83 research outputs found

    Step forward of Macedonian Agency for medicines and medical devices Establishment and strategic plan for development

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    Abstract Macedonian Agency for Medicines and Medical Devices (hereinafter: the Agency) on September 16 2014 has been established as an independent regulatory authority. Founder of the Agency is the Government of the Republic of Macedonia. Institutional building of the Agency is an important part of implementation of national medicines and medical devices policy aimed at ensuring access to medicines meeting recognized EU standards of quality, safety and efficacy as well as access to medical devices, meeting essential requirements set in EU legislation. It can be ensured by setting up efficient regulatory system, so the Agency should quickly develop its capacity in order to be able to ensure unimpeded transition from the Drug Bureau, to ensure its proper development and to play a key role in implementing the said aims. First strategic plan for the development of Macedonian Agency is for the period 2015-2017. This is a key period of action of this institution because it sets the groundwork for future work of the new competent authority for medicines and medical devices, which is built on the foundations of the Bureau of medicines. Agency Strategic Plan reflects not only the present moment, but also our duty to make the best possible way we fulfill our mission and develop the Agency in accordance with our vision. The new legal organizational structure allows us professional independence and the necessary flexibility. The strategic plan of the Agency allows to be based on an analysis of the current situation and the vision of who we want to become at the end of a given period

    Legal regulation and positioning of cannabis based products

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    The use of cannabis-based preparations in traditional medicine has existed for more than a thousand years and has been documented in many countries around the world for the treatment of muscle spasticity, convulsions, pain, nausea and vomiting, as well as appetite stimulation. However, the clinical use of cannabinoid substances is limited due to legal and ethical reasons, as well as limited evidence of the benefits of their use. In the European Union, a total of 14 countries have allowed the use of cannabis-based products for medical purposes, namely (in order): the Czech Republic, Finland, Romania, Italy, Spain, the Netherlands, France, Austria, Portugal, Germany, England, Slovenia, Croatia and the last Greece. Each of the mentioned countries is a signatory to the United Nations Convention on Narcotic Drugs from 1961, the United Nations Convention on Psychotropic Substances from 1971, and the United Nations Convention against Traffic in Drugs and Psychotropic Substances from 1988. The regulation covering this area is different in all countries, but the same for all states is the status of these preparations based on the concentration of tetrahydrocannabinol (THC) in the final product. Thus, preparations can be classified as borderline products (according to the new EU regulation Novel food) or medicines, depending on whether the concentration of tetrahydrocannabinol (THC) in the final product is below or above 0.2%. Since August 2016, patients of the Republic of North Macedonia have had access to these products with strictly controlled composition and quality. What is the therapeutic effect of cannabinoids? Is there sufficient evidence based on evidence-based medicine for the positive effects of cannabinoids? For which indications do we have enough positive experiences based on medical evidence? It is certain that the area is intensively researched. So far, there is enough evidence and positive experience about the effectiveness of cannabinoids for pain relief in patients with malignant diseases, for the relief of nausea and vomiting induced by chemotherapy, for the treatment of multiple sclerosis and for the treatment of anorexia associated with extreme weight loss in HIV-positive patients. The European Medicines Agency (EMA) has approved cannabidiol (CBD) for 13 indications under the status of Orphan designation. Also, under the same conditions, the EMA approved the combination of THC and CBD from Cannabis sativa extract for the treatment of glioma. The good side of cannabinoids is the possibility to combine them as an add-on therapy with existing conventional therapy

    Tirofiban as potential radiopharmaceutic for detection of thromboembolic disoreders: animal model

