Search results for: rapid drug releasing

Authors: Elena K. Schneider, Johnny X. Huang, Vincenzo Carbone, Mark Baker, Mohammad A. K. Azad, Matthew A. Cooper, Jian Li, Tony Velkov

Abstract:

Ivacaftor is a novel CF trans-membrane conductance regulator (CFTR) potentiator that improves the pulmonary function for cystic fibrosis patients bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs that compete for the same plasma protein binding sites and impact the free drug concentration. This in turn could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes. This study compares the binding affinity of ivacaftor and co-administered CF drugs for human serum albumin (HSA) and α1-acid glycoprotein (AGP) using surface plasmon resonance and fluorimetric binding assays that measure the displacement of site selective probes. Due to their high plasma protein binding affinities, drug-drug interactions between ivacaftor are to be expected with ducosate, montelukast, ibuprofen, dicloxacillin, omeprazole and loratadine. The significance of these drug-drug interactions is interpreted in terms of the pharmacodynamic/pharmacokinetic parameters and molecular docking simulations. The translational outcomes of the data are presented as recommendations for a staggered treatment regimen for future clinical trials which aims to maximize the effective free drug concentration and clinical efficacy of ivacaftor.

Keywords: human α-1-acid glycoprotein, binding affinity, human serum albumin, ivacaftor, cystic fibrosis

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Authors: Cesar Torres, Robert Briber, Nam Sun Wang

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Eye drops are the most commonly used treatment for short-term and long-term ophthalmic diseases. However, eye drops could deliver only about 5% of the functional ingredients contained in a burst dosage. To address the limitations of eye drops, the use of therapeutic contact lenses has been introduced. Drug-loaded contact lenses provide drugs a longer residence time in the tear film and hence, decrease the potential risk of side effects. Nevertheless, a major limitation of contact lenses as drug delivery devices is that most of the drug absorbed is released within the first few hours. This fact limits their use for extended release. The present study demonstrates the application of long-alkyl chain ionic surfactants on extending drug release kinetics from commercially available silicone hydrogel contact lenses. In vitro release experiments were carried by immersing drug-containing contact lenses in phosphate buffer saline at physiological pH. The drug concentration as a function of time was monitored using ultraviolet-visible spectroscopy. The results of the study demonstrate that release kinetics is dependent on the ionic surfactant weight percent in the contact lenses, and on the length of the hydrophobic alkyl chain of the ionic surfactants. The use of ionic surfactants in contact lenses can extend the delivery of drugs from a few hours to a few weeks, depending on the physicochemical properties of the drugs. Contact lenses embedded with ionic surfactants could be potential biomaterials to be used for extended drug delivery and in the treatment of ophthalmic diseases. However, ocular irritation and toxicity studies would be needed to evaluate the safety of the approach.

Keywords: contact lenses, drug delivery, controlled release, ionic surfactant

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Authors: Azwin Lubis, Rika Hapsari, Zahrah Hikmah, Anang Endaryanto, Ariyanto Harsono

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Erythema Multiforme Exudativum Major (EMEM) is one of the drug allergy diseases. Drug allergies caused by isoniazid rarely causes EMEM. Cutaneous reactions caused by isoniazid were obtained in 0.98% of patients, but the precise occurrence of Steven Johnson’s Syndrome (SJS) and Toxic Epidermolisis Necrolisis (TEN) due to isoniazid is not known for certain. We present this case to show hypersensitivity of isoniazid in a child. Based on the history of drug intake, physical diagnostic tests, drug elimination and provocation; we established the diagnosis of isoniazid hypersensitivity. The child showed improvement on skin manifestation after stopped isoniazid therapy.

Keywords: erythema multiforme exudativum major, hypersensitivity, elimination test, provocation test

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Authors: Nitin Dwivedi, Jigna Shah

Abstract:

Aim and objective of study: This article indicates a comparison among various generations of dendrimers, a dendrimer is a bioactive material has repetitively branched molecule and used for delivery of various therapeutic active agents. This debut report compares the effect various generations of PPI dendrimers for brain targeting and management of neurodegenerative disorders potential on single platform. This report involves the study of the various mechanism of synthesis ligand anchored various generations PPI dendrimers deliver the drug directly to the CNS, prove their effectiveness in the management of the various neurodegenerative disease. Material and Methods: The Memantine an anti-Alzheimer drug loaded in different generations (3.0G, 4.0G, and 5.0G) of PPI dendrimers which were synthesized were synthesized. The various studies investigate the effect of PPI dendrimers generation on different characteristic parameters i.e. synthesis procedure, drug loading, release behavior, hemolysis profile at different concentration, MRI study for determine the route drug from olfactory transfer, animal model study in vitro, as well as in vivo performance. The outcomes of the investigation indicate drug delivery benefit as well as superior biocompatibility of 4.0G PPI dendrimer over 3.0G and 5.0G dendrimer, respectively. Results and Conclusion: The above study indicate the superiority of in drug delivery system with maximum drug utilization and minimize the drug dose for neurodegenerative disorder over 5.0G PPI dendrimers. So, 4.0G PPI dendrimers are the safe formulations for the symptomatic treatment of the neurodegenerative disorder. The fifth-generation poly(propyleneimine) (PPI) dendrimers, inherent toxicity due to the presence of many peripheral cationic groups is the major issue that limits their applicability.

