Exergy Analysis of an Air Conditioning Process

The exergy analysis of an air conditioning process in wintertime is presented in this paper. This process consists of mixing outdoor air with conditioned air, heating, humidifying, and reheating the air mixture. The air is heated in the heat exchangers by warm water at a temperature of 80/60 °C and humidified by spraying water at a temperature of 12 °C. The ratio of the mass flow rates of outdoor and conditioned air is varied, and it is upon this variable that the exergy analysis is performed. The five cases are analyzed with different outdoor air temperature values. It is shown that the heat transfer rate in the heat exchangers is the smallest at the ratio of mass flow rates of outdoor and conditioned air g1 = 0.45. The greatest exergy destruction is apparent in the heat exchangers, and the maximum exergy efficiency of the whole process ɛex = 0.71 is achieved at the ratio g1 = 0.45. According to the exergy criterion, this air conditioning is a relatively efficient process

Smjernice za farmakološko liječenje epilepsije

SAŽETAK Međunarodne smjernice za farmakološko liječenje epilepsija općenite su, sveobuhvatne i ne prepoznaju lokalne specifičnosti poput ekonomskih i tehničkih mogućnosti u pojedinim državama, dostupnosti pojedinih antiepileptika ili drugih metoda liječenja i slično. Stoga se nameće potreba izrade nacionalnih smjernica, čiji su zapravo temelj međunarodne smjernice Internacionalne lige protiv epilepsije. Hrvatske smjernice za farmakološko liječenje epilepsija plod su suradnje svih relevantnih stručnih društava i referentnih centara u RH, na čelu s Hrvatskom ligom protiv epilepsije te Hrvatskim neurološkim društvom i Hrvatskim društvom za dječju neurologiju Hrvatskoga liječničkog zbora, a odražavaju aktualne socioekonomske i regulatorne specifičnosti u našoj zemlji, najnovije spoznaje farmakoloških profila i učinkovitosti pojedinih antiepileptika kao i ekspertna mišljenja. Antiepileptička terapija se uvodi nakon postavljanja dijagnoze epilepsije, stoga profilaktička primjena nije opravdana. Nakon postavljanja dijagnoze potrebno je bolesnika informirati o prognozi bolesti, mogućnostima liječenja i samopomoći, životnim ograničenjima te mogućim neželjenim događajima. Ciljevi farmakoterapije epilepsija su potpuna kontrola napada uz izbjegavanje nuspojava te održavanje ili poboljšanje kvalitete života. Zlatni standard liječenja je monoterapija odnosno primjena adekvatnog antiepileptika u adekvatnoj dozi. Izbor i titracija lijeka su individualni, a temelje se na smjernicama za liječenje pojedinih vrsta napada, karakteristikama bolesnika i regulatorno specifičnim čimbenicima. Nakon neuspjeha inicijalne monoterapije, potrebna je reevalucija anamnestičkih i dijagnostičkih podataka te potom postupna i spora zamjena antiepileptika. Racionalna politerapija podrazumijeva kombinaciju dvaju antiepileptika različitih mehanizama djelovanja, prvog ili eventualno drugog izbora za postavljenju dijagnozu, niskoga interakcijskog potencijala, različitog profila nuspojava i sinergističkog ili aditivnog djelovanja. Zamjena generičkih ili originalnog i generičkog oblika lijeka nije preporučljiva, a poglavito nakon postizanja remisije ili prilikom uzimanja visokih doza lijeka. Ukidanje antiepileptičke terapije treba biti postupno i sporo, u slučaju politerapije jedan po jedan lijek, a u donošenju odluke o ukidanju, kao i o uvođenju antiepileptika, mora biti uključen bolesnik i njegova obitelj

Development of formulations and 3D printing process of tablets with targeted release of paracetamol made by fused deposition modelling technique

