystal X-ray diffraction analysis. The conformations of the 5-, 6-, and 7-membered rings in the title compound, C15H24O2, have been probed by a Cremer-Pople puckering analysis. C-H···O hydrogen bonds generate chains in the crystal that stretch along the c-axis direction. The Hirshfeld surface analysis method was used to stabilize the crystal packing of the natural compound. Accompanied by experimental studies, quantum chemical calculations were also performed to compare the structural elucidation and the results of these geometrical parameters exhibited excellent agreement. The compound was also docked with several drug targets of the SARS-CoV-2 virus and found to show the best binding with the main protease enzyme, having a binding energy of -12.31 kcal/mol and interacting with His41 and Cys145 residues. The dynamic stability deciphered the complex to be stable with an average RMSD of 3.8 Å. The compound dynamics with the enzyme showed the compound conformation to be highly stable. The intermolecular binding free energy determined the compound-main protease enzyme to show high interaction energy of < 40 kcal/mol. Together, these studies demonstrate the compound to be a lead structure against SARS-CoV-2.

4.
Acta Crystallogr E Crystallogr Commun ; 78(Pt 8): 846-850, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-35974819

ABSTRACT

In the title mol-ecule, C23H20Cl2N4O3S, the thia-zole ring is planar while the pyrimidine unit fused to it adopts a screw-boat conformation. In the crystal, thick sheets parallel to the bc plane are formed by N-H⋯N, C-H⋯N and C-H⋯O hydrogen bonds together with π-π inter-actions between the formamido carbonyl groups and the thia-zole rings. Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H⋯H (30.9%), Cl⋯H/H⋯Cl (20.7%), C⋯H/H⋯C (16.8%) and O⋯H/H⋯O (11.4%) inter-actions.

5.
Trop Med Health ; 50(1): 39, 2022 Jun 06.
Article in English | MEDLINE | ID: mdl-35668541

ABSTRACT

BACKGROUND: The global consumption of herbal medicine is increasing steadily, posing an extinction risk to medicinal plants. Uganda is among the top ten countries with a high threat of herbal medicine extinction, and Traditional Medicinal Knowledge (TMK) erosion. This might be attributed to the inadequate documentation, plus many more unclear hindrances. In this study, plant species used to treat human diseases in Butaleja district in Eastern Uganda and their associated TMK were documented. The conservation methods for medicinal plants were also evaluated. The rationale was to support the preservation of ethnopharmacological knowledge. METHODS: Data were collected from 80 herbalists using semi-structured questionnaires, from July 2020 to March 2021. Additionally, guided field walks and observations were conducted. Quantitative indices such as, use categories and informant consensus factor (ICF) were evaluated to elucidate the importance of the medicinal plants. Data were analyzed using STATA version-15.0 software. RESULTS: In total, 133 species, belonging to 34 families and 125 genera were identified. Fabaceae (65%), and Solanaceae (29%) were the dominant families. Leaves (80%), and roots (15%), were the commonest parts used in medicinal preparations; mostly administered orally as decoctions (34.6%) and infusions (16%). The commonest illnesses treated were cough (7.74%), gastric ulcers (7.42%), and malaria (4.52%). The informant consensus factor was high for all disease categories (≥ 0.8), indicating homogeneity of knowledge about remedies used. Only 73% of the respondents made efforts to conserve medicinal plants. The commonest conservation strategy was preservation of forests with spiritually valued species (100%), while compliance with government regulations was the rarest (4.5%). Overall, efforts to stop the extinction of medicinal plants and TMK were inadequate. CONCLUSION AND RECOMMENDATIONS: There was enormous dependency on a rich diversity of medicinal plant species and TMK for healthcare and income generation. The potential for medicinal plant biodiversity loss was evident due to habitat destruction. Inclusion of traditional cultural norms in conservation strategies, and laboratory-based efficacy tests for the species identified are necessary, to promote the conservative and utilization of validated herbal medicines and TMK in rural settings.