Keywords: Alzheimer disease, generation, memantine, PPI

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Authors: Shilpa Bhilegaonkar, Ram Gaud

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Candesartan cilexetil is a poorly soluble antihypertensive agent with solubility limited bioavailability (15%). To initiate process of solubilisation, it is very much necessary to displace the air at the surface and wet the drug surface with a solvent, with which drug is compatible. Present research adopts the same principle to improve solubility and dissolution of candesartan cilexetil. Solvents used here are surfactant and modified surfactant in different drug: solvent (1:1-1:9) ratio’s for preparation of adsorbates. Adsorbates were then converted into free flowing powders as liquisolid compacts and compressed to form tablets. Liquisolid compacts were evaluated for improvement in saturation solubility and dissolution of candesartan cilexetil. All systems were evaluated for improvement in saturation solubility and dissolution in different medias such as water, 0.1 N HCl, Phosphate buffer pH 6.8 and media given by office of generic drugs along with other physicochemical testing. All systems exhibited a promising advantage in terms of solubility and dissolution without affecting the drug structure as confirmed by IR and XRD. No considerable advantage was seen of increasing solvent ratio with drug.

Keywords: candesartan cilexetil, improved dissolution, solubility, liquisolid

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Authors: Patcharakamon Nooeaid, Piyachat Chuysrinuan

Abstract:

Electrospun natural polymers-based nanofibers are one of the most interesting materials used in tissue engineering and drug delivery applications. Bead-on-string nanofibers have gained considerable interest for sustained drug release. Vancomycin was used as the model drug and sodium alginate (SA)/soy protein isolated (SPI) as the polymer blend to fabricate the bead-on-string nanofibers by aqueous-based electrospinning. The bead-on-string SA/SPI nanofibers were successfully fabricated by the addition of poly(ethylene oxide) (PEO) as a co-blending polymer. SA-PEO with mass ratio of 70/30 showed the best spinnability with continuous nanofibers without the occurrence of beads. Bead structure formed with the addition of SPI and bead number increased with increasing SPI content. The electrospinning of 80/20 SA-PEO/SPI was obtained as a great promising bead-on-string nanofibers for drug loading, while the solution of 50/50 was not able to obtain continuous fibers. In vitro release tests showed that a more sustainable release profile up to 14 days with less initial burst release on day 1 could be obtained from the bead-on-string fibers than from smooth fibers with uniform diameter. In addition, vancomycin-loaded beaded fibers inhibited the growth of Staphylococcus aureus (S. aureus) bacteria. Therefore, the SA-PEO/SPI nanofibers showed the potential to be used as biomaterials for tissue engineering and drug delivery.

Keywords: bead-on-string fibers, electrospinning, drug delivery, tissue engineering

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Authors: Indu Barwal, Shloka Thakur, Subhash C. Yadav

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The plant virus capsid protein based nanoparticles are extensively studied for their application in biomedical research for development of nanomedicines and drug delivery systems. We have developed a chimeric drug delivery system by controlled in vitro assembly of separately bioconjugated fluorescent dye (as reporting molecule), folic acid (as receptor binding biomolecule for targeted delivery) and doxorubicin (as anticancer drug) using modified EDC NHS chemistry on heterologously overexpressed (E. coli) capsid proteins of cowpea chlorotic mottle virus (CCMV). This chimeric vehicle was further encapsidated on gold nanoparticles (20nm) coated with 5≠ thiolated DNA probe to neutralize the positive charge of capsid proteins. This facilitates the in vitro assembly of modified capsid subunits on the gold nanoparticles to develop chimeric GNPs encapsidated targeted drug delivery system. The bioconjugation of functionalities, number of functionality on capsid subunits as well as virus like nanoparticles, structural stability and in vitro assembly were confirmed by SDS PAGE, relative absorbance, MALDI TOF, ESI-MS, Circular dichroism, intrinsic tryptophan fluorescence, zeta particle size analyzer and TEM imaging. This vehicle was stable at pH 4.0 to 8.0 suitable for many organelles targeting. This in vitro assembled chimeric plant virus like particles could be suitable for ideal drug delivery vehicles for subcutaneous cancer treatment and could be further modified for other type of cancer treatment by conjugating other functionalities (targeting, drug) on capsids.

Keywords: chimeric drug delivery vehicles, bioconjugated plant, virus, capsid

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Authors: Mona Mahmoud Abou Samra, Alaa Hamed Salama, Ghada Awad, Soheir Said Mansy

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Proniosomes are well documented for topical drug delivery and preferred over other vesicular systems because they are biodegradable, biocompatible, non-toxic, possess skin penetration ability and prolong the release of drugs by acting as depot in deeper layers of skin. Proniosome drug delivery was preferred due to improved stability of the system than niosomes. The present investigation aimed at formulation development and performance evaluation of proniosomal gel as a vesicular drug carrier system for antifungal drug tolnaftate. Proniosomes was developed using different nonionic surfactants such as span 60 and span 65 with cholesterol in different molar ratios by the Coacervation phase separation method in presence or absence of either lecithin or phospholipon 80 H. Proniosomal gel formulations of tolnaftate were characterized for vesicular shape & size, entrapment efficiency, rheological properties and release study. The effect of surfactants and additives on the entrapment efficiency, particle size and percent of drug released was studied. The selected proniosomal formulations for topical delivery of tolnaftate was subjected to a microbiological study in male rats infected with Trichophyton rubrum; the main cause of Tinea Pedis compared to the free drug and a market product and the results was recorded.

