Cannabidiol based borderline products – from development to registration processes

Cannabidiol (CBD) is the second most abundant phytocannabinoid structure in Cannabis sativa L., Cannabaceae family. It contains a bicyclic 21-carbon skeleton with a double bond in the terpene ring (Jacobs et al., 2016). Cannabidiol based products have been used mainly for additional treatment of pain, depression and anxiety in cancer suffering patients as well as immunostimulatory agents. They are used for treatment of nausea and vomiting, especially during chemotherapy or radiation therapy. Their effects are exerted through the endocannabinoid system through multiple receptors, including cannabinoid receptors (CBRs), opioid and serotonin receptors, adrenergic receptors, and G protein�coupled receptors (Pertwee & Cascio, 2014). At high doses can modulate the intoxicating effects of THC through CB1- dependent mechanisms despite having low CB1 binding affinity (Jacobs et al., 2016). In Republic of North Macedonia, the production, use and sale of registered cannabis products are regulated by the Law of Use of Narcotic Drugs and Psychotropic Substances (Official Gazette of R.M no. 37/2016). A borderline product is a product that contains: (1)probiotics; (2)active components of plant origin and it is classified as a food supplement in at least one member state of the European Union, and according to the special regulations applied in the Republic of Macedonia, it cannot be classified as a food supplement; (3)vitamins and minerals in quantities greater than the permitted prescribed in accordance with the special regulations applied in the Republic of Macedonia, if it is classified as a food supplement in at least one member state of the European Union and there is no registered product with the same strength in the Republic of Macedonia (Official Gazette of R.M no. 203/2015). According to the second term of this law CBD products are still registered as borderline products in our country

A text mining study on the utility of physiologically based pharmacokinetic/biopharmaceutics modeling (PBPK/PBBM) in formulation development

Physiologically based pharmacokinetic (PBPK) modeling is an evolving tool that has a profound impact on drug discovery and formulation development processes. A major advantage of PBPK models is that they have the ability to mechanistically explain how drug properties, product quality attributes and physiological factors influence the in vivo drug performance. To better specify the application field of these models and highlight the link between in vitro dissolution and drug’s in vivo behavior, a novel term, physiologically based biopharmaceutics modeling (PBBM), was recently introduced. The versatility of application of these models is perceived through the growth in the number of scientific publications that include the use of PBPK/PBBM (Krstevska et al, 2022). In the present study, the use of PBPK/PBBM across the publications from the past decade was analyzed, with the focus on the application of these models in pharmaceutical/formulation development.14th Central European Symposium on Pharmaceutical Technology, 28th - 30th September, Ohrid, N. Macedonia, 202

9th- International conference: Social changes in the global world

Предмет на овој труд се руско-украинските односи и нивниот ефект врз рамнотежата на моќ. Во првиот дел на трудот е даден краток историски осврт на сојузите кои се формираат после распадот на СССР и Варшавскиот пакт. Вториот дел е посветен на руско-украинските односи. Во третиот дел е даден краток осврт на балансирање на моќта во пост студениот период, додека во четвртиот дел се изведени заклучни видувања во однос на ефектот на украинското прашање врз рамнотежата на моќт

9th- International conference: Social changes in the global world

Правото на слобода на изразување е едно од основните права содржани во повеќе меѓународни документи, меѓу кои Универзалната декларација за човекови права, Европската конвенција за заштита на човековите права, меѓународните договори и други правни акти. На национално ниво во Република С. Македонија, уставниот член 16 гарантира слобода на говорот, јавно информирање, слободен пристап кон информации, примање и пренесување на информации како и слободно основање на институции за јавно информирање. Со цел да се добијат конкретни резултати во однос на имплементацијата на овие права, трудот ја анализира перцепцијата на медиумските работници за слободата на изразување, степенот на цензура и самоцензура на медиумските работници, а со крајна цел да се откријат кои се причините кои влијаат на ограничувањето на тоа право. Истражувањето, кое е направено преку анкета,се водеше од основното прашање „Каква е перцепцијата на медиумските работници за степенот на слобода на изразување во Република Македонија?„ и опфати медиумски работници вработени во медиумите во северниот и јужниот регион на Република С. Македониј

Property legal disputes of former spouses

The complex issues related to the property relations of the former spouses are covered in the Law on ownership and other real rights. Before these issues were regulated in this law, the property relations of the spouses were covered in the special part of the Law on Family. Property relations are an essential and indispensable part of family relations and family law. They are closely related and intertwined with the personal relationships that arise between family members. Therefore, in most legislations, property relations that arise between family members are regulated within the framework of family law. This is because in the arrangement of certain issues related to property relations between family members, due to the specificities of family relations, the general rules of civil law are deviated from. The presenter, through the analysis of the existing legal solutions through the prism of judicial practice, makes proposals for changes and additions to them