6.
Sci Rep ; 12(1): 4310, 2022 03 12.
Article in English | MEDLINE | ID: mdl-35279668

ABSTRACT

Tuberculosis (TB) is fatal in elephants, hence protecting elephants from TB is key not only in the conservation of this endangered animal, but also to prevent TB transmission from elephants to humans. Most human TB cases arise from long-term asymptomatic infections. Significant diagnostic challenges remain in the detection of both infection and disease development from latency in elephants due to their huge bodies. In this study, we assessed cryopreserved sera collected for over 16 years, from the first Japanese treatment case of elephant TB. Semi-quantification of IgG levels to 11 proteins showed high detection levels of 3 proteins, namely ESAT6/CFP10, MPB83 and Ag85B. The level of IgG specific to these 3 antigens was measured longitudinally, revealing high and stable ESAT6/CFP10 IgG levels regardless of onset or treatment. Ag85B-specifc IgG levels were largely responsive to onset or treatment, while those of MPB83 showed intermediate responses. These results suggest that ESAT6/CFP10 is immunodominant in both asymptomatic and symptomatic phases, making it useful in the detection of infection. On the other hand, Ag85B has the potential to be a marker for the prediction of disease onset and in the evaluation of treatment effectiveness in elephants.


Subject(s)
Elephants , Mycobacterium tuberculosis , Tuberculosis , Animals , Antigens, Bacterial , Bacterial Proteins , Elephants/microbiology , Immunoglobulin G , Tuberculosis/diagnosis , Tuberculosis/veterinary
7.
Sci Rep ; 10(1): 17997, 2020 10 22.
Article in English | MEDLINE | ID: mdl-33093577

ABSTRACT

Mycobacterium tuberculosis (Mtb) strains of Beijing lineage have caused great concern because of their rapid emergence of drug resistance and worldwide spread. DNA mutation rates that reflect evolutional adaptation to host responses and the appearance of drug resistance have not been elucidated in human-infected Beijing strains. We tracked and obtained an original Mtb isolate of Beijing lineage from the 1999 tuberculosis outbreak in Japan, as well as five other isolates that spread in humans, and two isolates from the patient caused recurrence. Three isolates were from patients who developed TB within one year after infection (rapid-progressor, RP), and the other three isolates were from those who developed TB more than one year after infection (slow-progressor, SP). We sequenced genomes of these isolates and analyzed the propensity and rate of genomic mutations. Generation time versus mutation rate curves were significantly higher for RP. The ratio of oxidative versus non-oxidation damages induced mutations was higher in SP than RP, suggesting that persistent Mtb are exposed to oxidative stress in the latent state. Our data thus demonstrates that higher mutation rates of Mtb Beijing strains during human infection is likely to account for the higher adaptability and an emergence ratio of drug resistance.


Subject(s)
DNA, Bacterial/genetics , Drug Resistance, Bacterial/genetics , Evolution, Molecular , Genome, Bacterial , Mutation , Mycobacterium tuberculosis/genetics , Tuberculosis/microbiology , Beijing , DNA, Bacterial/analysis , Humans , Japan/epidemiology , Mutation Rate , Mycobacterium tuberculosis/isolation & purification , Mycobacterium tuberculosis/pathogenicity , Tuberculosis/epidemiology , Tuberculosis/genetics
8.
Article in English | MEDLINE | ID: mdl-32152081

ABSTRACT

Delamanid (DLM), a nitro-dihydroimidazooxazole derivative currently approved for pulmonary multidrug-resistant tuberculosis (TB) therapy, is a prodrug activated by mycobacterial 7,8-didemethyl-8-hydroxy 5-deazaflavin electron transfer coenzyme (F420)-dependent nitroreductase (Ddn). Despite inhibiting the biosynthesis of a subclass of mycolic acids, the active DLM metabolite remained unknown. Comparative liquid chromatography-mass spectrometry (LC-MS) analysis of DLM metabolites revealed covalent binding of reduced DLM with a nicotinamide ring of NAD derivatives (oxidized form) in DLM-treated Mycobacterium tuberculosis var. Bacille de Calmette et Guérin. Isoniazid-resistant mutations in the type II NADH dehydrogenase gene (ndh) showed a higher intracellular NADH/NAD ratio and cross-resistance to DLM, which were restored by complementation of the mutants with wild-type ndh Our data demonstrated for the first time the adduct formation of reduced DLM with NAD in mycobacterial cells and its importance in the action of DLM.