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    Vaskularna oboljenja spadaju među vodeće uzročnike povećanog morbiditeta i mortaliteta kod ljudi koji žive u razvijenim zemljama. Duboka venska tromboza (DVT) i plućna embolija su ozbiljne komplikacije, pa je zato detekcija akutne i rane DVT-e veoma bitna, pre svega, zbog posledica koje one nosi sa sobom (rizik od plućne embolije, hronična venska insuficijencija). Kod ovih patoloških stanja uloga trombocita je suštinska, zbog njihove sposobnosti da formiraju agregate, koji nastaju kao posledica oštećenja krvnog suda. Trobocitni glikoproteinski IIb/IIIa (GPIIb/IIIa) receptor je ključna komponenta u procesu trombocitne agregacije, a samim tim i ciljno mesto za terapijsku intervenciju. Tirofiban (N-(butilsulfonil)-4-O-(4-(4-piperidil)-L-tirozin) je nepeptidni tirozinski derivat, visoko selektivni, kratkodelujući inhibitor fibrinogenskog vezivanja za trombocitni glikoproteinski receptor IIb/IIIa. Kao molekul sa malom molarnom masom tirofiban ima veliku prednost, kako u postupku za njegovo obeležavanje radioaktivnim izotopima, tako i pri njegovoj aplikaciji u organizam, bez opasnosti od pojave imunoloških reakcija nakon primene. Takođe, bitan parametar je i njegova brza eliminacija iz organizma. Tirofiban se vezuje za GPIIb/IIIa receptore na isti način kao što se vezuje i fibrinogen, a može se naći samo u aktivnom ugrušku. Ovaj fenomen pokazuje razliku između akutnog i hroničnog ugruška, pri upotrebi radiofarmaceutika. Obeležavanjem tirofibana radioaktivnim izotopom tehnecijuma (99mTc), kao optimalnim gama emiterom podobnim za dijagnostičku upotrebu, pokazali smo da možemo detektovati patološke promene krvnih sudova, identifikovati lokalizaciju tromba i odrediti morfološke karakteristike tromba. Vizuelizacione studije, rađene na eksperimentalnom animalnom modelu duboke venske tromboze, jasno su nam pokazale akumulaciju tirofibana u femoralnoj veni testiranih životinja. Praćenjem koncentracija neradioaktivnog i radioaktivno obeleženog tirofibana u plazmi, 5, 15, 30, 45 i 60 min. nakon i.v. bolus injekcije, utvrdili smo da 99mTc-tirofiban-a ima identično ponašanje kao i neradioaktivni tirofiban. Uvođenjem tehnecijuma i promenom strukture molekula ne menja se, već poznati, farmakokinetički profil leka...Vascular diseases are one of the leading reasons for increased morbidity and mortality in people living in high-income countries. Deep venous thrombosis (DVT) and pulmonary embolism (PE) are very serious complications and initial detection of them is always very important. In these pathological conditions the role of platelets is very important, their ability to generate aggregates, which occur as a result of damaged blood vessels. The platelet glycoprotein IIb/IIIa (GP IIb / IIIa) receptor is a key component in the process of platelet aggregation, and thus the target site for therapeutic action. Tirofiban (N-(methylsulfonyl)-4-O-(4-(4-piperidinyl)-L-tyrosine) is a non-peptide, derivative of tyrosine, highly selective, short-acting inhibitor of fibrinogen binding to the platelet glycoprotein IIb/IIIa receptor. As a molecule with a small molecular weight and simple chemical structure, tirofiban provide possibility to be used as radiolabeled potential radiopharmaceutical, to inject in the patient without the risk of the occurrence of immune reactions after administration. The size and structure also is an important parameter for its fast elimination from the body. Tirofiban binds GPIIb/IIIa receptors in the same way as fibrinogen, and can be seen only in the active clot. This phenomenon indicates the difference between acute and chronic blood clot, and can be used as advantage for vizualization. The idea to formulate radioactive Tirofiban using Technetium-99m as a radioisotope for labeling and use for diagnostic purpose, was following the demand to detect primary pathological deviations in the blood vessels, to identify the localization of the new fresh thromb and to define its morphological characteristics. Imaging studies performed using experimental animal model of deep vein thrombosis, clearly showed the pathological accumulation of tirofiban in the femoral vein of the animal. The concentration of non-radioactive and radiolabelled tirofiban in plasma 5, 15, 30, 45 and 60 min. observed after i.v. bolus injection, confirmed that 99mTc-Tirofiban has identical behavior as non-radioactive. The introduction of Technetium-99m iside of the structure of molecule of Tirofiban, does not change the regular pharmacokinetic profile of the drug..

    Approved indications for Cannabinoids

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    Review of all FDA and EMA approved indications of cannabinoids for medicinal purpose

    Reduced stability study design for herbal product „dry cannabis floss“

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    Stability of the final product, independently whether it is an active substance or a drug of herbal, mineral or other origin, according to the guide of the International Conference for Harmonization (ICH): "Stability testing of new drug substances and products Q1A(R2)" is defined as the ability of the final product to keep the quality (physical-chemical and microbiological) prescribed in the specification for quality within the expiry date if it is stored in the proposed packaging. Stability testing enables the establishment of recommended storage conditions, retesting period, or expiry date for the product. When it comes to determining the stability of a herbal product, the procedure is more complex, taking into account the inhomogeneity of herbal preparations, which depends on many factors. This is also the case with cannabis-based preparations, especially dried cannabis flowers, which can be very heterogeneous depending on the variety. Therefore, it is necessary to test the stability of such products with a precisely defined protocol, a properly selected series of flowers, properly selected parameters to be monitored and the justification of the choice of parameters. In such cases, the guide provides accurate guidance for developing a stability protocol using a reduced design that simultaneously provides more information about the quality of the product packaged in several different packages, while significantly reducing the number of analyzes performed. In this way, the manufacturer using this design has an advantage in terms of reduced financial burden, reduced time constraints for obtaining data and rapid scientific expertise for decision making. In this direction, the aim of our research was to develop a protocol for monitoring the stability of dried cannabis flowers in different sizes from the same package using a reduced design, according to the guidelines of the International Council for Harmonization for the preparation of this type of stability study. During creating the protocol, the following topics were taken into account: specifications and certificates on the quality of the materials used for the final packaging of the herbal product, technological files for each produced batch of flowers that are tested for stability, as well as procedures and instructions for the process of growing and processing the flower . The stability study included batches of the final plant product - dried cannabis flower, with the same potency, or uniform content of the active component with proven therapeutic activity (tetrahydrocannabinol), so that the results would be comparable. The final product, dried cannabis flower, was packaged in multi-layer aluminum packaging in three different sizes. A stability protocol was developed in a way to includ different sampling frequencies from different packaging size, using bracketing and matrix principles. When carrying out the reduced design of the stability study, it was considered that the deviation of any parameter at any point of the test would mean a further extension of the test to obtain more relevant data to support the proposed packaging in the appropriate shelf lif

