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.
4,4'-(pyridine-2,6-diylbis(1,3,4-oxadiazole-5,2-diyl))bisphenol monomer (3)was synthesized from cyclization of N'2,N'6-bis(4-hydroxybenzylidene)pyridine-2,6-dicarbohydrazide (2)in the presence of bromine in glacialacetic acid. Newly five polymers (P1-P5) were synthesized from reaction bis-1,3,4-oxadiazole bisphenolmonomer with five different di acid chloride. The antibacterial activity of the synthesized polymers was screened against gram positive and gram negative bacteria. Polymers P4 and P5 exhibited significant antibacterial against all microorganisms, as well these polymers showed highest antifungal activity.
Receipt date:12/7/2020 accepted date:24/1/2021 Publication date:31/12/2021
This work is licensed under a Creative Commons Attribution 4.0 International License.
The constant characteristic of international relations is the constant change due to political, economic and military developments in addition to technology, and this in turn has led to many transformations in the concept of power, its uses, and the elements that form power and its distribution, and according to those variables, the concept of power has shifted from hard to soft, up to smart powe
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renaissance in emirates of Arab Gulf from 1914-1945 between tow world war
has been attracting the attention of academic about the developments in many
fields in the Arab Gulf at this time.
The paper is divided into five sections. First section, deals with the
geographic importance for the Arab Gulf region. Second section, the economic
situations in the region before and after oil. The third section, talk for social
situations, like population, tribe and tribes in society, and immigration. The
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