Subject(s)
Antitubercular Agents/pharmacology , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/genetics , Nitroimidazoles/pharmacology , Oxazoles/pharmacology , Tuberculosis, Multidrug-Resistant/genetics , Tuberculosis, Pulmonary/drug therapy , Chromatography, Liquid , Drug Resistance, Multiple, Bacterial/genetics , Isoniazid/pharmacology , Mass Spectrometry , Mycolic Acids/metabolism , NAD/analysis , NADH Dehydrogenase/genetics , Oxidation-Reduction , Polymorphism, Single Nucleotide/genetics , Tuberculosis, Multidrug-Resistant/drug therapy
9.
ACS Omega ; 4(5): 8406-8412, 2019 May 31.
Article in English | MEDLINE | ID: mdl-31459929

ABSTRACT

A lot of insecticides are found nowadays, but neonicotinoids are considered the most famous. So, a series of pyridine derivatives neonicotinoids analogues, namely, 3-cyano-4,6-dimethylpyridine-2(1H)-one (1), 2-chloro-3-cyano-4,6-dimethylpyridine (2), 3-cyano-4,6-dimethylpyridine-2(1H)-thione (3), 3-cyano-4,6-distyrylpyridine-2(1H)-thione (4), 2-((3-cyano-4,6-distyrylpyridin-2-yl)thio)-N-phenylacetamide (5), 3-amino-N-phenyl-4,6-distyrylthieno[2,3-b]pyridine-2-carboxamide (6), 2-((3-cyano-4,6-distyrylpyridin-2-yl)thio)-N-(p-tolyl)acetamide (7), 3-amino-4,6-distyryl-N-(p-tolyl)thieno[2,3-b]pyridine-2-carboxamide (8), 2-((3-cyano-4,6-distyrylpyridin-2-yl)thio)-N-(4-methoxyphenyl)acetamide (9), and 3-amino-N-(4-methoxyphenyl)-4,6-distyrylthieno[2,3-b]pyridine-2-carboxamide (10), have been designed and synthesized in pure state, and their agricultural bioefficacy as insecticides against cowpea aphid Aphis craccivora Koch was screened. The structures of the synthesized compounds were verified by means of spectroscopic and elemental analyses. Insecticidal bioefficacy data illustrated that some compounds are excellent against cowpea aphid, and the bioefficacy of the rest of the tested compounds ranged from good to moderate against the same insects.

10.
Toxicol Rep ; 6: 100-104, 2019.
Article in English | MEDLINE | ID: mdl-30622903

ABSTRACT

Neonicotinoids are the most widely used from all existing pesticides. So, in purpose to discover new pesticides being more effective against the aphid, twelve heterocyclic compounds neonicotinoid analogs have been prepared in a pure state; pyrimidothienotetrahydroisoquinolines 1-12 and their toxicity as potential insecticidal agents against cowpea Aphid, Aphis craccivora Koch was screened. Their characterizations by using spectroscopic analyses were performed. The toxicity data exhibited that the 8-chloropyrimidine compound 4 is more toxic about 2-fold than a reference insecticide, acetamiprid. The other screened compounds showed weak to strong toxicological activities against cowpea aphid.

11.
AAPS PharmSciTech ; 19(8): 3403-3413, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30097806

ABSTRACT

An extrusion-based 3D printer was used to fabricate paracetamol tablets with different geometries (mesh, ring and solid) from a single paste-based formulation formed from standard pharmaceutical ingredients. The tablets demonstrate that tunable drug release profiles can be achieved from this single formulation even with high drug loading (> 80% w/w). The tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed well-defined release profiles (from immediate to sustained release) controlled by their different geometries. The dissolution results showed dependency of drug release on the surface area/volume (SA/V) ratio and the SA of the different tablets. The tablets with larger SA/V ratios and SA had faster drug release. The 3D printed tablets were also evaluated for physical and mechanical properties including tablet dimension, drug content, weight variation and breaking force and were within acceptable range as defined by the international standards stated in the US Pharmacopoeia. X-ray powder diffraction, differential scanning calorimetry and attenuated total reflectance Fourier transform infrared spectroscopy were used to identify the physical form of the active and to assess possible drug-excipient interactions. These data again showed that the tablets meet USP requirement. These results clearly demonstrate the potential of 3D printing to create unique pharmaceutical manufacturing, and potentially clinical, opportunities. The ability to use a single unmodified formulation to achieve defined release profiles could allow, for example, relatively straightforward personalization of medicines for individuals with different metabolism rates for certain drugs and hence could offer significant development and clinical opportunities.