Trodimenzionalna (3D) štampa je revolucionarna tehnika proizvodnje u farmaceutskoj industriji kojom se može skratiti vreme proizvodnje farmaceutskih preparata, smanjiti troškovi i omogućiti personalizovana terapija. Kao nova tehnika, 3D štampa je u svetu farmacije još uvek nedovoljno poznata, te je ovakav način razvoja i proizvodnje lekova jedan od najistraživanijih oblasti današnjice. Jedna od najpoznatijih tehnika 3D štampe jeste tehnika deponovanja istopljenog filamenta (engl. Fused deposition modelling, FDM). Cilj istraživanja u okviru ove disertacije bio je razvoj i optimizacija formulacija i procesa štampe FDM 3D tableta paracetamola. Eksperimentalni rad je podeljen u 3 faze. U prvoj fazi eksperimentalnog rada ispitivanje uticaja formulacionih i procesnih parametara na mogućnost ekstruzije/štampanja i karakteristike dobijenih filamenata/tableta sprovedeno je primenom tri različite vrste osnovnog polimera (kompolimera metakrilne kiseline (Eudragit®), polikaprolaktona (PCL) i polietilenoksida (PEO)). Prvi tip formulacija činile su formulacije sa smešom osnovnih polimera (Eudragit® i PEO), gde je pokazano da ovakva kombinacija osnovnih polimera nije pogodna za dobijanje filamenata i 3D štampanje tableta paracetamola. Drugu grupu činile su formulacije na bazi PCL gde je pokazana laka ekstruzija filamenata ujednačenog izgleda i jednostavna štampa FDM 3D tableta. Međutim, u ovim filamentima uočen je najveći gubitak sadržaja u odnosu na ostale formulacije, zbog neujednačenog prolaska smeše kroz hranilicu ekstrudera usled razlika u veličini čestica. FDM 3D tablete na bazi PCL su pokazale izrazito sporo oslobađanje lekovite supstance, gde se nakon 8 sati ispitivanja oslobodilo između 36,83% i 42,79% paracetamola. Treći tip formulacija činile su formulacije sa PEO (PEO molekulske mase 200000 g/mol (PEO 200 K) i PEO molekulske mase 100000 g/mol (PEO 100 K)), pri čemu nije uočen uticaj molekulske mase osnovnog polimera na mogućnost ekstruzije i printabilnost filamenata. Ovi filamenti su bili manje prikladni za dalju štampu, koja je bila praćena čestim zapušavanjem mlaznice štampača. Tablete na bazi PEO su pokazale znatno brže oslobađanje paracetamola (potpuno oslobađanje paracetamola nakon 4 sata ispitivanja) u odnosu na tablete na bazi PCL. U prvoj fazi istraživanja je primećeno da je sa porastom koncetracije paracetamola u formulaciji bila potrebna i viša temperatura za ekstruziju, a da je štampanje filamentima bilo moguće kada je procenat paracetamola u formulacijama bio do 60%. U drugoj fazi eksperimentalnog rada ispitane su mogućnosti ubrzanja oslobađanja paracetamola iz FDM 3D odštampanih tableta i mogućnosti dobijanja tableta kod kojih brzina oslobađanja i predviđeni obim apsorpcije lekovite supstance odgovaraju tabletama sa trenutnim oslobađanjem. Ispitivane su FDM 3D tablete odštampane od istog osnovnog polimera, polivinilalkohola (PVA), u kombinaciji sa plastifikatorom Affinisol™ HPMC HME 4M HYPROMELLOSE®, na kojima su primenjene četiri strategije za ubrzanje oslobađanja lekovite supstance. Ekstruzija filamenata sa PVA je bila jednostavna, a naknadno dodavanje različitih pomoćnih supstanci u cilju ubrzanja oslobađanja paracetamola iz tableta nije uticalo na mogućnost ekstruzije i printabilnost filamenata, ukoliko je udeo osnovnog polimera bio iznad 45%. Rezultati in vitro ispitivanja brzine oslobađanja paracetamola iz formulacije sa PVA i Affinisol™ HPMC HME 4M HYPROMELLOSE® su pokazali da se za 5 sati ispitivanja oslobodilo 58% paracetamola...Three-dimensional (3D) printing is a revolutionary technique in pharmaceutical industry that can shorten drug products production time, reduce costs and enable personalized therapy. As a new and still not fully explored technique, 3D printing in pharmacy has been intensively researched in recent years. One of the best known 3D printing techniques is fused deposition modelling (FDM). The aim of this dissertation was to develop and optimize formulation and 3D printing process of paracetamol-loaded tablets via FDM 3D printing technique. The research was divided into 3 phases. The first phase of the research focused on providing basic information about the experimental conditions of FDM 3D printing of paracetamol-loaded tablets. Evaluation of the influence of formulation and process parameters on the extrudion/printing potential and characteristics of the obtained filaments/tablets was carried out using three different types of the main polymer (methacrylic acid copolymers (Eudragit®), polycaprolactone (PCL) and polyethylene oxyde (PEO)). The first type of formulations consisted of a combination of the main polymers (Eudragit® and PEO) and the results showed that this combination is not suitable for obtaining filaments by melt extrusion process and for 3D printing of paracetamol-loaded tablets. The second group were formulations with PCL as the main polymer, where facile extrusion of uniformed filaments and effortless FDM 3D tablets printing were demonstrated. However, these filaments exhibited the greatest loss of content in comparison to the other formulations, due to the uneven feeding of the mixture through the extruder caused by differences in particle size. PCL-based FDM 3D tablets showed rather slow drug release, with 36.83-42.79% paracetamol released after 8 hours of testing. The third type of formulations were formulations with PEO (PEO with molecular weight of 200000 g/mol (PEO 200 K) and PEO with molecular weight of 100000 g/mol (PEO 100 K)), and in this case there was no observable effect of the polymer molecular weight on extrudability and printability of the filaments. These filaments were less suitable for consequent 3D printing process, which was demonstrated by frequent clogging of the printer nozzle. However, PEO-based 3D printed tablets showed notably faster drug release rate (complete paracetamol release after 4 hours of testing) compared to PCLbased tablets. In this research phase, it was noticed that increase in paracetamol concentration in the formulation required a higher extrusion temperature. Also, printing with filaments was possible only when the percentage of paracetamol in the formulations was up to 60%. The second phase of the research aimed to investigate possibilities of increasing the drug release rate from FDM 3D printed tablets to comply with drug release and consequent absorption rate that correspond to immediate release tablets. FDM 3D printed tablets containing the same main polymer, polyvinyl alcohol (PVA), in combination with a plasticizer Affinisol™ HPMC HME 4M HYPROMELLOSE® were tested, and four different strategies were applied to increase the drug release. The extrusion of filaments with PVA as the main polymer was simple. Subsequent addition of various excipients, in order to increase the drug release from tablets, did not affect extrudability and printability of the filaments when the percentage of the main polymer in formulations was above 45%. In vitro dissolution test results revealed that the formulation containing PVA and Affinisol™ HPMC HME 4M HYPROMELLOSE® released 58% of paracetamol within 5 hours of testing..

