Introduction: Methadone hydrochloride (MDN) is an effective pharmacological substitution treatment for opioids dependence, adopted in different countries as methadone maintenance treatment (MMT) programmes. However, MDN can exacerbate the addiction problem if it is abused and injected intravenously, and the frequent visits to the MMT centres can reduce patient compliance. The overall aim of this study is to develop a novel extended-release capsule of MDN using the sol-gel silica (SGS) technique that has the potential to counteract medication-tampering techniques and associated health risks and reduce the frequent visits to MMT centres. Methods: For MDN recrystallisation, a closed container method (CCM) and hot-stage method (HSM) were conducted, and MDN crystals were characterised using the polarised light microscope (PLM). MDN crystal thickness was determined by scanning electron microscopy (SEM) and confocal microscopy (CM) to establish a relationship between MDN crystals thickness and their birefringence colours using the Michel-Levy Birefringence Colour Chart. The experimental series was continued to produce novel silica-based MDN formulations A and B capsules by adding MDN powder at the end and beginning of the SGS process, respectively. The silica-based MDN formulations were characterised by Fourier transform infrared (FT-IR), SEM, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), PLM and mean grey value (MGV) analyses. The in vitro release studies (n=3) for the silica-based MDN formulations and pure MDN capsules were conducted in a phosphate buffer solution (pH= 7.2) for 7 days. Stability studies were conducted for 1 month by keeping the silica-based MDN capsules under 25°C and 57% RH. Results: The optimal method to produce large numbers of MDN crystals was the CCM, and MDN crystals were characterised as diamond shaped with an intrinsic angle of 62o. The SEM surpassed the CM in measuring MDN crystal thickness, and Mann-Whitney U Test showed statistically significant differences between SEM and confocal thickness measurements (U= 1283, p < 0.05) as the SEM exhibited thinner diamond crystals (6.62 ± 2.9 µm) than the CM measurements (9.6 ± 4.6µm). According to the Michel-Levey birefringence colour chart (using the SEM mean thickness of MDN crystals and their retardation value of 428 nm), most of MDN crystals demonstrated a yellow colour. The FT-IR, SEM, DSC, MGV and PLM analyses of both silica-based MDN formulations revealed that MDN was successfully incorporated inside the silica network producing amorphous material (with no appearance of the melting peak of pure MDN at 233.4°C) with evidence of no physical or chemical interaction between sol-gel silica and MDN. However, the TGA analysis revealed a significantly greater amount of MDN was loaded inside the silica-based MDN formulation B compared to A (t = 2.80, p = 0.009, n=6), as 28.3 ± 0.6 mg of MDN was loaded in the former while 25.6 ± 0.7 mg in the latter. In addition, the silica-based MDN formulation B released 10% more MDN after 7 days than formulation A, and both formulations were stable when stored for 1 month under 57% RH and 25°C. Conclusion: The novel combined use of SEM and PLM techniques shows a potential for the identification of MDN in forensic science as it established a range of birefringence colours of MDN crystals. Moreover, the new silica-based MDN formulation B can help to deter MDN abuse and increase patient adherence to MMT due to its potential to sustain MDN release and reduce the frequent visits to MDN treatment centres.
In this paper, a compact genetic algorithm (CGA) is enhanced by integrating its selection strategy with a steepest descent algorithm (SDA) as a local search method to give I-CGA-SDA. This system is an attempt to avoid the large CPU time and computational complexity of the standard genetic algorithm. Here, CGA dramatically reduces the number of bits required to store the population and has a faster convergence. Consequently, this integrated system is used to optimize the maximum likelihood function lnL(φ1, θ1) of the mixed model. Simulation results based on MSE were compared with those obtained from the SDA and showed that the hybrid genetic algorithm (HGA) and I-CGA-SDA can give a good estimator of (φ1, θ1) for the ARMA(1,1) model. Anot
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Flexible molecular docking is a computational method of structure-based drug design to evaluate binding interactions between receptor and ligand and identify the ligand conformation within the receptor pocket. Currently, various molecular docking programs are extensively applied; therefore, realizing accuracy and performance of the various docking programs could have a significant value. In this comparative study, the performance and accuracy of three widely used non-commercial docking software (AutoDock Vina, 1-Click Docking, and UCSF DOCK) was evaluated through investigations of the predicted binding affinity and binding conformation of the same set of small molecules (HIV-1 protease inhibitors) and a protein target HIV-1 protease enzy
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The article reflects the results of the analysis of the use of metaphors as one of the main means used by Lyudmila Ulitskaya when writing the novel “Sincerely Yours Shurik” to form the image of the main hero in the novel. The main purpose of the article is to consider metaphors, which helped the author to form the image of the main character Shurik in the text space through the stages of his life path, closely related to the people around him, who is always happy to be useful (hence the title "Sincerely Yours"), among which the female images of his relatives, girlfriends and others stand out as a special layer in the narrative. And in the course of the study, the following tasks were solved: the metaphors that make up the image of the
... Show MoreBackground: With the increasing demands for adult orthodontics, a growing need arises to bond attachments to porcelain surfaces. Optimal adhesion to porcelain surface should allow orthodontic treatment without bond failure but not jeopardize porcelain integrity after debonding.The present study was carried out to compare the shear bond strength of metal bracket bonded to porcelain surface prepared by two mechanical treatments and by using different etching systems (Hydrofluoric acid 9% and acidulated phosphate fluoride 1.23%). Materials and Methods: The samples were comprised of 60 models (28mm *15mm*28mm) of metal fused to porcelain (feldspathic porcelain). They were divided as the following: group I (control): the porcelain surface left u
... Show MoreThe administration on the basis of the activities designed to evaluate the performance of activities in terms of cost, time and quality by identifying activities that add value and those that are no add value and enables the administration of making up their own continuous improvement in production, through lower costs and reduce the time and improve the quality and reduce the incidence of spoilage and waste, y based search Ally premise that (the continuous improvement of the adoption of management style on the basis of the activities helps management in decision-making wise to reduce costs) to prove the hypothesis has sought research to achieve its goal of Alkadivh and Alkoppelan &nb
... Show MoreThe research seeks to identify the comprehensive electronic banking system and the role of the auditor in light of the customer's application of electronic systems that depend on the Internet in providing its services, as a proposed audit program has been prepared in accordance with international auditing controls and standards based on the study of the customer's environment and the analysis of external and internal risks in the light of financial and non-financial indicators, the research reached a set of conclusions, most notably, increasing the dependence of banks on the comprehensive banking system for its ability to provide new and diverse banking services, The researcher suggested several recommendations, the most important of whi
... Show MoreThis paper presents a study of the application of gas lift (GL) to improve oil production in a Middle East field. The field has been experiencing a rapid decline in production due to a drop in reservoir pressure. GL is a widely used artificial lift technique that can be used to increase oil production by reducing the hydrostatic pressure in the wellbore. The study used a full field model to simulate the effects of GL on production. The model was run under different production scenarios, including different water cut and reservoir pressure values. The results showed that GL can significantly increase oil production under all scenarios. The study also found that most wells in the field will soon be closed due to high water cuts. Howev
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