Search results for: Akhtar Naveed
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 160

Search results for: Akhtar Naveed

10 Effect of Fresh Concrete Curing Methods on Its Compressive Strength

Authors: Xianghe Dai, Dennis Lam, Therese Sheehan, Naveed Rehman, Jie Yang

Abstract:

Concrete is one of the most used construction materials that may be made onsite as fresh concrete and then placed in formwork to produce the desired shapes of structures. It has been recognized that the raw materials and mix proportion of concrete dominate the mechanical characteristics of hardened concrete, and the curing method and environment applied to the concrete in early stages of hardening will significantly influence the concrete properties, such as compressive strength, durability, permeability etc. In construction practice, there are various curing methods to maintain the presence of mixing water throughout the early stages of concrete hardening. They are also beneficial to concrete in hot weather conditions as they provide cooling and prevent the evaporation of water. Such methods include ponding or immersion, spraying or fogging, saturated wet covering etc. Also there are various curing methods that may be implemented to decrease the level of water lost which belongs to the concrete surface, such as putting a layer of impervious paper, plastic sheeting or membrane on the concrete to cover it. In the concrete material laboratory, accelerated strength gain methods supply the concrete with heat and additional moisture by applying live steam, coils that are subject to heating or pads that have been warmed electrically. Currently when determining the mechanical parameters of a concrete, the concrete is usually sampled from fresh concrete on site and then cured and tested in laboratories where standardized curing procedures are adopted. However, in engineering practice, curing procedures in the construction sites after the placing of concrete might be very different from the laboratory criteria, and this includes some standard curing procedures adopted in the laboratory that can’t be applied on site. Sometimes the contractor compromises the curing methods in order to reduce construction costs etc. Obviously the difference between curing procedures adopted in the laboratory and those used on construction sites might over- or under-estimate the real concrete quality. This paper presents the effect of three typical curing methods (air curing, water immersion curing, plastic film curing) and of maintaining concrete in steel moulds on the compressive strength development of normal concrete. In this study, Portland cement with 30% fly ash was used and different curing periods, 7 days, 28 days and 60 days were applied. It was found that the highest compressive strength was observed from concrete samples to which 7-day water immersion curing was applied and from samples maintained in steel moulds up to the testing date. The research results implied that concrete used as infill in steel tubular members might develop a higher strength than predicted by design assumptions based on air curing methods. Wrapping concrete with plastic film as a curing method might delay the concrete strength development in the early stages. Water immersion curing for 7 days might significantly increase the concrete compressive strength.

Keywords: compressive strength, air curing, water immersion curing, plastic film curing, maintaining in steel mould, comparison

Procedia PDF Downloads 294
9 The Implementation of Human Resource Information System in the Public Sector: An Exploratory Study of Perceived Benefits and Challenges

Authors: Aneeqa Suhail, Shabana Naveed

Abstract:

The public sector (in both developed and developing countries) has gone through various waves of radical reforms in recent decades. In Pakistan, under the influence of New Public Management(NPM) Reforms; best practices of private sector are introduced in the public sector to modernize public organizations. Human Resource Information System (HRIS) has been popular in the private sector and proven to be a successful system, therefore it is being adopted in the public sector too. However, implementation of private business practices in public organizations us very challenging due to differences in context. This implementation gets further critical in Pakistan due to a centralizing tendency and lack of autonomy in public organizations. Adoption of HRIS by public organizations in Pakistan raises several questions: What challenges are faced by public organizations in implementation of HRIS? Are benefits of HRIS such as efficiency, process integration and cost reduction achieved? How is the previous system improved with this change and what are the impacts? Yet, it is an under-researched topic, especially in public enterprises. This study contributes to the existing body of knowledge by empirically exploring benefits and challenges of implementation of HRIS in public organizations. The research adopts a case study approach and uses qualitative data based on in-depth interviews conducted at various levels in the hierarchy including top management, departmental heads and employees. The unit of analysis is LESCO, the Lahore Electric Supply Company, a state-owned entity that generates, transmits and distributes electricity to 4 big cities in Punjab, Pakistan. The findings of the study show that LESCO has not achieved the benefits of HRIS as established in literature. The implementation process remained quite slow and costly. Various functions of HR are still in isolation and integration is a big challenge for the organization. Although the data is automated, the previous system of manually record maintenance and paperwork is still in work, resulting in the presence of parallel practices. The findings also identified resistance to change from top management and labor workforce, lack of commitment and technical knowledge, and costly vendors as major barriers that affect the effective implementation of HRIS. The paper suggests some potential actions to overcome these barriers and to enhance effective implementation of HR-technology. The findings are explained in light of an institutional logics perspective. HRIS’ new logic of automated and integrated HR system is in sharp contrast with the prevailing logic of process-oriented manual data maintenance, leading to resistance to change and deadlock.

