U ovom radu istražuju se mogućnosti povećanja brzine oslobađanja lurasidon-hidroklorida, antipsihotika druge generacije, pripravom čvrstih disperzija procesom liofilizacije. FTIR, DSC te XRPD ...ispitivanja provedena su s ciljem detekcije potencijalnih interakcija između lurasidon-hidroklorida i polimernih matrica koje mogu znatno povećati topljivost djelatne tvari i osigurati brže oslobađanje iz dozirnog oblika. Takve čvrste disperzije i pomoćne tvari upotrijebljene su u pripravi tableta čija su vremena raspadanja manja od 3 min. Profili otapanja u laboratorijskom okruženju ukazuju na brže oslobađanje djelatne tvari iz raspadljivih tableta u odnosu na čisti lurasidon-hidroklorid.
This paper investigates the possibilities for release rate enhancement of lurasidone hydrochloride, a second-generation antipsychotic, by preparing solid dispersions via lyophilisation process. FTIR, DSC, and XRPD measurements have been performed in order to detect potential interactions between lurasidone hydrochloride and polymer matrices that might significantly increase drug solubility and provide faster release from the dosage form. Such solid dispersions and excipients have been used in the preparation of tablets that disintegrate in less than 3 min. In vitro dissolution profiles indicate a higher drug release rate from disintegrating tablets in comparison to pure LRS HCl.
Dissolution behaviour of a poorly water-soluble drug, tadalafil, from its solid dispersion systems with poloxamer 407 has been investigated. Solid dispersion systems of tadalafil were prepared with ...poloxamer 407 in 1:0.5, 1:1.5 and 1:2.5 ratios using the melting method. Characterization of binary systems with FTIR and XRPD studies demonstrated the presence of strong hydrogen bonding interactions, a significant decrease in crystallinity and the possibility of existence of amorphous entities of the drug. In the binary systems tested, 1:0.5 proportion of tadalafil/poloxamer 407 showed rapid dissolution of tadalafil (DE30 70.9 ± 3.6 %). In contrast, higher proportions of poloxamer 407 (1:1.5 and 1:2.5) offered no advantage towards dissolution enhancement of the drug, indicating altered rheological characteristics of the polymer at its higher concentration, which might have retarded the release rate of tadalafil.
U radu je ispitivano oslobađanje u vodi teško topljivog lijeka tadalafila iz čvrstih disperzijskih sustava. Ti sustavi pripravljeni su s poloksamerom 407 u omjeru lijeka i polimera 1:0,5, 1:1,5 i 1:2,5, koristeći metodu taljenja. Karakterizacija binarnih sustava s FTIR i rendgenskom difrakcijom praha XRD ukazuje na prisutnost snažnih vodikovih veza, značajno smanjenje kristaliničnosti i moguću prisutnost amorfnog lijeka. Iz binarnog sustava tadalafil/poloksamer 1:0,5 oslobađanje ljekovite tvari je brzo (DE30 70,9 ± 3,6 %). Nasuprot tome, iz pripravaka s višim omjerima lijeka i polimera (1:1,5 i 1:2,5) oslobađanje ljekovite tvari nije povećano. Usporavanje oslobađanja tadalafila moglo bi biti posljedicom promjene reoloških svojstava polimera pri višim koncentracijama.
