Search results for: controlled drug delivery
5425 Development and in vitro Evaluation of Polymer-Drug Conjugates Containing Potentiating Agents for Combination Therapy
Authors: Blessing A. Aderibigbe
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Combination therapy is a treatment approach that is used to prevent the emergence of drug resistance. This approach is used for the treatment of many chronic and infectious diseases. Potentiating agents are currently explored in combination therapy, resulting in excellent therapeutic outcomes. Breast cancer and malaria are two chronic conditions responsible globally for high death rates. In this research, a class of polymer-drug conjugates containing potentiating agents with either antimalarial or anticancer drugs were prepared by Michael Addition Polymerization reaction and ring-opening polymerization reaction. Conjugation of potentiating agents with bioactive compounds into the polymers resulted in conjugates with good water solubility, highly selective and non-toxic. In vitro cytotoxicity and in vitro antiplasmodial evaluation on the conjugates revealed that the conjugates were more effective when compared to the free drugs. The drug release studies further showed that the release profile of the drugs from the conjugates was sustained. The findings revealed the potential of polymer-drug conjugates to overcome drug toxicity and drug resistance, which is common with the currently used antimalarial and anticancer drugs.Keywords: anticancer, antimalarials, combination therapy, polymer-drug conjugates
Procedia PDF Downloads 1335424 Synthesis and Characterization of Novel Hollow Silica Particle through DODAB Vesicle Templating
Authors: Eun Ju Park, Wendy Rusli, He Tao, Alexander M. Van Herk, Sanggu Kim
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Hollow micro-/nano- structured materials have proven to be promising in wide range of applications, such as catalysis, drug delivery and controlled release, biotechnology, and personal and consumer care. Hollow sphere structures can be obtained through various templating approaches; colloid templates, emulsion templates, multi-surfactant templates, and single crystal templates. Vesicles are generally the self-directed assemblies of amphiphilic molecules including cationic, anionic, and cationic surfactants in aqueous solutions. The directed silica capsule formations were performed at the surface of dioctadecyldimethylammoniumbromide(DODAB) bilayer vesicles as soft template. The size of DODAB bilayer vesicles could be tuned by extrusion of a preheated dispersion of DODAB. The synthesized hollow silica particles were characterized by conventional TEM, cryo-TEM and SEM to determine the morphology and structure of particles and dynamic light scattering (DLS) method to measure the particle size and particle size distribution.Keywords: characterization, DODAB, hollow silica particle, synthesis, vesicle
Procedia PDF Downloads 3075423 A Photoredox (C)sp³-(C)sp² Coupling Method Comparison Study
Authors: Shasline Gedeon, Tiffany W. Ardley, Ying Wang, Nathan J. Gesmundo, Katarina A. Sarris, Ana L. Aguirre
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Drug discovery and delivery involve drug targeting, an approach that helps find a drug against a chosen target through high throughput screening and other methods by way of identifying the physical properties of the potential lead compound. Physical properties of potential drug candidates have been an imperative focus since the unveiling of Lipinski's Rule of 5 for oral drugs. Throughout a compound's journey from discovery, clinical phase trials, then becoming a classified drug on the market, the desirable properties are optimized while minimizing/eliminating toxicity and undesirable properties. In the pharmaceutical industry, the ability to generate molecules in parallel with maximum efficiency is a substantial factor achieved through sp²-sp² carbon coupling reactions, e.g., Suzuki Coupling reactions. These reaction types allow for the increase of aromatic fragments onto a compound. More recent literature has found benefits to decreasing aromaticity, calling for more sp³-sp² carbon coupling reactions instead. The objective of this project is to provide a comparison between various sp³-sp² carbon coupling methods and reaction conditions, collecting data on production of the desired product. There were four different coupling methods being tested amongst three cores and 4-5 installation groups per method; each method ran under three distinct reaction conditions. The tested methods include the Photoredox Decarboxylative Coupling, the Photoredox Potassium Alkyl Trifluoroborate (BF3K) Coupling, the Photoredox Cross-Electrophile (PCE) Coupling, and the Weix Cross-Electrophile (WCE) Coupling. The results concluded that the Decarboxylative method was very difficult in yielding product despite the several literature conditions chosen. The BF3K and PCE methods produced competitive results. Amongst the two Cross-Electrophile coupling methods, the Photoredox method surpassed the Weix method on numerous accounts. The results will be used to build future libraries.Keywords: drug discovery, high throughput chemistry, photoredox chemistry, sp³-sp² carbon coupling methods
Procedia PDF Downloads 1445422 Creation and Implementation of A New Palliative Care Drug Chart, via A Closed-Loop Audit
Authors: Asfa Hussain, Chee Tang, Mien Nguyen
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Introduction: The safe usage of medications is dependent on clear, well-documented prescribing. Medical drug charts should be regularly checked to ensure that they are fit for purpose. Aims: The purpose of this study was to evaluate whether the Isabel Hospice drug charts were effective or prone to medical errors. The aim was to create a comprehensive palliative care drug chart in line with medico-legal guidelines and to minimise drug administration and prescription errors. Methodology: 50 medical drug charts were audited from March to April 2020, to assess whether they complied with medico-legal guidelines, in a hospice within East of England. Meetings were held with the larger multi-disciplinary team (MDT), including the pharmacists, nursing staff and doctors, to raise awareness of the issue. A preliminary drug chart was created, using the input from the wider MDT. The chart was revised and trialled over 15 times, and each time feedback from the MDT was incorporated into the subsequent template. In the midst of the COVID-19 pandemic in September 2020, the finalised drug chart was trialled. 50 new palliative drug charts were re-audited, to evaluate the changes made. Results: Prescribing and administration errors were high prior to the implementation of the new chart. This improved significantly after introducing the new drug charts, therefore improving patient safety and care. The percentage of inadequately documented allergies went down from 66% to 20% and incorrect oxygen prescription from 40% to 16%. The prescription drug-drug interactions decreased by 30%. Conclusion: It is vital to have clear standardised drug charts, in line with medico-legal standards, to allow ease of prescription and administration of medications and ensure optimum patient-centred care. This closed loop audit demonstrated significant improvement in documentation and prevention of possible fatal drug errors and interactions.Keywords: palliative care, drug chart, medication errors, drug-drug interactions, COVID-19, patient safety