Keywords: human resource information system, technological changes, state-owned enterprise, implementation challenges

Procedia PDF Downloads 146
8 Artificial Neural Network and Satellite Derived Chlorophyll Indices for Estimation of Wheat Chlorophyll Content under Rainfed Condition

Authors: Muhammad Naveed Tahir, Wang Yingkuan, Huang Wenjiang, Raheel Osman

Abstract:

Numerous models used in prediction and decision-making process but most of them are linear in natural environment, and linear models reach their limitations with non-linearity in data. Therefore accurate estimation is difficult. Artificial Neural Networks (ANN) found extensive acceptance to address the modeling of the complex real world for the non-linear environment. ANN’s have more general and flexible functional forms than traditional statistical methods can effectively deal with. The link between information technology and agriculture will become more firm in the near future. Monitoring crop biophysical properties non-destructively can provide a rapid and accurate understanding of its response to various environmental influences. Crop chlorophyll content is an important indicator of crop health and therefore the estimation of crop yield. In recent years, remote sensing has been accepted as a robust tool for site-specific management by detecting crop parameters at both local and large scales. The present research combined the ANN model with satellite-derived chlorophyll indices from LANDSAT 8 imagery for predicting real-time wheat chlorophyll estimation. The cloud-free scenes of LANDSAT 8 were acquired (Feb-March 2016-17) at the same time when ground-truthing campaign was performed for chlorophyll estimation by using SPAD-502. Different vegetation indices were derived from LANDSAT 8 imagery using ERADAS Imagine (v.2014) software for chlorophyll determination. The vegetation indices were including Normalized Difference Vegetation Index (NDVI), Green Normalized Difference Vegetation Index (GNDVI), Chlorophyll Absorbed Ratio Index (CARI), Modified Chlorophyll Absorbed Ratio Index (MCARI) and Transformed Chlorophyll Absorbed Ratio index (TCARI). For ANN modeling, MATLAB and SPSS (ANN) tools were used. Multilayer Perceptron (MLP) in MATLAB provided very satisfactory results. For training purpose of MLP 61.7% of the data, for validation purpose 28.3% of data and rest 10% of data were used to evaluate and validate the ANN model results. For error evaluation, sum of squares error and relative error were used. ANN model summery showed that sum of squares error of 10.786, the average overall relative error was .099. The MCARI and NDVI were revealed to be more sensitive indices for assessing wheat chlorophyll content with the highest coefficient of determination R²=0.93 and 0.90 respectively. The results suggested that use of high spatial resolution satellite imagery for the retrieval of crop chlorophyll content by using ANN model provides accurate, reliable assessment of crop health status at a larger scale which can help in managing crop nutrition requirement in real time.

Keywords: ANN, chlorophyll content, chlorophyll indices, satellite images, wheat

Procedia PDF Downloads 147
7 Study on Co-Relation of Prostate Specific Antigen with Metastatic Bone Disease in Prostate Cancer on Skeletal Scintigraphy

Authors: Muhammad Waleed Asfandyar, Akhtar Ahmed, Syed Adib-ul-Hasan Rizvi

Abstract:

Objective: To evaluate the ability of serum concentration of prostate specific antigen between two cutting points considering it as a predictor of skeletal metastasis on bone scintigraphy in men with prostate cancer. Settings: This study was carried out in department of Nuclear Medicine at Sindh Institute of Urology and Transplantation (SIUT) Karachi, Pakistan. Materials and Method: From August 2013 to November 2013, forty two (42) consecutive patients with prostate cancer who underwent technetium-99m methylene diphosphonate (Tc-99mMDP) whole body bone scintigraphy were prospectively analyzed. The information was collected from the scintigraphic database at a Nuclear medicine department Sindh institute of urology and transplantation Karachi Pakistan. Patients who did not have a serum PSA concentration available within 1 month before or after the time of performing the Tc-99m MDP whole body bone scintigraphy were excluded from this study. A whole body bone scintigraphy scan (from the toes to top of the head) was performed using a whole-body Moving gamma camera technique (anterior and posterior) 2–4 hours after intravenous injection of 20 mCi of Tc-99m MDP. In addition, all patients necessarily have a pathological report available. Bony metastases were determined from the bone scan studies and no further correlation with histopathology or other imaging modalities were performed. To preserve patient confidentiality, direct patient identifiers were not collected. In all the patients, Prostate specific antigen values and skeletal scintigraphy were evaluated. Results: The mean age, mean PSA, and incidence of bone metastasis on bone scintigraphy were 68.35 years, 370.51 ng/mL and 19/42 (45.23%) respectively. According to PSA levels, patients were divided into 5 groups < 10ng/mL (10/42), 10-20 ng/mL (5/42), 20-50 ng/mL (2/42), 50-100 (3/42), 100- 500ng/mL (3/42) and more than 500ng/mL (0/42) presenting negative bone scan. The incidence of positive bone scan (%) for bone metastasis for each group were O1 patient (5.26%), 0%, 03 patients (15.78%), 01 patient (5.26%), 04 patients (21.05%), and 10 patients (52.63%) respectively. From the 42 patients 19 (45.23%) presented positive scintigraphic examination for the presence of bone metastasis. 1 patient presented bone metastasis on bone scintigraphy having PSA level less than 10ng/mL, and in only 1 patient (5.26%) with bone metastasis PSA concentration was less than 20 ng/mL. therefore, when the cutting point adopted for PSA serum concentration was 10ng/mL, a negative predictive value for bone metastasis was 95% with sensitivity rates 94.74% and the positive predictive value and specificities of the method were 56.53% and 43.48% respectively. When the cutting point of PSA serum concentration was 20ng/mL the observed results for Positive predictive value and specificity were (78.27% and 65.22% respectively) whereas negative predictive value and sensitivity stood (100% and 95%) respectively. Conclusion: Results of our study allow us to conclude that serum PSA concentration of higher than 20ng/mL was the most accurate cutting point than a serum concentration of PSA higher than 10ng/mL to predict metastasis in radionuclide bone scintigraphy. In this way, unnecessary cost can be avoided, since a considerable part of prostate adenocarcinomas present low serum PSA levels less than 20 ng/mL and for these cases radionuclide bone scintigraphy could be unnecessary.

Keywords: bone scan, cut off value, prostate specific antigen value, scintigraphy

Procedia PDF Downloads 320
6 Controlled Nano Texturing in Silicon Wafer for Excellent Optical and Photovoltaic Properties

Authors: Deb Kumar Shah, M. Shaheer Akhtar, Ha Ryeon Lee, O-Bong Yang, Chong Yeal Kim

Abstract:

The crystalline silicon (Si) solar cells are highly renowned photovoltaic technology and well-established as the commercial solar technology. Most of the solar panels are globally installed with the crystalline Si solar modules. At the present scenario, the major photovoltaic (PV) market is shared by c-Si solar cells, but the cost of c-Si panels are still very high as compared with the other PV technology. In order to reduce the cost of Si solar panels, few necessary steps such as low-cost Si manufacturing, cheap antireflection coating materials, inexpensive solar panel manufacturing are to be considered. It is known that the antireflection (AR) layer in c-Si solar cell is an important component to reduce Fresnel reflection for improving the overall conversion efficiency. Generally, Si wafer exhibits the 30% reflection because it normally poses the two major intrinsic drawbacks such as; the spectral mismatch loss and the high Fresnel reflection loss due to the high contrast of refractive indices between air and silicon wafer. In recent years, researchers and scientists are highly devoted to a lot of researches in the field of searching effective and low-cost AR materials. Silicon nitride (SiNx) is well-known AR materials in commercial c-Si solar cells due to its good deposition and interaction with passivated Si surfaces. However, the deposition of SiNx AR is usually performed by expensive plasma enhanced chemical vapor deposition (PECVD) process which could have several demerits like difficult handling and damaging the Si substrate by plasma when secondary electrons collide with the wafer surface for AR coating. It is very important to explore new, low cost and effective AR deposition process to cut the manufacturing cost of c-Si solar cells. One can also be realized that a nano-texturing process like the growth of nanowires, nanorods, nanopyramids, nanopillars, etc. on Si wafer can provide a low reflection on the surface of Si wafer based solar cells. The above nanostructures might be enhanced the antireflection property which provides the larger surface area and effective light trapping. In this work, we report on the development of crystalline Si solar cells without using the AR layer. The Silicon wafer was modified by growing nanowires like Si nanostructures using the wet controlled etching method and directly used for the fabrication of Si solar cell without AR. The nanostructures over Si wafer were optimized in terms of sizes, lengths, and densities by changing the etching conditions. Well-defined and aligned wires like structures were achieved when the etching time is 20 to 30 min. The prepared Si nanostructured displayed the minimum reflectance ~1.64% at 850 nm with the average reflectance of ~2.25% in the wavelength range from 400-1000 nm. The nanostructured Si wafer based solar cells achieved the comparable power conversion efficiency in comparison with c-Si solar cells with SiNx AR layer. From this study, it is confirmed that the reported method (controlled wet etching) is an easy, facile method for preparation of nanostructured like wires on Si wafer with low reflectance in the whole visible region, which has greater prospects in developing c-Si solar cells without AR layer at low cost.