Development of formulations and 3D printing process of tablets with targeted release of paracetamol made by fused deposition modelling technique

Trodimenzionalna (3D) štampa je revolucionarna tehnika proizvodnje u farmaceutskojindustriji kojom se može skratiti vreme proizvodnje farmaceutskih preparata, smanjiti troškovii omogućiti personalizovana terapija. Kao nova tehnika, 3D štampa je u svetu farmacije jošuvek nedovoljno poznata, te je ovakav način razvoja i proizvodnje lekova jedan odnajistraživanijih oblasti današnjice. Jedna od najpoznatijih tehnika 3D štampe jeste tehnikadeponovanja istopljenog filamenta (engl. Fused deposition modelling, FDM).Cilj istraživanja u okviru ove disertacije bio je razvoj i optimizacija formulacija i procesaštampe FDM 3D tableta paracetamola. Eksperimentalni rad je podeljen u 3 faze.U prvoj fazi eksperimentalnog rada ispitivanje uticaja formulacionih i procesnih parametara namogućnost ekstruzije/štampanja i karakteristike dobijenih filamenata/tableta sprovedeno jeprimenom tri različite vrste osnovnog polimera (kompolimera metakrilne kiseline (Eudragit®),polikaprolaktona (PCL) i polietilenoksida (PEO)). Prvi tip formulacija činile su formulacije sasmešom osnovnih polimera (Eudragit® i PEO), gde je pokazano da ovakva kombinacijaosnovnih polimera nije pogodna za dobijanje filamenata i 3D štampanje tableta paracetamola.Drugu grupu činile su formulacije na bazi PCL gde je pokazana laka ekstruzija filamenataujednačenog izgleda i jednostavna štampa FDM 3D tableta. Međutim, u ovim filamentimauočen je najveći gubitak sadržaja u odnosu na ostale formulacije, zbog neujednačenog prolaskasmeše kroz hranilicu ekstrudera usled razlika u veličini čestica. FDM 3D tablete na bazi PCLsu pokazale izrazito sporo oslobađanje lekovite supstance, gde se nakon 8 sati ispitivanjaoslobodilo između 36,83% i 42,79% paracetamola. Treći tip formulacija činile su formulacijesa PEO (PEO molekulske mase 200000 g/mol (PEO 200 K) i PEO molekulske mase 100000g/mol (PEO 100 K)), pri čemu nije uočen uticaj molekulske mase osnovnog polimera namogućnost ekstruzije i printabilnost filamenata. Ovi filamenti su bili manje prikladni za daljuštampu, koja je bila praćena čestim zapušavanjem mlaznice štampača. Tablete na bazi PEO supokazale znatno brže oslobađanje paracetamola (potpuno oslobađanje paracetamola nakon 4sata ispitivanja) u odnosu na tablete na bazi PCL. U prvoj fazi istraživanja je primećeno da jesa porastom koncetracije paracetamola u formulaciji bila potrebna i viša temperatura zaekstruziju, a da je štampanje filamentima bilo moguće kada je procenat paracetamola uformulacijama bio do 60%.U drugoj fazi eksperimentalnog rada ispitane su mogućnosti ubrzanja oslobađanjaparacetamola iz FDM 3D odštampanih tableta i mogućnosti dobijanja tableta kod kojih brzinaoslobađanja i predviđeni obim apsorpcije lekovite supstance odgovaraju tabletama sa trenutnimoslobađanjem. Ispitivane su FDM 3D tablete odštampane od istog osnovnog polimera,polivinilalkohola (PVA), u kombinaciji sa plastifikatorom Affinisol™ HPMC HME 4MHYPROMELLOSE®, na kojima su primenjene četiri strategije za ubrzanje oslobađanjalekovite supstance. Ekstruzija filamenata sa PVA je bila jednostavna, a naknadno dodavanjerazličitih pomoćnih supstanci u cilju ubrzanja oslobađanja paracetamola iz tableta nije uticalona mogućnost ekstruzije i printabilnost filamenata, ukoliko je udeo osnovnog polimera bioiznad 45%. Rezultati in vitro ispitivanja brzine oslobađanja paracetamola iz formulacije saPVA i Affinisol™ HPMC HME 4M HYPROMELLOSE® su pokazali da se za 5 sati ispitivanjaoslobodilo 