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1.
PLoS One ; 17(8): e0271442, 2022.
Article En | MEDLINE | ID: mdl-36018842

Propranolol hydrochloride is a beta-blocker used for the management and treatment of hypertension, angina, coronary artery disease, heart failure, fibrillation, tremors, migraine etc. The objective of the present study was to design Propranolol Hydrochloride floating tablets by direct compression method and to explore the role of a new gum as a matrix former. A 22 full factorial design was selected for the present study. Prunus domestica gum and HPMC (K4M) were used as independent variables, swelling index and drug dissolution at 12 hours as dependent variables. Formulations were subjected to pre- and post-compression tests that showed good micromeritics and buoyancy characteristics (Carr's index 11.76%-14.00%, Hausner's ratio 1.13°-1.16°, angle of repose 22.67°-25.21°, floating lag time 56-76 seconds, total floating time 18-25 hours and swelling index 59.87%-139.66%). The cumulative drug release in 0.1 N HCl at 12 hours was 72%-90% (p<0.05). Weibull model was found to be the best fit model (R2>0.99) among all other studied models. Multiple regression showed a significant effect of Prunus domestica gum and HPMC K4M on the swelling index and dissolution profiles of propranolol HCl (p<0.05). On the basis of better in-vitro performance and cost-effectiveness, formulation F4 was the best formulation. It is evident from the results that Prunus domestica gum possesses excellent drug release retardant potential for the floating drug delivery system and this new gum should be further explored alone or with other natural and synthetic polymers in future studies.


Propranolol , Prunus domestica , Delayed-Action Preparations , Drug Delivery Systems , Drug Liberation , Tablets
3.
ACS Omega ; 7(16): 14165-14179, 2022 Apr 26.
Article En | MEDLINE | ID: mdl-35559189

The main goal of this study is to monitor the stability of crude oils in terms of both precipitation and deposition magnitude with respect to time. To achieve this goal, two experimental techniques which include a deposit level test and a spot test were integrated and applied simultaneously. The method was implemented using six crude oils, namely A, B, D, E, F, and G, and tests were performed at different times which split them into short duration tests and long duration tests. All crude oils were found to exhibit potential for asphaltene precipitation and subsequent deposition at different rates. Crude oils B, G, and D were observed to have started asphaltene precipitation and subsequent deposition relatively quicker. Similarly, crude oils B, A, and F exhibit a higher potential for producing asphaltene deposits in terms of deposition level. Crude oil E produces relatively fewer deposits at comparatively slower rates. The overall result indicates that crude oil B was found to be the most risky crude oil as it produces a higher quantity of deposits at higher rates, while crude oil E proved to be the least risky. Sensitivity analysis was also performed via the computing relevancy factor to determine the relative importance of two input parameters, namely the specific gravity of crude oil and the time for two-output precipitation intensity and deposition level. Precipitation intensities were found by the implementation of an image-processing tool on spot test results. The relationship between time and precipitation intensity was found to be negligible; however, the correlation between time and deposition level was found to be strongly positive with a relevancy factor value of approximately 0.521. Similarly, the relationship of the specific gravity of oil with precipitation intensity and deposition level was found to be moderately negative and very close to each other, i.e., -0.228 and -0.247, respectively. The integration of the deposit level test with the spot test allows the continuous and simultaneously reliable monitoring of both asphaltene precipitation and deposition at different times without involving cost, complex instrumentation, or interpretation, irrespective of the type of oil. The method enables the successful determination of stability ranking of different crude oils both in terms of precipitation and deposition.

