Search results for: rapid drug releasing

Authors: M. A. Khanday, Aasma Rafiq, Khalid Nazir

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This paper is an attempt to establish the mathematical models to understand the distribution of drug administration in the human body through oral and intravenous routes. Three models were formulated based on diffusion process using Fick’s principle and the law of mass action. The rate constants governing the law of mass action were used on the basis of the drug efficacy at different interfaces. The Laplace transform and eigenvalue methods were used to obtain the solution of the ordinary differential equations concerning the rate of change of concentration in different compartments viz. blood and tissue medium. The drug concentration in the different compartments has been computed using numerical parameters. The results illustrate the variation of drug concentration with respect to time using MATLAB software. It has been observed from the results that the drug concentration decreases in the first compartment and gradually increases in other subsequent compartments.

Keywords: Laplace transform, diffusion, eigenvalue method, mathematical model

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Authors: Sarada Nivedita Bhuyan

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Earthquake is the sudden, rapid movement of the earth’s crust and is the natural means of releasing stress. Tectonic plates play a major role for earthquakes as tectonic plates are the crust of the planet. The boundary lines of tectonic plates are usually known as fault lines. To understand an earthquake before its occurrence, different types of earthquake precursors are studied by different researchers. Surface temperature, strange cloud cover, earth’s electric field, geomagnetic phenomena, ground water level, active faults, ionospheric anomalies, tectonic movements are taken as parameters for earthquake study by different researchers. In this paper we tried to gather complete and helpful information of earthquake precursors which have been studied until now.

Keywords: earthquake precursors, earthquake, tectonic plates, fault

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Authors: Leandra Prempeh, Emily Malugen

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Prenatal drug exposure can have a molecular impact on the hypothalamic and reward genes that regulate feeding behavior. This can impact feeding regulation, resulting in feeding difficulties and growth failure. This was potentially seen in “McKayla,” a 19- month old girl with a history of in-utero drug exposure, patent ductus arteriosus, and gastroesophageal reflux disease who presented for intensive day treatment feeding therapy. She was diagnosed with Avoidant Restrictive Food Intake Disorder, described as total food refusal and meeting 100% of her caloric needs from a gastrostomy tube. The primary goals during intensive feeding therapy were to increase her oral intake and decrease her reliance on supplementation with formula. Several behavioral antecedent manipulations were implemented to establish consistent responding and make progress towards treatment goals. This included multiple modified bolus placements (using underloaded and Nuk brush), reinforcement contingencies, and variety fading before stability was finally achieved. Following, increasing retention of bites then increasing volume and variety were goals targeted. From treatment onset to the last 3 days of treatment, McKayla's rate of rapid acceptance of bite presentations increased significantly from 33.33% to 93.13%, rapid swallowing went from 0.00% to 92.32%, and her percentage of inappropriate mealtime behavior and expels decreased from 58.33% and 100% to 2.31% and 7.68%, respectively. Overall, the treatment team successfully introduced and increased the bite size of 7 pureed foods, generalize the treatment to caregivers with high integrity, and began facilitating tube weaning. She was receiving about 33.42% of her needs by mouth at the time of discharge. Other nutritional concerns addressed during treatment included drinking a nutritionally complete drink out of an open cup and age appropriate growth. McKayla continued to have emesis almost daily, as was her baseline before starting treatment; however, the frequency during mealtime decreased. Overall, McKayla responded well to treatment. She had a very slow response to treatment and required a lot of antecedent manipulations to establish consistent responding. As the literature suggests, [drug]-exposed neonates, like McKayla, may be at increased risk for nutritional and growth challenges that may persist throughout development. This supports the need for longterm follow-up of infant growth.