This article presents a method for assessing the hit probability for stationary shooting targets as a function of the projectile horizontal range (PHR), the target type and the point of aim (POA) ...location. The proposed procedure consists of three blocks. Block I is devoted to the double integral formula taking into account changes in the point of impact (POI) location as a function of the PHR. The characteristics of bullet accuracy and precision versus the PHR are determined in block II. The basis of blocks I and II is the bi-variate uncorrelated Laplace-Gauss probability distribution. The functions of the POI location (ordinate/abscissa) versus the PHR and the functions of the characteristics of the bullet dispersion versus the PHR are represented in the form of polynomials. The description of the target silhouette contour is given in block III. Mathematically, the target contour is a piecewise function which defines the upper and lower edges of the shooting target and it also represents the limit for the double integral formula of block I. The proposed method is built on a modular basis and allows a user to change types of weapons and shooting targets. For demo calculations, the accuracy and precision characteristics of the 5.45×39 Kalashnikov assault rifle model MPi AK-74N were selected. Five types of Swiss military targets imitating an OPFOR combatant's silhouette were used as shooting targets. For illustrating the operability of the proposed method, the hit probabilities for the K, H, G, F, and E shooting targets were evaluated for the PHR from 50 to 400 m. All computations are implemented in the PTC Mathcad v.15. / Оценка вероятности попадания является важной частью процедуры анализа эффективности стрельбы. В статье предложен метод оценки вероятности попадания в статическую стрелковую мишень как функция горизонтальной дальности до мишении (ГДМ), её типа и положения точки прицеливания. Предлагаемая процедура оценки состоит из трех частей. Часть I посвящена двойной интегральной формуле с учётом изменений в местоположении средней точки попадания (СТП) на поверхности мишени в зависимости от ГДМ. Характеристики дисперсии пуль в зависимости от ГДМ определены в части II. Основой части I и части II является двумерное некоррелированное распределение вероятностей Лапласа-Гаусса. Как правило, функции ординат (абсцисс) СТП от аргумента ГДМ и функции ординат (абсцисс) рассеивания пули как функции ГДМ представлены в виде классических полиномов. В части III даётся описание контура мишени. В математическом плане контур цели является кусочной функцией, которая описывает верхний и нижний края стрелковой мишени, а во-вторых, контур цели в формуле двойного интеграла выступает как предел интегральной формулы части I. Все вычисления реализованы в PTC Mathcad. Предлагаемый метод построен на модульной основе и позволяет пользователю изменять типы оружия и виды мишеней. Для демонстрационных расчётов использованы данные характеризующие внешнюю баллистику и характеристики рассеивания 5.45×39 автомата Калашникова. В качестве рассматриваемой модели автомата была выбрана MPi AK-74N. В качестве стрелковых мишеней использовались пять видов швейцарских армейских мишеней, которые имитируют различные части силуэта комбатанта. Для иллюстрации работоспособности предложенного метода оценена вероятность попадания в мишени K, H, G, F, E и для диапазона ГДМ от 50 до 400 м. / U članku je predstavljena metoda za određivanje verovatnoće pogotka stacionarnih meta u zavisnosti od horizontalnog rastojanja do mete (HRM), vrste mete i lokacije tačke cilja. Predloženi postupak sastoji se od tri bloka. Prvi blok se bavi formulom dvostrukog integrala koja uzima u obzir promene u lokaciji tačke pogotka u zavisnosti od HRM. Karakteristike disperzije metka, u zavisnosti od HRM, određuju se u drugom bloku. Bivarijantna nekorelisana Gaus- Laplasova raspodela verovatnoće uzeta je za osnov prva dva bloka. Funkcije lokacije tačke cilja (ordinata/apcisa) u zavisnosti od HRM i funkcije karakteristika disperzije pogodaka u zavisnosti od HRM prikazane su u obliku polinoma. U trećem bloku naveden je opis kontura silueta meta. U matematičkom smislu, kontura mete je hibridna funkcija koja definiše gornje i donje ivice mete i, takođe, predstavlja granicu formule dvostrukog integrala prvog bloka. Svi proračuni su se vršili u PTC Mathcad. Predloženi metod zasnovan je na modularnom principu i omogućava korisniku da menja vrste oružja i meta. Za ilustraciju je izabran prikaz izračunavanja karakteristika disperzije pogotka koji je postignut iz automatske puške 'kalašnjikov', kalibra 5.45×39, model MPi AK-74N. Za mete je izabrano pet tipova švajcarskih vojnih meta koje imitiraju različite delove siluete vojnika. Operabilnost predloženog metoda ilustrovana je određivanjem verovatnoća pogađanja meta K, N, G, F i E na udaljenosti od 50 do 400 m.
