Antimicrobial activity assessment of time-dependent release bilayer tablets of amoxicillin trihydrate

O objetivo do presente estudo foi avaliar a atividade antimicrobiana de formulações de comprimidos de dupla camada contendo amoxicilina triidratada para liberação tempo dependente e avaliação da liberação in vitro do fármaco pelo ensaio de atividade antimicrobiana utilizando o método de difusão em placa de ágar. Os comprimidos de dupla camada consistem em uma camada para liberação retardada e outra sustentada. O método de compressão direta foi usado para a preparação dos comprimidos de dupla camada contendo Eudragit-L 100 D55 como polímero para liberação retardada e HPMCK4M ou HPMCK15 como polímeros para liberação sustentada. As formulações de comprimidos de dupla camada contendo amoxicilina triidratada foram avaliadas quanto a dureza, espessura, friabilidade, variação de peso e conteúdo de fármaco. Além disso, a liberação do fármaco in vitro foi avaliada por ensaio de atividade antimicrobiana usando S. aureus e E. coli como microrganismos teste. A alíquota das amostras do estudo de liberação do fármaco in vitro demonstrou ser efetiva contra ambos os microrganismos por um período de 16 horas devido à ação sustentada. O estudo de liberação do fármaco in vitro e o ensaio de atividade antimicrobiana mostraram que os comprimidos de dupla camada tiveram um perfil de liberação sustentada do fármaco com um pico de liberação após 2 horas de ensaio. O menor valor de MIC (2 ug/mL) dos comprimidos de dupla camada quando comparados à formulação comercial (5 ug/mL) representa uma boa atividade antimicrobiana.The aim of present study was the assessment of antimicrobial activity of prepared time-dependent release bilayer tablets of amoxicillin trihydrate and in vitro evaluation of drug release by antimicrobial assay using agar plate diffusion method. The bilayer tablets comprised of a delayed and sustained release layer. Direct compression method was used for the preparation of bilayer tablets containing Eudragit-L100 D55 as delayed release polymer, and HPMCK4M and HPMCK15 as sustained release polymers. The prepared bilayer tablets containing amoxicillin trihydrate were evaluated for hardness, thickness, friability, weight variation and drug content. Further, in vitro drug release was assessed by antimicrobial assay using S. aureus and E. coli as test microorganisms. The aliquot samples of in vitro drug release study were found to be effective against both microorganisms for 16 hours due to sustained action. The in vitro drug release study and antimicrobial assay showed that bilayer tablets have sustained release profile of drug delivery with time-dependent burst release after a lag-time of 2 hours. The lower MIC value (2 µg/mL) of prepared bilayer tablets vis-à-vis marketed preparation (5 µg/mL) represented its good antimicrobial activity

Chemometrics-assisted development of a validated LC method for simultaneous estimation of temozolomide and γ-linolenic acid: Greenness assessment and application to lipidic nanoparticles

The described work entails the development of a simple, sensitive, green, and robust high-performance liquid chromatographic (HPLC) method for simultaneous estimation of temozolomide (TMZ) and γ-linolenic acid (GLA). The chemometric factor screening study helped identify the critical method parameters optimized using Box-Behnken design for improved understanding and enhancing the method performance. Chromatographic separation was performed on a Kinetex® C18 column (150 × 4.6 mm, 5 µm particle size) using methanol: water (pH adjusted to 3.5 using 0.5% v/v O-phosphoric acid) as the mobile phase at 0.5 mL/min flow rate and diode array detection between 210 and 360 nm. The linearity of the method was observed for concentrations of TMZ and GLA ranging between 1 and 100 µg.mL−1 (R2 = 0.999, p < 0.05). Accuracy evaluation showed good percent recovery within 97.9–100%, while intra- and inter-day precision showed RSD values within 0.37%-1.01%. The limit of detection and quantification for TMZ was found to be 0.75 and 1.0 μg.mL−1, respectively, while the values 0.55 and 1.0 μg.mL−1, respectively, were observed for GLA. System suitability (96.9–102.8%), its limits, and robustness evaluation indicated good percent recovery within, while RSD values were found to be within the acceptable limit of less than 2%. The method was specific for its ability to detect the analytes and their degradation products during forced degradation studies, which also indicated that TMZ was highly prone to alkaline conditions while GLA showed mild degradation in all the studied conditions. The estimation of both the analytes from lipid nanoparticles formulation showed good values for total drug content (82.6–85.3%), entrapment efficiency (95.4 to 98.7%), and drug loading (25.2 to 38.4%). Overall, the results indicated that the developed method was reliable for its accuracy, precision, sensitivity, and specificity for simultaneous estimation of the analytes. The method was found to be stability-indicating in nature and suitable for simultaneous estimation of TMZ and GLA from the developed nanoparticles formulation. Further, employing a greenness assessment approach established the method greenness

Neurological involvement associated with plasmodium vivax malaria from Pakistan

Plasmodium vivax is the most common specie causing malaria outside Africa with approximately 13.8 million reported cases worldwide. We report case of P. vivax infection with cerebral involvement. A nine year old boy presented with high grade fever accompanied by projectile vomiting and abnormal behavior later he developed seizures, shock, and unconsciousness. P. vivax monoinfection was diagnosed based on peripheral smears and PCR. After antimalarial therapy, patient made full recovery. Current case highlights increasing trend of cerebral complications caused by P. vivax

Tumor necrosis factor -α, interleukin-10, intercellular and vascular adhesion molecules are possible biomarkers of disease severity in complicated Plasmodium vivax isolates from Pakistan.