Keywords: behavioral intervention, feeding problems, in-utero drug exposure, intensive multidisciplinary intervention

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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

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Authors: Weitao Zhou, Qing Wang, Jianxin He, Shizhong Cui

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Mesoporous Tussah silk fibroin (TSF) spheres were fabricated via the self-assembly of TSF molecules in aqueous solutions. The results showed that TSF particles were approximately three-dimensional spheres with the diameter ranging from 500nm to 6μm without adherence. More importantly, the surface morphology is mesoporous structure with nano-pores of 20nm - 200nm in size. Fourier transform infrared (FT-IR) and X-ray diffraction (XRD) studies demonstrated that mesoporous TSF spheres mainly contained beta-sheet conformation (44.1 %) as well as slight amounts of random coil (13.2 %). Drug release test was performed with 5-fluorouracil (5-Fu) as a model drug and the result indicated the mesoporous TSF microspheres had a good capacity of sustained drug release. It is expected that these stable and high-crystallinity mesoporous TSF sphere produced without organic solvents, which have significantly improved drug release properties, is a very promising material for controlled gene medicines delivery.

Keywords: Tussah silk fibroin, porous materials, microsphere, drug release

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Authors: Abraham J. Domb

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Nearly every eye disorder and treatment of post operated eyes evolve around ocular drug delivery. Most ocular diseases are treated with repeated topical applications administered as eye drops. Various attempts have been made to improve drug bioavailability by increasing both the retention of the drug in the pre-corneal area and the penetration of the drug through the cornea. However, currently marketed products are associated with vision blurring, irritability, patient discomfort, toxicity, low drug bioavailability, manufacturing difficulties and inadequate aqueous stability. It has been suggested to use iontophoresis for the non-invasive delivery of drugs. The iontophoretic device is composed of a control panel, two electrodes, a cylindrical well for the insertion of a disposable hydrogel, and a disposable hydrogel pellet. The drug-loaded hydrogel is attached to a cylindrical well at the edge of the electrode of the device and placed onto the eye. The device applies a variable electrical current that can vary from 0.1 mA to 1.5 mA for pre-set periods from 10 seconds to 300 seconds. The iontophoretic device developed in the lab was found to be effective in the delivery of the drugs: gentamicin, water-soluble steroids, and various anticancer agents. When testing in rabbits for safety, the device was considered to be non-toxic and effective.

Keywords: iontophoresis, eye disorder, drug delivery, hydrogel

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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

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Authors: Dwarakanadha Reddy Peram, D. Swarnalatha, C. Gopinath

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The main aim of this research work was to design and development characterization of Pioglitazone transdermal drug delivery system by using various polymers such as Olibanum with different concentration by solvent evaporation technique. The prepared formulations were evaluated for different physicochemical characteristics like thickness, folding endurance, drug content, percentage moisture absorption, percentage moisture loss, percentage elongation break test and weight uniformity. The diffusion studies were performed by using modified Franz diffusion cells. The result of dissolution studies shows that formulation, F3 (Olibanum with 50 mg) showed maximum release of 99.95 % in 12hrs, whereas F1 (Olibanum and EC backing membrane) showed minimum release of 93.65% in 12 hr. Based on the drug release and physicochemical values obtained the formulation F3 is considered as an optimized formulation which shows higher percentage of drug release of 99.95 % in 12 hr. The developed transdermal patches increase the therapeutic efficacy and reduced toxic effect of pioglitazone.

Keywords: pioglitazone, olibanum, transdermal drug delivery system, drug release percantage

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Authors: Suhas Pednekar, Prashant Chavan, Ramesh Chaughule, Deepak Patkar

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Iron oxide (Fe3O4) magnetic nanoparticles (MNPs) are one of the most attractive nanomaterials for various biomedical applications. An important potential medical application of polymer-coated iron oxide nanoparticles (NPs) is as imaging agents. Composition, size, morphology and surface chemistry of these nanoparticles can now be tailored by various processes to not only improve magnetic properties but also affect the behavior of nanoparticles in vivo. MNPs are being actively investigated as the next generation of magnetic resonance imaging (MRI) contrast agents. Also, there is considerable interest in developing magnetic nanoparticles and their surface modifications with therapeutic agents. Our study involves the synthesis of biocompatible cancer drug coated with iron oxide nanoparticles and to evaluate their efficacy as MRI contrast agents. A simple and rapid microwave method to prepare Fe3O4 nanoparticles has been developed. The drug was successfully conjugated to the Fe3O4 nanoparticles which can be used for various applications. The relaxivity R2 (reciprocal of the spin-spin relaxation time T2) is an important factor to determine the efficacy of Fe nanoparticles as contrast agents for MRI experiments. R2 values of the coated magnetic nanoparticles were also measured using MRI technique and the results showed that R2 of the Fe complex consisting of Fe3O4, polymer and drug was higher than that of bare Fe nanoparticles and polymer coated nanoparticles. This is due to the increase in hydrodynamic sizes of Fe NPs. The results with various amounts of iron molar concentrations are also discussed. Using MRI, it is seen that the R2 relaxivity increases linearly with increase in concentration of Fe NPs in water.

