Search results for: drug therapy problem

Authors: Zuhrotun Ulya, Muchammad Syamsulhadi, Debree Septiawan

Abstract:

Patients with bipolar disorder are three times more likely to suffer cardiovascular disorders than the general population, which will influence their level of morbidity and rate of mortality. Bipolar disorder also affects the pulmonary system. The choice of long term-monotherapy and other combinative therapies have clinical impacts on patients. This study investigates the case of a woman who has been suffering from bipolar disorder for 16 years, and who has a history of Steven Johnson Syndrome. At present she is suffering also from cardiovascular and pulmonary disorder. An analysis of the results of this study suggests that there is a relationship between cardiovascular disorder, drug therapies, Steven Johnson Syndrome and mood stabilizer obtained from the PubMed, Cochrane, Medline, and ProQuest (publications between 2005 and 2015). Combination therapy with mood stabilizer is recommended for patients who do not have side effect histories from these drugs. The replacement drugs and combinations may be applied, especially for those with bipolar disorders, and the combination between atypical antipsychotic groups and mood stabilizers is often made. Clinicians, however, should be careful with the patients’ physical and metabolic changes, especially those who have experienced long-term therapy and who showed a history of Steven Johnson Syndrome (for which clinicians probably prescribed one type of medicine).

Keywords: cardiopulmonary disease, bipolar disorder, SJS, therapy

Procedia PDF Downloads 431

Authors: Elmeida Effendy, Mustafa M. Amin, Nauli Aulia Lubis, P. J. Sirait

Abstract:

Music therapy may have an effect on mental illnesses. This is a comparative, quasi-experimental study to examine the effect of music therapy added to standard care on Positive Negative Syndrome Scale, Cognitive Function and Quality of Life in female schizophrenic patients. 50 schizophrenic participants who were diagnosed with semistructured MINI ICD-X, were assigned into two groups received pharmacotherapy. Participants were assigned into each group of therapy by using matched allocation method. Music therapy added on to the first group. They received music therapy, using Mozart Sonata four times a week, over a period of six week. Positive and negative symptoms were measured by using Positive and Negative Syndrome Scale (PANSS). Cognitive function were measured by using Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA). All rating scale were administrated by certified skill residents every week after music therapy session. The participants who were received pharmaco-and-music therapy significantly showed greater response than who received pharmacotherapy only. The mean difference of response were -6,6164 (p=0,001) for PANNS, 2,911 (p=0,004) for MMSE, 3,618 (p=0,001) for MOCA, 4,599 (p=0,001) for SF-36. Music therapy have beneficial effects on PANSS, Cognitive Function and Quality of Life in schizophrenic patients.

Keywords: music therapy, rating scale, schizophrenia, symptoms

Procedia PDF Downloads 348

Authors: Babak Bahri, Fatemeh Yassaee Meybodi, Changiz Eslahchi

Abstract:

In the pursuit of effective cancer therapies, the exploration of combinatorial drug regimens is crucial to leverage synergistic interactions between drugs, thereby improving treatment efficacy and overcoming drug resistance. However, identifying synergistic drug pairs poses challenges due to the vast combinatorial space and limitations of experimental approaches. This study introduces ClusterSyn, a machine learning (ML)-powered framework for classifying anti-cancer drug synergy scores. ClusterSyn employs a two-step approach involving drug clustering and synergy score prediction using a fully connected deep neural network. For each cell line in the training dataset, a drug graph is constructed, with nodes representing drugs and edge weights denoting synergy scores between drug pairs. Drugs are clustered using the Markov clustering (MCL) algorithm, and vectors representing the similarity of drug pairs to each cluster are input into the deep neural network for synergy score prediction (synergy or antagonism). Clustering results demonstrate effective grouping of drugs based on synergy scores, aligning similar synergy profiles. Subsequently, neural network predictions and synergy scores of the two drugs on others within their clusters are used to predict the synergy score of the considered drug pair. This approach facilitates comparative analysis with clustering and regression-based methods, revealing the superior performance of ClusterSyn over state-of-the-art methods like DeepSynergy and DeepDDS on diverse datasets such as Oniel and Almanac. The results highlight the remarkable potential of ClusterSyn as a versatile tool for predicting anti-cancer drug synergy scores.

Keywords: drug synergy, clustering, prediction, machine learning., deep learning

Procedia PDF Downloads 81

Authors: Prosper Kudzanai Mushauri

Abstract:

Shock therapy has been used in persons living with depression and deeply depressed persons. It has been used in children also. Shock therapy has been also among its pros believed to improve the quality of life and an effective treatment of depression. The review of the literature on ECT papers have highlighted that benefits to users of ECT are elusive, and iatrogenic harm often occurs showing that the approach will always fall far in comporting to psychological ethics. On the contrary, ECT is known as shock therapy which is the administration of electric shock within the brain; it has been challenged on ethical grounds if it’s proper ethically. From this ethical aperture, it has emerged that relapse rates are approximately higher than 50%, it results in diencephalon disturbances and has also side effects related to cognitive function among other negative effects. It is from these reviewed studies that that ECT should not be viewed as an effective treatment of depression as it does not comport to the mores of psychological ethics.