Subject(s)
Acetaminophen/chemistry , Acetaminophen/pharmacokinetics , Drug Liberation , Printing, Three-Dimensional , Technology, Pharmaceutical/methods , Calorimetry, Differential Scanning , Drug Compounding/methods , Excipients/chemistry , Spectroscopy, Fourier Transform Infrared , Tablets/chemistry , X-Ray Diffraction
12.
Sci Rep ; 8(1): 8197, 2018 05 29.
Article in English | MEDLINE | ID: mdl-29844400

ABSTRACT

The architecture of the genome influences the functions of DNA from bacteria to eukaryotes. Intrinsically disordered regions (IDR) of eukaryotic histones have pivotal roles in various processes of gene expression. IDR is rare in bacteria, but interestingly, mycobacteria produce a unique histone-like protein, MDP1 that contains a long C-terminal IDR. Here we analyzed the role of IDR in MDP1 function. By employing Mycobacterium smegmatis that inducibly expresses MDP1 or its IDR-deficient mutant, we observed that MDP1 induces IDR-dependent DNA compaction. MDP1-IDR is also responsible for the induction of growth arrest and tolerance to isoniazid, a front line tuberculosis drug that kills growing but not growth-retardated mycobacteria. We demonstrated that MDP1-deficiency and conditional knock out of MDP1 cause spreading of the M. smegmatis genome in the stationary phase. This study thus demonstrates for the first time a C-terminal region-dependent organization of the genome architecture by MDP1, implying the significance of IDR in the function of bacterial histone-like protein.


Subject(s)
Bacterial Proteins/metabolism , DNA-Binding Proteins/metabolism , Genome, Bacterial , Intrinsically Disordered Proteins/metabolism , Mycobacterium smegmatis/genetics , Mycobacterium smegmatis/metabolism , Amino Acid Sequence , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , DNA Replication , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/genetics , Gene Deletion , Gene Expression , Histones/chemistry , Histones/genetics , Histones/metabolism , Humans , Intrinsically Disordered Proteins/chemistry , Intrinsically Disordered Proteins/genetics , Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium smegmatis/chemistry , Mycobacterium smegmatis/growth & development
13.
Int J Pharm ; 538(1-2): 223-230, 2018 Mar 01.
Article in English | MEDLINE | ID: mdl-29353082

ABSTRACT

The manufacture of immediate release high drug loading paracetamol oral tablets was achieved using an extrusion based 3D printer from a premixed water based paste formulation. The 3D printed tablets demonstrate that a very high drug (paracetamol) loading formulation (80% w/w) can be printed as an acceptable tablet using a method suitable for personalisation and distributed manufacture. Paracetamol is an example of a drug whose physical form can present challenges to traditional powder compression tableting. Printing avoids these issues and facilitates the relatively high drug loading. The 3D printed tablets were evaluated for physical and mechanical properties including weight variation, friability, breaking force, disintegration time, and dimensions and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). X-ray Powder Diffraction (XRPD) was used to identify the physical form of the active. Additionally, XRPD, Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC) were used to assess possible drug-excipient interactions. The 3D printed tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed a profile characteristic of the immediate release profile as intended based upon the active/excipient ratio used with disintegration in less than 60 s and release of most of the drug within 5 min. The results demonstrate the capability of 3D extrusion based printing to produce acceptable high-drug loading tablets from approved materials that comply with current USP standards.