Keywords: cancer drug, hydrodynamic size, magnetic nanoparticles, MRI

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Authors: Sajjad Seifi Mofarah, S. K. Sadrnezhaad, Shokooh Moghadam, Javad Tavakoli

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In recent years a new method of combination treatment for cancer has been developed and studied that has led to significant advancements in the field of cancer therapy. Hyperthermia is a traditional therapy that, along with a creation of a medically approved level of heat with the help of an alternating magnetic AC current, results in the destruction of cancer cells by heat. This paper gives details regarding the production of the spherical nanocomposite PVA/γ-Fe2O3 in order to be used for medical purposes such as tumor treatment by hyperthermia. To reach a suitable and evenly distributed temperature, the nanocomposite with core-shell morphology and spherical form within a 100 to 200 nanometer size was created using phase separation emulsion, in which the magnetic nano-particles γ-Fe2O3 with an average particle size of 20 nano-meters and with different percentages of 0.2, 0.4, 0.5, and 0.6 were covered by polyvinyl alcohol. The main concern in hyperthermia and heat treatment is achieving desirable specific absorption rate (SAR) and one of the most critical factors in SAR is particle size. In this project all attempts has been done to reach minimal size and consequently maximum SAR. The morphological analysis of the spherical structure of the nanocomposite PVA/γ-Fe2O3 was achieved by SEM analyses and the study of the chemical bonds created was made possible by FTIR analysis. To investigate the manner of magnetic nanocomposite particle size distribution a DLS experiment was conducted. Moreover, to determine the magnetic behavior of the γ-Fe2O3 particle and the nanocomposite PVA/γ-Fe2O3 in different concentrations a VSM test was conducted. To sum up, creating magnetic nanocomposites with a spherical morphology that would be employed for drug loading opens doors to new approaches in developing nanocomposites that provide efficient heat and a controlled release of drug simultaneously inside the magnetic field, which are among their positive characteristics that could significantly improve the recovery process in patients.

Keywords: nanocomposite, hyperthermia, cancer therapy, drug releasing

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Authors: Vishal Kumar Gupta

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Purpose: This study has been undertaken to develop novel pH sensitive interpenetrating network hydrogel beads. Methods: The pH sensitive PAAM-g-Guar gum copolymer was synthesized by free radical polymerization followed by alkaline hydrolysis. Beads of guar gum-grafted-polyacrylamide and sodium Carboxy methyl cellulose (Na CMC) loaded with Pantoprazole sodium were prepared and evaluated for pH sensitivity, swelling properties, drug entrapment efficiency and in vitro drug release characteristics. Seven formulations were prepared for the drug with varying polymer and cross linker concentrations. Results: The grafting and alkaline hydrolysis reactions were confirmed by FT-IR spectroscopy. Differential scanning calorimetry was carried out to know the compatibility of encapsulated drug with the polymers. Scanning electron microscopic study revealed that the IPN beads were spherical. The entrapment efficiency was found to be in the range of 85-92%. Particle size analysis was carried out by optical microscopy. As the pH of the medium was changed from 1.2 to 7.4, a considerable increase in swelling was observed for all beads. Increase in the copolymer concentration showed sustained the drug release up to 12 hrs. Drug release from the beads followed super case II transport mechanism. Conclusion: It was concluded that guar gum-acrylamide beads, cross-linked with aluminum chloride offer an opportunity for controlled drug release of pantoprazole sodium.