4.
Pak J Pharm Sci ; 34(4(Supplementary)): 1519-1525, 2021 Jul.
Article En | MEDLINE | ID: mdl-34799327

Empagliflozin is a selective inhibitor of sodium glucose co-transporter II, given as mono therapy or an add-on treatment to reduce the glycated hemoglobin levels in type 2 diabetes. This work deals with designing, formulating and optimizing empagliflozin (10mg) immediate release (IR) tablets by direct compression technique using different excipients. Through central composite rotatable design (CCRD), total nine formulations (EF1-EF9) were generated by changing the composition of binder avicel PH 102® (X1) and superdisintegrant acdisol⌖ (X2). Formulation runs with in suitable weight range and powder properties were subjected to compression. The influence of interaction of excipients on friability (Y1), hardness (Y2) and disintegration (Y3) were analyzed by fitting the polynomial quadratic model with response surface methodology (RSM). Trials EF2, EF7, EF8 and EF9 exhibited acceptable tablet attributes upon physico-chemical testing. Different dissolution models were applied to observe the in vitro drug release pattern in phosphate buffer of pH 6.8. The cumulative drug release of IR tablet batches followed the Weibull kinetics with regression coefficient (r2) values of 0.983-0.992. Empagliflozin trials were exposed to accelerated storage conditions (40±2°C/ 75±5% RH) for stability testing. Shelf life period of exposed formulations were computed in range of 22 to 25 months. Keeping in view of the results, it is concluded that the employed technique of preparation and optimization are observed to be excellent for developing immediate release empagliflozin (10mg) tablets.


Benzhydryl Compounds/chemistry , Drug Compounding/methods , Drug Liberation , Excipients/chemistry , Glucosides/chemistry , Sodium-Glucose Transporter 2 Inhibitors/chemistry , Hardness , Kinetics , Powders , Solubility , Tablets/chemistry
5.
J Biomed Inform ; 123: 103932, 2021 11.
Article En | MEDLINE | ID: mdl-34628064

OBJECTIVE: Causality mining is an active research area, which requires the application of state-of-the-art natural language processing techniques. In the healthcare domain, medical experts create clinical text to overcome the limitation of well-defined and schema driven information systems. The objective of this research work is to create a framework, which can convert clinical text into causal knowledge. METHODS: A practical approach based on term expansion, phrase generation, BERT based phrase embedding and semantic matching, semantic enrichment, expert verification, and model evolution has been used to construct a comprehensive causality mining framework. This active transfer learning based framework along with its supplementary services, is able to extract and enrich, causal relationships and their corresponding entities from clinical text. RESULTS: The multi-model transfer learning technique when applied over multiple iterations, gains substantial performance improvements. We also present a comparative analysis of the presented techniques with their common alternatives, which demonstrate the correctness of our approach and its ability to capture most causal relationships. CONCLUSION: The presented framework has provided cutting-edge results in the healthcare domain. However, the framework can be tweaked to provide causality detection in other domains, as well. SIGNIFICANCE: The presented framework is generic enough to be utilized in any domain, healthcare services can gain massive benefits due to the voluminous and various nature of its data. This causal knowledge extraction framework can be used to summarize clinical text, create personas, discover medical knowledge, and provide evidence to clinical decision making.


Data Mining , Natural Language Processing , Machine Learning , Semantics
6.
Pak J Pharm Sci ; 34(2(Supplementary)): 657-663, 2021 Mar.
Article En | MEDLINE | ID: mdl-34275799

Risperidone is an atypical antipsychotic agent clinically used to treat schizophrenia, bipolar diseases, and autism. Usually, the frequency of doses is twice daily. In the present study, risperidone controlled release matrices formulated using hydrophilic and hydrophobic polymers. The tablets were prepared by direct compression. The pre-compression and post-compression properties were assessed, along with swelling studies. The morphology of particles observed using scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). The stability study on the drug was performed using thermal gravimetric analysis (TGA) and differential thermal analysis (DTA). The optimized formulation was prepared with the help of hydrophilic polymer K100M (40% ratio). Furthermore, release kinetics had investigated. The release pattern of optimized formulation FT5 fitted best to zero-order kinetics and showed excellent release characteristics. The model-independent approach had been used, formulations FT6 and FT8 showed resemblance with FT5 in all three media, respectively. The once daily formulation of risperidone could be beneficial for schizophrenia patients and their caregivers and will improve patient compliance.