Keywords: fungal infection, proniosome, tolnaftate, trichophyton rubrum

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Authors: Ghaleb A. Husseini, Salma E. Ahmed, Hesham G. Moussa, Ana M. Martins, Mohammad Al-Sayah, Nasser Qaddoumi

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This abstract aims to investigate the use of targeted liposomes as anticancer drug carriers in vitro in combination with ultrasound applied as drug trigger; in order to reduce the side effects caused by traditional chemotherapy. Pegylated liposomes were used to encapsulate calcein and then release this model drug when 20-kHz, 40-kHz, 1-MHz and 3-MHz ultrasound were applied at different acoustic power densities. Fluorescence techniques were then used to measure the percent drug release of calcein from these targeted liposomes. Results showed that as the power density increases, at the four frequencies studied, the release of calcein also increased. Based on these results, we believe that ultrasound can be used to increase the rate and amount of chemotherapeutics release from liposomes.

Keywords: liposomes, calcein release, high frequency ultrasound, low frequency ultrasound, fluorescence techniques

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Authors: Somdutt Mujwar, Kamal Raj Pardasani

Abstract:

Cholera pandemics are caused by facultative pathogenic Vibrio cholera bacteria persisting in the countries having warmer climatic conditions as well as the presence of large water bodies with huge amount of organic matter, it is responsible for the millions of deaths annually. Presently the available therapy for cholera is Oral Rehydration Therapy (ORT) with an antibiotic drug. Excessive utilization of life saving antibiotics drugs leads to the development of resistance by the infectious micro-organism against the antibiotic drugs resulting in loss of effectiveness of these drugs. Also, many side effects are also associated with the use of these antibiotic drugs. This riboswitch is explored as an alternative drug target for Vibrio cholera bacteria to overcome the problem of drug resistance as well as side effects associated with the antibiotics drugs. The bacterial riboswitch is virtually screened with 24407 legends to get possible drug candidates. The 10 ligands showing best binding with the riboswitch are selected to design a pharmacophore, which can be utilized to design lead molecules by using the phenomenon of bioisosterism.

Keywords: cholera, drug design, ligand, riboswitch, pharmacophore

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Authors: Klazina T. Havinga, Hilde R. H. de Geus

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Introduction: Pre-operative coagulation management of Apixaban prescribed patients, a new oral anticoagulant (a factor Xa inhibitor), is difficult, especially when chronic kidney disease (CKD) causes drug overdose. Apixaban is not dialyzable due to its high level of protein binding. An antidote, Andexanet α, is available but expensive and has an unfavorable short half-life. We report the successful extracorporeal removal of Apixaban prior to emergency surgery with the CytoSorb® Hemoadsorption device. Methods: A 89-year-old woman with CKD, with an Apixaban prescription for atrial fibrillation, was presented at the ER with traumatic rib fractures, a flail chest, and an unstable spinal fracture (T12) for which emergency surgery was indicated. However, due to very high Apixaban levels, this surgery had to be postponed. Based on the Apixaban-specific anti-factor Xa activity (AFXaA) measurements at admission and 10 hours later, complete clearance was expected after 48 hours. In order to enhance the Apixaban removal and reduce the time to operation, and therefore reduce pulmonary complications, CRRT with CytoSorb® cartridge was initiated. Apixaban-specific anti-factor Xa activity (AFXaA) was measured frequently as a substitute for Apixaban drug concentrations, pre- and post adsorber, in order to calculate the adsorber-related clearance. Results: The admission AFXaA concentration, as a substitute for Apixaban drug levels, was 218 ng/ml, which decreased to 157 ng/ml after ten hours. Due to sustained anticoagulation effects, surgery was again postponed. However, the AFXaA levels decreased quickly to sub-therapeutic levels after CRRT (Multifiltrate Pro, Fresenius Medical Care, Blood flow 200 ml/min, Dialysate Flow 4000 ml/h, Prescribed renal dose 51 ml-kg-h) with Cytosorb® connected in series into the circuit was initiated (within 5 hours). The adsorber-related (indirect) Apixaban clearance was calculated every half hour (Cl=Qe * (AFXaA pre- AFXaA post/ AFXaA pre) with Qe=plasma flow rate calculated with Ht=0.38 and system blood flow rate 200 ml-min): 100 ml/min, 72 ml/min and 57 ml/min. Although, as expected, the adsorber-related clearance decreased quickly due to saturation of the beads, still the reduction rate achieved resulted in a very rapid decrease in AFXaA levels. Surgery was ordered and possible within 5 hours after Cytosorb initiation. Conclusion: The CytoSorb® Hemoadsorption device enabled rapid correction of Apixaban associated anticoagulation.