Subject(s)
Acetaminophen/administration & dosage , Analgesics, Non-Narcotic/administration & dosage , Printing, Three-Dimensional , Technology, Pharmaceutical/methods , Acetaminophen/chemistry , Analgesics, Non-Narcotic/chemistry , Calorimetry, Differential Scanning , Drug Liberation , Excipients/chemistry , Powders , Solubility , Spectroscopy, Fourier Transform Infrared , Tablets , X-Ray Diffraction
14.
Int J Cardiovasc Imaging ; 33(3): 371-382, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27832419

ABSTRACT

To assess the feasibility of four-dimensional (4D) whole-heart computed tomography perfusion (CTP) of the myocardium and the added value of temporal averaging of consecutive 3D datasets from different heartbeats for analysis. We included 30 patients with suspected or known coronary artery disease (CAD) who underwent 320-row coronary CT angiography (CTA) and myocardial CTP. Out of these, 15 patients underwent magnetic resonance myocardial perfusion imaging (MR MPI). All CTP examinations were initiated after 3 min of intravenous infusion of adenosine (140 µg/kg/min) and were performed dynamically covering the entire heart every heart beat over a period of 20 ± 3 heart beats. Temporal averaging for dynamic CTP visualisation was analysed for the combination of two, three, four, six, and eight consecutive 3D datasets. Input time attenuation curves (TAC) were delivered from measurement points in the centre of the left ventricle. In all 30 patients, myocardial 4D CTP was feasible and temporal averaging was successfully implemented for all planned combinations of 3D datasets. Temporal averaging of three consecutive 3D datasets showed best performance in the analysis of all CTP image quality parameters: noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), subjective image quality, and diagnostic accuracy with an improvement of SNR and CNR by a factor of 2.2 ± 1.3 and 1.3 ± 0.9. With increasing level of temporal averaging, the input TACs became smoother, but also shorter. Out of the 11 perfusion defects detected with MR MPI, 9 defects were also visible on the 4D CTP images. Whole-heart CTP of the myocardium is feasible and temporal averaging of dynamic datasets improves quantitative image quality parameters and visualization of perfusion defects while further studies are needed to assess its added value for quantification of perfusion parameters.


Subject(s)
Computed Tomography Angiography , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Coronary Circulation , Coronary Vessels/diagnostic imaging , Four-Dimensional Computed Tomography , Multidetector Computed Tomography , Myocardial Perfusion Imaging/methods , Aged , Coronary Artery Disease/physiopathology , Coronary Vessels/physiopathology , Feasibility Studies , Female , Heart Rate , Humans , Male , Middle Aged , Pilot Projects , Predictive Value of Tests , Radiographic Image Interpretation, Computer-Assisted , Reproducibility of Results , Signal-To-Noise Ratio , Time Factors
15.
J Control Release ; 217: 308-14, 2015 Nov 10.
Article in English | MEDLINE | ID: mdl-26390808

ABSTRACT

We have used three dimensional (3D) extrusion printing to manufacture a multi-active solid dosage form or so called polypill. This contains five compartmentalised drugs with two independently controlled and well-defined release profiles. This polypill demonstrates that complex medication regimes can be combined in a single personalised tablet. This could potentially improve adherence for those patients currently taking many separate tablets and also allow ready tailoring of a particular drug combination/drug release for the needs of an individual. The polypill here represents a cardiovascular treatment regime with the incorporation of an immediate release compartment with aspirin and hydrochlorothiazide and three sustained release compartments containing pravastatin, atenolol, and ramipril. X-ray powder diffraction (XRPD) and Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) were used to assess drug-excipient interaction. The printed polypills were evaluated for drug release using USP dissolution testing. We found that the polypill showed the intended immediate and sustained release profiles based upon the active/excipient ratio used.


Subject(s)
Delayed-Action Preparations/chemistry , Drug Combinations , Printing, Three-Dimensional , Tablets/chemistry , Aspirin/chemistry , Atenolol/chemistry , Drug Liberation , Excipients/chemistry , Hydrochlorothiazide/chemistry , Powder Diffraction , Pravastatin/chemistry , Ramipril/chemistry , Solubility , Spectroscopy, Fourier Transform Infrared , X-Ray Diffraction
16.
Int J Pharm ; 494(2): 643-650, 2015 Oct 30.
Article in English | MEDLINE | ID: mdl-26235921