Procedia PDF Downloads 1765421 Self-Regenerating, Vascularizing Hybrid Scaffold-Hydrogel For Bone Tissue Engineering
Authors: Alisha Gupta
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Osteoarthritis (OA) is the most common form of arthritis which is a degenerative joint disease causing joints to begin to break down and underlying bones to change. This “wear and tear” most frequently affects hands, hips, and knees. This is important because OA pain is considered to be a leading cause of mobility impairment in older adults, with hip and knee OA ranked 11th highest contributors to global disability. Bone tissue engineering utilizing polymer scaffolds and hydrogels is an emerging field for treating osteoarthritis. Polymer scaffolds provide a three-dimensional structure for tissue growth, and hydrogels can be used to deliver drugs and growth factors. The combination of the two materials creates a hybrid structure that can better withstand physiological and mechanical demands while also providing a more controlled environment for drug and nutrient delivery. I think using bone tissue engineering for making scaffold-hydrogel composites that are self-regenerating and vascularizing might be useful in solving this problem. Successful implementation can reconstruct healthy, simulated bone tissue on deficient applicants.Keywords: tissue engineering, regenerative medicine, scaffold-hydrogel composites, osteoarthritis
Procedia PDF Downloads 1195420 Nanoparticles-Protein Hybrid-Based Magnetic Liposome
Authors: Amlan Kumar Das, Avinash Marwal, Vikram Pareek
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Liposome plays an important role in medical and pharmaceutical science as e.g. nano scale drug carriers. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment. Magnet-driven liposome used for the targeted delivery of drugs to organs and tissues1. These liposome preparations contain encapsulated drug components and finely dispersed magnetic particles. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment that are generated in vitro. These are useful in terms of biocompatibility, biodegradability, and low toxicity, and can control biodistribution by changing the size, lipid composition, and physical characteristics2. Furthermore, liposomes can entrap both hydrophobic and hydrophilic drugs and are able to continuously release the entrapped substrate, thus being useful drug carriers. Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate magneticor paramagnetic nanoparticles. They are applied as contrast agents for magnetic resonance imaging (MRI)3. The biological synthesis of nanoparticles using plant extracts plays an important role in the field of nanotechnology4. Green-synthesized magnetite nanoparticles-protein hybrid has been produced by treating Iron (III)/Iron(II) chloride with the leaf extract of Dhatura Inoxia. The phytochemicals present in the leaf extracts act as a reducing as well stabilizing agents preventing agglomeration, which include flavonoids, phenolic compounds, cardiac glycosides, proteins and sugars. The magnetite nanoparticles-protein hybrid has been trapped inside the aqueous core of the liposome prepared by reversed phase evaporation (REV) method using oleic and linoleic acid which has been shown to be driven under magnetic field confirming the formation magnetic liposome (ML). Chemical characterization of stealth magnetic liposome has been performed by breaking the liposome and release of magnetic nanoparticles. The presence iron has been confirmed by colour complex formation with KSCN and UV-Vis study using spectrophotometer Cary 60, Agilent. This magnet driven liposome using nanoparticles-protein hybrid can be a smart vesicles for the targeted drug delivery.Keywords: nanoparticles-protein hybrid, magnetic liposome, medical, pharmaceutical science
Procedia PDF Downloads 2485419 Development and Characterization of a Film Based on Hydroxypropyl Methyl Cellulose Incorporated by a Phenolic Extract of Fennel and Reinforced by Magnesium Oxide: In Vivo - in Vitro
Authors: Mazouzi Nourdjihane, K. Boutemak, A. Haddad, Y. Chegreouche
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In the last decades, biodegradable polymers have been considered as one of the most popular options for the delivery of drugs and various conventional doses. The film forming system (FFS) can be used in topical, transdermal, ophthalmic, oral and gastric applications. Recently this system has focused on improving drug delivery, which can promote drug release. In this context, the aim of this study is to create polymeric film-forming systems for the stomach and to evaluate and test their gastroprotective effects, comparing the effects of changes in composition on film characteristics. It uses a plant-derived polyphenol extract extracted from fennel to demonstrate anti-inflammatory activity in the film. The films are made from hydroxypropyl methylcellulose polymer and different types of plastic, glycerol and polyethylene glycol. The ffs properties show that MgO-glycerol-reinforced hydroxypropylmethylcellulose (HPMC-MgO-Gly) is better than that based on MgO-PEG-reinforced hydroxypropylmethylcellulose (HPMC-MgO-PEG). It is durable, has a faster drying time and allows for maximum recovery. Water vapor strength and blowing speed and other additions show another advantage of HPMC-MgO-Gly compared to HPMC-MgO-PEG, indicating good adhesion between the support (top) and film production. In this study, the gastroprotective effect of fennel phenol extract was found, showing that this plant material has a gastroprotective effect on ulcers and that the film can absorb the active substance.Keywords: film formin system, hydroxypropyl methylcellulose, magnesium oxide, in vivo
Procedia PDF Downloads 665418 Development, Optimization and Characterization of Gastroretentive Multiparticulate Drug Delivery System
Authors: Swapnila V. Vanshiv, Hemant P. Joshi, Atul B. Aware
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Current study illustrates the formulation of floating microspheres for purpose of gastroretention of Dipyridamole which shows pH dependent solubility, with the highest solubility in acidic pH. The formulation involved hollow microsphere preparation by using solvent evaporation technique. Concentrations of rate controlling polymer, hydrophilic polymer, internal phase ratio, stirring speed were optimized to get desired responses, namely release of Dipyridamole, buoyancy of microspheres, entrapment efficiency of microspheres. In the formulation, the floating microspheres were prepared by using ethyl cellulose as release retardant and HPMC as a low density hydrophilic swellable polymer. Formulated microspheres were evaluated for their physical properties such as particle size and surface morphology by optical microscopy and SEM. Entrapment efficiency, floating behavior and drug release study as well the formulation was evaluated for in vivo gastroretention in rabbits using gamma scintigraphy. Formulation showed 75% drug release up to 10 hr with entrapment efficiency of 91% and 88% buoyancy till 10 hr. Gamma scintigraphic studies revealed that the optimized system was retained in the gastric region (stomach) for a prolonged period i.e. more than 5 hr.Keywords: Dipyridamole microspheres, gastroretention, HPMC, optimization method