    Comparative examination of the speed of release of Pyridoxin HCL of vitamin B6 tablets á 20 mg

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    Of commercial reasons, Vitamin B6 20 mg tablets which are produced in Radovis were needed to be produced in Skopje. In order to get licenses for the production of the new location was necessary to carry out a confirmation of the existing by technology. To this end was made comparison to the more parameters (appearance, weight, strength, dimensions, fragility, disintegration, contents, uniformity of content and solubility) of tablets produced in both locations. In order to confirm the technology was needed to compare the solubility of the two products in three different media (0.1 M HCl with pH=1.2, acetate buffer with pH=4.5 and phosphate buffer with pH=6.8). Liberation of HCl was monitored pyridoxine in 12 tablets of the old site and 12 tablets of the new location, in three intervals of Solubility of tablets in all three media. It is made statistical processing of the received data confirming the transfer of technology

    Forced degradation of timolol maleate on high temperature for verification of HPLC method for related substances in Timolol eye drop 0.5%

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    Timolol is a potent β-adrenergic blocker, useful in treatment of ocular hypertension or open-angle glaucoma. Many chromatographic analysis methods have been applied for the determination of pharmaceutical compounds containing heterocyclic rings (as timolol maleate), but the most commonly applied chromatographic technique is HPLC. Understanding the stability characteristics for both the active pharmaceutical ingredient (API) and for the drug product (DP) is crucial for the development of a safe and effective pharmaceutical agent. For this purpose, samples from API and DP during product development are disposed under strictly controlled storage conditions to assess stability testing. Forced degradation studies are being conducted to identify the degradation products that are likely to occur during long term storage as the worst- case scenario

    Forced degradation of timolol maleate on high temperature for verification of HPLC method for related substances in Timolol eye drop 0.5%

    Get PDF
    Timolol is a potent β-adrenergic blocker, useful in treatment of ocular hypertension or open-angle glaucoma. Many chromatographic analysis methods have been applied for the determination of pharmaceutical compounds containing heterocyclic rings (as timolol maleate), but the most commonly applied chromatographic technique is HPLC. Understanding the stability characteristics for both the active pharmaceutical ingredient (API) and for the drug product (DP) is crucial for the development of a safe and effective pharmaceutical agent. For this purpose, samples from API and DP during product development are disposed under strictly controlled storage conditions to assess stability testing. Forced degradation studies are being conducted to identify the degradation products that are likely to occur during long term storage as the worst- case scenario

    Development and validation of LC/MS/MS method for determination of mycotoxins

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    Mycotoxins (aflatoxins and ochratoxin A) are secondary toxic metabolites, that contaminate raw materials that are usually used in the preparation of products for human use. Presence of these contaminants in herbal drugs, used in the preparation of products for human use, can causes various acute and chronic impacts on human health. A novel LC/MS/MS method was developed and validated for determination of aflatoxins and ochratoxin A in cannabis flowers and extracts

    Pharmacoepidemiology and antimicrobial resistance data for bacterial infections in hospitalized children

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    Antimicrobial resistance is a global problem that needs an urgent action. The irrational use of antibiotics is widespread and leads to potential usefulness of medicines and negative therapeutic outcome.In April 2016, WHO stated that the problem of antibiotic resistance is a major clinical problem resulting in treatment failures even in a case ofeasy to treat diseases. Resistance to first line medicines results in huge spending on new generation of antibiotics. In some instances resistance to second- and third-line agents is seriously compromising treatment outcome.Seriousness of the situation requires extensive research and constantly monitoring of the spread of bacteria resistance.Another problem regarding bacteria resistance is the lack of new antibiotics reported by the US Center for Control and Prevention of Disease.A systematic literature search of databasesgave us enough information about the use of antibiotics, most often isolated bacteria and resistance to different classes of antibiotics. According to the official data, bacterial resistance is lowest in the countries where guidelines for prescribing and use of antibiotics are consistently implemented, such as Scandinavian countries, The Netherlands, Germany and Great Britain. It is necessary to create a complete database of bacterial resistance and information on whether patients receive medicines appropriate to their clinical condition in our country
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