Background: Cytokine-mediated endothelial activation pathway is a known mechanism of pathogenesis employed by Plasmodium falciparum to induce severe disease symptoms in human host. Though considered benign, complicated cases of Plasmodium vivax are being reported worldwide and from Pakistan. It has been hypothesized that P.vivax utilizes similar mechanism of pathogenesis, as that of P.falciparum for manifestations of severe malaria. Therefore, the main objective of this study was to characterize the role of cytokines and endothelial activation markers in complicated Plasmodium vivax isolates from Pakistan. Methods and Principle Findings: A case control study using plasma samples from well-characterized groups suffering from P.vivax infection including uncomplicated cases (n=100), complicated cases (n=82) and healthy controls (n=100) were investigated. Base line levels of Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-10 (IL-10), Intercellular adhesion molecule-1 (ICAM-1), Vascular adhesion molecule-1(VCAM-1) and Eselectin were measured by ELISA. Correlation of cytokines and endothelial activation markers was done using Spearman’s correlation analysis. Furthermore, significance of these biomarkers as indicators of disease severity was also analyzed. The results showed that TNF-α, IL-10, ICAM-1and VCAM-1 were 3-fold, 3.7 fold and 2 fold increased between uncomplicated and complicated cases. Comparison of healthy controls with uncomplicated cases showed no significant difference in TNF-α concentrations while IL-6, IL-10, ICAM-1, VCAM-1 and E-selectin were found to be elevated respectively. In addition, significant positive correlation was observed between TNF-α and IL-10/ ICAM-1, IL-6 and IL-10, ICAM-1 and VCAM-1.A Receiver operating curve (ROC) was generated which showed that TNF-α, IL-10, ICAM-1 and VCAM-1 were the best individual predictors of complicated P.vivax malaria. Conclusion: The results suggest that though endothelial adhesion molecules are inducible by pro-inflammatory cytokine TNF-α, however, cytokine-mediated endothelial activation pathway is not clearly demonstrated as a mechanism of pathogenesis in complicated P.vivax malaria cases from Pakistan

A collaborative healthcare framework for shared healthcare plan with ambient intelligence

The fast propagation of the Internet of Things (IoT) devices has driven to the development of collaborative healthcare frameworks to support the next generation healthcare industry for quality medical healthcare. This paper presents a generalized collaborative framework named collaborative shared healthcare plan (CSHCP) for cognitive health and fitness assessment of people using ambient intelligent application and machine learning techniques. CSHCP provides support for daily physical activity recognition, monitoring, assessment and generate a shared healthcare plan based on collaboration among different stakeholders: doctors, patient guardians, as well as close community circles. The proposed framework shows promising outcomes compared to the existing studies. Furthermore, the proposed framework enhances team communication, coordination, long-term plan management of healthcare information to provide a more efficient and reliable shared healthcare plans to people

Enhancing biopharmaceutical performance of an anticancer drug by long chain PUFA based self-nanoemulsifying lipidic nanomicellar system.

The aim of this study was to develop polyunsaturated fatty acid (PUFA) long chain glyceride (LCG) enriched self-nanoemulsifying lipidic nanomicelles systems (SNELS) for augmenting lymphatic uptake and enhancing oral bioavailability of docetaxel and compare its biopharmaceutical performance with a medium-chain fatty acid glyceride (MCG) SNELS. Equilibrium solubility and pseudo ternary phase studies facilitated the selection of suitable LCG and MCG. The critical material attributes (CMAs) and critical process parameters (CPPs) were earmarked using Placket-Burman Design (PBD) and Fractional Factorial Design (FFD) for LCG- and MCG-SNELS respectively, and nano micelles were subsequently optimized using I- and D-optimal designs. Desirability function unearthed the optimized SNELS with Temul 85% and Perm45min >75%. The SNELS demonstrated efficient biocompatibility and energy dependent cellular uptake, reduced P-gp efflux and increased permeability using bi-directional Caco-2 model. Optimal PUFA enriched LCG-SNELS exhibited distinctly superior permeability and absorption parameters during ex vivo permeation, in situ single pass intestinal perfusion, lymphatic uptake and in vivo pharmacokinetic studies over MCG-SNELS. [Abstract copyright: Copyright © 2017. Published by Elsevier B.V.