Procedia PDF Downloads 3855417 The Effect of the Combination of Methotrexate Nanoparticles and TiO2 on Breast Cancer
Authors: Nusaiba Al-Nemrawi, Belal Al-Husein
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Methotrexate (MTX) is a stoichiometric inhibitor of dihydrofolate reductase, which is essential for DNA synthesis. MTX is a chemotherapeutic agent used for treating many types of cancer cells. However, cells’ resistant to MTX is very common and its pharmacokinetic behavior is highly problematic. of MTX within tumor cells, we propose encapsulation of antitumor drugs in nanoparticulated systems. Chitosan (CS) is a naturally occurring polymer that is biocompatibe, biodegradable, non-toxic, cationic and bioadhesive. CS nanoparticles (CS-NPs) have been used as drug carrier for targeted delivery. Titanium dioxide (TiO2), a natural mineral oxide, which is used in biomaterials due to its high stability and antimicrobial and anticorrosive properties. TiO2 showed a potential as a tumor suppressor. In this study a new formulation of MTX loaded in CS NPs (CS-MTX NPs) and coated with Titanium oxide (TiO2) was prepared. The mean particle size, zeta potential, polydispersity index were measured. The interaction between CS NPs and TiO2 NPs was confirmed using FTIR and XRD. CS-MTX NPs was studied in vitro using the tumor cell line MCF-7 (human breast cancer). The results showed that CS-MTX has a size around 169 nm and as they were coated with TiO2, the size ranged between and depending on the ratio of CS-MTX to TiO2 ratio used in the preparation. All NPs (uncoated and coated carried positive charges and were monodispersed. The entrapment efficacy was around 65%. Both FTIR and XRD proved that TiO2 interacted with CS-MTX NPs. The drug invitro release was controlled and sustained over days. Finally, the studied in vitro using the tumor cell line MCF-7 suggested that combining nanomaterials with anticancer drugs CS-MTX NPs may be more effective than free MTX for cancer treatment. In conclusion, the combination of CS-MTX NPs and TiO2 NPs showed excellent time-dependent in vitro antitumor behavior, therefore, can be employed as a promising anticancer agent to attain efficient results towards MCF-7 cells.Keywords: Methotrexate, Titanium dioxide, Chitosan nanoparticles, cancer
Procedia PDF Downloads 955416 Investigation of an Approach in Drug Delivery: Orally Fast Disintegrating Tablets
Authors: Tansel Comoglu
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Orally fast disintegrating tablets (FDTs or ODTs) have become popular during the last decade, and manufacturing of ODTs is getting a rapidly growing area in the pharmaceutical industry. The concept of ODTs has emerged from the desire to provide patients with more conventional means of taking their medication. Drugs, that have satisfactory absorption from the oral mucosa or aimed for immediate therapeutic activity can be formulated in ODTs. After placing the ODT into the mouth, these tablets dissolve or disintegrate in the mouth usullay less than a minute, in the absence of additional water. Even though the ODT technology has taken an important path, as proved by a large group of commercial products on the drug market, there are so many problems to be solved in ODT formulations such as; formulation of hydrophobic drugs is stil a challenge, especially when the amount of drug is high. As these tablets dissolve or disintegrate in the mouth without the need of additional water, taste masking of active ingredients becomes essential in these systems because the drug is entirely released in the mouth. In ODT technology, coping with the taste of drugs is still a challenge. Resins or sweeteners or other techniques are also used in the formulation to aid taste-masking of the API. Another important factor to consider is whether they can be manufactured using conventional equipment and processes, as this will have a positive influence on manufacturing costs. Some products, however, may require a more costly, special unitdose packaging if the dosage form is fragile. In this overview, benefits, various formulation technologies, clinical studies and some future research trends of ODTs will be discussed.Keywords: orally fast disintegrating tablets, benefits, formulation technologies, future research trends
Procedia PDF Downloads 3605415 Layer-by-Layer Coated Dexamethasone Microcrystals for Experimental Inflammatory Bowel Disease Therapy
Authors: Murtada Ahmed Oshi, Jin-Wook Yoo
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Layer-by-layer (LBL) coating has gained popularity for drug delivery of therapeutic drugs. Herein we described a novel approach for enhancing the therapeutic efficiency of the locally administered dexamethasone (Dex) for inflammatory bowel disease (IBD). We utilized a LBL-coating technique on Dex microcrystals (DexMCs) with multiple layers of polyelectrolytes composed of poly (allylamine hydrochloride) (PAH), poly (sodium 4-styrene sulfonate) (PSS) and Eudragit® S100 (ES). The successful deposition of the layers onto DexMCs surfaces were confirmed through zeta potential measurement and confocal laser scanning microscopy. The surface morphology was investigated through scanning electron microscopy. The drug encapsulation efficiency was 95% with a mean particle size of 2 µm and negative surface charge (-40 mV). Moreover, in vitro drug release study showed a minimum release of the drug ( 15%) at an acidic condition during initial first 5 h, followed by sustained-release at an alkaline condition. For in vivo study, LBL-DxMCs were administered orally to ICR mice suffering from dextran sulfate sodium-induced colitis. LBL-DxMCs substantially enhanced anti-IBD activities as compared to DxMCs. Macroscopic, histological and biochemical (tumor necrosis factor-α, interleukin-6 and myeloperoxidase) examinations revealed marked improvements of colitis signs in the mice treated with LBL-DxMCs compared with those treated with DxMCs. Overall, LBL-DxMCs could be a suitable candidate for the treatment of IBD.Keywords: dexamethasone, inflammatory bowel disease, LBL-coating, polyelectrolytes
Procedia PDF Downloads 1965414 Importance of Infrastucture Delivery and Management in South Africa
Authors: Onyeka Nkwonta, Theo Haupt, Karana Padayachee
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This study aims primarily to identify potential causes of the bottlenecks in the public sector that affect delivery and formulate evidence-based interventions to improve delivery and management of infrastructure projects. An initial literature review was carried out on infrastructural development and delivery in South Africa, with the aim to formulate evidence-based interventions to improve delivery within the sector. The infrastructure delivery management model was developed to map out best practice delivery processes. These will become the backbone on which improvement initiatives that will be developed within participating stakeholders. The model will, in turn, support a range of methodologies, including the risk system and a knowledge management framework. It will also look at key challenges facing departments with the ability to ensure knowledge and skills transfer at various sectors. The research is limited because the findings were based on existing literature. This study adopted an indirect approach for infrastructure management by focussing on the challenges faced and approaches adopted to overcome these challenges. This may narrow the consideration of some of the viewpoints, thereby limiting the richness of experience available to this research.Keywords: infrastructure, management, challenges, South Africa