Since the beginning of the Varaždin Baroque Evenings in 1971 and untill 2006 the programming of the festival was led by one of its founders Prof. Vladimir Kranjčević, the respected Croatian ...conductor. Prof. Davor Bobić was nominated as the director of the festival in 2006 and so the programming, organization and realisation of the festival became his duties. It should be stressed that the new director dedicated his attention to soloists and ensembles specialized in authentic interpretation which results from the research of the musical practice during the baroque era as well as in the performance practice which means usage of the original instruments of baroque period or their copies. Much has been acheaved concerning this authentic interpretation and performance and the most of the musicians from abroad as well from Croatia belong to this kind of interested performers. Another important achievemnt of Prof. Bobić was his idea of billateral cooperation with different states and the plan to invite one of them each year to be the partner-states of the festival. The idea was very successfull in its realisation and the audience could get to know different national baroque music heritages. The partner-states have been Slovakia, Israel, Czech Republic, Germany, Polen, Austria, Russia, Italy and in 2015 France. So it was really possible to hear the less known music and perfect interpretations of the international musicians. Further programmes have been organized in Varaždin and concerts have been given in many neighbouring states as well as in Croatia spreading the fame of the festival and getting critical reviews in many cities. For this fame the festival awards „Ivan Lukačić“, „Jurica Murai“ and „Kantor“, which was given by the Croatian daily newspaper „Vjesnk“ for several years, were allways very important because they are incorporated into the biographies of the winners and so spread the fame of the festival. It is right to say that Prof. Bobić continued the tradition of the Varaždin Baroque Evenings but he also achieved greater recognition of the festival on the international level which without any doubt will be of great importance for its future. New partner-states, and for 2016 it will be Spain, will certainly be important for the promotion of the baroque town of Varaždin and of Croatia, as culturally interesting city and state.
Irbesartan (IBS) is a hydrophobic drug with poor aqueous solubility and dissolution rate. Solid dispersions (SDs) of IBS were prepared with both small molecules (tartaric acid and mannitol) and ...polymeric additives (polyvinyl-pyrrolidone, PVP, and hydroxypropyl methylcellulose, HPMC). A 9.5 and 7 folds enhancement in solubility over the crystalline form (14.6 μg mL-1) was observed for tartaric acid (138 μg mL-1) and PVP (103 μg mL-1), respectively. Powder X-ray diffraction confirmed that IBS existed in the glassy state in all cases, even with excipients having low glass transition temperature. Thermal methods (differential scanning calorimetry and hot stage microscopy) were used to evaluate the miscibility of the drug and additives. These techniques suggested that tartaric acid led to generation of >amorphous solutions< in contrast to >amorphous suspensions< in other three cases. The in vitro dissolution of IBS depended on the additive load and increased with increasing concentration in the case of tartaric acid, an acidifying excipient. The results indicate the suitability of even small molecules for providing solubility benefits, which can be attributed to the good glass forming ability and reasonable ability of IBS to remain in the glassy state.
Irbesartan (IBS) je hidrofobni lijek teško topljiv u vodi koji se slabo oslobađa iz ljekovitih pripravaka. U radu je opisana priprava čvrstih disperzija (SDs) IBS-a pomoću aditiva male relativne molekulske mase (vinska kiselina i manitol) i polimera (polivinilpirolidona, PVP, i hidroksipropil metilceluloze, HPMC). Koristeći vinsku kiselinu i PVP topljivost je povećana 9,5 puta (138 μg mL-1), odnosno 7 puta (103 μg mL-1) u odnosu na kristaliničnu formu (14,6 μg mL-1). Difrakcijom X-zrakama praškastog uzorka potvrđeno je da je IBS uvijek u staklastom stanju, pa i s pomoćnim tvarima koje pri niskim temperaturama prelaze u staklasto stanje. Termičke metode (diferencijalna pretražna kalorimetrija i mikroskopija s vrućom pločom) korištene su za procjenu sposobnosti miješanja lijeka s aditivima. Rezultati ukazuju da vinska kiselina stvara amorfnu otopinu, a ostale tvari amorfne suspenzije. Oslobađanje IBS-a in vitro ovisi o količini aditiva i raste s povećanjem koncentracije vinske kiseline, (kisele pomoćne tvari). Poboljšanje topljivosti dodatkom malih molekula može se pripisati sposobnosti prelaska IBS-a u staklasto stanje i sposobnosti zadražavanja u tom stanju.
The objective of the present work was to improve the dissolution properties of the poorly water-soluble drug meloxicam by preparing solid dispersions with hydroxyethyl cellulose (HEC), mannitol and ...polyethylene glycol (PEG) 4000 and to develop a dosage form for geriatric population. Differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy and scanning electron microscopy were used to investigate the solid-state physical structure of the prepared solid dispersions. Higher in vitro dissolution of solid dispersions was recorded compared to their corresponding physical mixtures and the pure drug. PEG 4000 in 1: 9 drug to carrier ratio exhibited the highest drug release (100.2%), followed by mannitol (98.2%) and HEC (89.5%) in the same ratio. Meloxicam-PEG 4000 solid dispersion was formulated into suspension and optimization was carried out by 23 factorial design. Formulations containing higher levels of methyl cellulose and higher levels of either sodium citrate or Tween 80 exhibited the highest drug release.