Keywords: IPN, hydrogels, DSC, SEM

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Authors: Fateme Nokhodchi Bonab

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Studies related to magnetic resonance imaging (MRI) and drug delivery are reviewed in this study to demonstrate the role of transport theory in porous media in facilitating advances in biomedical applications. Diffusion processes are believed to be important in many therapeutic modalities such as: B. Delivery of drugs to the brain. We analyse the progress in the development of diffusion equations using the local volume average method and the evaluation of applications related to diffusion equations. Torsion and porosity have significant effects on diffusive transport. In this study, various relevant models of torsion are presented and mathematical modeling of drug release from biodegradable delivery systems is analysed. In this study, a new model of drug release kinetics from porous biodegradable polymeric microspheres under bulk and surface erosion of the polymer matrix is presented. Solute drug diffusion, drug dissolution from the solid phase, and polymer matrix erosion have been found to play a central role in controlling the overall drug release process. This work paves the way for MRI and drug delivery researchers to develop comprehensive models based on porous media theory that use fewer assumptions compared to other approaches.

Keywords: MRI, porous media, drug delivery, biomedical applications

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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

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Authors: Sarah E. Casey

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Epilepsy is the most common neurological disorder in children and approximately one-third of children with epilepsy have seizures that are uncontrolled on anticonvulsants alone. Cannabidiol is shown to be an effective treatment at reducing the amount of breakthrough seizures experienced by children with drug resistant epilepsy. Improvements in quality of life and overall condition were noted during cannabidiol treatment. Adverse side effects were experienced and were generally mild to moderate in nature. Additional double-blind, controlled studies with a more diverse sample population and standardized dosing are needed to ensure the efficacy and safety of cannabidiol use in children with drug resistant epilepsy.

Keywords: cannabis, drug resistant epilepsy, children, epilepsy

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Authors: Li-Yu Lee, Yu-Shuan Chen, Jun Sheng Wang, I-Ming Chu

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Microneedle patch is a painless transdermal drug delivery method, It could solve some problems in traditional drug delivery such as digestive system causing drug metabolism and subcutaneous injection causing some side effects. Coating drug on or loading drug in microneedle can carry active ingredient through stratum corneum, also can control dose well when microneedle patch apply on localized topical area. We used hyaluronic acid to fabricate dissolvable microneedle patch and encapsulated minoxidil into microneedles. Minoxdil is a drug for exterior use that can be used to treat Androgenetic alopecia, but related commercial products have some shortcomings, for example, propylene glycol which is used to soften stratum corneum cause skin allergic reaction, comparing chemical promotion, microneedle patch provide physical way to make drugs through nature barrier of skin. In this research, we designed a two-step process to fabricate microneedle patch, that can effectively reduce drug waste, and gentle production process could maintain drug activity well. We also do in vitro test on cadaver to make sure patch has enough mechanical strength to penetrate stratum corneum. In the release test and animal test, we found microneedle patch has higher delivery efficiency than tradition way. In this study, we may determine that germinal MNs patch is a potential commodity.

Keywords: dissolving microneedles, androgenetic alopecia, minoxidil, transdermal drug delivery

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Authors: Parth Shah

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The author examines the recent trend where business organizations are significantly reducing their developmental cycle times to stay competitive in today’s global marketspace. The author proposes a rapid systems engineering framework to address late design changes and allow for flexibility (i.e. to react to unexpected or late changes and its impacts) during the product development cycle using a Systems Engineering approach. A System Engineering approach is crucial in today’s product development to deliver complex products into the marketplace. Design changes can occur due to shortened timelines and also based on initial consumer feedback once a product or service is in the marketplace. The ability to react to change and address customer expectations in a responsive and cost-efficient manner is crucial for any organization to succeed. Past literature, research, and methods such as concurrent development, simultaneous engineering, knowledge management, component sharing, rapid product integration, tailored systems engineering processes, and studies on reducing product development cycles all suggest a research gap exist in specifically addressing late design changes due to the shortening of life cycle environments in increasingly competitive markets. The author’s research suggests that 1) product development cycles time scales are now measured in months instead of years, 2) more and more products have interdepended systems and environments that are fast-paced and resource critical, 3) product obsolesce is higher and more organizations are releasing products and services frequently, and 4) increasingly competitive markets are leading to customization based on consumer feedback. The author will quantify effectiveness with respect to success factors such as time-to-market, return-of-investment, life cycle time and flexibility in late design changes by complexity of product or service, number of late changes and ability to react and reduce late design changes.