58% paracetamola...Three-dimensional (3D) printing is a revolutionary technique in pharmaceutical industry thatcan shorten drug products production time, reduce costs and enable personalized therapy. As anew and still not fully explored technique, 3D printing in pharmacy has been intensivelyresearched in recent years. One of the best known 3D printing techniques is fused depositionmodelling (FDM).The aim of this dissertation was to develop and optimize formulation and 3D printing processof paracetamol-loaded tablets via FDM 3D printing technique. The research was divided into3 phases.The first phase of the research focused on providing basic information about the experimentalconditions of FDM 3D printing of paracetamol-loaded tablets. Evaluation of the influence offormulation and process parameters on the extrudion/printing potential and characteristics ofthe obtained filaments/tablets was carried out using three different types of the main polymer(methacrylic acid copolymers (Eudragit®), polycaprolactone (PCL) and polyethylene oxyde(PEO)). The first type of formulations consisted of a combination of the main polymers(Eudragit® and PEO) and the results showed that this combination is not suitable for obtainingfilaments by melt extrusion process and for 3D printing of paracetamol-loaded tablets. Thesecond group were formulations with PCL as the main polymer, where facile extrusion ofuniformed filaments and effortless FDM 3D tablets printing were demonstrated. However,these filaments exhibited the greatest loss of content in comparison to the other formulations,due to the uneven feeding of the mixture through the extruder caused by differences in particlesize. PCL-based FDM 3D tablets showed rather slow drug release, with 36.83-42.79%paracetamol released after 8 hours of testing. The third type of formulations were formulationswith PEO (PEO with molecular weight of 200000 g/mol (PEO 200 K) and PEO with molecularweight of 100000 g/mol (PEO 100 K)), and in this case there was no observable effect of thepolymer molecular weight on extrudability and printability of the filaments. These filamentswere less suitable for consequent 3D printing process, which was demonstrated by frequentclogging of the printer nozzle. However, PEO-based 3D printed tablets showed notably fasterdrug release rate (complete paracetamol release after 4 hours of testing) compared to PCLbasedtablets. In this research phase, it was noticed that increase in paracetamol concentrationin the formulation required a higher extrusion temperature. Also, printing with filaments waspossible only when the percentage of paracetamol in the formulations was up to 60%.The second phase of the research aimed to investigate possibilities of increasing the drugrelease rate from FDM 3D printed tablets to comply with drug release and consequentabsorption rate that correspond to immediate release tablets. FDM 3D printed tablets containingthe same main polymer, polyvinyl alcohol (PVA), in combination with a plasticizer Affinisol™HPMC HME 4M HYPROMELLOSE® were tested, and four different strategies were appliedto increase the drug release. The extrusion of filaments with PVA as the main polymer wassimple. Subsequent addition of various excipients, in order to increase the drug release fromtablets, did not affect extrudability and printability of the filaments when the percentage of themain polymer in formulations was above 45%. In vitro dissolution test results revealed that theformulation containing PVA and Affinisol™ HPMC HME 4M HYPROMELLOSE® released58% of paracetamol within 5 hours of testing..