Cilj rada bio je poboljšati topljivost meloksikama u vodi pripravom čvrstih disperzija s hidroksietilcelulozom (HEC), manitolom i polietilen glikolom 4000 (PEG 4000) te razviti dozirani pripravak za gerijatrijsku populaciju. Za ispitivanje fizičke strukture pripravljenih čvrstih disperzija korištene su diferencijalna pretražna kalorimetrija, difraktometrija rentgentskim zrakama, FTIR i pretražna elektronska mikroskopija. Čvrste disperzije su u in vitro uvjetima pokazale bolju topljivost u odnosu na fizičku smjesu i čistu ljekovitu tvar. Najbolje oslobađanje lijeka (100,2%). Postignuto je iz disperzija s PEG 4000 (omjer ljekovite tvari i nosača 1:9). Slijede manitol (98,2%) i HEC (89,5%) (isti omjer meloksikama i polimera). Čvrsta disperzija meloksikama s PEG 4000 prevedena je u suspenziju te optimirana 23 faktorijalnim dizajnom. Najbolje oslobađanje ljekovite tvari postignuto je iz pripravaka koji sadrže veći udio etilceluloze i natrijevog citrata, odnosno Tween 80.
The purpose of this study was to obtain an amorphous system with minimum unit operations that will prevent recrystallization of amorphous drugs since preparation, during processing (compression) and ...further storage. Amorphous celecoxib, solid dispersion (SD) of celecoxib with polyvinyl pyrrollidone (PVP) and co-precipitate with PVP and carrageenan (CAR) in different ratios were prepared by the spray drying technique and compressed into tablets. Saturation solubility and dissolution studies were performed to differentiate performance after processing. Differential scanning calorimetry and X-ray powder difraction revealed the amorphous form of celecoxib, whereas infrared spectroscopy revealed hydrogen bonding between celecoxib and PVP. The dissolution profile of the solid dispersion and co-precipitate improved compared to celecoxib and amorphous celecoxib. Amorphous celecoxib was not stable on storage whereas the solid dispersion and co-precipitate powders were stable for 3 months. Tablets of the solid dispersion of celecoxib with PVP and physical mixture with PVP and carrageenan showed better resistance to recrystallization than amorphous celecoxib during compression but recrystallized on storage. However, tablets of co-precipitate with PVP and carageenan showed no evidence of crystallinity during stability studies with comparable dissolution profiles. This extraordinary stability of spray-dried co-precipitate tablets may be attributed to the cushioning action provided by the viscoelastic polymer CAR and hydrogen bonding interaction between celecoxib and PVP. The present study demonstrates the synergistic effect of combining two types of stabilizers, PVP and CAR, on the stability of amorphous drug during compression and storage as compared to their effect when used alone.
Cilj rada bio je pripraviti u što manje proizvodnih stupnjeva amorfni sustav iz kojeg ljekovita tvar neće kristalizirati za vrijeme proizvodnje i skladištenja. Metodom sprej-sušenja pripravljeni su amorfni celekoksib, čvrsta disperzija celekoksiba s polivinil pirolidonom (PVP) i koprecipitat s PVP i karagenanom (CAR) u različitim omjerima. Dobiveni pripravci su zatim komprimirani u tablete iz kojih je praćeno oslobađanje ljekovite tvari. DSC i XRPD analize ukazuju na amorfnu formu celekoksiba, a IR spektroskopija na vodikove veze između celekoksiba i PVP. Oslobađanje celekoksiba iz čvrstih disperzija i koprecipitata bilo je poboljšano u odnosu na celekoksib i amorfni celekoksib. Amorfni celekoksib nije bio stabilan tijekom skladištenja dok su čvrste disperzije i koprecipitati bili stabilni tijekom tri mjeseca. Tablete čvrstih disperzija celekoksiba s PVP i fizičke smjese s PVP i karagenanom bile su otpornije na kristalizaciju nego amorfni celekoksib za vrijeme kompresije, ali ne i tijekom skladištenja. Tablete s koprecipitatom s PVP i karagenanom imale su sličan profil oslobađanja, a u njima se za vrijeme skladištenja nije kristalizirala ljekovita tvar. Ova iznimna stabilnost može se objasniti viskoelastičnošću polimera CAR i vodikovim vezama između celekoksiba i PVP. Kombinacijom dvaju stabilizatora postignut je sinergistički učinak.