Procedia PDF Downloads 1385413 Parameters Influencing Human Machine Interaction in Hospitals
Authors: Hind Bouami
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Handling life-critical systems complexity requires to be equipped with appropriate technology and the right human agents’ functions such as knowledge, experience, and competence in problem’s prevention and solving. Human agents are involved in the management and control of human-machine system’s performance. Documenting human agent’s situation awareness is crucial to support human-machine designers’ decision-making. Knowledge about risks, critical parameters and factors that can impact and threaten automation system’s performance should be collected using preventive and retrospective approaches. This paper aims to document operators’ situation awareness through the analysis of automated organizations’ feedback. The analysis of automated hospital pharmacies feedbacks helps to identify and control critical parameters influencing human machine interaction in order to enhance system’s performance and security. Our human machine system evaluation approach has been deployed in Macon hospital center’s pharmacy which is equipped with automated drug dispensing systems since 2015. Automation’s specifications are related to technical aspects, human-machine interaction, and human aspects. The evaluation of drug delivery automation performance in Macon hospital center has shown that the performance of the automated activity depends on the performance of the automated solution chosen, and also on the control of systemic factors. In fact, 80.95% of automation specification related to the chosen Sinteco’s automated solution is met. The performance of the chosen automated solution is involved in 28.38% of automation specifications performance in Macon hospital center. The remaining systemic parameters involved in automation specifications performance need to be controlled.Keywords: life-critical systems, situation awareness, human-machine interaction, decision-making
Procedia PDF Downloads 1815412 Risk Assessment for Aerial Package Delivery
Authors: Haluk Eren, Ümit Çelik
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Recent developments in unmanned aerial vehicles (UAVs) have begun to attract intense interest. UAVs started to use for many different applications from military to civilian use. Some online retailer and logistics companies are testing the UAV delivery. UAVs have great potentials to reduce cost and time of deliveries and responding to emergencies in a short time. Despite these great positive sides, just a few works have been done for routing of UAVs for package deliveries. As known, transportation of goods from one place to another may have many hazards on delivery route due to falling hazards that can be exemplified as ground objects or air obstacles. This situation refers to wide-range insurance concept. For this reason, deliveries that are made with drones get into the scope of shipping insurance. On the other hand, air traffic was taken into account in the absence of unmanned aerial vehicle. But now, it has been a reality for aerial fields. In this study, the main goal is to conduct risk analysis of package delivery services using drone, based on delivery routes.Keywords: aerial package delivery, insurance estimation, territory risk map, unmanned aerial vehicle, route risk estimation, drone risk assessment, drone package delivery
Procedia PDF Downloads 3415411 Sustainability Assessment of Food Delivery with Last-Mile Delivery Droids, A Case Study at the European Commission's JRC Ispra Site
Authors: Ada Garus
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This paper presents the outcomes of the sustainability assessment of food delivery with a last-mile delivery service introduced in a real-world case study. The methodology used in the sustainability assessment integrates multi-criteria decision-making analysis, sustainability pillars, and scenario analysis to best reflect the conflicting needs of stakeholders involved in the last mile delivery system. The case study provides an application of the framework to the food delivery system of the Joint Research Centre of the European Commission where three alternative solutions were analyzed I) the existent state in which individuals frequent the local cantine or pick up their food, using their preferred mode of transport II) the hypothetical scenario in which individuals can only order their food using the delivery droid system III) a scenario in which the food delivery droid based system is introduced as a supplement to the current system. The environmental indices are calculated using a simulation study in which decision regarding the food delivery is predicted using a multinomial logit model. The vehicle dynamics model is used to predict the fuel consumption of the regular combustion engines vehicles used by the cantine goers and the electricity consumption of the droid. The sustainability assessment allows for the evaluation of the economic, environmental, and social aspects of food delivery, making it an apt input for policymakers. Moreover, the assessment is one of the first studies to investigate automated delivery droids, which could become a frequent addition to the urban landscape in the near future.Keywords: innovations in transportation technologies, behavioural change and mobility, urban freight logistics, innovative transportation systems
Procedia PDF Downloads 1935410 Resveratrol-Phospholipid Complex for Sustained Delivery of Resveratrol via the Skin for the Treatment of Inflammatory Diseases
Authors: Malay K. Das, Bhupen Kalita
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The poor oral bioavailability of resveratrol (RSV) due to presystemic metabolism can be avoided via dermal route of administration. The hydrophilic-lipophilic nature of resveratrol-phospholipid complex (RSVPs) favors the delivery of resveratrol via the skin. The RSVPs embedded polymeric patch with moderate adhesiveness was developed for dermal application for sustained anti-inflammatory effect. The prepared patches were evaluated for various physicochemical properties, surface morphology by SEM, TEM, and compatibility of patch components by FT-IR and DSC studies. The dermal flux of the optimized patch formulation was found to be at 4.28 ± 0.48 mg/cm2/24 h. The analysis of skin extract after permeation study revealed the presence of resveratrol, which confirmed the localization of RSVPs in the skin. The stability of RSVPs in the polymeric patch and the physiologic environment was confirmed by FE-SEM studies on the patches after drug release and skin permeation studies. The RSVPs particles released from the polymer matrix maintaining the structural integrity and permeate the keratinized horney layer of skin. The optimized patch formulation showed sustained anti-inflammatory effect (84.10% inhibition of inflammation at 24 h) in carrageenan-induced rat paw edema model compared to marketed diclofenac sodium gel (39.58% inhibition of inflammation at 24 h). The CLSM study confirmed the localization of RSVPs for a longer period, thus enabling drug targeting to the dermis for sustained anti-inflammatory effect. Histological studies with phase contrast trinocular microscope suggested no alteration of skin integrity and no evidence of the presence of inflammatory cells after exposure to the permeants. The patch was found to be safe for skin application as evaluated by Draize method for skin irritation scoring in a rabbit model. These results suggest the therapeutic efficacy of the developed patch in both acute and chronic inflammatory diseases.Keywords: resveratrol-phospholipid complex, skin delivery, sustained anti-inflammatory effect, inflammatory diseases, dermal patch