Nanostructured Lipid Carrier-Based Codelivery of Raloxifene and Naringin: Formulation, Optimization, In Vitro, Ex Vivo, In Vivo Assessment, and Acute Toxicity Studies

This work aimed to develop dual drug-loaded nanostructured lipid carriers of raloxifene and naringin (RLX/NRG NLCs) for breast cancer. RLX/NRG NLCs were prepared using Compritol 888 ATO and oleic acid using a hot homogenization−sonication method and optimized using central composite design (CCD). The optimized RLX/NRG NLCs were characterized and evaluated using multiple technological means. The optimized RLX/NRG NLCs exhibited a particle size of 137.12 nm, polydispersity index (PDI) of 0.266, zeta potential (ZP) of 25.9 mV, and entrapment efficiency (EE) of 91.05% (raloxifene) and 85.07% (naringin), respectively. In vitro release (81 ± 2.2% from RLX/NRG NLCs and 31 ± 1.9% from the RLX/NRG suspension for RLX and 93 ± 1.5% from RLX/NRG NLCs and 38 ± 2.01% from the RLX/NRG suspension for NRG within 24 h). Concurrently, an ex vivo permeation study exhibited nearly 2.3 and 2.1-fold improvement in the permeability profiles of RLX and NRG from RLX/NRG NLCs vis-à-vis the RLX/NRG suspension. The depth of permeation was proved with CLSM images which revealed significant permeation of the drug from the RLX/NRG NLCs formulation, 3.5-fold across the intestine, as compared with the RLX/NRG suspension. An in vitro DPPH antioxidant study displayed a better antioxidant potential of RLX/NRG in comparison to RLX and NRG alone due to the synergistic antioxidant effect of RLX and NRG. An acute toxicity study in Wistar rats showed the safety profile of the prepared nanoformulations and their excipients. Our findings shed new light on how poorly soluble and poorly permeable medicines can be codelivered using NLCs in an oral nanoformulation to improve their medicinal performance

Enhancing Biopharmaceutical Attributes of Phospholipid Complex-loaded Nanostructured Lipidic Carriers of Mangiferin: Systematic Development, Characterization and Evaluation

Mangiferin (Mgf), largely expressed out from the leaves and stem bark of Mango, is a potent antioxidant. However, its in vivo activity gets tremendously reduced owing to poor aqueous solubility and inconsistent gastrointestinal absorption, high hepatic first-pass metabolism and high P-gp efflux. The current research work, therefore, was undertaken to overcome the biopharmaceutical hiccups by developing the Mgf-phospholipid complex (PLCs) loaded in nanostructured lipidic carriers (NLCs). The PLCs and NLCs were prepared using refluxing, solvent evaporation and hot emulsification technique, respectively with various molar ratios of Mgf and Phospholipon 90 G, i.e., 1:1; 1:2; and 1:3. The complex was evaluated for various physicochemical parameters like drug content (96.57%), aqueous solubility (25-fold improved) and oil-water partition coefficient (10-fold enhanced). Diverse studies on the prepared complex using FTIR, DSC, PXRD and SEM studies ratified the formation of PLCs at 1:1 ratio. The PLCs were further incorporated onto NLCs, which were systematically optimized employing a face centered cubic design (FCCD), while evaluating for particle size, zeta potential, encapsulation efficiency and in vitro drug release as the CQAs. Caco-2 cell line indicated insignificant cytotoxicity, and P-gp efflux, bi-directional permeability model and in situ perfusion studies specified enhanced intestinal permeation parameters. In vivo pharmacokinetic studies revealed notable increase in the values of Cmax (4.7-fold) and AUC (2.1-fold), respectively, from PLCs-loaded NLCs vis-à-vis Mgf solution. In a nutshell, the promising results observed from the present research work signified boosted biopharmaceutical potential of the optimized PLCs-loaded NLCs for potentially augmenting the therapeutic efficacy of Mgf

Phytoremediation of heavy metal-contaminated sites: Eco-environmental concerns, field studies, sustainability issues and future prospects

Environmental contamination due to heavy metals (HMs) is of serious ecotoxicological concern worldwide because of their increasing use at industries. Due to non-biodegradable and persistent nature, HMs cause serious soil/water pollution and severe health hazards in living beings upon exposure. HMs can be genotoxic, carcinogenic, mutagenic, and teratogenic in nature even at low concentration. They may also act as endocrine disruptors and induce developmental as well as neurological disorders and thus, their removal from our natural environment is crucial for the rehabilitation of contaminated sites. To cope with HM pollution, phytoremediation has emerged as a low-cost and eco-sustainable solution to conventional physico-chemical cleanup methods that require high capital investment and labor alter soil properties and disturb soil microflora. Phytoremediation is a green technology wherein plants and associated microbes are used to remediate HM-contaminated sites to safeguard the environment and protect public health. Hence, in view of the above, the present paper aims to examine the feasibility of phytoremediation as a sustainable remediation technology for the management of metals-contaminated sites. Therefore, this paper provides an in-depth review on both the conventional and novel phytoremediation approaches, evaluate their efficacy to remove toxic metals from our natural environment, explore current scientific progresses, field experiences and sustainability issues and revise world over trends in phytoremediation research for its wider recognition and public acceptance as a sustainable remediation technology for the management of contaminated sites in 21st century