Keywords: product development, rapid systems engineering, scalability, systems engineering, systems integration, systems life cycle

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Authors: Veronika Lesáková, Silvia Slezáková, František Štěpánek

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Drug dosage forms consisting of multi-unit particle systems (MUPS) for modified drug release provide a promising route for overcoming the limitation of conventional tablets. Despite the conventional use of pellets as units for MUP systems, 3D printed polymers loaded with a drug seem like an interesting candidate due to the control over dosing that 3D printing mechanisms offer. Further, 3D printing offers high flexibility and control over the spatial structuring of a printed object. The final MUPS tablets include PVP and HPC as granulate with other excipients, enabling the compaction process of this mixture with 3D printed inclusions, also termed minitablets. In this study, we have developed the multi-step production process for MUPS tablets, including the 3D printing technology. The MUPS tablets with incorporated 3D printed minitablets are a complex system for drug delivery, providing modified drug release. Such structured tablets promise to reduce drug fluctuations in blood, risk of local toxicity, and increase bioavailability, resulting in an improved therapeutic effect due to the fast transfer into the small intestine, where particles are evenly distributed. Drug loaded 3D printed minitablets were compacted into the excipient mixture, influencing drug release through varying parameters, such as minitablets size, matrix composition, and compaction parameters. Further, the mechanical properties and morphology of the final MUPS tablets were analyzed as many properties, such as plasticity and elasticity, can significantly influence the dissolution profile of the drug.

Keywords: 3D printing, dissolution kinetics, drug delivery, hot-melt extrusion

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Authors: Nungki Rositaningsih, Emil Budianto

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Starch has been widely used as an encapsulation material for drug delivery system. However, starch hydrogel is very easily degraded during metabolism in human stomach. Modification of this material is needed to improve the encapsulation process in drug delivery system, especially for gastrointestinal drug. In this research, three modified starch-based hydrogels are synthesized i.e. Crosslinked starch hydrogel, Semi- and Full- Interpenetrating Polymer Network (IPN) starch hydrogel using Poly(N-Vinyl-Pyrrolidone). Non-modified starch hydrogel was also synthesized as a control. All of those samples were compared as biomaterials, floating drug delivery, and their ability in loading drug test. Biomaterial characterizations were swelling test, stereomicroscopy observation, Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared Spectroscopy (FTIR). Buoyancy test and stereomicroscopy scanning were done for floating drug delivery characterizations. Lastly, amoxicillin was used as test drug, and characterized with UV-Vis spectroscopy for loading drug observation. Preliminary observation showed that Full-IPN has the most dense and elastic texture, followed by Semi-IPN, Crosslinked, and Non-modified in the last position. Semi-IPN and Crosslinked starch hydrogel have the most ideal properties and will not be degraded easily during metabolism. Therefore, both hydrogels could be considered as promising candidates for encapsulation material. Further analysis and issues will be discussed in the paper.

Keywords: biomaterial, drug delivery system, interpenetrating polymer network, poly(N-vinyl-pyrrolidone), starch hydrogel

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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

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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

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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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Authors: Zohreh Bayat, Dariush Minai-Tehrani

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Lipases constitute one of the most important groups of industrial enzymes that catalyze the hydrolysis of triacylglycerol to glycerol and fatty acids. Muscarinic antagonist relieves smooth muscle spasm of the gastrointestinal tract and effect on the cardiovascular system. In this research, the effect of a muscarinic antagonist on the lipase activity of Pseudomonas aeruginosa was studied. Lineweaver–Burk plot showed that the drug inhibited the enzyme by competitive inhibition. The IC50 value (60 uM) and Ki (30 uM) of the drug revealed the drug bound to the enzyme with high affinity. Determination of enzyme activity in various pH and temperature showed that the maximum activity of lipase was at pH 8 and 60°C both in presence and absence of the drug.