Procedia PDF Downloads 2305409 Targeted Delivery of Docetaxel Drug Using Cetuximab Conjugated Vitamin E TPGS Micelles Increases the Anti-Tumor Efficacy and Inhibit Migration of MDA-MB-231 Triple Negative Breast Cancer
Authors: V. K. Rajaletchumy, S. L. Chia, M. I. Setyawati, M. S. Muthu, S. S. Feng, D. T. Leong
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Triple negative breast cancers (TNBC) can be classified as one of the most aggressive with a high rate of local recurrences and systematic metastases. TNBCs are insensitive to existing hormonal therapy or targeted therapies such as the use of monoclonal antibodies, due to the lack of oestrogen receptor (ER) and progesterone receptor (PR) and the absence of overexpression of human epidermal growth factor receptor 2 (HER2) compared with other types of breast cancers. The absence of targeted therapies for selective delivery of therapeutic agents into tumours, led to the search for druggable targets in TNBC. In this study, we developed a targeted micellar system of cetuximab-conjugated micelles of D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) for targeted delivery of docetaxel as a model anticancer drug for the treatment of TNBCs. We examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. The targeting micelles were found preferentially accumulated in tumours immediately after the administration of the micelles compare to normal tissue. The fluorescence signal gradually increased up to 12 h at the tumour site and sustained for up to 24 h, reflecting the increases in targeted micelles (TPFC) micelles in MDA-MB-231/Luc cells. In comparison, for the non-targeting micelles (TPF), the fluorescence signal was evenly distributed all over the body of the mice. Only a slight increase in fluorescence at the chest area was observed after 24 h post-injection, reflecting the moderate uptake of micelles by the tumour. The successful delivery of docetaxel into tumour by the targeted micelles (TPDC) exhibited a greater degree of tumour growth inhibition than Taxotere® after 15 days of treatment. The ex vivo study has demonstrated that tumours treated with targeting micelles exhibit enhanced cell cycle arrest and attenuated proliferation compared with the control and with those treated non-targeting micelles. Furthermore, the ex vivo investigation revealed that both the targeting and non-targeting micellar formulations shows significant inhibition of cell migration with migration indices reduced by 0.098- and 0.28-fold, respectively, relative to the control. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGF-overexpressing MDA-MB-231 tumours.Keywords: biodegradable polymers, cancer nanotechnology, drug targeting, molecular biomaterials, nanomedicine
Procedia PDF Downloads 2815408 Solution Approaches for Some Scheduling Problems with Learning Effect and Job Dependent Delivery Times
Authors: M. Duran Toksari, Berrin Ucarkus
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In this paper, we propose two algorithms to optimally solve makespan and total completion time scheduling problems with learning effect and job dependent delivery times in a single machine environment. The delivery time is the extra time to eliminate adverse effect between the main processing and delivery to the customer. In this paper, we introduce the job dependent delivery times for some single machine scheduling problems with position dependent learning effect, which are makespan are total completion. The results with respect to two algorithms proposed for solving of the each problem are compared with LINGO solutions for 50-jobs, 100-jobs and 150-jobs problems. The proposed algorithms can find the same results in shorter time.Keywords: delivery Times, learning effect, makespan, scheduling, total completion time
Procedia PDF Downloads 4695407 Novel Wound Healing Biodegradable Patch of Bioactive
Authors: Abhay Asthana, Shally Toshkhani, Gyati Shilakari
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The present research was aimed to develop a biodegradable dermal patch formulation for wound healing in a novel, sustained and systematic manner. The goal is to reduce the frequency of dressings with improved drug delivery and thereby enhance therapeutic performance. In present study optimized formulation was designed using component polymers and excipients (e.g. Hydroxypropyl methyl cellulose, Ethylcellulose, and Gelatin) to impart significant folding endurance, elasticity and strength. Gelatin was used to get a mixture using ethylene glycol. Chitosan dissolved in suitable medium was mixed with stirring to gelatin mixture. With continued stirring to the mixture Curcumin was added in optimized ratio to get homogeneous dispersion. Polymers were dispersed with stirring in final formulation. The mixture was sonicated casted to get the film form. All steps were carried out under under strict aseptic conditions. The final formulation was a thin uniformly smooth textured film with dark brown-yellow color. The film was found to have folding endurance was around 20 to 21 times without a crack in an optimized formulation at RT (23C). The drug content was in range 96 to 102% and it passed the content uniform test. The final moisture content of the optimized formulation film was NMT 9.0%. The films passed stability study conducted at refrigerated conditions (4±0.2C) and at room temperature (23 ± 2C) for 30 days. Further, the drug content and texture remained undisturbed with stability study conducted at RT 23±2C for 45 and 90 days. Percentage cumulative drug release was found to be 80% in 12 h and matched the biodegradation rate as drug release with correlation factor R2 > 0.9. The film based formulation developed shows promising results in terms of stability and release profiles.Keywords: biodegradable, patch, bioactive, polymer
Procedia PDF Downloads 5165406 Students' Experience Perception in Courses Taught in New Delivery Modes Compared to Traditional Modes
Authors: Alejandra Yanez, Teresa Benavides, Zita Lopez