Keywords: anterograde amnesia, depression, electroconvulsive therapy, ethics, retrograde amnesia

Procedia PDF Downloads 192

Authors: Dipali Nagaonkar, Mahendra Rai

Abstract:

Chitosan, a carbohydrate polymer at nanoscale level has gained considerable momentum in drug delivery applications due to its inherent biocompatibility and non-toxicity. However, conventional synthetic strategies for chitosan nanoparticles mainly rely upon physicochemical techniques, which often yield chitosan microparticles. Hence, there is an emergent need for development of controlled synthetic protocols for chitosan nanoparticles within the nanometer range. In this context, we report the green synthesis of size controlled chitosan nanoparticles by using Pongamia pinnata (L.) leaf extract. Nanoparticle tracking analysis confirmed formation of nanoparticles with mean particle size of 85 nm. The stability of chitosan nanoparticles was investigated by zetasizer analysis, which revealed positive surface charged nanoparticles with zeta potential 20.1 mV. The green synthesized chitosan nanoparticles were further explored for encapsulation and controlled release of antioxidant biomolecule, quercetin. The resulting drug loaded chitosan nanoparticles showed drug entrapment efficiency of 93.50% with drug-loading capacity of 42.44%. The cumulative in vitro drug release up to 15 hrs was achieved suggesting towards efficacy of green synthesized chitosan nanoparticles for drug delivery applications.

Keywords: Chitosan nanoparticles, green synthesis, Pongamia pinnata, quercetin

Procedia PDF Downloads 578

Authors: Vikram Chowdhary, Marek Vins

Abstract:

The profitability of the pharmaceutical drug business has attracted considerable interest, but it also faces significant challenges. Counterfeiters take advantage of the industry's vulnerabilities, which are further exacerbated by the globalization of the market, online trading, and complex supply chains. Governments and organizations worldwide are dedicated to creating a secure environment that ensures a consistent and genuine supply of pharmaceutical products. In 2019, the European authorities implemented regulation EU 2016/161 to strengthen traceability and transparency throughout the entire drug supply chain. This regulation requires the addition of enhanced security features, such as serializing items to the saleable unit level or individual packs. Despite these efforts, the incidents of pharmaceutical counterfeiting continue to rise globally, with regulated territories being particularly affected. This paper examines the effectiveness of the drug serialization system implemented by European authorities. By conducting a systematic literature review, we assess the implementation of drug serialization and explore the potential benefits of integrating emerging digital technologies, such as RFID and Blockchain, to improve traceability and management. The objective is to fortify pharmaceutical supply chains against counterfeiters and manipulators and ensure their security.

Keywords: blockchain, counterfeit drugs, EU drug serialization, pharmaceutical industry, RFID

Procedia PDF Downloads 112

Authors: Tasnuva Tamanna, Aimin Yu

Abstract:

Application of nanoscience in biomedical field has come across as a new era. This study involves the synthesis of nano drug carrier with antibiotic loading. Based on the founding that polydopamine (PDA) nanoparticles could be formed via self-polymerization of dopamine at alkaline pH, one-step synthesis of rifampicin coupled polydopamine (PDA-R) nanoparticles was achieved by adding rifampicin into the dopamine solution. The successful yield of PDA nanoparticles with or without the presence of rifampicin during the polymerization process was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and Raman spectroscopy. Drug loading was monitored by UV-vis spectroscopy and the loading efficiency of rifampicin was calculated to be 76%. Such highly capacious nano-reservoir was found very stable with little drug leakage at pH 3.

Keywords: drug loading, nanoparticles, polydopamine, rifampicin

Procedia PDF Downloads 480

Authors: Shahana Sharmin

Abstract:

In the present study, the effect of cellulose polymers Ethyl Cellulose and Hydroxy Propyl Methyl Cellulose was evaluated on the release profile of drug from sustained release pellet. Diltiazem Hydrochloride, an antihypertensive, cardio-protective agent and slow channel blocker were used as a model drug to evaluate its release characteristics from different pellets formulations. Diltiazem Hydrochloride sustained release pellets were prepared by drug loading (drug binder suspension) on neutral pellets followed by different percentages of spraying, i.e. 2%,4%, 6%, 8% and 10% coating suspension using ethyl cellulose and hydroxy-propyl methyl cellulose polymer in a fixed 85:15 ratios respectively. The in vitro dissolution studies of Diltiazem Hydrochloride from these sustained release pellets were carried out in pH 7.2 phosphate buffer for 1, 2, 3, 4, 5, 6, 7, and 8 hrs using USP-I method. Statistically, significant differences were found among the drug release profile from different formulations. Polymer content with the highest concentration of Ethyl cellulose on the pellets shows the highest release retarding rate of the drug. The retarding capacity decreases with the decreased concentration of ethyl cellulose. The release mechanism was explored and explained with zero order, first order, Higuchi and Korsmeyer’s equations. Finally, the study showed that the profile and kinetics of drug release were functions of polymer type, polymer concentration & the physico-chemical properties of the drug.

Keywords: diltiazem hydrochloride, ethyl cellulose, hydroxy propyl methyl cellulose, release kinetics, sustained release pellets

Procedia PDF Downloads 414

Authors: Hardeep

Abstract:

The aim of this research work to improve the solubility and bioavailability of Simvastatin using a self nanoemulsifying drug delivery system (SNEDDS). Self emulsifying property of various oils including essential oils was evaluated with suitable surfactants and co-surfactants. Validation of a method for accuracy, repeatability, Interday and intraday precision, ruggedness, and robustness were within acceptable limits. The liquid SNEDDS was prepared and optimized using a ternary phase diagram, thermodynamic, centrifugation and cloud point studies. The globule size of optimized formulations was less than 200 nm which could be an acceptable nanoemulsion size range. The mean droplet size, drug loading, PDI and zeta potential were found to be 141.0 nm, 92.22%, 0.23 and -10.13 mV and 153.5nm, 93.89 % ,0.41 and -11.7 mV and 164.26 nm, 95.26% , 0.41 and -10.66mV respectively.