Keywords: Apixaban, CytoSorb, emergency surgery, Hemoadsorption

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Authors: Rachmat Mauludin, Nurmazidah

Abstract:

Background and purpose: Famotidine is an H2 receptor blocker. Absorption orally is rapid enough, but famotidine can be degraded by stomach acid causing dose reduction until 35.8% after 50 minutes. This drug also undergoes first-pass metabolism which reduced its bio availability only until 40-50%. To overcome these problems, Solid Lipid Nano particles (SLNs) as alternative delivery systems can be formulated. SLNs is a lipid-based drug delivery technology with 50-1000 nm particle size, where the drug incorporated into the bio compatible lipids and the lipid particles are stabilized using appropriate stabilizers. When the particle size is 200 nm or below, lipid containing famotidine can be absorbed through the lymphatic vessels to the subclavian vein, so first-pass metabolism can be avoided. Method: Famotidine SLNs with various compositions of stabilizer was prepared using a high-speed homogenization and sonication method. Then, the particle size distribution, zeta potential, entrapment efficiency, particle morphology and in vitro release profiles were evaluated. Optimization of sonication time also carried out. Result: Particle size of SLN by Particle Size Analyzer was in range 114.6 up to 455.267 nm. Ultrasonicated SLNs within 5 minutes generated smaller particle size than SLNs which was ultrasonicated for 10 and 15 minutes. Entrapment efficiency of SLNs were 74.17 up to 79.45%. Particle morphology of the SLNs was spherical and distributed individually. Release study of Famotidine revealed that in acid medium, 28.89 up to 80.55% of famotidine could be released after 2 hours. Nevertheless in basic medium, famotidine was released 40.5 up to 86.88% in the same period. Conclusion: The best formula was SLNs which stabilized by 4% Poloxamer 188 and 1 % Span 20, that had particle size 114.6 nm in diameter, 77.14% famotidine entrapped, and the particle morphology was spherical and distributed individually. SLNs with the best drug release profile was SLNs which stabilized by 4% Eudragit L 100-55 and 1% Tween 80 which had released 36.34 % in pH 1.2 solution, and 74.13% in pH 7.4 solution after 2 hours. The optimum sonication time was 5 minutes.

Keywords: famotodine, SLN, high speed homogenization, particle size, release study

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Authors: N. A. Zainuddin, I. Norhuda, I. S. Adeib, A. N. Mustapa, S. H. Sarijo

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Recently, RESS (Rapid Expansion Supercritical Solution) method has been used by researchers to produce fine particles for pharmaceutical drug substances. Since RESS technology acknowledges a lot of benefits compare to conventional method of ginger extraction, it is suggested to use this method to explore particle formation of bioactive compound from powder ginger. The objective of this research is to produce direct solid oil particles formation from ginger rhizome which contains valuable compounds by using RESS-CO₂ process. RESS experiments were carried using extraction pressure of 3000, 4000, 5000, 6000 and 7000psi and at different extraction temperature of 40, 45, 50, 55, 60, 65 and 70°C for 40 minutes extraction time and contant flowrate (24ml/min). From the studies conducted, it was found that at extraction pressure 5000psi and temperature 40°C, the smallest particle size obtained was 2.22μm on 99 % reduction from the original size of 370μm.

Keywords: particle size, RESS, solid oil particle, supercritical carbon dioxide,

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Authors: Renato Santos Paulinelli Raposo, Vinicius Resende Domingues, Manoel Porfirio Cordao Neto

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Rapid drawdown is one of the cases referred to ground stability study in dam projects. Due to the complexity generated by the combination of loads and the difficulty in determining the parameters, analyses of rapid drawdown are usually performed considering the immediate reduction of water level upstream. The proposal of a simulation, considering the gradual reduction in water level upstream, requires knowledge of parameters about consolidation and those related to unsaturated soil. In this context, the purpose of this study is to understand the methodology of collection and analysis of parameters to simulate a rapid drawdown in dams. Using a numerical tool, the study is complemented with a hypothetical case study that can assist the practical use of data compiled. The referenced dam presents homogeneous section composed of clay soil, a height of 70 meters, a width of 12 meters, and upstream slope with inclination 1V:3H.

Keywords: dam, GeoStudio, rapid drawdown, stability analysis

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Authors: Vano Tsertsvadze, Marina Chavchanidze, Lali Khurtsia

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Problem of drug use is often seen as a combination of psychological and social problems, but this problem can be considered as economically rational decision in the process of buying pleasure (looking after children, reading, harvesting fruits in the fall, sex, eating, etc.). Before the adoption of the decisions people face to a trade-off - when someone chooses a delicious meal, she takes a completely rational decision, that the pleasure of eating has a lot more value than the pleasure which she will experience after two months diet on the summer beach showing off her beautiful body. This argument is also true for alcohol, drugs and cigarettes. Smoking has a negative effect on health, but smokers are not afraid of the threat of a lung cancer after 40 years, more valuable moment is a pleasure from smoking. Our hypothesis - unsatisfied pleasure and frustration, probably determines the risk of dependence on drug abuse. The purpose of research: 1- to determine the relative measure unit of pleasure, which will be used to measure and assess the intensity of various human pleasures. 2- to compare the intensity of the pleasure from different kinds of activity, with pleasures received from drug use. 3- Based on the analysis of data, to identify factors affecting the rational decision making. Research method: Respondents will be asked to recall the greatest pleasure of their life, which will be used as a measure of the other pleasures. The study will use focus groups and structured interviews.