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Even before COVID-19, one of the most important challenges that Higher Education faces today is the need for innovative educational methodologies and flexibility. We could all agree that one of the objectives of Higher Education is to provide students with a variety of intellectual and practical skills that, at the same time, will help them develop competitive advantages such as adaptation and critical thinking. Among the strategic objectives of Universidad de Monterrey (UDEM) has been to provide flexibility and satisfaction to students in the delivery modes of the academic offer. UDEM implemented a methodology that combines face to face with synchronous and asynchronous as delivery modes. UDEM goal, in this case, was to implement new technologies and different teaching methodologies that will improve the students learning experience. In this study, the experience of students during courses implemented in new delivery mode was compared with students in courses with traditional delivery modes. Students chose openly either way freely. After everything students around the world lived in 2020 and 2021, one can think that the face to face (traditional) delivery mode would be the one chosen by students. The results obtained in this study reveal that both delivery modes satisfy students and favor their learning process. We will show how the combination of delivery modes provides flexibility, so the proposal is that universities can include them in their academic offer as a response to the current student's learning interests and needs.Keywords: flexibility, new delivery modes, student satisfaction, academic offer
Procedia PDF Downloads 1015405 A Systematic Literature Review of the Influence of New Media-Based Interventions on Drug Abuse
Authors: Wen Huei Chou, Te Lung Pan, Tsu Wen Yeh
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New media have recently received increasing attention as a new communication form. The COVID-19 outbreak has pushed people’s lifestyles into the digital age, and the drug market has infiltrated formal e-commerce platforms. The self-media boom has fostered growth in online drug myths. To set the record straight, it is imperative to develop new media-based interventions. However, the usefulness of new media on this issue has not yet been fully examined. This study selected 13 articles on the development of new media-based interventions to prevent drug abuse from Airiti Library and Pub-Med as of October 3, 2021. The key conclusions are that (1) new media have a significantly positive influence on skills, self-efficacy, and behavior; (2) most interventions package traditional course learning into new media formats; and (3) new media can create a covert, interactive environment that cannot be replicated offline, which may merit attention in future research.Keywords: drug abuse, interventions, new media, systematic review
Procedia PDF Downloads 1525404 Preparation and in vivo Assessment of Nystatin-Loaded Solid Lipid Nanoparticles for Topical Delivery against Cutaneous Candidiasis
Authors: Rawia M. Khalil, Ahmed A. Abd El Rahman, Mahfouz A. Kassem, Mohamed S. El Ridi, Mona M. Abou Samra, Ghada E. A. Awad, Soheir S. Mansy
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Solid lipid nanoparticles (SLNs) have gained great attention for the topical treatment of skin associated fungal infection as they facilitate the skin penetration of loaded drugs. Our work deals with the preparation of nystatin loaded solid lipid nanoparticles (NystSLNs) using the hot homogenization and ultrasonication method. The prepared NystSLNs were characterized in terms of entrapment efficiency, particle size, zeta potential, transmission electron microscopy, differential scanning calorimetry, rheological behavior and in vitro drug release. A stability study for 6 months was performed. A microbiological study was conducted in male rats infected with Candida albicans, by counting the colonies and examining the histopathological changes induced on the skin of infected rats. The results showed that SLNs dispersions are spherical in shape with particle size ranging from 83.26±11.33 to 955.04±1.09 nm. The entrapment efficiencies are ranging from 19.73±1.21 to 72.46±0.66% with zeta potential ranging from -18.9 to -38.8 mV and shear-thinning rheological Behavior. The stability studies done for 6 months showed that nystatin (Nyst) is a good candidate for topical SLN formulations. A least number of colony forming unit/ ml (cfu/ml) was recorded for the selected NystSLN compared to the drug solution and the commercial Nystatin® cream present in the market. It can be fulfilled from this work that SLNs provide a good skin targeting effect and may represent promising carrier for topical delivery of Nyst offering the sustained release and maintaining the localized effect, resulting in an effective treatment of cutaneous fungal infection.Keywords: candida infections, hot homogenization, nystatin, solid lipid nanoparticles, stability, topical delivery
Procedia PDF Downloads 3935403 Cyclic NGR Peptide Anchored Block Co-Polymeric Nanoparticles as Dual Targeting Drug Delivery System for Solid Tumor Therapy
Authors: Madhu Gupta, G. P. Agrawa, Suresh P. Vyas
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Certain tumor cells overexpress a membrane-spanning molecule aminopeptidase N (CD13) isoform, which is the receptor for peptides containing the NGR motif. NGR-modified Docetaxel (DTX)-loaded PEG-b-PLGA polymeric nanoparticles (cNGR-DNB-NPs) were developed and evaluated for their in vitro potential in HT-1080 cell line. The cNGR-DNB-NPs containing particles were about 148 nm in diameter with spherical shape and high encapsulation efficiency. Cellular uptake was confirmed both qualitatively and quantitatively by Confocal Laser Scanning Microscopy (CLSM) and flow cytometry. Both quantitatively and qualitatively results confirmed the NGR conjugated nanoparticles revealed the higher uptake of nanoparticles by CD13-overexpressed tumor cells. Free NGR inhibited the cellular uptake of cNGR-DNB-NPs, revealing the mechanism of receptor mediated endocytosis. In vitro cytotoxicity studies demonstrated that cNGR-DNB-NPs, formulation was more cytotoxic than unconjugated one, which were consistent well with the observation of cellular uptake. Hence, the selective delivery of cNGR-DNB-NPs formulation in CD13-overexpressing tumors represents a potential approach for the design of nanocarrier-based dual targeted delivery systems for targeting the tumor cells and vasculature.Keywords: solid Tumor, docetaxel, targeting, NGR ligand
Procedia PDF Downloads 4825402 Localized Treatment of Cutaneous Candidiasis through Cubosomes in vitro Evaluation
Authors: Aakanchha Jain, D. V. Kohli
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Cubosomes are nanoparticles but instead of the solid particles, cubosomes are self-assembled liquid crystalline particles of certain surfactant with proper ratio of water with a microstructure that provides unique properties of practical interest. Cubosomes encapsulating Fluconazole were prepared by emulsification method and characterized for particle size, entrapment efficiency. The cubosomes prepared were 257.2±2.94 nm in size with drug entrapment efficiency of 66.2±2.69%. The optimized formulation characterized for shape and surface morphology by TEM and SEM analysis. SEM photograph showed the smooth surface of optimized cubosomes and TEM photograph revealed square somewhat circular intact shapes of cubosomes. MIC was determined by XTT based method and antifungal activity was determined in vitro. The cumulative percentage of Fnz from cubosomes permeated via dialysis membrane (MWCO 12-14 KD) showed a percent cumulative drug release of 76.86% while Fnz solution showed release up to 91.04% in 24 hours in PBS (pH 6.5)(p < 0.005).Keywords: Candids albicans, cubosomes, fluconazole, topical delivery