Keywords: simvastatin, self nanoemulsifying drug delivery system, solubility, bioavailability

Procedia PDF Downloads 201

Authors: Nunila Ferreira de Oliveira, Silvana Martins Mishima

Abstract:

Diabetes mellitus type 2 (DM2) prevalence, is increasing on the world, in Brazil is considered a public health problem. Treatment focuses on glycemic control depending primarily of lifestyle changes - not drug treatment (NDT), may involve drug therapy (DT) and requires continuous health monitoring. In Brazil this monitoring is performed by the Unified Health System (SUS) through Primary Health Care (PHC), which stimulate people with DM2 empowerment for care management. SUS was approved in 1988 and the PHC operationalization was strengthened with the creation of the Family Health Strategy (FHS) in 1994. Our aim was to analyze the people with DM2 participation in front of the care management health monitoring in the FHS. Qualitative research was carried out through non-participant observation of attendance of 25 people with DM2 in the FHS and interviewed at home. Ethical guidelines were followed. It was found that people with DM2 only follow professionals’ recommendations that make sense according to their own conceptions of health/disease; most of them emphasize the importance of (DT) with little emphasis on the NDT, was found great difficulty in the NDT and lack of knowledge about the disease and care. As regards monitoring the FHS, were observed therapeutic practices based on the bio medical model, although the APS search for another care perspective; NDT is not systematically accompanied by the health team and takes place a few educational activities on the DM2 in the FHS, with low user adoption. The work of the FHS is done by multidisciplinary teams, but we see the need for greater participation of nurses in clinical-care follow-up of this population and may also act in adapting to the NDT. Finally we emphasize the need for professional practices that consider the difficulties to care management by people with DM2, especially because of the NDT. It is noticed that the measures recommended by the FHS professionals are not always developed by people with DM2. We must seek the empowerment of people with DM2 to manage the form of care associated with the FHS team, seeking to reduce the incidence of complications and higher quality of life.

Keywords: diabetes mellitus, primary health care, nursing, management of care

Procedia PDF Downloads 457

Authors: Nagasamy Venkatesh Dhandapani

Abstract:

The objective of the present study was to develop sustained release oral matrix tablets of anti epileptic drug levetiracetam. The sustained release matrix tablets of levetiracetam were prepared using hydrophilic matrix hydroxypropyl methylcellulose (HPMC) as a release retarding polymer by wet granulation method. Prior to compression, FTIR studies were performed to understand the compatibility between the drug and excipients. The study revealed that there was no chemical interaction between drug and excipients used in the study. The tablets were characterized by physical and chemical parameters and results were found in acceptable limits. In vitro release study was carried out for the tablets using 0.1 N HCl for 2 hours and in phosphate buffer pH 7.4 for remaining time up to 12 hours. The effect of polymer concentration was studied. Different dissolution models were applied to drug release data in order to evaluate release mechanisms and kinetics. The drug release data fit well to zero order kinetics. Drug release mechanism was found as a complex mixture of diffusion, swelling and erosion.

Keywords: levetiracetam, sustained-release, hydrophilic matrix tablet, HPMC grade K 100 MCR, wet granulation, zero order release kinetics

Procedia PDF Downloads 316

Authors: Elena G. Salina, Laurent R. Chiarelli, Maria R. Pasca, Vadim A. Makarov

Abstract:

Tuberculosis is one of the most challenging threats to human health, confronted by the problem of drug resistance. Evidently, new drugs for tuberculosis are urgently needed. Thienopyrimidine TP053 is one of the most promising new antitubercular prodrugs. Mycothiol-dependent reductase Mrx2, encoded by rv2466c, is known to be a TP053 activator; however, the precise mode of action of this compound remained unclear. Being highly active against both replicating and non-replicating tuberculosis bacilli, TP053 also revealed dose-escalating activity for M. tuberculosis-infected murine macrophages. The chemical structure of TP053 is characterized by the presence of NO₂ group which was suggested to be responsible for the toxic effects of the activated compound. Reduction of a nitroaromatic moiety of TP53 by Mrx2 was hypothesized to result in NO release. Analysis of the products of enzymatic activation of TP053 by Mrx2 by the Greiss reagent clearly demonstrated production of nitric oxide in a time-dependent manner. Mass-spectra of cell lysates of TP-treated M. tuberculosis bacilli demonstrated the transformation of TP053 to its non-active metabolite with Mw=261 that corresponds NO release. The mechanism of NO toxicity for bacteria includes DNA damage and degradation of iron-sulfur centers, especially under oxygen depletion. Thus, TP-053 drug-like scaffold is prospective for further development of novel anti-TB drug. This work was financially supported by the Russian Foundation for Basic Research (Grant 17-04-00342).

Keywords: drug discovery, M. tuberculosis, nitric oxide, NO donors

Procedia PDF Downloads 154

Authors: K. Yu Vlasova, M. A. Abakumov, H. Wishwarsao, M. Sokolsky, N. V. Nukolova, A. G. Majouga, Y. I. Golovin, N. L. Klyachko, A. V. Kabanov

Abstract:

Introduction:Nowadays pharmaceutical medicine is aimed to create systems for combined therapy, diagnostic, drug delivery and controlled release of active molecules to target cells. Magnetic nanoparticles (MNPs) are used to achieve this aim. MNPs can be applied in molecular diagnostics, magnetic resonance imaging (T1/T2 contrast agents), drug delivery, hyperthermia and could improve therapeutic effect of drugs. The most common drug containers, containing MNPs, are liposomes, micelles and polymeric molecules bonded to the MNPs surface. Usually superparamagnetic nanoparticles are used (the general diameter is about 5-6 nm) and all effects of high frequency magnetic field (MF) application are based on Neel relaxation resulting in heating of surrounded media. In this work we try to develop a new method to improve drug release from MNPs under super low frequency MF. We suppose that under low frequency MF exposures the Brown’s relaxation dominates and MNPs rotation could occur leading to conformation changes and release of bioactive molecules immobilized on MNPs surface.The aim of this work was to synthesize different systems with active drug (biopolymers coated MNPs nanoclusters with immobilized enzymes and doxorubicin (Dox) loaded magnetic liposomes/micelles) and investigate the effect of super low frequency MF on these drug containers. Methods: We have synthesized MNPs of magnetite with magnetic core diameter 7-12 nm . The MNPs were coated with block-copolymer of polylysine and polyethylene glycol. Superoxide dismutase 1 (SOD1) was electrostatically adsorbed on the surface of the clusters. Liposomes were prepared as follow: MNPs, phosphatidylcholine and cholesterol were dispersed in chloroform, dried to get film and then dispersed in distillated water, sonicated. Dox was added to the solution, pH was adjusted to 7.4 and excess of drug was removed by centrifugation through 3 kDa filters. Results: Polylysine coated MNPs formed nanosized clusters (as observed by TEM) with intensity average diameter of 112±5 nm and zeta potential 12±3 mV. After low frequency AC MF exposure we observed change of immobilized enzyme activity and hydrodynamic size of clusters. We suppose that the biomolecules (enzymes) are released from the MNPs surface followed with additional aggregation of complexes at the MF in medium. Centrifugation of the nanosuspension after AC MF exposures resulted in increase of positive charge of clusters and change in enzyme concentration in comparison with control sample without MF, thus confirming desorption of negatively charged enzyme from the positively charged surface of MNPs. Dox loaded magnetic liposomes had average diameter of 160±8 nm and polydispersity index (PDI) 0.25±0.07. Liposomes were stable in DW and PBS at pH=7.4 at 370C during a week. After MF application (10 min of exposure, 50 Hz, 230 mT) diameter of liposomes raised to 190±10 nm and PDI was 0.38±0.05. We explain this by destroying and/or reorganization of lipid bilayer, that leads to changes in release of drug in comparison with control without MF exposure. Conclusion: A new application of low frequency AC MF for drug delivery and controlled drug release was shown. Investigation was supported by RSF-14-13-00731 grant, K1-2014-022 grant.

Keywords: magnetic nanoparticles, low frequency magnetic field, drug delivery, controlled drug release

Procedia PDF Downloads 483

Authors: Waraporn Boonchieng, Ekkarat Boonchieng, Sivaporn Aungwattana, Decha Tamdee, Wongamporn Pinyavong

Abstract:

Drug addiction represents one of the most important public health issues in both developed and developing countries. The purpose of this study was to develop a drug abuse health information in a community in Northern Thailand using developmental research design. The developmental researchers performed four phases to develop drug abuse health information, including 1) synthesizing knowledge related to drug abuse prevention and identifying the components of drug abuse health information; 2) developing the system in mobile application and website; 3) implementing drug abuse health information in the rural community; and 4) evaluating the feasibility of drug abuse health information. Data collection involved both qualitative and quantitative procedures. The qualitative data and quantitative data were analyzed using content analysis and descriptive statistics, respectively. The findings of this study showed that drug abuse health information consisted of five sections, including drug-related prevention knowledge for teens, drug-related knowledge for adults and professionals, the database for drug dependence treatment centers, self-administered questionnaires, and supportive counseling sections. First, in drug-related prevention knowledge for teens, the developmental researchers designed four infographics and animation to provide drug-related prevention knowledge, including types of illegal drugs, causes of drug abuse, consequences of drug abuse, drug abuse diagnosis and treatment, and drug abuse prevention. Second, in drug-related knowledge for adults and professionals, the developmental researchers developed many documents in a form of PDF file to provide drug-related knowledge, including types of illegal drugs, causes of drug abuse, drug abuse prevention, and relapse prevention guideline. Third, database for drug dependence treatment centers included the place, direction map, operation time, and the way for contacting all drug dependence treatment centers in Thailand. Fourth, self-administered questionnaires comprised preventive drugs behavior questionnaire, drug abuse knowledge questionnaire, the stages of change readiness and treatment eagerness to drug use scale, substance use behaviors questionnaire, tobacco use behaviors questionnaire, stress screening, and depression screening. Finally, for supportive counseling, the developmental researchers designed chatting box through which each user could write and send their concerns to counselors individually. Results from evaluation process showed that 651 participants used drug abuse health information via mobile application and website. Among all users, 48.8% were males and 51.2% were females. More than half (55.3%) were 15-20 years old and most of them (88.0%) were Buddhists. Most users reported ever getting knowledge related to drugs (86.1%), and drinking alcohol (94.2%) while some of them (6.9%) reported ever using tobacco. For satisfaction with using the drug abuse health information, more than half of users reflected that the contents of drug abuse health information were interesting (59%), up-to date (61%), and highly useful to their self-study (59%) at high level. In addition, half of them were satisfied with the design in terms of infographics (54%) and animation (51%). Thus, this drug abuse health information can be adopted to explore drug abuse situation and serves as a tool to prevent drug abuse and addiction among Thai community people.

Keywords: drug addiction, health informatics, big data, development research

Procedia PDF Downloads 113

Authors: Rostyslav Horbay, Nick Korolis, Vahid Anvari, Rostyslav Stoika

Abstract:

Introduction: Giant cancer cells (GCC) are common in all types of cancer, especially after poor therapy. Some specific features of such cells include ~10-fold enlargement, drug resistance, and the ability to propagate similar daughter cells. We used murine NK/Ly lymphoma, an aggressive and fast growing lymphoma model that has already shown drastic changes in GCC comparing to parental cells (chromatin condensation, nuclear fragmentation, tighter OXPHOS/cellular respiration coupling, multidrug resistance). Materials and methods: In this study, we compared morpho-functional changes of GCC that predominantly show either a cytostatic or a cytotoxic effect after treatment with drugs. We studied the effect of a combined cytostatic/cytotoxic drug treatment to determine the correlation of drug efficiency and GCC formation. Doses of G1/S-specific drug paclitaxel/PTX (G2/M-specific, 50 mg/mouse), vinblastine/VBL (50 mg/mouse), and DNA-targeting agents doxorubicin/DOX (125 ng/mouse) and cisplatin/CP (225 ng/mouse) on C57 black mice. Several tests were chosen to estimate morphological and physiological state (propidium iodide, Rhodamine-123, DAPI, JC-1, Janus Green, Giemsa staining and other), which included cell integrity, nuclear fragmentation and chromatin condensation, mitochondrial activity, and others. A single and double factor ANOVA analysis were performed to determine correlation between the criteria of applied drugs and cytomorphological changes. Results: In all cases of treatment, several morphological changes were observed (intracellular vacuolization, membrane blebbing, and interconnected mitochondrial network). A lower gain in ascites (49.97% comparing to control group) and longest lifespan (22+9 days) after tumor injection was obtained with single VBL and single DOX injections. Such ascites contained the highest number of GCC (83.7%+9.2%), lowest cell count number (72.7+31.0 mln/ml), and a strong correlation coefficient between increased mitochondrial activity and percentage of giant NK/Ly cells. A high number of viable GCC (82.1+9.2%) was observed compared to the parental forms (15.4+11.9%) indicating that GCC are more drug resistant than the parental cells. All this indicates that the giant cell formation and its ability to obtain drug resistance is an expanding field in cancer research.

Keywords: ANOVA, cisplatin, doxorubicin, drug resistance, giant cancer cells, NK/Ly lymphoma, paclitaxel, vinblastine

Procedia PDF Downloads 217

Authors: Tamer M. Shehata, Heba S. Elsewedy, Mashel Al Dosary, Alaa Elshehry, Mohamed A. Khedr, Maged E. Mohamed

Abstract:

Objective: 2,4-Dichlorophenoxy acetic acid (2,4-D) is a well-known herbicide widely used as a weed killer. Recently, 2,4-D was rediscovered as a new anti-inflammatory agent through in silico as well as in-vivo experiments. However, poor solubility of 2,4-D could represent a problems during pharmaceutical development in addition to lower bioavailability. Solid dispersion (SD) refers to a group of solid products consisting of at least two different components, usually a hydrophobic drug and hydrophilic matrix. It is well known technique for enhancing drug solubility. Therefore, selecting SD as a tool for enhancing 2,4-D could be of great interest to the formulator. Method: In our project, several polymers were investigated (such as PEG, HPMC, citric acid and others) in addition to drug polymer ratios and its effect on solubility. Evaluation of drug polymer interaction was investigated through both Fourier Transform Infrared (FTIR) and Differential Scanning Calorimetry (DSC). Finally, in-vivo evaluation was performed for the best selected preparation through inflammatory response of rat induce hind paw. Results: Results indicated that, citric acid 2,4-D and in ratio of 0.75 : 1 showed modified the dissolution profile of the drug. The FTIR resltes indicated no significant chemical interaction, however DSC showed shifting of the drug melting point. Finally, Carragenan induced rat hind paw edema showed significant reduction of the drug solid dispersion in comparison to the pure drug, indicating rapid and complete absorption of the drug in solid dispersion form. Conclusion: Solid dispersion technology can be utilized efficiently to enhance the solubility of 2,4-D.

Keywords: solid dispersion, 2, 4-D solubility, carragenan induced edema

Procedia PDF Downloads 456

Authors: Christi Jackson, Chuka Onaga

Abstract:

Introduction: We report a case of delayed diagnosis of extra-pulmonary INH-mono-resistant Tuberculosis (TB) in a South African patient with drug-resistant HIV. Case Presentation: A 36-year old male was initiated on 1st line (NNRTI-based) anti-retroviral therapy (ART) in September 2009 and switched to 2nd line (PI-based) ART in 2011, according to local guidelines. He was following up at the outpatient wellness unit of a public hospital, where he was diagnosed with Protease Inhibitor resistant HIV in March 2016. He had an HIV viral load (HIVVL) of 737000 copies/mL, CD4-count of 10 cells/µL and presented with complaints of productive cough, weight loss, chronic diarrhoea and a septic buttock wound. Several investigations were done on sputum, stool and pus samples but all were negative for TB. The patient was treated with antibiotics and the cough and the buttock wound improved. He was subsequently started on a 3rd-line ART regimen of Darunavir, Ritonavir, Etravirine, Raltegravir, Tenofovir and Emtricitabine in May 2016. He continued losing weight, became too weak to stand unsupported and started complaining of abdominal pain. Further investigations were done in September 2016, including a urine specimen for Line Probe Assay (LPA), which showed M. tuberculosis sensitive to Rifampicin but resistant to INH. A lymph node biopsy also showed histological confirmation of TB. Management and outcome: He was started on Rifabutin, Pyrazinamide and Ethambutol in September 2016, and Etravirine was discontinued. After 6 months on ART and 2 months on TB treatment, his HIVVL had dropped to 286 copies/mL, CD4 improved to 179 cells/µL and he showed clinical improvement. Pharmacy supply of his individualised drugs was unreliable and presented some challenges to continuity of treatment. He successfully completed his treatment in June 2017 while still maintaining virological suppression. Discussion: Several laboratory-related factors delayed the diagnosis of TB, including the unavailability of urine-lipoarabinomannan (LAM) and urine-GeneXpert (GXP) tests at this facility. Once the diagnosis was made, it presented a treatment dilemma due to the expected drug-drug interactions between his 3rd-line ART regimen and his INH-resistant TB regimen, and specialist input was required. Conclusion: TB is more difficult to diagnose in patients with severe immunosuppression, therefore additional tests like urine-LAM and urine-GXP can be helpful in expediting the diagnosis in these cases. Patients with non-standard drug regimens should always be discussed with a specialist in order to avoid potentially harmful drug-drug interactions.