Antipsychotic Agents/therapeutic use , Risperidone/therapeutic use , Schizophrenia/drug therapy , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/pharmacokinetics , Delayed-Action Preparations , Differential Thermal Analysis , Drug Liberation , Drug Stability , Humans , Kinetics , Microscopy, Electron, Scanning , Risperidone/administration & dosage , Risperidone/pharmacokinetics , Spectroscopy, Fourier Transform Infrared , Tablets , Thermogravimetry
7.
Article En | MEDLINE | ID: mdl-35010486

Clinical decision support systems (CDSSs) represent the latest technological transformation in healthcare for assisting clinicians in complex decision-making. Several CDSSs are proposed to deal with a range of clinical tasks such as disease diagnosis, prescription management, and medication ordering. Although a small number of CDSSs have focused on treatment selection, areas such as medication selection and dosing selection remained under-researched. In this regard, this study represents one of the first studies in which a CDSS is proposed for clinicians who manage patients with end-stage renal disease undergoing maintenance hemodialysis, almost all of whom have some manifestation of chronic kidney disease-mineral and bone disorder (CKD-MBD). The primary objective of the system is to aid clinicians in dosage prescription by levering medical domain knowledge as well existing practices. The proposed CDSS is evaluated with a real-world hemodialysis patient dataset acquired from Kyung Hee University Hospital, South Korea. Our evaluation demonstrates overall high compliance based on the concordance metric between the proposed CKD-MBD CDSS recommendations and the routine clinical practice. The concordance rate of overall medication dosing selection is 78.27%. Furthermore, the usability aspects of the system are also evaluated through the User Experience Questionnaire method to highlight the appealing aspects of the system for clinicians. The overall user experience dimension scores for pragmatic, hedonic, and attractiveness are 1.53, 1.48, and 1.41, respectively. A service reliability for the Cronbach's alpha coefficient greater than 0.7 is achieved using the proposed system, whereas a dependability coefficient of the value 0.84 reveals a significant effect.


Chronic Kidney Disease-Mineral and Bone Disorder , Decision Support Systems, Clinical , Delivery of Health Care , Humans , Prescriptions , Reproducibility of Results
8.
Water Res ; 189: 116642, 2021 Feb 01.
Article En | MEDLINE | ID: mdl-33246215

The current Sphere guideline for water chlorination in humanitarian emergencies fails to reliably ensure household water safety in refugee camps. We investigated post-distribution chlorine decay and household water safety in refugee camps in South Sudan, Jordan, and Rwanda between 2013-2015 with the goal of demonstrating an approach for generating site-specific and evidence-based chlorination targets that better ensure household water safety than the status quo Sphere guideline. In each of four field studies we conducted, we observed how water quality changed between distribution and point of consumption. We implemented a nonlinear optimization approach for the novel technical challenge of modelling post-distribution chlorine decay in order to generate estimates on what free residual chlorine (FRC) levels must be at water distribution points, in order to provide adequate FRC protection up to the point of consumption in households many hours later at each site. The site-specific FRC targets developed through this modelling approach improved the proportion of households having sufficient chlorine residual (i.e., ≥0.2 mg/L FRC) at the point of consumption in three out of four field studies (South Sudan 2013, Jordan 2014, and Rwanda 2015). These sites tended to be hotter (i.e., average mid-afternoon air temperatures >30°C) and/or had poorer water, sanitation, and hygiene (WASH) conditions, contributing to considerable chlorine decay between distribution and consumption. Our modelling approach did not work as well where chlorine decay was small in absolute terms (Jordan 2015). In such settings, which were cooler (20 to 30°C) and had better WASH conditions, we found that the upper range of the current Sphere chlorination guideline (i.e., 0.5 mg/L FRC) provided sufficient residual chlorine for ensuring household water safety up to 24 hours post-distribution. Site-specific and evidence-based chlorination targets generated from post-distribution chlorine decay modelling could help improve household water safety and public health outcomes in refugee camp settings where the current Sphere chlorination guideline does not provide adequate residual protection. Water quality monitoring in refugee/IDP camps should shift focus from distribution points to household points of consumption in order to monitor if the intended public health goal of safe water at the point of consumption is being achieved.