Procedia PDF Downloads 3025401 Unveiling the Self-Assembly Behavior and Salt-Induced Morphological Transition of Double PEG-Tailed Unconventional Amphiphiles
Authors: Rita Ghosh, Joykrishna Dey
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PEG-based amphiphiles are of tremendous importance for its widespread applications in pharmaceutics, household purposes, and drug delivery. Previously, a number of single PEG-tailed amphiphiles having significant applications have been reported from our group. Therefore, it was of immense interest to explore the properties and application potential of PEG-based double tailed amphiphiles. Herein, for the first time, two novel double PEG-tailed amphiphiles having different PEG chain lengths have been developed. The self-assembly behavior of the newly developed amphiphiles in aqueous buffer (pH 7.0) was thoroughly investigated at 25 oC by a number of techniques including, 1H-NMR, and steady-state and time-dependent fluorescence spectroscopy, dynamic light scattering, transmission electron microscopy, atomic force microscopy, and isothermal titration calorimetry. Despite having two polar PEG chains both molecules were found to have strong tendency to self-assemble in aqueous buffered solution above a very low concentration. Surprisingly, the amphiphiles were shown to form stable vesicles spontaneously at room temperature without any external stimuli. The results of calorimetric measurements showed that the vesicle formation is driven by the hydrophobic effect (positive entropy change) of the system, which is associated with the helix-to-random coil transition of the PEG chain. The spectroscopic data confirmed that the bilayer membrane of the vesicles is constituted by the PEG chains of the amphiphilic molecule. Interestingly, the vesicles were also found to exhibit structural transitions upon addition of salts in solution. These properties of the vesicles enable them as potential candidate for drug delivery.Keywords: double-tailed amphiphiles, fluorescence, microscopy, PEG, vesicles
Procedia PDF Downloads 1175400 Increased Retention of Nanoparticle by Small Molecule Inhibitor in Cancer Cells
Authors: Neha Singh
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Background: Nowadays, the nanoparticle is gaining unexceptional attention in targeted drug delivery. But before proceeding to this episode of accomplishment, the journey and closure of these nanoparticles inside the cells should be disentangle. Being foreign for the cells, nanoparticles will easily getcleared off without any effective outcome. As the cancer cells withhold these nanoparticles for a longer period of time, more will be the drug’s effect. Chlorpromazine is a cationic amphiphilic drug which is believed to inhibit clathrin-coated pit formation by a reversible translocation of clathrin and its adapter proteins from the plasma membrane to intracellular vesicles. Chlorpromazine has a role in increasing the retention of nanoparticles in cancer cells. The mechanism of action how this small molecule increases the retention of nanoparticles is still uncovered. Method: Polymeric nanoparticle (PLGA) with Cyanine3.5 dye were synthesized by solvent evaporation method and characterized for size and zeta potential. FTIR was also done. Pulse and chase studies with and without inhibitor were done to check the retention of nanoparticle using fluorescence microscopy. Mean fluorescence intensity was measured by ImageJ software. Results: Increased retention of nanoparticle with inhibitor was observed in both pulse and chase studies. Conclusion: Our results demonstrate that by repurposing these small molecule inhibitor, we can increase the retention of nanoparticle at the targeted site.Keywords: nanoparticle, endocytosis, clathrin inhibitor, cancer cell
Procedia PDF Downloads 1055399 Health Sector Budgetary Allocations and Their Implications on Health Service Delivery and Universal Health Coverage in Uganda
Authors: Richard Ssempala, Francis Kintu, Christine K. Tashobya
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Funding for health remains a key constraint facing many developing countries, Uganda inclusive. Uganda’s health sector budget to the national budgetary allocation has stagnated between 8.2% to 10% over the years. Using data collected from different government documents, we sought to establish the implications of the budget allocation over the period (FY2010/11-2018/19) on health services delivery in Uganda to inform policymakers specifically Members of Parliament who are critical in making sectorial allocation on the steps they can adapt to change the terrain of health financing in Uganda. Findings revealed that the contribution of public funding to the health sector is low (15.7%) with private sources (42.6%) and donors contributing much more, with the bulk of private funds, are out of pocket. The study further revealed that low budget allocation had been manifested in inadequate and poorly motivated health workers, essential drug stock-outs that ultimately contribute to poor access to services, catastrophic health expenditures, and high morbidity rates. We recommend for a substantial and sustained increase in the government health budget, optimizing the available resources by addressing wastages, prioritizing health promotion, prevention and finally, institutionalizing the National Health Insurance Scheme.Keywords: budget allocations, universal health coverage, health service delivery, Uganda
Procedia PDF Downloads 1885398 Drug and Poison Information Centers: An Emergent Need of Health Care Professionals in Pakistan
Authors: Asif Khaliq, Sayeeda A. Sayed
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The drug information centers provide drug related information to the requesters that include physicians, pharmacist, nurses and other allied health care professionals. The International Pharmacist Federation (FIP) describes basic functions of a drug and poison information centers as drug evaluation, therapeutic counseling, pharmaceutical advice, research, pharmaco-vigilence and toxicology. Continuous advancement in the field of medicine has expanded the medical literature, which has increased demand of a drug and poison information center for the guidance, support and facilitation of physicians. The objective of the study is to determine the need of drug and poison information centers in public and private hospitals of Karachi, Pakistan. A cross sectional study was conducted during July 2013 to April 2014 using a self-administered, multi-itemed questionnaire. Non Probability Convenient sampling was used to select the study participants. A total of 307 physicians from public and private hospitals of Karachi participated in the study. The need for 24/7 Drug and poison information center was highlighted by 92 % of physicians and 67% physicians suggested opening a drug information center at