ABSTRACT

We have employed three-dimensional (3D) extrusion-based printing as a medicine manufacturing technique for the production of multi-active tablets with well-defined and separate controlled release profiles for three different drugs. This 'polypill' made by a 3D additive manufacture technique demonstrates that complex medication regimes can be combined in a single tablet and that it is viable to formulate and 'dial up' this single tablet for the particular needs of an individual. The tablets used to illustrate this concept incorporate an osmotic pump with the drug captopril and sustained release compartments with the drugs nifedipine and glipizide. This combination of medicines could potentially be used to treat diabetics suffering from hypertension. The room temperature extrusion process used to print the formulations used excipients commonly employed in the pharmaceutical industry. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and X-ray powder diffraction (XRPD) were used to assess drug-excipient interaction. The printed formulations were evaluated for drug release using USP dissolution testing. We found that the captopril portion showed the intended zero order drug release of an osmotic pump and noted that the nifedipine and glipizide portions showed either first order release or Korsmeyer-Peppas release kinetics dependent upon the active/excipient ratio used.


Subject(s)
Drug Combinations , Drug Delivery Systems/instrumentation , Precision Medicine/instrumentation , Printing, Three-Dimensional/instrumentation , Technology, Pharmaceutical/instrumentation , Captopril/administration & dosage , Delayed-Action Preparations , Drug Liberation , Excipients/chemistry , Glipizide/administration & dosage , Humans , Nifedipine/administration & dosage , Spectroscopy, Fourier Transform Infrared , Temperature , X-Ray Diffraction
17.
J Agric Food Chem ; 62(41): 9982-6, 2014 Oct 15.
Article in English | MEDLINE | ID: mdl-25226271

ABSTRACT

Five pyridine derivatives, namely, N-morpholinium 7,7-dimethyl-3-cyano-4-(4'-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-2-thiolate (1), sodium 5-acetyl-3-amino-4-(4'-methoxyphenyl)-6-methylthieno[2,3-b] pyridine-2-carboxylate (2), piperidinium 3,5-dicyano-2-oxo-4-spirocyclopentane-1,2,3,4-tetrahydropyridine-6-thiolate (3), piperidinium 5-acetyl-3-cyano-4-(4'-methoxyphenyl)-6-methylpyridine-2-thiolate (4), and piperidinium 5-acetyl-4-(4'-chlorophenyl)-3-cyano-6-methyl-pyridine-2-thiolate (5) were prepared in pure state and subjected to the title study. The bioassay results indicated that the insecticidal activity of compound 1 is about 4-fold that of acetamiprid insecticide. The rest of the tested compounds possess moderate to strong aphidicidal activities.


Subject(s)
Aphids/drug effects , Insecticides/chemistry , Insecticides/toxicity , Pyridines/chemistry , Pyridines/toxicity , Animals , Insecticides/chemical synthesis , Molecular Structure
18.
Int J Pharm ; 461(1-2): 105-11, 2014 Jan 30.
Article in English | MEDLINE | ID: mdl-24280018

ABSTRACT

Three dimensional (3D) printing was used as a novel medicine formulation technique for production of viable tablets capable of satisfying regulatory tests and matching the release of standard commercial tablets. Hydroxypropyl methylcellulose (HPMC 2208) (Methocel™ K100M Premium) and poly(acrylic acid) (PAA) (Carbopol(®) 974P NF) were used as a hydrophilic matrix for a sustained release (SR) layer. Hypromellose(®) (HPMC 2910) was used as a binder while microcrystalline cellulose (MCC) (Pharmacel(®) 102) and sodium starch glycolate (SSG) (Primojel(®)) were used as disintegrants for an immediate release (IR) layer. Commercial guaifenesin bi-layer tablets (GBT) were used as a model drug (Mucinex(®)) for this study. There was a favourable comparison of release of the active guaifenesin from the printed hydrophilic matrix compared with the commercially available GBT. The printed formulations were also evaluated for physical and mechanical properties such as weight variation, friability, hardness and thickness as a comparison to the commercial tablet and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). All formulations (standard tablets and 3D printed tablets) showed Korsmeyer-Peppas n values between 0.27 and 0.44 which indicates Fickian diffusion drug release through a hydrated HPMC gel layer.