Halogenation , Refugee Camps , Jordan , Rwanda , South Sudan
9.
Pak J Pharm Sci ; 33(3): 1073-1078, 2020 May.
Article En | MEDLINE | ID: mdl-33191231

The consumption of probiotics in the prevention and treatment of diarrhea have been clinically justified, comprehensive studied and explored in many products around the world. In Pakistan, recommendation of probiotic formulations is being emerged to control the increased mortality and morbidity from diarrhea under 5 years of age children. The objective of the study was to evaluate the antimicrobial potential of isolated Lactobacillus strains against diarrheagenic Escherichia coli. Twelve strains were isolated from different probiotic pharmaceutical formulations available in Pakistan. Physiological and biochemical characteristics of isolates were analyzed. Selective media was used for the growth of probiotic isolates and E. coli. Agar spot and well diffusion methods were employed to evaluate the antimicrobial activity of isolates and measured as a zone of inhibition (mm). Changes in cell morphology was observed by Scanning Electron Microscopy. Statistical analysis was adopted with a level of significance p<0.05. L. reuteri (28 mm) and L.plantarum (26 mm) showed significant inhibitory actions against E. coli due to increased organic acids and bacteriocins formations. Rest of isolates exhibited mild to moderate activity with an average inhibition (20 mm). L. sporogenes demonstrated weak antagonistic behavior. Use of multiple strains of Lactobacillus along with L. reuteri or L.plantarum as a therapeutic agent or in nutritional supplements could be a novel approach for the prevention and treatment of pediatric diarrhea.


Diarrhea/therapy , Enterotoxigenic Escherichia coli/growth & development , Escherichia coli Infections/therapy , Lactobacillus/growth & development , Probiotics , Acids/metabolism , Bacteriocins/metabolism , Diarrhea/microbiology , Disk Diffusion Antimicrobial Tests , Enterotoxigenic Escherichia coli/metabolism , Enterotoxigenic Escherichia coli/pathogenicity , Escherichia coli Infections/microbiology , Humans , Lactobacillus/metabolism , Lactobacillus/ultrastructure
10.
Pak J Pharm Sci ; 33(3): 1095-1103, 2020 May.
Article En | MEDLINE | ID: mdl-33191234

The aim of study was to synthesize 1-indanyl isoniazid and sixteen other hydrazide Schiff base derivatives from 1-indanone. All synthesized derivatives were screened for the inhibitory activity against Mycobacterium tuberculosis on three Mycobacterial strains ATCC H37Rv, known INH-sensitive (INH-S) and INH-resistant strains (INH-R) by proportion method. The derivatives were characterized using different spectroscopic techniques such as UV-Visible, FTIR, 1H NMR, and HREIMS. In addition, to gain more insight into morphology of the structures, Scanning electron microscopy (SEM) was also performed. The results revealed that 1-indanyl isoniazid derivative (UN-1) exhibited more potent and high anti-mycobacterial activity against both INH-sensitive and INH-resistant strains of Mycobacterium tuberculosis when compared to standard anti-tubercular drug isoniazid which might be a novel isoniazid derivative as a new anti-tubercular agent.


Antitubercular Agents/pharmacology , Indans/pharmacology , Isoniazid/pharmacology , Microscopy, Electrochemical, Scanning , Mycobacterium tuberculosis/drug effects , Schiff Bases/pharmacology , Antitubercular Agents/chemical synthesis , Drug Resistance, Bacterial , Humans , Indans/chemical synthesis , Isoniazid/analogs & derivatives , Isoniazid/chemical synthesis , Microbial Viability , Molecular Structure , Proton Magnetic Resonance Spectroscopy , Schiff Bases/chemical synthesis , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , Structure-Activity Relationship
11.
Int J Med Inform ; 141: 104181, 2020 09.
Article En | MEDLINE | ID: mdl-32559726