Oral–surgical treatment of periodontal pocket with guided bone and soft tissue regeneration

Periodontal disease is defined as a complex, multifactorial disease characterized by the loss of connective tissue attachment with destruction of periodontal tissues. The aim of periodontal therapy is to eliminate inflammatory process, prevent the progression of periodontal disease and also to regenerate the lost of periodontal tissues. Loss of the bone support by creating a periodontal pocket is one of the most common cause of tooth extraction. Their treatment can be conservative and surgical. The purpose of this paper is to demonstrate the treatment of infrabony periodontal defects with bone and soft tissue regeneration. On periodontal examination and radiographic evaluation, the female 56-year-old patient presented with an infrabony defect extending up to apical third of the mesial side of the right maxillary second molar with a probing depth of 8 mm. After conservative periodontal treatment, oral surgical intervention was performed including open flap debridement and filling the defect with xenograft and plasma rich fibrin. The application of xenograft and Plasma rich fibrin resulted in bone regeneration of the defect and successful fixed prosthodontic solution. Guided bone and soft tissue regeneration using xenograft and fibrin-rich plasma gives successful radiological and clinical signs of bone augmentation and consolidation of defects caused by loss of tooth attachment. Keywords: periodontal pocket, xenograft, PRF

Care and treatment of patients with ruptured aneurysm in spasm

Bleeding occurred in the subarachnoid space was significantly associated with high mortality and morbidity. About 20-30% die while coming to a medical facility in hospitalized patients mortality is about 40%. According to its origin endokranijalnite aneurysms can be congenital and acquired. Objective: to show the incidence of ruptured intracranial aneurysms in RM Thus the Republic Makedinija there are about 200 new cases of ruptured aneurysms year (Pemova) or about 10 per 100,000 population per year

Polycyclic aromatic hydrocarbons in medicinal herbs: analytical method development

Polycyclic aromatic hydrocarbons (PAHs) are among the most toxic compounds knownto man. Several PAHs are proven to be carcinogenic, mutagenic and teratogenic. Due to their widedistribution in the environment and their toxicity, it is considered important to monitor the levels ofthese compounds in foodstuff. PAHs have been detected in many foods including plant-based suchas vegetable oils, cereal grains, herbs, spices, teas and supplements. As the awareness for thehealthy lifestyle has increased globally, the intake of medicinal herbs as tea and spices has alsogrown immensely. Therefore, even stronger emphasis must be made to monitor the toxic levels ofPAHs in herbs. The legislations of the maximum concentrations of certain contaminants in food ofthe Republic of Serbia included PAHs values in dry herbs only by the end of 2019 (Official GazetteRS, No. 81/2019) in comparison to European Commission Regulation dating from 2011. Therefore,herein we focused on analytical method development for PAHs determination in medicinal herbs

Alkali modification of fly ash for adsorption of selected dyes

Fly ash (FA) is an industrial waste material generated during coal combustion in thermalpower plants. In order to reuse this kind of industrial waste, and at the same time to reduce itsquantity, fly ash was used as a cheap material for the preparation of efficient adsorbents for theremoval of selected dyes from water. For that purpose, different modification methods were used toobtain alkali-activated fly ash samples. The success of the modification process and characterizationof the unmodified and modified materials was monitored by Fourier transform infrared spectroscopy,and scanning electron microscopy/energy dispersive spectroscopy. The adsorption properties ofexamined samples were studied through the adsorption of methylene blue, crystal violet, alizarin red,and methyl orange. All samples showed the highest adsorption efficiency for crystal violet removal,while the sample modified with a combination of NaOH, Na2SiO3, and diatomaceous earth(FA/geopolymer) was the most efficient adsorbent for all selected dyes. Therefore, the influence ofinitial pH value and contact time on adsorption was examined for the adsorption of crystal violetonto FA/geopolymer. It was found that alkaline modification improves the adsorption characteristicsof fly ash making it a promising candidate to solve the problem of colored wastewater

Simulation of toolpaths and program verification of a CNC lathe machine tool

This paper presents the simulation and verification of programs created for the CNC Hitachi Seiki Seicos LIII lathe machine tool. The main purpose of program simulation and verification is to ensure the quality and accuracy of the cutting process, which can significantly improve production efficiency. In addition to defining the toolpath, simulation can perform linear and circular interpolation according to specific programs based on G - codes. Therefore, all the motions of the moving parts of the real lathe machine tool can be clearly visualized. The use of simulation is a good solution not only to precise the toolpath, but also verify the program and detect any possible collision between cutting tools and mobile components, before loading the program into the lathe machine tool and starting cutting processes. Keywords: manufacturing, machining, programming, codes, softwar