Keywords: drug, drug-user, measurement, satisfaction

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Authors: Nagasamy Venkatesh Dhandapani, Amged Awad El-Gied

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Cefixime, a BCS class II drug, is insoluble in water but freely soluble in acetone and in alcohol. The aqueous solubility of cefixime in water is poor and exhibits exceptionally slow and intrinsic dissolution rate. In the present study, cefixime and β-Cyclodextrin (β-CD) solid dispersions were prepared with a view to study the effect and influence of β-CD on the solubility and dissolution rate of this poorly aqueous soluble drug. Phase solubility profile revealed that the solubility of cefixime was increased in the presence of β-CD and was classified as A_L-type. Effect of variable, such as drug:carrier ratio, was studied. Physical characterization of the solid dispersion was characterized by Fourier transform infrared spectroscopy (FT-IR) and Differential scanning calorimetry (DSC). These studies revealed that a distinct loss of drug crystallinity in the solid molecular dispersions is ostensibly accounting for enhancement of dissolution rate in distilled water. The drug release from the prepared solid dispersion exhibited a first order kinetics. Solid dispersions of cefixime showed a 6.77 times fold increase in dissolution rate over the pure drug.

Keywords: β-cyclodextrin, cefixime, dissolution, Kneading method, solid dispersions, release kinetics

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Authors: Desalegn Feyissa Desu

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Drug therapy problem is a significant challenge to provide high quality health care service for the patients. It is associated with morbidity, mortality, increased hospital stay, and reduced quality of life. Moreover, pediatric patients are quite susceptible to drug therapy problems. Thus this study aimed to assess drug therapy problem and its contributing factors among pediatric patients diagnosed with infectious disease admitted to pediatric ward of Jimma university medical center, from April 1 to June 30, 2018. Prospective observational study was conducted among pediatric patients with infectious disease admitted from April 01 to June 30, 2018. Drug therapy problems were identified by using Cipolle’s and strand’s drug related problem classification method. Patient’s written informed consent was obtained after explaining the purpose of the study. Patient’s specific data were collected using structured questionnaire. Data were entered into Epi data version 4.0.2 and then exported to statistical software package version 21.0 for analysis. To identify predictors of drug therapy problems occurrence, multiple stepwise backward logistic regression analysis was done. The 95% CI was used to show the accuracy of data analysis and statistical significance was considered at p-value < 0.05. A total of 304 pediatric patients were included in the study. Of these, 226(74.3%) patients had at least one drug therapy problem during their hospital stay. A total of 356 drug therapy problems were identified among two hundred twenty six patients. Non-compliance (28.65%) and dose too low (27.53%) were the most common type of drug related problems while disease comorbidity [AOR=3.39, 95% CI= (1.89-6.08)], Polypharmacy [AOR=3.16, 95% CI= (1.61-6.20)] and more than six days stay in hospital [AOR=3.37, 95% CI= (1.71-6.64) were independent predictors of drug therapy problem occurrence. Drug therapy problems were common in pediatric patients with infectious disease in the study area. Presence of comorbidity, polypharmacy and prolonged hospital stay were the predictors of drug therapy problem in study area. Therefore, to overcome the significant gaps in pediatric pharmaceutical care, clinical pharmacists, Pediatricians, and other health care professionals have to work in collaboration.

Keywords: drug therapy problem, pediatric, infectious disease, Ethiopia

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Authors: M. N. Osman Zahid, K. Case, D. Watts

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This paper reports an advanced approach in the application of CNC machining for rapid manufacturing processes (CNC-RM). The aim of this study is to improve the quality of machined parts by introducing different cutting tools during finishing operations. As the cutting is performed in different directions, the surfaces presented on part can be classified into several categories. Therefore, suitable cutting tools are assigned to machine particular surfaces and to improve the quality. Experimental studies have been carried out by fabricating several parts based on the suggested approach. The results provide further support for implementing this approach in rapid machining processes.

Keywords: CNC machining, end mill tool, finishing operation, rapid manufacturing

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Authors: Dada Kolawole Segun

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Transdermal drug delivery has gained popularity as a non-invasive method for controlled drug release compared to traditional delivery routes. Dissolvable transdermal patches have emerged as a promising platform for delivering a variety of drugs due to their ease of use. The objective of this research was to create and characterize dissolvable transdermal patches using various compositions and ratios of hyaluronic acid and zinc oxide nanoparticles. A micromolding technique was utilized to fabricate the patches, which were subsequently characterized using scanning electron microscopy, atomic force microscopy, and tensile strength testing. In vitro drug release studies were conducted to evaluate the drug release kinetics of the patches. The study found that the mechanical strength and dissolution properties of the patches were influenced by the hyaluronic acid and zinc oxide nanoparticle ratios used in the fabrication process. Moreover, the patches demonstrated controlled delivery of model drugs through the skin, highlighting their potential for transdermal drug delivery applications. The results suggest that dissolvable transdermal patches can be tailored to meet specific requirements for drug delivery applications using different compositions and ratios of hyaluronic acid and zinc oxide nanoparticles. This development has the potential to improve treatment outcomes and patient compliance in various therapeutic areas.

