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

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

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

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..

Правна Регулатива и законодавство у Републици Македонији

Са циљем да се помогне људима које траже природан начин лечења да би продужили и побољшају квалитет свог живота и у истом моменту да превенирамо злоупотребу, наметнула се потреба за легализацију производа на бази канабиса. Измјеном и допуном Закона о контроли опојних дрога и психотропних супстанци у Републици Македонији, омогућено је коришћење ових производа са строго контролисаним саставом и квалитетом искључиво само у медицинске сврхе као адјувантна терапија, али никако као замјена конвенционалне медицинске терапије. На овај начин Република Македонија прати развојни тренд у Европској унији, где је закључно до октобра 2015 године укупно 13 земаља омогућило коришћење производа канабиса за медицинске сврхе и то (редоследно): Чешка, Финска, Румунија, Италија, Шпанија, Холандија, Француска, Аустрија, Португал, Њемачка, Енглеска, Словенија и посљедња Хрватска. Свака од наведених земаља је потписница Јединствене конвенције Уједињених нација о опојним дрогама из 1961 године, Конвенција уједињених нација о психотропним сусптанцијама из 1971 године, Конвенција уједињених нација против недозвољеног промета дрога и психотропних супстанци из 1988 године, као и Република Македонија. Измена и допуна Закона о контроли опојних дрога и психотропних супстанци у циљу легализације канабиса је ишла у два корака: 1) измене и допуне Закона са циљем да се регулира одгајање, прерада и промет препарата на бази канабиса на идентичан начин као што је регулисана употреба опијумског мака у медицинске сврхе и 2) померање канабиса из групе I контролисаних супстанци за које важи правило „коришћење дрога у веома ограничене медицинске сврхе“ у групи II контролисаних супстанци како би ови производи могли да се издају или продају појединцима само уз лекарски рецепт. Од август 2016 године, пацијенти Републике Македоније имају приступ овим производима са строго контролисаним саставом и квалитетом, умјесто да их купују "на црном" и да се суочавају са правним посљедицама

Legal regulation and positioning of cannabis based products

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

Клиничка фармација и фармакотерапија - скрипта

Скриптата ,,Клиничка фармација и фармакотерапија” е наменета првенствено на студентите на студиската програма - магистер по фармација, кои го слушаат предметот Клиничка фармација и фармакотерапија на Факултетот за медицински науки, на Универзитетот ,,Гоце Делчев” во Штип. Текстот е претставен во согласност со наставниот план и програма по клиничка фармација и фармакотерапија, а подготвен со цел да им помогне на студентите во совладување на предвидениот материјал и да им го направи учењето полесно и поинтересно. Со помош на овој текст студентите ќе се запознаат со поимот и дефиницијата за клиничка фармација, главната цел и нивоата на дејствување на клиничките фармацевти, нивната улога и задачи во современиот интегриран здравствен систем. Оваа скрипта ќе им овозможи на студентите да ги прошират своите знаења за интеракциите на лекови и механизмите на нивно настанување, да ги препознаваат лековите со висок потенцијал за појава на интеракции, како и групите пациенти со зголемен ризик за интеракции на лекови. Посебно внимание е посветено на несаканите реакции на лекови, нивната класификација на тип А и тип Б, најважните фактори на предиспозиција, механизмите за нивно настанување, утврдување и следење, како и со системот за известување за несакани реакции на лековите. Во текстот се повторуваат и утврдуваат и најважните поими од областа на клиничката фармакологија, а се воведува и поимот за клиничка фармакокинетика како примена на фармакокинетиката во широк опсег на клинички случаи. Студентите се запознаваат и со основните принципи на фармакоекономијата и управувањето со лекови. Целта на фармакоекономијата е да се постигне оптимален однос помеѓу цената и ефектите на фармацевтските продукти, притоа земајќи ги предвид етичките вредности на фармацијата кои го ставаат „здравјето на пациентот пред економскиот бенефит“. Фармакоекономските методи се користат да им помогнат на пациентите, болниците, осигурителните компании и на здравствените работници во донесувањето на правилна одлука за тоа кои лекови да бидат избрани за терапија. Посебно поглавје во ова учебно помагало е посветено на интерпретација на лабораториските резултати, неопходно за успешно функционирање на клиничките фармацевти. Исто така, во текстот се претставени и препораки за примена на лекови во специфични популациони групи (деца, стари, новороденчиња...), како и примена на лекови кај болни со пореметена функција на работа на бубрег/црн дроб

Approved indications for Cannabinoids

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

Development and validation of reverse phase high performance liquid chromatographic method for determination of Tirofiban in serum

А specific, sensitive and rapid RP-HPLC method has been developed for the determination of Tirofiban in serum. The chromatographic separation was realized using reverse phase LiChrospher® 100 RP-18 column (4.0 mm × 250 mm, 5 μm) and mobile phase consisting the mixture of 0.1 M KH2PO4 (pH 5.2, adjusted with 1.0 N sodium hydroxide solution) and acetonitrile, with the ratio of 70:30% (v/v) and flow rate of 1.0 ml/min. The detection was carried out at 274 nm. The response was linear over the range of 0.03 – 0.18 mgmL-1 in mobile phase and serum samples. The limit of detection (LOD) for Tirofiban was 1.84, 13.8 and 14.6 μg mL-1 in methanol, spiked rat serum and spiked human serum, respectively. The described method can be quickly and routinely applied, without any interference from endogenous substances, for therapeutic monitoring of levels of Tirofiban in the serum samples

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

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

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

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