Keywords: bacteria, inhibition, kinetics, lipase

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Authors: Ephrem Mebratu Dagnew, Mohammed Biset Ayalew, Gizework Alemnew Mekonnen, Alehegn Bishaw Geremew, Ousman Abubeker Abdela

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Objective: To assess the prevalence of drug-related problems and associated factors among adult psychiatric inpatients. Method: Hospital-based multicenter cross-sectional observational study was conducted from April to July 2021 at five randomly selected hospitals in North-west Ethiopia. A total of 325 consecutively sampled patients participated in the study. Clinical pharmacists assessed the DRPs based on clinical judgment supported by updated evidence-based diseases guidelines. A Medscape drug-interactions checker was used to check drug-drug interactions. The results were summarized using descriptive statistics, including frequency, mean, and standard deviation. Odds ratio (OR) with 95% confidence interval were also computed for each variable for the corresponding P-value. The value of P ≤ 0.05 was considered statistically significant. Result : From the total of 325 study participants, more than half of them (52.9%) were females and the mean age ± (standard deviation) was 30.8±11.3 years. At least one drug-related problem was recorded from 60.9%, 95% CI (55.7-65.8) of study participants with a mean of 0.6±0.49 per patient. Need additional drug therapy was the most common DRP (22.8%), followed by non-adherence to medicine (20.6%) and adverse drug reactions (11%), respectively. Factors independently associated with drug-related problems were rural residence [AOR=1.96,95%CI:1.01-2.84, P-value=0.046], self-employed [AOR=6.0 ,95% CI: 1.0-36.9, P-value=0.035] and alcohol drinkers [AOR=6.40,95%CI:1.12-37.5, p-value=0.034]. Conclusion: The prevalence of drug-related problems among adult psychiatric patients admitted to psychiatric wards was high. Healthcare providers give more attention to tackling these problems. Being a rural residence, self-employed, and Alcohol drinkers were associated with drug-related problems.

Keywords: psychiatric patients, drug-relatedproblems, multicenter, Ethiopia

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Authors: Judith Stein, Elfriede Friedmann

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The injection of a drug into the vitreous body for the treatment of retinal diseases like wet aged-related macular degeneration (AMD) is the most common medical intervention worldwide. We develop mathematical models for drug transport in the vitreous body of a human eye to analyse the impact of different rheological models of the vitreous on drug distribution. In addition to the convection diffusion equation characterizing the drug spreading, we use porous media modeling for the healthy vitreous with a dense collagen network and include the steady permeating flow of the aqueous humor described by Darcy's law driven by a pressure drop. Additionally, the vitreous body in a healthy human eye behaves like a viscoelastic gel through the collagen fibers suspended in the network of hyaluronic acid and acts as a drug depot for the treatment of retinal diseases. In a completely liquefied vitreous, we couple the drug diffusion with the classical Navier-Stokes flow equations. We prove the global existence and uniqueness of the weak solution of the developed initial-boundary value problem describing the drug distribution in the healthy vitreous considering the permeating aqueous humor flow in the realistic three-dimensional setting. In particular, for the drug diffusion equation, results from the literature are extended from homogeneous Dirichlet boundary conditions to our mixed boundary conditions that describe the eye with the Galerkin's method using Cauchy-Schwarz inequality and trace theorem. Because there is only a small effective drug concentration range and higher concentrations may be toxic, the ability to model the drug transport could improve the therapy by considering patient individual differences and give a better understanding of the physiological and pathological processes in the vitreous.

Keywords: coupled PDE systems, drug diffusion, mixed boundary conditions, vitreous body