The evaluation of the effect of different infill patterns on the drug release from hollow paracetamol-loaded tablets 3D printed via fused deposition modelling technique

Deponovanje istopljenog filamenta (FDM) je jedna od najviše istraživanih tehnika 3D štampe, čiji princip rada se zasniva na depoziciji tankih polimernih niti na ravnu ploču, sloj po sloj. Postoji veliki broj parametara štampe koji se mogu podešavati u FDM 3D tehnici, a neki od njih su: temperatura štampe, brzina štampe, obrazac punjenja, gustina punjenja itd. Navedeni parametric mogu imati uticaj na brzinu oslobadđanja ljekovite supstance iz 3D odštampanih farmaceutskih preparata. Cilj ovog rada bio je da se ispita uticaj obrasca punjenja na brzinu oslobađanja paracetamola iz FDM 3D tabteta zasnovanih na polivinil alkoholu (PVA). ...Fused deposition modelling (FDM) is currently one of the most commonly used technique in 3D printing and its principle is based on deposition of thin polymer strands on a build plate, in a layer-by-layer manner. The whole process is controlled by a software. There are many printing parameters in FDM 3D printing technique that can be varied, such as: printing temperature, printing speed, infill density, infill pattern etc. ...Book of abstracts - The pover of pharmacy the strength of our healt

The evaluation of the effect of different superdisintegrants on the drug release from FDM 3D printed tablets through different applied strategies: In vitro-in silico assessment

Paracetamol-loaded tablets were printed by fused deposition modelling technique, using polyvinyl alcohol as a backbone polymer and Affinisol™ HPMC as a plasticizer in all formulations. Four different strategies were applied in order to accelerate the drug release from the tablets. First, different release enhancers were added: sodium starch glycolate, croscarmellose sodium, Kollidon CL and mannitol. Kollidon CL and mannitol showed the greatest influence on the drug dissolution rate. The second strategy included lowering the infill density, which did not make any significant changes in dissolution profiles, according to the calculated similarity factor. Then the best two release enhancers from the first strategy were combined (Kollidon CL and mannitol) and this proved to be the most effective in the drug release acceleration. The fourth strategy, increasing the percentage of the release enhancers in formulation, revealed the importance of their concentration limits. In summary, the drug release accelerated from 58% released after 5 h to reaching the plateau within 2 h. In silico physiologically-based biopharmaceutics modelling showed that formulations with mannitol and Kollidon CL, especially the formulation containing a combination of these release enhancers, can provide relatively fast drug release and extent of drug absorption that complies with an immediate release tablet