The paper discusses the breeding and non-breeding distribution and population density of the Kestrel Falco tinnunculus in Slovenia, its movements, breeding biology, hunting behaviour, diet and ...interactions with other species. The data were collected from published works and directly from observers. The species’ breeding distribution is shown as a comparison of both national breeding bird atlases, which indicated no convincing changes in its distribution. The non-breeding season population estimate (1,000-2,000 ind.) is lower than the breeding population estimate (1,500-2,000 pairs). The Kestrel breeds at altitudes from 0 to 2,050 m a.s.l.; outside the breeding season, it has been observed at altitudes of up to 1,700 m a.s.l. At least part of the breeding population migrates, apparently more or less towards SSW. The breeding season lasts from February to July. It nests in trees, buildings, cliffs, nestboxes and on electricity pylons. In trees it uses abandoned nests of corvids. On buildings it nests mainly on ledges and in various openings. It often nests on industrial and residential buildings. On cliffs it nests in natural openings and in abandoned nests of other species. It lays 3-9 eggs, usually five. It hunts over open terrain by windhovering, active aerial pursuit and stooping onto the ground from perches. It feeds mainly on small mammals and, to a lesser extent, on passerines, reptiles and invertebrates. It interacts with other species during hunting, nest-site selection and breeding itself. Platyhelminthic, nematode, ixodid and insect parasites have all been recorded on the Kestrel
The within-patch microdistribution and movements of adults of the critically endangered butterfly, Coenonympha oedippus, were studied using mark-recapture data from an isolated patch network, which ...consisted of 8 patches in central Slovenia. The impact of patch characteristics on both parameters was analyzed. Males fly longer distances and spend more time flying than females. The distances and seasonal pattern of male movements were dependent on the patch size, and on the microdistribution and density of freshly emerged (receptive) females. The spatial and temporal pattern of female microdistribution was influenced by vegetation height, the homogeneity of host plant stands and the shading of the ground and/or the lowest parts of herb layer. In the case of near continuous distribution of host plants within a patch, the structure of herb vegetation appears to be the major determinant of adult microdistribution. It affects the dynamics of butterfly emergence and the selection of oviposition sites. The per cent cover of the nectar plant, Potentilla erecta, does not play an important role in butterfly microdistribution.
V izoliranem omrežju osmih habitatnih krp v osrednji Sloveniji smo z metodo markiranja, izpusta in ponovnega ulova raziskovali prostorsko razporeditev in gibanja imagov kritično ogrožene vrste Coenonympha oedippus v habitatni krpi in vpliv značilnosti krpe na oba proučevana parametra. Samci preletavajo daljše razdalje in v dnevni aktivnosti več časa porabijo za let kot samice. Preletne razdalje in vzorci preletavanja samcev v sezoni so odvisni od velikosti krpe ter prostorske razporeditve in populacijske gostote sveže izleglih (receptivnih) samic. Na prostorske in časovne vzorce disperzije samic vplivajo višina vegetacije, homogenost sestoja hranilnih rastlin gosenic in osončenost spodnje plasti zeliščne vegetacije. Če je razporeditev larvalnih hranilnih rastlin v krpi enakomerna in kontinuirana, je struktura zeliščne vegetacije najpomembnejši dejavnik, ki določa disperzijo imagov, saj vpliva na dinamiko izleganja iz bub in izbiro mest za ovipozicijo. Pokrovnost vrste Potentilla erecta, ki je hranilna rastlina odraslih osebkov, ne vpliva na razporeditev odraslih osebkov v krpi.
Ovo istraživanje doprinos je izračunima doze zračenja hipotetske nesreće istraživačkog reaktora Triga Mark II od 1 MW primjenom HotSpot koda. Razmatrano je slučajno oslobađanje plemenitih plinova i ...halogena. Određena je vrijednost ukupne učinkovite doze nakon 1 dana i nakon 50 godina. Razmatrano je ukupno oštećenje obloge dijela s maksimalnom radioaktivnošću. Dobiveni rezultati pokazuju minimalne vrijednosti ukupne učinkovite doze na početku ispuštanja i na manjoj udaljenosti od izvora. Maksimalni rezultati izračuna su prihvatljivi i ispod preporučenog doznog ograničenja.
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