Keywords: drug-resistance, HIV, line probe assay, tuberculosis

Procedia PDF Downloads 173

Authors: Brajesh Tiwari, Yuvraj Dangi, Abhishek Jain, Ashok Jain

Abstract:

The purpose of the investigation was to evaluate the potential of sphingosomes as nanoscale drug delivery units for site-specific delivery of anti-cancer agents. Doxorubicin Hydrochloride (DOX) was selected as a model anti-cancer agent. Sphingosomes were prepared and loaded with DOX and optimized for size and drug loading. The formulations were characterized by Malvern zeta-seizer and Transmission Electron Microscopy (TEM) studies. Sphingosomal formulations were further evaluated for in-vitro drug release study under various pH profiles. The in-vitro drug release study showed an initial rapid release of the drug followed by a slow controlled release. In vivo studies of optimized formulations and free drug were performed on albino rats for comparison of drug plasma concentration. The in- vivo study revealed that the prepared system enabled DOX to have had enhanced circulation time, longer half-life and lower elimination rate kinetics as compared to free drug. Further, it can be interpreted that the formulation would selectively enter highly porous mass of tumor cells and at the same time spare normal tissues. To summarize, the use of sphingosomes as carriers of anti-cancer drugs may prove to be a fascinating approach that would selectively localize in the tumor mass, increasing the therapeutic margin of safety while reducing the side effects associated with anti-cancer agents.

Keywords: sphingosomes, anti-cancer, doxorubicin, formulation

Procedia PDF Downloads 303

Authors: Rajinikanth Siddalingam, Poonguzhali Subramanian

Abstract:

The present study aims to prepare and evaluate the self-nano emulsifying drug delivery (SNEDDS) system to enhance the dissolution rate of a poorly soluble drug dutasteride. The formulation was prepared using capryol PGMC, Cremophor EL, and polyethylene glycol (PEG) 400 as oil, surfactant and co-surfactant, respectively. The pseudo-ternary phase diagrams with presence and absence of drug were plotted to find out the nano emulsification range and also to evaluate the effect of dutasteride on the emulsification behavior of the phases. Prepared SNEDDS formulations were evaluated for its particle size distribution, nano emulsifying properties, robustness to dilution, self-emulsification time, turbidity measurement, drug content and in-vitro dissolution. The optimized formulations are further evaluated for heating cooling cycle, centrifugation studies, freeze-thaw cycling, particle size distribution and zeta potential were carried out to confirm the stability of the formed SNEDDS formulations. The particle size, zeta potential and polydispersity index of the optimized formulation found to be 35.45 nm, -15.45 and 0.19, respectively. The in vitro results are revealed that the prepared formulation enhanced the dissolution rate of dutasteride significantly as compared with pure drug. The in vivo studies in was conducted using rats and the results are revealed that SNEDDS formulation has enhanced the bioavailability of dutasteride drug significantly as compared with raw drug. Based the results, it was concluded that the dutasteride-loaded SNEDDS shows potential to enhance the dissolution of dutasteride, thus improving the bioavailability and therapeutic effects.

Keywords: self-emulsifying drug delivery system, dutasteride, enhancement of bioavailability, dissolution enhancement

Procedia PDF Downloads 267

Authors: Ana-Maria Gheldiu, Bianca M. Abrudan, Maria A. Neag, Laurian Vlase, Dana M. Muntean

Abstract:

Background information: The objective of this study was to investigate the effect of multiple-dose fluvoxamine on the pharmacokinetic profile of single-dose carvedilol in rats, in order to evaluate this possible drug-drug pharmacokinetic interaction. Methods: A preclinical study, in 28 white male Wistar rats, was conducted. Each rat was cannulated on the femoral vein, prior to being connected to BASi Culex ABC®. Carvedilol was orally administrated in rats (3.57 mg/kg body mass (b.m.)) in the absence of fluvoxamine or after a pre-treatment with multiple oral doses of fluvoxamine (14.28 mg/kg b.m.). The plasma concentrations of carvedilol were estimated by high performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters of carvedilol were analyzed by non-compartmental method. Results: After carvediol co-administration with fluvoxamine, an approximately 2-fold increase in the exposure of carvedilol was observed, considering the significantly elevated value of the total area under the concentration versus time curve (AUC₀₋∞). Moreover, an increase by approximately 145% of the peak plasma concentration was found, as well as an augmentation by approximately 230% of the half life time of carvedilol was observed. Conclusion: Fluvoxamine co-administration led to a significant alteration of carvedilol’s pharmacokinetic profile in rats, these effects could be explained by the existence of a drug-drug interaction mediated by CYP2D6 inhibition. Acknowledgement: This work was supported by CNCS Romania – project PNII-RU-TE-2014-4-0242.

Keywords: carvedilol, fluvoxamine, drug-drug pharmacokinetic interaction, rats

Procedia PDF Downloads 274

Authors: Papon Thamvasupong, Kwanchanok Viravaidya-Pasuwat

Abstract:

Osteoarthritis affects a lot of people worldwide. Local injection of glucosamine is one of the alternative treatment methods to replenish the natural lubrication of cartilage. However, multiple injections can potentially lead to possible bacterial infection. Therefore, a drug delivery system is desired to reduce the frequencies of injections. A hydrogel is one of the delivery systems that can control the release of drugs. Thermo-reversible hydrogels can be beneficial to the drug delivery system especially in the local injection route because this formulation can change from liquid to gel after getting into human body. Once the gel is in the body, it will slowly release the drug in a controlled manner. In this study, various formulations of Pluronic-based hydrogels were synthesized for the controlled release of glucosamine. One of the challenges of the Pluronic controlled release system is its fast dissolution rate. To overcome this problem, alginate and calcium sulfate (CaSO₄) were added to the polymer solution. The characteristics of the hydrogels were investigated including the gelation temperature, gelation time, hydrogel dissolution and glucosamine release mechanism. Finally, a mathematical model of glucosamine release from Pluronic-alginate-hyaluronic acid hydrogel was developed. Our results have shown that crosslinking Pluronic gel with alginate did not significantly extend the dissolution rate of the gel. Moreover, the gel dissolution profiles and the glucosamine release mechanisms were best described using the zeroth-order kinetic model, indicating that the release of glucosamine was primarily governed by the gel dissolution.