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Authors: Molly Parker

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Unintended pregnancy rates in Australia are amongst the highest in the developed world. Women with Substance Use Disorder often have riskier sexual behavior with nil contraceptive use and face disproportionately higher unintended pregnancies and Sexually Transmitted Infections, alongside Substance Use in Pregnancy (SUP) climbing at an alarming rate. In an inner-city Drug and Alcohol (D&A) service, significant barriers to sexual and reproductive health services have been identified, aligning with research. Rapid pathways were created for women seeking D&A treatment to be referred to Sexual and Reproductive Health services for the administration of Long-acting reversible contraception (LARC) and sexual health screening. For clients attending a D&A service, this is an opportunistic time to offer sexual and reproductive health services. Collaboration and multidisciplinary team input between D&A and sexual health and reproductive services are paramount, with rapid referral pathways being identified as the main strategy to improve access to sexual and reproductive health support for this population. With this evidence, a rapid referral pathway was created for women using the D&A service to access LARC, particularly in view of fertility often returning once stable on D&A treatment. A closed-ended survey was used for D&A staff to identify gaps in reproductive health knowledge and views of referral accessibility. Results demonstrated a lack of knowledge of contraception and appropriate referral processes. A closed-ended survey for clients was created to establish the need and access to services and to quantify data. A follow-up data collection will be reviewed to access uptake and satisfaction of the intervention from clients. Sexual health screening access was also identified as a deficit, particularly concerning due to the higher rates of STIs in this cohort. A rapid referral pathway will be undergoing implementation, reducing risks of untreated STIS both pre and post-conception. Similarly, pre and post-intervention structured surveys will be used to identify client satisfaction from the pathway. Although currently in progress, the research and pathway aim to be completed by December 2023. This research and implementation of sexual and reproductive health pathways from the D&A service have significant health and well-being benefits to clients and the wider community, including possible fetal/infancy outcomes. Women now have rapid access to sexual and reproductive health services, with the aim of reducing unplanned pregnancies, poor outcomes associated with SUP, client/staff trauma from termination of pregnancy, and client/staff trauma following the assumption of care of the child due to substance use, the financial cost for out of home care as required, the poor outcomes of untreated STIs to the fetus in pregnancy and the spread of STIs in the wider community. As evidence suggests, the implementation of a streamlined referral process is required between D&A and sexual and reproductive health services and has positive feedback from both clinicians and clients in improving care.

Keywords: substance use in pregnancy, drug and alcohol, substance use disorder, sexual health, reproductive health, contraception, long-acting reversible contraception, neonatal abstinence syndrome, FASD, sexually transmitted infections, sexually transmitted infections pregnancy

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Authors: Esra Cansever Mutlu, Muge Sennaroglu Bostan, Fatemeh Bahadori, Ebru Toksoy Oner, Mehmet S. Eroglu

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Paclitaxel is used in treatment of different cancer types mainly breast, ovarian, lung and Kaposi’s sarcoma. It is poorly soluble in water; therefore, currently used formulations tremendously show side-effects and high toxicity. Encapsulation of the drug in a nano drug carrier which causes both reducing side effects and increasing drug activity is a desired new approach for the nano-medicine to target the site of cancer. In this study, synthesis of a novel nano paclitaxel formulation made of a new amphiphilic monomer was followed by the investigation of its pharmacological properties. UV radical polymerization was carried out by using the monomer Lecithin-2-Acrylamido-2-methylpropane (L-AMPS) and the drug-spacer, to obtain sterically high stabilized, biocompatible and biodegradable phospholipid nanoparticles, in which the drug paclitaxel (Pxl) was encapsulated (NanoPxl). Particles showed high drug loading capacity (68%) and also hydrodynamic size less than 200 nm with slight negative surface charge. The drug release profile was obtained and in vitro cytotoxicity test was performed on MCF-7 cell line. Consequently, these data indicated that paclitaxel loaded Lecithin-AMPS/PCL-MAC nanoparticles can be considered as a new, safe and effective nanocarrier for the treatment of breast cancer.

Keywords: paclitaxel, nanoparticle, drug delivery, L-AMPS

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Authors: Suyeon Kwon, Ik Joong Kang, Wang Bingjie

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Chitosan is a polymer that is usually produced from N-deacetylation of chitin. It is emerging as a promising biocompatible polymer that is harmless to humans. For the reason that many merits such as good adsorptive, biodegradability, many researches are being done on the chitosan for drug delivery system. Drug delivery system (DDS) has been developed for the control of drug. It makes the drug can be delivered effectively and safely into the targeted human body. The drug used in this work is hydrocortisone that is used in Rheumatism, skin diseases, allergy treatment. In this work, hydrocortisone was used to make allergic rhinitis medicine. Our study focuses on drug delivery through the nasal mucosa by using hydrocortisone impregnated chitosan nanoshells. This study has performed an investigation in order to establish the optimal conditions, changing concentration, quantity of hydrocortisone. DLS, SEM, TEM, FT-IR, UV spectrum were used to analyze the manufactured chitosan-hydrocortisone silver nanoshell and silver nanoshell, whose function as drug carriers. This study has performed an investigation on new drug carriers and delivery routes for hydrocortisone. Various methods of manufacturing chitosan-hydrocortisone nanoshells were attempted in order to establish the optimal condition. As a result, the average size of chitosan-hydrocortisone silver nanoshell is about 80 nm. So, chitosan-hydrocortisone silver nanoshell is suitable as drug carriers because optimal size of drug carrier in human body is less than 120 nm. UV spectrum of Chitosan-hydrocortisone silver nanoshell shows the characteristic peak of silver nanoshell at 420 nm. Likewise, the average size of chitosan-hydrocortisone silver nanoshell is about 100nm. It is also suitable for drug carrier in human body. Also, multi-layered silver shell over chitosan nanoshells induced the red-shift of absorption peak and increased the intensity of absorption peak. The resultant chitosan–silver nanocomposites (or nanoshells) exhibited the absorption peak around 430nm attributed to silvershell formation. i.e. the absorption peak was red-shifted by ca. 40 nm in reference to 390 nm of silver nanoshells.