Keywords: transdermal drug delivery, characterization, skin permeation, biodegradable materials

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Authors: Warda Fatima, Hasnain Javed

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The emerging trend of Drug resistance in childhood Tuberculosis is increasing worldwide and now becoming a priority challenge for National TB Control Programs of the world. Childhood TB accounts for 10-15% of total TB burden across the globe and same proportion is quantified in case of drug resistant TB. One third population suffering from MDR TB dies annually because of non-diagnosis and unavailability of appropriate treatment. However, true Childhood MDR TB cannot be estimated due to non-confirmation. Diagnosis of Pediatric TB by sputum Smear Microscopy and Culture inoculation are limited due to paucibacillary nature and difficulties in obtaining adequate sputum specimens. Diagnosis becomes more difficult when it comes to HIV infected child. New molecular advancements for early case detection of TB and MDR TB in adults have not been endorsed in children. Multi centered trials are needed to design better diagnostic approaches and efficient and safer treatments for DR TB in high burden countries. The aim of the present study is to sketch out the current situation of the childhood Drug resistant TB especially in the developing world and to highlight the classic and novel methods that are to be implemented in high-burden resource-limited locations.

Keywords: drug resistant TB, childhood, diagnosis, novel methods

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Authors: Jinfeng Zhang, Chun-Sing Lee

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The use of different nanocarriers for delivering hydrophobic pharmaceutical agents to tumor sites has garnered major attention. Despite the merits of these nanocarriers, further studies are needed for improving their drug loading capacities (typically less than 10%) and reducing their potential systemic toxicity. So development of alternative self-carried nanodrug delivery strategies without using any inert carriers is highly desirable. In this study, we developed a self-carried theranostic curcumin (Cur) nanodrug for highly effective cancer therapy in vitro and in vivo with real-time monitoring of drug release. With a biocompatible C18PMH-PEG functionalization, the Cur nanoparticles (NPs) showed excellent dispersibility and outstanding stability in physiological environment, with drug loading capacity higher than 78 wt.%. Both confocal microscopy and flow cytometry confirmed the cellular fluorescent “OFF-ON” activation and real-time monitoring of Cur molecule release, showing its potential for cancer diagnosis. In vitro and in vivo experiments clearly show that therapeutic efficacy of the PEGylated Cur NPs is much better than that of free Cur. This self-carried theranostic strategy with real-time monitoring of drug release may open a new way for simultaneous cancer therapy and diagnosis.

Keywords: drug delivery, in vitro and in vivo cancer therapy, real-time monitoring, self-carried

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Authors: Meena Kumari, Ajitha Sharma, Mohan Babu Amberkar, Hasitha Manohar, Joseph Thomas, K. L. Bairy

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Aim: To evaluate the pattern of occurrence of adverse drug reactions (ADRs) with platinum compounds in cancer chemotherapy at a tertiary care hospital. Methods: It was a retrospective, descriptive case record study done on patients admitted to the medical oncology ward of Kasturba Hospital, Manipal from July to November 2012. Inclusion criteria comprised of patients of both sexes and all ages diagnosed with cancer and were on platinum compounds, who developed at least one adverse drug reaction during or after the treatment period. CDSCO proforma was used for reporting ADRs. Causality was assessed using Naranjo Algorithm. Results: A total of 65 patients was included in the study. Females comprised of 67.69% and rest males. Around 49.23% of the ADRs were seen in the age group of 41-60 years, followed by 20 % in 21-40 years, 18.46% in patients over 60 years and 12.31% in 1-20 years age group. The anticancer agents which caused adverse drug reactions in our study were carboplatin (41.54%), cisplatin (36.92%) and oxaliplatin (21.54%). Most common adverse drug reactions observed were oral candidiasis (21.53%), vomiting (16.92%), anaemia (12.3%), diarrhoea (12.3%) and febrile neutropenia (0.08%). The results of the causality assessment of most of the cases were probable. Conclusion: The adverse effect of chemotherapeutic agents is a matter of concern in the pharmacological management of cancer as it affects the quality of life of patients. This information would be useful in identifying and minimizing preventable adverse drug reactions while generally enhancing the knowledge of the prescribers to deal with these adverse drug reactions more efficiently.

Keywords: adverse drug reactions, platinum compounds, cancer, chemotherapy

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Authors: Baljinder Singh, Navneet Sharma

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The skin can be used as the site for drug administration for continuous transdermal drug infusion into the systemic circulation. For the continuous diffusion/penetration of the drugs through the intact skin surface membrane-moderated systems, matrix dispersion type systems, adhesive diffusion controlled systems and micro reservoir systems have been developed. Various penetration enhancers are used for the drug diffusion through skin. In matrix dispersion type systems, the drug is dispersed in the solvent along with the polymers and solvent allowed to evaporate forming a homogeneous drug-polymer matrix. Matrix type systems were developed in the present study. In the present work, an attempt has been made to develop a matrix-type transdermal therapeutic system comprising of ondansetron-HCl with different ratios of hydrophilic and hydrophobic polymeric combinations using solvent evaporation technique. The physicochemical compatibility of the drug and the polymers was studied by infrared spectroscopy. The results obtained showed no physical-chemical incompatibility between the drug and the polymers. The patches were further subjected to various physical evaluations along with the in-vitro permeation studies using rat skin. On the basis of results obtained form the in vitro study and physical evaluation, the patches containing hydrophilic polymers i.e. polyvinyl alcohol and poly vinyl pyrrolidone with oleic acid as the penetration enhancer(5%) were considered as suitable for large scale manufacturing with a backing layer and a suitable adhesive membrane.