OBJECTIVE: Ubiquitous computing has supported personalized health through a vast variety of wellness and healthcare self-quantification applications over the last decade. These applications provide insights for daily life activities but unable to portray the comprehensive impact of personal habits on human health. Therefore, in order to facilitate the individuals, we have correlated the lifestyle habits in an appropriate proportion to determine the overall impact of influenced behavior on the well-being of humans. MATERIALS AND METHODS: To study the combined impact of personal behaviors, we have proposed a methodology to derive the comprehensive Healthy Behavior Index (HBI) consisting of two major processes: (1) Behaviors' Weight-age Identification (BWI), and (2) Healthy Behavior Quantification and Index (HBQI) modeling. The BWI process identifies the high ranked contributing behaviors through life-expectancy based weight-age, whereas HBQI derives a mathematical model based on quantification and indexing of behavior using wellness guidelines. RESULTS: The contributing behaviors are identified through text mining technique and verified by seven experts with a Kappa agreement level of 0.379. A real-world user-centric statistical evaluation is applied through User Experience Questionnaire (UEQ) method to evaluate the impact of HBI service. This HBI service is developed for the Mining Minds, a wellness management application. This study involves 103 registered participants (curious about the chronic disease) for a Korean wellness management organization. They used the HBI service over 12 weeks, the results for which were evaluated through UEQ and user feedback. The service reliability for the Cronbach's alpha coefficient greater than 0.7 was achieved using HBI service whereas the stimulation coefficient of the value 0.86 revealed significant effect. We observed an overall novelty of the value 0.88 showing the potential interest of participants. CONCLUSIONS: The comprehensive HBI has demonstrated positive user experience concerning the stimulation for adapting the healthy behaviors. The HBI service is designed independently to work as a service, so any other wellness management service-enabled platform can consume it to evaluate the healthy behavior index of the person for recommendation generation, behavior indication, and behavior adaptation.


Health Behavior , Health Promotion , Health Status , Humans , Life Style , Reproducibility of Results
12.
Iran J Pharm Res ; 19(3): 171-182, 2020.
Article En | MEDLINE | ID: mdl-33680020

We report thermal, X-ray diffraction (XRD) and cytotoxicity studies of complexes of fluconazole (FCZ) with Cu (II), Fe(II), Cd(II), Co(II), Ni(II), and Mn(II). From XRD measurements, FCZ and its metal complexes were identified as polycrystalline. Marked differences in the X-ray patterns of drug and its metal complexes revealed that the complexes are indeed different compounds and not just the mixture of the starting materials. Unlike pristine FCZ, which did not exhibit cytotoxicity, three complexes derived from Fe(II), Cu(II) and Co (II) proved to be effective in the cytotoxicity assay. The Cu(II)-FCZ exhibited significant activity against SNB-19, HCT-15, COLO-205, and KB-3-1 cell lines, while Fe(II)-FCZ and Co(II)-FCZ were found cytotoxic only to KB-3-1 cell line. For the pure FCZ, thermogravimetry revealed massive weight loss in the temperature range of 215 to 297 °C, due to the volatilization of FCZ. All the complexes followed multi-stage degradation profiles, eventually resulting in the formation of metal oxides. For pure FCZ, differential scanning calorimetry revealed melting point at 137 °C, followed by two further endothermic transitions at 294 °C and 498.44 °C representing the volatilization and subsequent degradation of FCZ, respectively. The absence of endothermic FCZ melting peak at around 137 °C indicates that the complexes represent different compounds. All complexes exhibit endothermic transitions at around 240-300 °C, representing melting and removal of ligand moiety, followed by another endothermic transition at around 498-499 °C, representing the ligand decomposition.

13.
Pak J Pharm Sci ; 32(2 (Supplementary)): 853-858, 2019 Mar.
Article En | MEDLINE | ID: mdl-31103982

A sensitive, reproducible and modest analytical procedure was developed and validated for evaluation of irbesartan in human plasma. LLE (Liquid-Liquid extraction) of the drug was carried out with acetonitrile (1:1 v/v). Chromatographic separation of irbesartan was conducted by the help of 4.0mm × 25cm column having L1 packing from plasma and mobile phase utilizing HPLC. The mobile phase comprise of phosphate buffer and acetonitrile in a ratio of 67:33 v/v. The flow rate was set at 1ml/minute and the detector at a wavelength of 220 nm. The resolution of irbesartan was well performed from plasma components. This method was validated and demonstrated linearity with a concentration range of 0.1to 6µg/ml of irbesartan in plasma. Intra-day, inter-day accuracy was found 89.33% to 96.37% while intra-day, inter-day precision was found within the limit of 0.02 and 2.15 respectively. The mean recovery of irbesartan was 97.28%. The efficacy of extraction was proved by above-mentioned results. In plasma, the 0.05 and 0.1µg/ml dilutions were exhibited as the LOD and LOQ of irbesartan. Stability studies disclosed that irbesartan showed stability at -20°C storage.