Subject(s)
Excipients/chemistry , Guaifenesin/administration & dosage , Printing/methods , Technology, Pharmaceutical/methods , Acrylates/chemistry , Cellulose/chemistry , Chemistry, Pharmaceutical/methods , Delayed-Action Preparations , Guaifenesin/chemistry , Hardness , Hypromellose Derivatives/chemistry , Imaging, Three-Dimensional/methods , Starch/analogs & derivatives , Starch/chemistry , Tablets
19.
Ann R Coll Surg Engl ; 95(4): 285-90, 2013 May.
Article in English | MEDLINE | ID: mdl-23676815

ABSTRACT

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) is indispensable in everyday surgical practice. Despite this, as an invasive procedure, it has its own mortality and morbidity, the most feared of which is periduodenal perforations. Our experience with ERCP related periduodenal perforations and its treatment strategies are presented. Additionally, a rarely encountered subtype is highlighted. METHODS: Patients who underwent ERCP and sustained a periduodenal perforation between August 2008 and October 2011 were reviewed. RESULTS: During the period from August 2008 to October 2011, 597 ERCP procedures were performed in our hospital. Ten of these patients (3 male, 7 female) had a perforation. The mean patient age was 56.6 years. During the procedure, injury was suspected in four patients; it passed unnoticed in the remaining six. The decision to operate or follow a conservative policy was based on a combination of clinical and radiological findings. Operative intervention was required in three patients, with one mortality, while conservative treatment was followed in the remaining seven. A laparotomy was performed early in two patients whereas it was performed after an initial period of conservative treatment in one. The presence of periduodenal fluid collection, contrast extravasation or free intraperitoneal air were decisive factors for performing laparotomy. CONCLUSIONS: ERCP-related periduodenal perforations include different categories. Certain types require operative repair while others should be treated conservatively. The choice of the management approach should be individualised, depending on the clinical picture and radiological findings. Although rare, these are potentially serious complications that may end fatally. Early recognition and appropriate intervention is the only way to avert a fatal outcome.


Subject(s)
Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Duodenum/injuries , Intestinal Perforation/therapy , Adult , Aged , Aged, 80 and over , Digestive System Diseases/surgery , Female , Humans , Intestinal Perforation/etiology , Intestinal Perforation/surgery , Laparotomy , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed
20.
J Endourol ; 22(1): 29-34, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18095859

ABSTRACT

BACKGROUND AND PURPOSE: During percutaneous renal surgery, subcostal access is preferred because it carries no risk of injury to either the lungs or pleura. However, in some situations, a supracostal approach may provide more direct access and achieve a more satisfactory result than the subcostal approach. In this prospective study, we evaluated the safety and efficacy of supracostal approaches in percutaneous renal surgery. MATERIALS AND METHODS: Between 2004 and 2006, 30 patients underwent percutaneous renal surgery with a supracostal approach either as the sole or as a secondary access. The indications were staghorn stones, upper caliceal stones, upper ureteral stones, secondary ureteropelvic junction obstruction, disturbed lower caliceal anatomy, and high-lying kidneys. The puncture was above the eleventh rib in six procedures and above the twelfth rib in 24 procedures. All patients were examined for equal air entry on both sides of the chest, and all had chest radiography performed immediately after surgery to exclude pneumothorax or hydrothorax. Bleeding was assessed with evaluation of preoperative and postoperative hemoglobin, levels and vital signs; urine was also examined for gross hematuria. A routine nephrostogram was obtained for all patients. RESULTS: Supracostal was the sole access in 63.3% of patients and a secondary access in 36.7% of patients. Intraoperatively, bleeding occurred in one patient. Hydrothorax in another patient necessitated insertion of an intercostal chest drain. A renopleural fistula developed in another patient 2 days postoperatively that necessitated placement of a chest drain and Double J stent. Access in both patients with pleural complications had been above the eleventh rib. The mean drop in hemoglobin level was 0.79 +/- 0.72 g/dL. Our overall stone-free rate was 88.9%. CONCLUSION: Supracostal access above the twelfth rib is relatively safe; however, access above the eleventh rib should be limited to necessity because a higher incidence of pleural complications can be expected. A chest radiograph should be obtained immediately postoperatively for early detection of hydrothorax or pneumothorax.


Subject(s)
Nephrostomy, Percutaneous/methods , Adult , Female , Humans , Kidney/diagnostic imaging , Male , Nephrostomy, Percutaneous/adverse effects , Radiography , Ureter/diagnostic imaging
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