the hospital. It was reported that 70% physicians take at least 15 minutes for searching the information about the drug while managing a case. Regarding the poisoning case management, 52% physicians complaint about the unavailability of medicines in hospitals; and mentioned the importance of medicines for safe and timely management of patients. Although 73% physicians attended continued medical education (CME) sessions, 92 % physicians insisted on the need of 24/7 Drug and poison information center. The scarcity of organized channel for obtaining the information about drug and poisons is one of the most crucial problems for healthcare workers in Pakistan. The drug and poison information center is an advisory body that assists health care professional and patients in provision of appropriate drug and hazardous substance information. Drug and poison information center is one of the integral needs for running an effective health care system. Provision of a 24 /7 drug information centers with specialized staff offer multiple benefits to the hospitals while reducing treatment delays, addressing awareness gaps of all stakeholders and ensuring provision of quality health care.Keywords: drug and poison information centers, Pakistan, physicians, public and private hospitals
Procedia PDF Downloads 3275397 Genetics of Pharmacokinetic Drug-Drug Interactions of Most Commonly Used Drug Combinations in the UK: Uncovering Unrecognised Associations
Authors: Mustafa Malki, Ewan R. Pearson
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Tools utilized by health care practitioners to flag potential adverse drug reactions secondary to drug-drug interactions ignore individual genetic variation, which has the potential to markedly alter the severity of these interactions. To our best knowledge, there have been limited published studies on the impact of genetic variation on drug-drug interactions. Therefore, our aim in this project is the discovery of previously unrecognized, clinically important drug-drug-gene interactions (DDGIs) within the list of most commonly used drug combinations in the UK. The UKBB database was utilized to identify the top most frequently prescribed drug combinations in the UK with at least one route of interaction (over than 200 combinations were identified). We have recognised 37 common and unique interacting genes considering all of our drug combinations. Out of around 600 potential genetic variants found in these 37 genes, 100 variants have met the selection criteria (common variant with minor allele frequency ≥ 5%, independence, and has passed HWE test). The association between these variants and the use of each of our top drug combinations has been tested with a case-control analysis under the log-additive model. As the data is cross-sectional, drug intolerance has been identified from the genotype distribution as presented by the lower percentage of patients carrying the risky allele and on the drug combination compared to those free of these risk factors and vice versa with drug tolerance. In GoDARTs database, the same list of common drug combinations identified by the UKBB was utilized here with the same list of candidate genetic variants but with the addition of 14 new SNPs so that we have a total of 114 variants which have met the selection criteria in GoDARTs. From the list of the top 200 drug combinations, we have selected 28 combinations where the two drugs in each combination are known to be used chronically. For each of our 28 combinations, three drug response phenotypes have been identified (drug stop/switch, dose decrease, or dose increase of any of the two drugs during their interaction). The association between each of the three phenotypes belonging to each of our 28 drug combinations has been tested against our 114 candidate genetic variants. The results show replication of four findings between both databases : (1) Omeprazole +Amitriptyline +rs2246709 (A > G) variant in CYP3A4 gene (p-values and ORs with the UKBB and GoDARTs respectively = 0.048,0.037,0.92,and 0.52 (dose increase phenotype)) (2) Simvastatin + Ranitidine + rs9332197 (T > C) variant in CYP2C9 gene (0.024,0.032,0.81, and 5.75 (drug stop/switch phenotype)) (3) Atorvastatin + Doxazosin + rs9282564 (T > C) variant in ABCB1 gene (0.0015,0.0095,1.58,and 3.14 (drug stop/switch phenotype)) (4) Simvastatin + Nifedipine + rs2257401 (C > G) variant in CYP3A7 gene (0.025,0.019,0.77,and 0.30 (drug stop/switch phenotype)). In addition, some other non-replicated, but interesting, significant findings were detected. Our work also provides a great source of information for researchers interested in DD, DG, or DDG interactions studies as it has highlighted the top common drug combinations in the UK with recognizing 114 significant genetic variants related to drugs' pharmacokinetic.Keywords: adverse drug reactions, common drug combinations, drug-drug-gene interactions, pharmacogenomics
Procedia PDF Downloads 1635396 Pattern of ICU Admission due to Drug Problems
Authors: Kamel Abd Elaziz Mohamed
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Introduction: Drug related problems (DRPs) are of major concern, affecting patients of both sex. They impose considerable economic burden on the society and the health-care systems. Aim of the work: The aim of this work was to identify and categorize drug-related problems in adult intensive care unit. Patients and methods: The study was a prospective, observational study as eighty six patients were included. They were consecutively admitted to ICU through the emergency room or transferred from the general ward due to DRPs. Parameters included in the study as length of stay in ICU, need for cardiovascular support or mechanical ventilation, dialysis, as well as APACHE II score were recorded. Results: Drug related problems represent 3.6% of the total ICU admission. The median (range) of APACHE II score for 86 patients included in the study was 17 (10-23), and length of ICU stay was 2.4 (1.5-4.2) days. In 45 patients (52%), DRP was drug over dose (group 1), while other DRP was present in the other 41 patients (48%, group 11). Patients in group 1 were older (39 years versus 32 years in group 11), with significant impaired renal function. The need of inotropic drugs and mechanical ventilation as well as the length of stay (LOS) in ICU was significantly higher in group 1. There were no significant difference in GCS between both groups, however APACHE II score was significantly higher in group 1. Only four patients (4.6%) were admitted by suicidal attempt as well as three patients (3.4%) due to trauma drug-related admissions, all were in (group 1). Nineteen percent of the patients had drug related problem due to hypoglycaemic medication followed by tranquilizer (15%). Adverse drug effect followed by failure to receive medication were the most causes of drug problem in (group11).The total mortality rate was 4.6%, all of them were eventually non preventable. Conclusion: The critically ill patients admitted due to drug related problems represented a small proportion (3.6%) of admissions to the ICU. Hypoglycaemic medication was one of the most common causes of admission by drug related problems.Keywords: drug related problems, ICU, cost, safety
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