Angiotensin II Type 1 Receptor Blockers/blood , Chromatography, High Pressure Liquid/methods , Irbesartan/blood , Angiotensin II Type 1 Receptor Blockers/pharmacokinetics , Calibration , Chromatography, Reverse-Phase/methods , Drug Stability , Humans , Irbesartan/pharmacokinetics , Limit of Detection , Sensitivity and Specificity
14.
Pak J Pharm Sci ; 31(5(Supplementary)): 2169-2177, 2018 Sep.
Article En | MEDLINE | ID: mdl-30393229

Carica papaya Linn is the member of Caricaceae family of Kingdom Plantae. The study was executed for the development of qualitative standards of male and female leaves of the plant. The study included evaluation of macroscopial, physico-chemical and preliminary phytochemical parameters to authorize the purity and authenticity of leaf of Carica papaya Linn based on guidelines provided by WHO. Qualitative phytochemical screening of extracts revealed the existence of alkaloids, flavonoids, tannins, phenolic compounds, glycosides including cardiac glycosides, proteins and carbohydrate in different extracts of Carica papaya Linn which are majorly rich in female leaves as compared to male. Mean ash values, acid insoluble ash, water soluble ash, foaming index, swelling index and moisture contents were also evaluated which are more or less similar. FTIR profile of the samples were also generated that confirmed distinct peak values with respective functional groups exhibited by Carica papaya male and female plant. The current research reflected that female and male plant showed variations in phyto-constituents. This data will be utilized for additional Pharmacological and Instrumental evaluation of the plant which can not only be beneficial in discriminating and refining the type as well as nature of various phytochemicals present in Carica papaya male and female leaves but also establish the quality standards for future researches.


Carica/chemistry , Phytochemicals/chemistry , Phytochemicals/standards , Plant Extracts/chemistry , Plant Extracts/standards , Plant Leaves/chemistry , Phytochemicals/isolation & purification , Plant Extracts/isolation & purification , Qualitative Research , Reference Standards
15.
PLoS One ; 13(8): e0202705, 2018.
Article En | MEDLINE | ID: mdl-30153294

Feature selection is considered to be one of the most critical methods for choosing appropriate features from a larger set of items. This task requires two basic steps: ranking and filtering. Of these, the former necessitates the ranking of all features, while the latter involves filtering out all irrelevant features based on some threshold value. In this regard, several feature selection methods with well-documented capabilities and limitations have already been proposed. Similarly, feature ranking is also nontrivial, as it requires the designation of an optimal cutoff value so as to properly select important features from a list of candidate features. However, the availability of a comprehensive feature ranking and a filtering approach, which alleviates the existing limitations and provides an efficient mechanism for achieving optimal results, is a major problem. Keeping in view these facts, we present an efficient and comprehensive univariate ensemble-based feature selection (uEFS) methodology to select informative features from an input dataset. For the uEFS methodology, we first propose a unified features scoring (UFS) algorithm to generate a final ranked list of features following a comprehensive evaluation of a feature set. For defining cutoff points to remove irrelevant features, we subsequently present a threshold value selection (TVS) algorithm to select a subset of features that are deemed important for the classifier construction. The uEFS methodology is evaluated using standard benchmark datasets. The extensive experimental results show that our proposed uEFS methodology provides competitive accuracy and achieved (1) on average around a 7% increase in f-measure, and (2) on average around a 5% increase in predictive accuracy as compared with state-of-the-art methods.