Keywords: transdermal drug delivery, penetration enhancers, hydrophilic and hydrophobic polymers, ondansetron HCl

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Authors: Pankaj Prashar, Bimlesh Kumar, Ankita Sood, Anamika Gautam

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Pharmacovigilance (PV) is a rapidly growing discipline in pharmaceutical industries as an integral part of clinical research and drug development over the past few decades. PV carries a breadth of scope from drug manufacturing to its regulation with safer utilization. The fundamental steps of PV not only includes data collection and verification, coding of drugs with adverse drug reactions, causality assessment and timely reporting to the authorities but also monitoring drug manufacturing, safety issues, product quality and conduction of due diligence. Standardization of adverse event information, collaboration of multiple departments in different companies, preparation of documents in accordance to both governmental as well as non-governmental organizations (FDA, EMA, GVP, ICH) are the advancements in discipline of PV. De-harmonization, lack of predictive drug safety models, improper funding by government, non-reporting, and non-acceptability of ADRs by developing countries and reports directly from patients to the monitoring centres respectively are the major road backs of PV. Mandatory pharmacovigilance reporting, frequent inspections, funding by government, educating and training medical students, pharmacists and nurses in this segment can bring about empowerment in PV. This area needs to be addressed with a sense of urgency for the safe utilization of pharmaceuticals.

Keywords: pharmacovigilance, regulatory, adverse event, drug safety

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Authors: Zeynep R. Ege, Aydin Akan, Faik N. Oktar, Betul Karademir, Oguzhan Gunduz

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Early detection of cancer could save human life and quality in insidious cases by advanced biomedical imaging techniques. Designing targeted detection system is necessary in order to protect of healthy cells. Electrospun nanofibers are efficient and targetable nanocarriers which have important properties such as nanometric diameter, mechanical properties, elasticity, porosity and surface area to volume ratio. In the present study, indocyanine green (ICG) organic dye was stabilized and encapsulated in polymer matrix which polyethylene oxide (PEO) and chitosan (CHI) multilayer nanofibers via co-axial electrospinning method at one step. The co-axial electrospun nanofibers were characterized as morphological (SEM), molecular (FT-IR), and entrapment efficiency of Indocyanine Green (ICG) (confocal imaging). Controlled release profile of PEO/CHI/ICG nanofiber was also evaluated up to 40 hours.

Keywords: chitosan, coaxial electrospinning, controlled releasing, drug delivery, indocyanine green, polyethylene oxide

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Authors: Lee Rui, Rajeev Ramachandran

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The approach to recurrent fevers in the paediatric or adolescent age group is not a straightforward one. Causes range from infectious diseases to rheumatological conditions to endocrinopathies, and are usually accompanied by weight loss rather than weight gain. We present an interesting case of a 16-year-old girl brought by her mother to the General Pediatrics Clinic for concerns of recurrent fever paired with significant weight gain over 1.5 years, with no identifiable cause found despite extensive work-up by specialists ranging from Rheumatologists to Oncologists. This case provides a learning opportunity on the approach to weight gain paired with persistent fevers in a paediatric population, one which is not commonly encountered and prompts further evaluation and consideration of less common diagnoses. In a span of 2 years, the girl’s weight had increased from 55 kg at 13 years old (75th centile) to 73.9 kg at 16 years old (>97th centile). About 1 year into her rapid weight gain, she started developing recurrent fevers of documented temperatures > 37.5 – 38.6 every 2-3 days, resulting in school absenteeism when she was sent home after temperature-taking in school found her to be febrile. The rapid onset of weight gain paired with unexplained fevers prompted the treating physician to consider the diagnosis of ROHHAD syndrome. Rapid onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) syndrome is a rare disorder first described in 2007. It is characterized by dysfunction of the autonomic and endocrine system, characterized by hyperphagia and rapid-onset weight gain. This rapid weight gain is classically followed by hypothalamic manifestations with neuroendocrine deficiencies, hypo-ventilatory breathing abnormalities, and autonomic dysregulation. ROHHAD is challenging to diagnose with and diagnosis is made based mostly on clinical judgement. However if truly diagnosed, the condition is characterized by high morbidity and mortality rates. Early recognition of sleep disorders breathing and targeted therapeutic interventions helps limit morbidity and mortality associated with ROHHAD syndrome. This case poses an interesting diagnostic challenge and a diagnosis of ROHHAD has to be considered, given the serious complications that can come with disease progression while conditions such as Munchausen’s or drug fever remain as diagnoses of exclusion until we have exhausted all other possible conditions.

Keywords: pediatrics, endocrine, weight gain, recurrent fever, adolescent

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Authors: Magdalena Hałupka-Bryl, Magdalena Bednarowicz, Ryszard Krzyminiewski, Yukio Nagasaki

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Due to their unique physical properties, superparamagnetic iron oxide nanoparticles are increasingly used in medical applications. They are very useful carriers for delivering antitumor drugs in targeted cancer treatment. Magnetic nanoparticles (PEG-PIONs/DOX) with chemotherapeutic were synthesized by coprecipitation method followed by coating with biocompatible polymer PEG-derivative (poly(ethylene glycol)-block-poly(4-vinylbenzylphosphonate). Complete physicochemical characterization was carried out (ESR, HRTEM, X-ray diffraction, SQUID analysis) to evaluate the magnetic properties of obtained PEG-PIONs/DOX. Nanoparticles were investigated also in terms of their stability, drug loading efficiency, drug release and antiproliferative effect on cancer cells. PEG-PIONs/DOX have been successfully used for the efficient delivery of an anticancer drug into the tumor region. Fluorescent imaging showed the internalization of PEG-PIONs/DOX in the cytoplasm. Biodistribution studies demonstrated that PEG-PIONs/DOX preferentially accumulate in tumor region via the enhanced permeability and retention effect. The present findings show that synthesized nanosystem is promising tool for potential magnetic drug delivery.