Keywords: chitosan, drug delivery, hydrocortisone, rhinitis, nanoshell

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Authors: Haile F. Darge, Hsieh C. Tsai

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The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

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Authors: Morteza Keshavarz

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In this work, using density functional theory (DFT) thermodynamic stability and quantum molecular descriptors of cyclophoshphamide (an anticancer drug)-functionalized zigzag (8,0) CNT, armchair (4,4) CNT and nanocone complexes in water, for two attachment namely the sidewall and tip, is considered. Calculation of the total electronic energy (Et) and binding energy (Eb) of all complexes indicates that the most thermodynamic stability belongs to the sidewall-attachment of cyclophosphamide into functional nanocone. On the other hand, results from chemical hardness show that drug-functionalized zigzag (8,0) and armchair (4,4) complexes in the tip-attachment configuration possess the smallest and greatest chemical hardness, respectively. By computing the solvation energy, it is found that the solution of the drug and all complexes are spontaneous in water. Furthermore, chirality, type of nanovector (nanotube or nanocone), or attachment configuration have no effects on solvation energy of complexes.

Keywords: carbon nanotube, drug delivery, cyclophosphamide drug, density functional theory (DFT)

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Authors: Sharif Abdelghany

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Polymeric nanoparticles have been widely investigated as a controlled release drug delivery platform for the treatment of tuberculosis (TB). These nanoparticles were also readily internalised into macrophages, leading to high intracellular drug concentration. In this study two anti-TB drugs, amikacin and moxifloxacin were encapsulated into PLGA nanoparticles. The novelty of this work appears in: (1) the efficient encapsulation of two hydrophilic second-line anti-TB drugs, and (2) intramacrophage delivery of this synergistic combination potentially for rapid treatment of multi-drug resistant TB (MDR-TB). Two water-oil-water (w/o/w) emulsion strategies were employed in this study: (1) alginate coated PLGA nanoparticles, and (2) alginate entrapped PLGA nanoparticles. The average particle size and polydispersity index (PDI) of the alginate coated PLGA nanoparticles were found to be unfavourably high with values of 640 ± 32 nm and 0.63 ± 0.09, respectively. In contrast, the alginate entrapped PLGA nanoparticles were within the desirable particle size range of 282 - 315 nm and the PDI was 0.08 - 0.16, and therefore were chosen for subsequent studies. Alginate entrapped PLGA nanoparticles yielded a drug loading of over 10 µg/mg powder for amikacin, and more than 5 µg/mg for moxifloxacin and entrapment efficiencies range of approximately 25-31% for moxifloxacin and 51-59% for amikacin. To study macrophage uptake efficiency, the nanoparticles of alginate entrapped nanoparticle formulation were loaded with acridine orange as a marker, seeded to THP-1 derived macrophages and viewed under confocal microscopy. The particles were readily internalised into the macrophages and highly concentrated in the nucleus region. Furthermore, the anti-mycobacterial activity of the drug-loaded particles was evaluated using M. tuberculosis-infected macrophages, which revealed a significant reduction (4 log reduction) of viable bacterial count compared to the untreated group. In conclusion, the amikacin-moxifloxacin alginate entrapped PLGA nanoparticles are promising for further in vivo studies.

Keywords: moxifloxacin and amikacin, nanoparticles, multidrug resistant TB, PLGA

Procedia PDF Downloads 345