Algorithms , Benchmarking , Databases, Factual
16.
Pak J Pharm Sci ; 31(5): 1871-1879, 2018 Sep.
Article En | MEDLINE | ID: mdl-30150183

Use of drug-metal complexes for the treatment of several human diseases has resulted in significant progress in the field of medicinal inorganic chemistry. The current study describes the synthesis and characterization of Cu (II) and Ni (II) complexes of Losartan, an antihypertensive drug. These complexes were evaluated for their cytotoxic activity against four human cancer cell lines; SNB-19, HCT-15, COLO-205 and KB-3-1. Spectroscopic characterization revealed that during complex formation, the metal was bound through the nitrogen atoms of the tetrazole moiety of the losartan molecule. The molecular formulas of copper ([Cu (LS) 2 Cl2].6H2O) and nickel ([Ni (LS) 2Cl2]. H2O) complexes were found to be in agreement with the analytical data obtained through elemental analysis. For both the complexes, metal to ligand ratios of 1:2 were calculated. As revealed by FTIR, UV-Visible, and 1H-NMR studies, both the complexes displayed octahedral geometries. Scanning electron microscopy (SEM) revealed marked changes in the morphology of the complexes, compared to the pure drug. From XRD studies, characteristic crystalline peaks of pure losartan were observed whereas no prominent peaks were observed for its complexes. Complexes were found to be inactive in the cytotoxic activity test performed using SNB-19, HCT-15, COLO-205 and KB-3-1 cell lines.


Anti-Arrhythmia Agents/analysis , Coordination Complexes/analysis , Cytotoxins/analysis , Losartan/analysis , Magnetic Resonance Spectroscopy/methods , Anti-Arrhythmia Agents/toxicity , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/physiology , Coordination Complexes/toxicity , Cytotoxins/toxicity , Humans , Losartan/toxicity
17.
Pak J Pharm Sci ; 31(4(Supplementary)): 1489-1494, 2018 Jul.
Article En | MEDLINE | ID: mdl-30058540

Pioglitazone is widely used for the management of type-II diabetes mellitus. The objective of the present study was to develop a simple and cost-effective HPLC method for the quantification of pioglitazone in human plasma. The mobile phase comprises of Acetonitrile, 0.1 M ammonium acetate and glacial acetic acid (25:25:1 v/v/v) at a flow rate of 1.2 mL/min., using Macherey-Nagel Column C18, (dimensions: 5 µm; 250 × 4.6mm) with a guard column. The UV detector was set at 269nm. The method was validated according to FDA guidelines. The present method showed good linearity (R2=0.9998) from 0.1 to 2.0µg/ml standards, with a limit of detection 0.1 µg/ml. Intra-day accuracy and precision in terms of %CV (range: 93.33% to 100.4% and 3.8% to 9.2%) and interday accuracy and precision (range: 94.1% to 102.7% and 4.8% to 9.6%) were in agreement with FDA guidelines. Freeze thaw stability showed that the plasma samples could be stored for one month at -20oC without any appreciable degradation. The present method was successfully applied to the blood samples obtained from one volunteer after oral administration of 30 mg pioglitazone tablet. Some preliminary pharmacokinetic parameters were calculated. It is concluded that the present method could be conveniently used for the routine analysis of pioglitazone blood samples obtained in pharmacokinetics studies.


Hypoglycemic Agents/blood , Pioglitazone/blood , Technology, Pharmaceutical/standards , Administration, Oral , Chromatography, High Pressure Liquid/standards , Humans , Hypoglycemic Agents/administration & dosage , Male , Pioglitazone/administration & dosage , Reproducibility of Results , Technology, Pharmaceutical/trends
18.
Pak J Pharm Sci ; 31(3(Supplementary)): 979-984, 2018 May.
Article En | MEDLINE | ID: mdl-29731433

A simple, sensitive and rigorous method for estimation of dimenhydrinate in human plasma was searched and its validation was carried out. LLE (Liquid-Liquid extraction) of analyte with mixture of Hexane and ethyl acetate (1:1 v/v) was carried out for the preparation of Plasma Samples, Chromatographic elution of dimenhydrinate was conducted in human plasma and mobile phase with C-18 bonda Pack column (10µm; 250 × 4.6), using a mobile phase consisting a solution of ammonium bicarbonate in water and methanol at a flow rate of 0.5ml/minute with UV detection at 229 nm. The resolution of dimenhydrinate was well performed from plasma components. This method was validated and exhibited linearity with concentration range of 6 to 380ng/ml of dimenhydrinate in plasma. The Intra day precision was 89.2 to 96.89% and Inter day precision was 88.6% to 93.26%, the average recovery of dimenhydrinate was 97.02%. The efficacy of extraction was proved by above mentioned results. 2ng/ml and 6ng/ml, were appraised as the LOD and LOQ of dimenhydrinate, stability studies disclosed that dimenhydrinate exhibited stability in Plasma after Freeze & thaw cycles and upon -20°C storage, the method was developed well.