Keywords: targeted drug delivery, magnetic properties, iron oxide nanoparticles, biodistribution

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Authors: Raquel Galante, Marina Braga, Daniela Ghisleni, Terezinha J. A. Pinto, Rogério Colaço, Ana Paula Serro

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The sensitive nature of soft biomaterials, such as hydrogels, renders their sterilization a particularly challenging task for the biomedical industry. Widely used contact lenses are now studied as promising platforms for topical corneal drug delivery. However, to the best of the authors knowledge, the influence of sterilization methods on these systems has yet to be evaluated. The main goal of this study was to understand how different pairs drug-hydrogel would interact under an ozone-based sterilization method in comparison with two conventional processes (steam heat and gamma irradiation). For that, Si-Hy containing hydroxylethyl methacrylate (HEMA) and [tris(trimethylsiloxy)silyl]propyl methacrylate (TRIS) was produced and soaked in different drug solutions, commonly used for the treatment of ocular diseases (levofloxacin, chlorhexidine, diclofenac and timolol maleate). The drug release profiles and main material properties were evaluated before and after the sterilization. Namely, swelling capacity was determined by water uptake studies, transparency was accessed by UV-Vis spectroscopy, surface topography/morphology by scanning electron microscopy (SEM) and mechanical properties by performing tensile tests. The drug released was quantified by high performance liquid chromatography (HPLC). The effectiveness of the sterilization procedures was assured by performing sterility tests. Ozone gas method led to a significant reduction of drug released and to the formation of degradation products specially for diclofenac and levofloxacin. Gamma irradiation led to darkening of the loaded Si-Hys and to the complete degradation of levofloxacin. Steam heat led to smoother surfaces and to a decrease of the amount of drug released, however, with no formation of degradation products. This difference in the total drug released could be the related to drug/polymer interactions promoted by the sterilization conditions in presence of the drug. Our findings offer important insights that, in turn, could be a useful contribution to the safe development of actual products.

Keywords: drug delivery, silicone hydrogels, sterilization, gamma irradiation, steam heat, ozone gas

Procedia PDF Downloads 287

Authors: Mahboubeh Kabiri, Saba Aslani

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Among various approaches used for the treatment of cardiovascular diseases, the occlusion of the small-diameter vascular graft (SDVG) is still an unresolved problem which seeks further research to address them. Though autografts are now the gold standards to be replaced for blocked coronary arteries, they suffer from inadequate quality and quantity. On the other hand, the major problems of the tissue engineered grafts are thrombosis and intimal hyperplasia. Provision of a suitable spatiotemporal release pattern of anticoagulant agents such as heparin and aspirin can be a step forward to overcome such issues . Herein, we fabricated electrospun scaffolds from FDA (Food and Drug Administration) approved poly-L-lactic acid (PLLA) with aspirin loaded into the nanofibers. Also, we surface coated the scaffolds with Amniotic Membrane lysate as a source for natural elastic polymers and a mimic of endothelial basement membrane. The scaffolds were characterized thoroughly structurally and mechanically for their morphology, fiber orientation, tensile strength, hydrophilicity, cytotoxicity, aspirin release and cell attachment support. According to the scanning electron microscopy (SEM) images, the size of fibers ranged from 250 to 500 nm. The scaffolds showed appropriate tensile strength expected for vascular grafts. Cellular attachment, growth, and infiltration were proved using SEM and MTT (3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide) assay. Drug-loaded scaffolds showed a sustained release profile of aspirin in 7 days. An enhanced cytocompatibility was observed in AM-coated electrospun PLLA fibers compared to uncoated scaffolds. Our results together indicated that AM lysate coated ASA releasing scaffolds have promising potentials for development of a biocompatible SDVG.

Keywords: vascular tissue engineering, vascular grafts, anticoagulant agent, aspirin, amniotic membrane

Procedia PDF Downloads 139

Authors: Ashish Jain, Satish Nayak

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Transdermal iontophoretic drug delivery system is viable drug delivery platform technology and has a strong market worldwide. Transdermal drug delivery system is particularly desirable for therapeutic agents that need prolonged administration at controlled plasma level. This makes appropriateness to antihypertensive and anti-diabetic agents for their transdermal development. Controlled zero order absorption, easily termination of drug delivery and easy to administration also support for popularity of transdermal delivery. In this current research iontophoretic delivery of various anti diabetic agents like glipizide, glibenclamide and glimepiride were carried out. The experiments were carried out at different drug concentrations and different current densities using cathodal iontophoresis. Diffusion cell for iontophoretic permeation study was modified according to Glikfield Design. Pig skin was used for in vitro permeation study and for the in-vivo study New Zealand rabbits were used. At all concentration level iontophoresis showed enhanced permeation rate compared to passive controls. Iontophoretic transports of selected drugs were found to be increased with the current densities. Results showed that target permeation rate for selected drugs could be achieved with the aid of iontophoresis by increasing the area in an appreciable range.

Keywords: transdermal, iontophoresis, pig skin, rabbits, glipizide, glibeclamide

Procedia PDF Downloads 360