Keywords: chemical etching, conversion efficiency, silicon nanostructures, silicon solar cells, surface modification

Procedia PDF Downloads 125
5 Poly (3,4-Ethylenedioxythiophene) Prepared by Vapor Phase Polymerization for Stimuli-Responsive Ion-Exchange Drug Delivery

Authors: M. Naveed Yasin, Robert Brooke, Andrew Chan, Geoffrey I. N. Waterhouse, Drew Evans, Darren Svirskis, Ilva D. Rupenthal

Abstract:

Poly(3,4-ethylenedioxythiophene) (PEDOT) is a robust conducting polymer (CP) exhibiting high conductivity and environmental stability. It can be synthesized by either chemical, electrochemical or vapour phase polymerization (VPP). Dexamethasone sodium phosphate (dexP) is an anionic drug molecule which has previously been loaded onto PEDOT as a dopant via electrochemical polymerisation; however this technique requires conductive surfaces from which polymerization is initiated. On the other hand, VPP produces highly organized biocompatible CP structures while polymerization can be achieved onto a range of surfaces with a relatively straight forward scale-up process. Following VPP of PEDOT, dexP can be loaded and subsequently released via ion-exchange. This study aimed at preparing and characterising both non-porous and porous VPP PEDOT structures including examining drug loading and release via ion-exchange. Porous PEDOT structures were prepared by first depositing a sacrificial polystyrene (PS) colloidal template on a substrate, heat curing this deposition and then spin coating it with the oxidant solution (iron tosylate) at 1500 rpm for 20 sec. VPP of both porous and non-porous PEDOT was achieved by exposing to monomer vapours in a vacuum oven at 40 mbar and 40 °C for 3 hrs. Non-porous structures were prepared similarly on the same substrate but without any sacrificial template. Surface morphology, compositions and behaviour were then characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and cyclic voltammetry (CV) respectively. Drug loading was achieved by 50 CV cycles in a 0.1 M dexP aqueous solution. For drug release, each sample was exposed to 20 mL of phosphate buffer saline (PBS) placed in a water bath operating at 37 °C and 100 rpm. Film was stimulated (continuous pulse of ± 1 V at 0.5 Hz for 17 mins) while immersed into PBS. Samples were collected at 1, 2, 6, 23, 24, 26 and 27 hrs and were analysed for dexP by high performance liquid chromatography (HPLC Agilent 1200 series). AFM and SEM revealed the honey comb nature of prepared porous structures. XPS data showed the elemental composition of the dexP loaded film surface, which related well with that of PEDOT and also showed that one dexP molecule was present per almost three EDOT monomer units. The reproducible electroactive nature was shown by several cycles of reduction and oxidation via CV. Drug release revealed success in drug loading via ion-exchange, with stimulated porous and non-porous structures exhibiting a proof of concept burst release upon application of an electrical stimulus. A similar drug release pattern was observed for porous and non-porous structures without any significant statistical difference, possibly due to the thin nature of these structures. To our knowledge, this is the first report to explore the potential of VPP prepared PEDOT for stimuli-responsive drug delivery via ion-exchange. The produced porous structures were ordered and highly porous as indicated by AFM and SEM. These porous structures exhibited good electroactivity as shown by CV. Future work will investigate porous structures as nano-reservoirs to increase drug loading while sealing these structures to minimize spontaneous drug leakage.