Keywords: controlled release, drug delivery system, glucosamine, pluronic, thermoreversible hydrogel

Procedia PDF Downloads 270

Authors: Eslam Dabbish, Fortuna Ponte, Stefano Scoditti, Emilia Sicilia, Gloria Mazzone

Abstract:

The medical techniques based on the use of light for activating the drug are occupying a prominent place in the cancer treatment due to their selectivity that contributes to reduce undesirable side effects of conventional chemotherapy. Among these therapeutic treatments, photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) are emerging as complementary approaches for selective destruction of neoplastic tissue through direct cellular damage. Both techniques rely on the employment of a molecule, photosensitizer (PS), able to absorb within the so-called therapeutic window. Thus, the exposure to light of otherwise inert molecules promotes the population of excited states of the drug, that in PDT are able to produce the cytotoxic species, such as 1O2 and other ROS, in PACT can be responsible of the active species release or formation. Following the success of cisplatin in conventional treatments, many other transition metal complexes were explored as anticancer agents for applications in different medical approaches, including PDT and PACT, in order to improve their chemical, biological and photophysical properties. In this field, several crucial characteristics of candidate PSs can be accurately predicted from first principle calculations, especially in the framework of density functional theory and its time-dependent formulation, contributing to the understanding of the entire photochemical pathways involved which can ultimately help in improving the efficiency of a drug. A brief overview of the outcomes on some platinum and ruthenium-based PSs proposed for the application in the two phototherapies will be provided.

Keywords: TDDFT, metal complexes, PACT, PDT

Procedia PDF Downloads 105

Authors: Sumeet Dwivedi, Shweta Shriwas, Raghvendra Dubey

Abstract:

The number of products based on new drug delivery systems has significantly increased in the past few years, and this growth is expected to continue in the near future. These biopharmaceuticals present challenges to drug delivery scientists because of their unique nature and difficulty in delivery through conventional routes. Therefore, future research will focus on the delivery of these complex molecules through different routes, including oral, nasal, pulmonary, vaginal, rectal, etc. The aim of present study was to formulate and evaluate ethosomes of Plumeria indica flowers which may deliver the drug to targeted site more efficiently than marketed preparation and also overcome the problems related with oral administration of drug. The formulations were prepared with ethanol, lecithin, propylene glycol and were evaluated.

Keywords: ethosomes, herbal extract, plumeria alba, lecithin

Procedia PDF Downloads 264

Authors: B. J. Mahen, N. E. Lloyd-Gale, S. Johnson, W. P. Rakowicz, M. J. Harris, A. D. Miller

Abstract:

Background: Migraine is a leading cause of disability in the world. Calcitonin gene-related peptide (CGRP) receptor antagonists offer an approach to migraine prophylaxis by inhibiting the inflammatory and vasodilatory effects of CGRP. In recent years, NICE licensed the use of three CGRP-receptor antagonists: Fremanezumab, Galcanezumab, and Erenumab. Here, we present the outcomes of CGRP-antagonist treatment in a cohort of patients who suffer from episodic or chronic migraine and have failed at least three oral prophylactic therapies. Methods: We offered CGRP antagonists to 86 patients who met the NICE criteria to start therapy. We recorded the number of headache days per month (HDPM) at 0 weeks, 3 months, and 12 months. Of those, 26 patients were switched to an alternative treatment due to poor response or side effects. Of the 112 total cases, 9 cases did not sufficiently maintain their headache diary, and 5 cases were not followed up at 3 months. We have therefore included 98 sets of data in our analysis. Results: Fremanezumab achieved a reduction in HDPM by 51.7% at 3 months (p<0.0001), with 63.7% of patients meeting NICE criteria to continue therapy. Patients trialed on Galcanezumab attained a reduction in HDPM by 47.0% (p=0.0019), with 51.6% of patients meeting NICE criteria to continue therapy. Erenumab, however, only achieved a reduction in HDPM by 17.0% (p=0.29), and this was not statistically significant. Furthermore, 34.4%, 9.7%, and 4.9% of patients taking Fremanezumab, Galcanezumab, and Erenumab, respectively, continued therapy beyond 12 months. Of those who attempted drug holidays following 12 months of treatment, migraine symptoms relapsed in 100% of cases. Conclusion: We observed a significant improvement in HDPM amongst episodic and chronic migraine patients following treatment with Fremanezumab or Galcanezumab.