Paracetamol extended release FDM 3D printlets: Evaluation of formulation variables on printability and drug release

Paracetamol printlets were prepared via hot-melt extrusion process and fused deposition modelling, using two types of backbone polymers. Polycaprolactone (PCL) and Polyethylene oxides (PEO) 100 K and 200 K were used, while Arabic gum was used as a plasticizer to facilitate the material flow and Gelucire® 44/14 as an enhancer of drug release. Different drug/polymer ratios were prepared. Extrusion temperature was adjusted according to the mixture/polymer types. It was possible to produce filaments with maximum of 60% w/w of drug. Mechanical properties of filaments were evaluated using three-point bend test, while obtained parameters were modelled using decision tree as a data mining method. Correlation between maximum displacement, maximum force and printability was obtained with accuracy of 84.85% and can be a useful tool for predicting printability of filaments. This study briefly demonstrated that backbone polymer in formulation plays crucial role in obtaining FDM printlets with desired properties. PEO-based filaments were more prone to be clogged in printcore, but their printlets showed much faster drug release. Drug release from all printlets was prolonged: from 50% in 8 h (PCL), to complete release in 4 h (PEO). Paracetamol release kinetics was guided by anomalous transport, attributed to the diffusion and erosion process

Role of platelet gene polymorphisms in ischemic pediatric stroke subtypes: a case-control study

Aim: To assess the role of human platelet antigens (HPA), P-selectin gene (SELP) polymorphisms, and HPA and SELP haplotypes with factor V (FV) R506Q in ischemic pediatric stroke (IPS) subtypes: cerebral sinovenous thrombosis (CSVT), perinatal (PAIS), and childhood (CAIS) arterial ischemic stroke. ----- Methods: This case-control study enrolled 150 children with confirmed IPS and 150 age- and sex-matched controls. FV R506Q and HPA-1 were genotyped with CVD StripAssay®, HPA-2 and HPA-3 with real-time polymerase chain reaction, SELP S290N, V599L, and T715P with high resolution melting analysis, and SELP N562D with sequence-specific polymerase chain reaction. ----- Results: HPA-1b allele (odds ratio [OR] 2.75, 95% confidence interval [CI] 1.02-7.42, P=0.048) and HPA-1a2a3b (OR 5.46, 95% CI 1.51-19.76, P=0.011), HPA-1b2a3a (OR 7.00, 95% CI 1.25-39.13, P=0.028), and HPA-1b2b3a (OR 11.39, 95% CI 1.39-92.95, P=0.024) haplotypes increased the risk for CSVT. HPA-3b allele was significantly associated with 2-fold lower risk for PAIS (OR 0.49, 95% CI 0.26-0.89, P=0.020) and CAIS (OR 0.47, 95% CI 0.26-0.86, P=0.014) and non-significantly associated with increased risk for CSVT (OR 6.43, 95% CI 0.83-50.00, P=0.022). HPA-1a2b3a haplotype was significantly associated with CAIS (OR 6.76, 95% CI 2.13-21.44, P=0.001). The inclusion of FV R506Q in SELP haplotype analysis increased the risk for PAIS 4-fold in QNDVT carriers (OR 8.14, 95% CI 0.93-71.33, P=0.060) compared with NDVT haplotype (OR 2.45, 95% CI 0.98-6.18, P=0.058), but the result was not significant. ----- Conclusion: Individual HPAs, and particularly HPA haplotypes, are involved in IPS subtypes pathogenesis. A possible risk-inducing synergistic effect of SELP haplotypes with FV R506Q is restricted to PAIS only