Keywords: PEDOT for ion-exchange drug delivery, stimuli-responsive drug delivery, template based porous PEDOT structures, vapour phase polymerization of PEDOT

Procedia PDF Downloads 231
4 Role of Toll Like Receptor-2 in Female Genital Tuberculosis Disease Infection and Its Severity

Authors: Swati Gautam, Salman Akhtar, S. P. Jaiswar, Amita Jain

Abstract:

Background: FGTB is now a major global health problem mostly in developing countries including India. In humans, Mycobacterium Tuberculosis (M.tb) is a causating agent of infection. High index of suspicion is required for early diagnosis due to asymptomatic presentation of FGTB disease. In macrophages Toll Like Receptor-2 (TLR-2) is one which mediated host’s immune response to M.tb. The expression of TLR-2 on macrophages is important to determine the fate of innate immune responses to M.tb. TLR-2 have two work. First its high expression on macrophages worsen the outer of infection and another side, it maintains M.tb to its dormant stage avoids activation of M.tb from latent phase. Single Nucleotide Polymorphism (SNP) of TLR-2 gene plays an important role in susceptibility to TB among different populations and subsequently, in the development of infertility. Methodology: This Case-Control study was done in the Department of Obs and Gynae and Department of Microbiology at King George’s Medical University, U.P, Lucknow, India. Total 300 subjects (150 Cases and 150 Controls) were enrolled in the study. All subjects were enrolled only after fulfilling the given inclusion and exclusion criteria. Inclusion criteria: Age 20-35 years, menstrual-irregularities, positive on Acid-Fast Bacilli (AFB), TB-PCR, (LJ/MGIT) culture in Endometrial Aspiration (EA). Exclusion criteria: Koch’s active, on ATT, PCOS, and Endometriosis fibroid women, positive on Gonococal and Chlamydia. Blood samples were collected in EDTA tubes from cases and healthy control women (HCW) and genomic DNA extraction was carried out by salting-out method. Genotyping of TLR2 genetic variants (Arg753Gln and Arg677Trp) were performed by using single amplification refractory mutation system (ARMS) PCR technique. PCR products were analyzed by electrophoresis on 1.2% agarose gel and visualized by gel-doc. Statistical analysis of the data was performed using the SPSS 16.3 software and computing odds ratio (OR) with 95% CI. Linkage Disequiliribium (LD) analysis was done by SNP stats online software. Results: In TLR-2 (Arg753Gln) polymorphism significant risk of FGTB observed with GG homozygous mutant genotype (OR=13, CI=0.71-237.7, p=0.05), AG heterozygous mutant genotype (OR=13.7, CI=0.76-248.06, p=0.03) however, G allele (OR=1.09, CI=0.78-1.52, p=0.67) individually was not associated with FGTB. In TLR-2 (Arg677Trp) polymorphism a significant risk of FGTB observed with TT homozygous mutant genotype (OR= 0.020, CI=0.001-0.341, p < 0.001), CT heterozygous mutant genotype (OR=0.53, CI=0.33-0.86, p=0.014) and T allele (OR=0.463, CI=0.32-0.66, p < 0.001). TT mutant genotype was only found in FGTB cases and frequency of CT heterozygous more in control group as compared to FGTB group. So, CT genotype worked as protective mutation for FGTB susceptibility group. In haplotype analysis of TLR-2 genetic variants, four possible combinations, i.e. (G-T, A-C, G-C, and A-T) were obtained. The frequency of haplotype A-C was significantly higher in FGTB cases (0.32). Control group did not show A-C haplotype and only found in FGTB cases. Conclusion: In conclusion, study showed a significant association with both genetic variants of TLR-2 of FGTB disease. Moreover, the presence of specific associated genotype/alleles suggest the possibility of disease severity and clinical approach aimed to prevent extensive damage by disease and also helpful for early detection of disease.