Keywords: migraine, CGRP, fremanezumab, galcanezumab, erenumab

Procedia PDF Downloads 95

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

Procedia PDF Downloads 310

Authors: Cesar Torres, Robert Briber, Nam Sun Wang

Abstract:

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

Procedia PDF Downloads 144

Authors: Minh-Phuong Ngoc Bui, Abdennour Abbas

Abstract:

Microbial spoilage of food/drug has been a constant nuisance and an unavoidable problem throughout history that affects food/drug quality and safety in a variety of ways. A simple and rapid test of fungi and bacteria in food/drugs and environmental clinical samples is essential for proper management of contamination. A number of different techniques have been developed for detection and enumeration of foodborne microorganism including plate counting, enzyme-linked immunosorbent assay (ELISA), polymer chain reaction (PCR), nucleic acid sensor, electrical and microscopy methods. However, the significant drawbacks of these techniques are highly demand of operation skills and the time and cost involved. In this report, we introduce a rapid method for detection of bacteria and fungi in food/drug products using a specific interaction between a reducing agent (tris(2-carboxylethyl)phosphine (TCEP)) and the microbial surface proteins. The chemical reaction was transferred to a transduction system using gold nanoplates-enhanced chemiluminescence. We have optimized our nanoplates synthetic conditions, characterized the chemiluminescence parameters and optimized conditions for the microbial assay. The new detection method was applied for rapid detection of bacteria (E.coli sp. and Lactobacillus sp.) and fungi (Mucor sp.), with limit of detection as low as single digit cells per mL within 10 min using a portable luminometer. We expect our simple and rapid detection method to be a powerful alternative to the conventional plate counting and immunoassay methods for rapid screening of microorganisms in food/drug products.

Keywords: microorganism testing, gold nanoplates, chemiluminescence, reducing agents, luminol

Procedia PDF Downloads 299

Authors: B. Parchem, M. Watanabe, D. Modrakovic, L. Mathew, A. Franklin, M. Cao, R. E. Broudy

Abstract:

Objective: Executive functioning (EF) deficits underlie several mental health diagnoses including ADHD, anxiety, and depression. Community mental health clinics face extensive waitlists for services with many referrals involving EF deficits. A pilot trial of a four-week group therapy was developed using key components from Cognitive-Behavioral Therapy (CBT), Dialectical Behavior Therapy (DBT), and mindfulness with an aim to improve EF skills and offer low-fee services. Method: Eight adults (M = 34.5) waiting for services at a community clinic were enrolled in a four-week group therapy at an in-house training clinic for doctoral trainees. Baseline EF, pre-/post-intervention ADHD and distress symptoms, group satisfaction, and curriculum helpfulness were assessed. Results: Downward trends in ADHD and distress symptoms pre/post-intervention were not significant. Favorable responses on group satisfaction and helpfulness suggest clinical utility. Conclusion: Preliminary pilot data from a brief group therapy to improve EF may be an efficacious, acceptable, and feasible intervention for adults waiting for services at community mental health and training clinics where there are high demands and limits to services and staffs.

Keywords: executive functioning, cognitive-behavioral therapy, dialectical behavior therapy, mindfulness, adult group therapy

Procedia PDF Downloads 164

Authors: Mahmoud S. Zaghloul, Mohammed M. Khalaf, Wael N. Thabet, Haidy N. Asham

Abstract:

Background. Hypertrophic scarring is a difficult problem for burn patients, and scar management is an essential aspect of outpatient burn therapy. Post-burn pathologic scars involve functional and aesthetic limitations that have a dramatic influence on the patient’s quality of life. The aim was to investigate the use of extracorporeal shock wave therapy (ESWT), which targets the fibroblasts in scar tissue, as an effective modality for scar treatment in burn patients. Subjects and methods: forty patients with post-burn scars were assigned randomly into two equal groups; their ages ranged from 20-45 years. The study group received ESWT and traditional physical therapy program (deep friction massage, stretching exercises). The control group received traditional physical therapy program (deep friction massage, stretching exercises). All groups received two sessions per week for six successful weeks. The data were collected before and after the same period of treatment for both groups. Evaluation procedures were carried out to measure scar thickness using ultrasonography and Vancouver Scar Scale (VSS) was completed before and after treatment. Results: Post-treatment results showed that there was a significant improvement difference in scar thickness in both groups in favor of the study group. Percentage of improvement in scar thickness in the study group was 42.55%, while it was 12.15% in the control group. There was also a significant improvement difference between results obtained using VSS in both groups in favor of the study group. Conclusion: ESWT is effective in management of pathologic post burn scars.

Keywords: extracorporeal shock wave therapy, post-burn scars, ultrasonography, Vancouver scar scale

Procedia PDF Downloads 256

Authors: Londeka Ntuli, Frasia Oosthuizen

Abstract:

Background: Tenefovir disiproxil fumarate (TDF) is a nephrotoxic drug and has been proven to contribute to renal insufficiency necessitating intensive monitoring and management of adverse effects arising from prolonged exposure to the drug. TDF is one of the preferred first-line drugs used in combination therapy in most regions. There are estimated 300 000 patients being initiated on the Efavirenz/TDF/Emtricitabine first-line regimen annually in South Africa. It is against this background that this study aims to investigate the effects of TDF on renal sufficiency of HIV positive patients. Methodology: A retrospective quantitative study was conducted, analysing clinical charts of HIV positive patient’s older than 18 years of age and on a TDF-containing regimen for more than 1 year. Data were obtained from the analysis of patient files and was transcribed into Microsoft® Excel® spreadsheet. Extracted data were coded, categorised and analysed using STATA®. Results: A total of 275 patient files were included in this study. Renal function started decreasing after 3 months of treatment (with 93.5% patients having a normal EGFR), and kept on decreasing as time progressed with only 39.6% normal renal function at year 4. Additional risk factors for renal insufficiency included age below 25, female gender, and additional medication. Conclusion: It is clear from this study that the use of TDF necessitates intensive monitoring and management of adverse effects arising from prolonged exposure to the drug. The findings from this study generated pertinent information on the safety profile of the drug TDF in a resource-limited setting of a public health institution. The appropriate management is of tremendous importance in the South African context where the majority of HIV positive individuals are on the TDF containing regimen; thus it is beneficial to ascertain the possible level of toxicities these patients may be experiencing.

Keywords: renal insufficiency, tenefovir, HIV, risk factors

Procedia PDF Downloads 122