Chromatography, High Pressure Liquid/methods , Chromatography, Reverse-Phase/methods , Dimenhydrinate/blood , Drug Stability , Humans , Limit of Detection , Liquid-Liquid Extraction , Reference Standards , Spectrophotometry, Ultraviolet , Temperature
19.
Pak J Pharm Sci ; 30(1): 187-194, 2017 Jan.
Article En | MEDLINE | ID: mdl-28603130

The human digestive tract contains some 100 trillion cells and thousands of species of micro-organisms may be present as normal flora of this tract as well as other mucocutaneous junctions of the body. Candida specie is the most common organism residing in these areas and can easily invade the internal tissues in cases of loss of host defenses. Modifications of previously existing antifungal agents may provide new options to fight against these species. Inorganic compounds of different antifungals are under investigations. Present study report six complexes of fluconazole with Cu (II)), Fe(II), Cd(II), Co(II), Ni(II) and Mn(II) have been synthesized and characterized by elemental analysis, IR, UV and H-NMR. The elemental analysis and spectroscopic data were found in agreement with the expected values as the metal to ligand value was 1:2 ratios with two chlorides in coordination sphere. The morphology of each complex was studied using scanning electron microscope and compared with fluconazole molecule the flaky-slab rock like particles of pure fluconazole was also observed as reported earlier. However, the complexes of fluconazole were showed different morphology in their micrograph. Fluconazole and its complex derivatives have also been screened in vitro for their antifungal activity against Candida albican and Aspergillus niger by MIC method. The complexes showed varied activity ranging from 2-20%.


Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Fluconazole/chemistry , Fluconazole/pharmacology , Metals, Heavy/chemistry , Microscopy, Electron, Scanning , Technology, Pharmaceutical/methods , Aspergillus niger/drug effects , Aspergillus niger/growth & development , Candida albicans/drug effects , Candida albicans/growth & development , Chlorides/chemistry , Chlorides/pharmacology , Fluconazole/analogs & derivatives , Microbial Sensitivity Tests , Proton Magnetic Resonance Spectroscopy , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , Surface Properties
20.
Bull World Health Organ ; 93(8): 550-8, 2015 Aug 01.
Article En | MEDLINE | ID: mdl-26478612

OBJECTIVE: To investigate the concentration of residual chlorine in drinking water supplies in refugee camps, South Sudan, March-April 2013. METHODS: For each of three refugee camps, we measured physical and chemical characteristics of water supplies at four points after distribution: (i) directly from tapstands; (ii) after collection; (iii) after transport to households; and (iv) after several hours of household storage. The following parameters were measured: free and total residual chlorine, temperature, turbidity, pH, electrical conductivity and oxidation reduction potential. We documented water handling practices with spot checks and respondent self-reports. We analysed factors affecting residual chlorine concentrations using mathematical and linear regression models. FINDINGS: For initial free residual chlorine concentrations in the 0.5-1.5 mg/L range, a decay rate of ~5x10(-3) L/mg/min was found across all camps. Regression models showed that the decay of residual chlorine was related to initial chlorine levels, electrical conductivity and air temperature. Covering water storage containers, but not other water handling practices, improved the residual chlorine levels. CONCLUSION: The concentrations of residual chlorine that we measured in water supplies in refugee camps in South Sudan were too low. We tentatively recommend that the free residual chlorine guideline be increased to 1.0 mg/L in all situations, irrespective of diarrhoeal disease outbreaks and the pH or turbidity of water supplies. According to our findings, this would ensure a free residual chlorine level of 0.2 mg/L for at least 10 hours after distribution. However, it is unknown whether our findings are generalizable to other camps and further studies are therefore required.


Chlorine/analysis , Drinking Water/analysis , Water Purification/methods , Developing Countries , Humans , Linear Models , Refugees , South Sudan , Water Quality , Water Supply/standards
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