Keywords: ARMS, EDTA, FGTB, TLR

Procedia PDF Downloads 308
3 Navigating Rapids And Collecting Medical Insights: A Data Collection Of Athletes Presenting To The Medical Team At The International Canoe Federation Canoe Slalom World Championships 2023

Authors: Grace Scaplehorn, Muhammad Adeel Akhtar, Jane Gibson

Abstract:

Background: Canoe Slalom entails the skilful navigation of a carbon composite canoe or kayak through a series of 18-25 hanging gates, strategically positioned along the course, either upstream or downstream, amidst currents of whitewater rapids in natural and man-made river settings. Athletes compete individually in timed trials, competing for the fastest course time, typically around 80 to 120 seconds. In the new discipline of Kayak Cross, descents of the course are initiated by groups of four athletes freefalling simultaneously from a starting platform situated 3m above the river. Kayak Cross athletes, in contrast to Canoe Slalom, can make physical contact with suspended gates without incurring time penalties and are required to perform a kayak roll half way down the course. The Canoe Slalom World Championships were held at Lee Valley Whitewater Centre, London, from 19th to 24th September 2023. The event comprised 299 international athletes competing for 10 World Championship titles in Canoe/Kayak Slalom events (Olympic Debut Munich 1972), and the new Kayak Cross discipline (Olympic Debut Paris 2024). The inaugural appearance of Kayak Cross at the World Championships occurred in 2017, in Pau, France. There is limited literature surrounding Kayak Cross and the incidence of athlete injuries compared to traditional Canoe Slalom, hence it was felt important to undertake this review to address the perception that the event is dangerous. Aim: The study aimed to quantify and collate data collected from athletes presenting to the event medical centre. Methods: Athletes’ details were collected at initial assessments from the start of the practice period (16th–18th September) and throughout the event. Demographics such as age, sex and nationality were recorded along with presenting complaints, treatment, medication administered and outcome. Specifically, injuries were then sub-classified into body regions. The data does not include athletes who sought medical attention from their own governing body’s medical team. Results: During the 8-day period, there were 11 individual presentations to the medical centre, 3.7% of the athlete population (n=299). The mean age was 23.9 years (n=7), 6 were male (n=10). The most common presentation was minor injury (n=9), with 6 being musculoskeletal and 3 comprising skin damage, followed by insect sting/allergy (n=1) and pain relief requests (n=1). Five presentations were event-related, all being musculoskeletal injuries; 2 shoulder/arm, 1 head/neck, 1 hand/wrist and 1 other (data was not recorded). Of these injuries, the only intervention was 2 cases of 400mg Ibuprofen, which was given to both shoulder/arm injuries. Four of the 11 presentations were pre-existing injuries, which had been exacerbated due to increased intensity of practice. Two patients were advised to return for review, with 100% compliance. There were no unplanned re-presentations, and no emergency transfers to secondary care. Both the Kayak Cross and Canoe Slalom competitions resulted in 1 new event-related athlete presentation each. Conclusion: The event resulted in a negligible incidence of presentations at the medical centre, for both Kayak Cross and Canoe Slalom. This data holds significance in informing risk assessments and medical protocols necessary for the organisation of canoe slalom events.

Keywords: canoe slalom, kayak cross, athlete injuries, event injuries

Procedia PDF Downloads 57
2 De-convolution Based IVIVC Correlation for Tacrolimus ER Tablet (Narrow Therapeutic Index Drug) With Widening of Dissolution Prediction for Virtual Bioequivalence

Authors: Sajad Khaliq Dar, Dipanjan Goswami, Arshad H. Khuroo, Mohd. Akhtar, Pulak Kumar Metia, Sudershan Kumar

Abstract:

Background: Development of modified-release oral dosage formulations (OSD) like tacrolimus in narrow therapeutic categories, together with high levels of intra-individual variability, impose greater challenges. The risk assessment for bioequivalence studies requires developing a suitable design through pilot studies involving the comparison of multiple formulations of the same product with a marketed product to understand the in-vivo behaviour. These formulations could have varying coating levels and other minor quantitative differences to achieve the desired release rate for the final product. Although small-scale studies are critical before the conduct of full-scale Pharmacokinetic (PK) studies, regulatory agencies evaluate critical bioavailability attributes (CBA) before approving the submitted dossiers. Since Tacrolimus is a BCS Class II drug, therefore developing the extended-release formulation, in addition to associated challenges, provides an opportunity to present the In vitro-in vivo correlations (IVIVC) to regulatory agencies, not only to exhibit product quality but also to reduce the burden of additional human trials and cost involved to them for bringing the product to market. Objective: The objective of this study was to develop a Level-A In vitro - In vivo Correlation (IVIVC) model for Sun Pharma’s test formulation Tacrolimus ER tablet 4mg and extend its application to a widened dissolution window of 25% at 2.5 hours (critical release time) sampling time point. Experimental Procedure: Post the conduct of two in-vivo studies, a pilot study evaluating two test prototypes on 24 subjects (under fasting) and a pivotal study having 50 subjects (under fasting), the observed pharmacokinetic profile was used for IVIVC model development. The dissolution media used was 0.005% HPC + 0.25% SLS in Water 900 mL at pH 4.50 using USP II (Paddle) apparatus with alternative sinkers operated at 100 RPM. The sampling time points were chosen to mimic the drug absorption in vivo. The dissolution best fit to data was obtained using Makoid Banakar kinetics. Then deconvolution, anchoring to concepts of the single compartment by Wagner Nelson method was applied for tacrolimus slow-release formulation batch with film coating weight build-up of 5.4% (used in pilot bio study), medium release with Hypromellose (retard-release exhibit batch used in the pivotal study) and fast release formulation batch with film coating weight build-up of 5.05% (used in pilot bio study). Results and Conclusion: The results were deemed acceptable as prediction errors for internal and external validation were < 3% depicting in-vitro drug release mimics in-vivo absorption. Moreover, the prediction result for the Test/Reference ratio was <15% for all test formulations and widening dissolution (i.e., 39%-64% drug release at 2.5hrs) predictions were well within 80-125% when compared against Envarsus XR (reference drug). This IVIVC-validated model can be used in the futuristic exploration of dose titration with 1mg tacrolimus ER OSD as a surrogate for In-vivo bioequivalence trials.

Keywords: pharmacokinetics, BCS, oral dosage form, Bioavailability, intra-individual variability

Procedia PDF Downloads 5
1 Integrated Mathematical Modeling and Advance Visualization of Magnetic Nanoparticle for Drug Delivery, Drug Release and Effects to Cancer Cell Treatment

Authors: Norma Binti Alias, Che Rahim Che The, Norfarizan Mohd Said, Sakinah Abdul Hanan, Akhtar Ali

Abstract:

This paper discusses on the transportation of magnetic drug targeting through blood within vessels, tissues and cells. There are three integrated mathematical models to be discussed and analyze the concentration of drug and blood flow through magnetic nanoparticles. The cell therapy brought advancement in the field of nanotechnology to fight against the tumors. The systematic therapeutic effect of Single Cells can reduce the growth of cancer tissue. The process of this nanoscale phenomena system is able to measure and to model, by identifying some parameters and applying fundamental principles of mathematical modeling and simulation. The mathematical modeling of single cell growth depends on three types of cell densities such as proliferative, quiescent and necrotic cells. The aim of this paper is to enhance the simulation of three types of models. The first model represents the transport of drugs by coupled partial differential equations (PDEs) with 3D parabolic type in a cylindrical coordinate system. This model is integrated by Non-Newtonian flow equations, leading to blood liquid flow as the medium for transportation system and the magnetic force on the magnetic nanoparticles. The interaction between the magnetic force on drug with magnetic properties produces induced currents and the applied magnetic field yields forces with tend to move slowly the movement of blood and bring the drug to the cancer cells. The devices of nanoscale allow the drug to discharge the blood vessels and even spread out through the tissue and access to the cancer cells. The second model is the transport of drug nanoparticles from the vascular system to a single cell. The treatment of the vascular system encounters some parameter identification such as magnetic nanoparticle targeted delivery, blood flow, momentum transport, density and viscosity for drug and blood medium, intensity of magnetic fields and the radius of the capillary. Based on two discretization techniques, finite difference method (FDM) and finite element method (FEM), the set of integrated models are transformed into a series of grid points to get a large system of equations. The third model is a single cell density model involving the three sets of first order PDEs equations for proliferating, quiescent and necrotic cells change over time and space in Cartesian coordinate which regulates under different rates of nutrients consumptions. The model presents the proliferative and quiescent cell growth depends on some parameter changes and the necrotic cells emerged as the tumor core. Some numerical schemes for solving the system of equations are compared and analyzed. Simulation and computation of the discretized model are supported by Matlab and C programming languages on a single processing unit. Some numerical results and analysis of the algorithms are presented in terms of informative presentation of tables, multiple graph and multidimensional visualization. As a conclusion, the integrated of three types mathematical modeling and the comparison of numerical performance indicates that the superior tool and analysis for solving the complete set of magnetic drug delivery system which give significant effects on the growth of the targeted cancer cell.

Keywords: mathematical modeling, visualization, PDE models, magnetic nanoparticle drug delivery model, drug release model, single cell effects, avascular tumor growth, numerical analysis

Procedia PDF Downloads 428