The analysis of the alloy from the archaeological finding by thin-layer chromatography after anodic sampling

Analiza slitina, kao i svaka druga kemijska analiza započinje uzorkovanjem. Metode uzorkovanja slitina uglavnom uključuju destruktivne metode kao što su struganje, svrdlanje i rezanje, a dobiveni komadi slitina otapaju se u jakim anorganskim kiselinama. Otopine takvih uzoraka najčešće se analiziraju atomskom apsorpcijskom spektrometrijom (AAS) ili optičkom emisijskom spektrometrijom sa pobudom u induktivno spregnutoj plazmi (ICP – OES). U slučajevima ograničenih količina uzoraka slitine ili u situacijama kad destruktivno uzorkovanje slitine nije poželjno, poseže se za nedestruktivnim metodama uzorkovanja, a jedna je od tih metoda, metoda anodnog uzorkovanja, odnosno mikrodestruktivno anodno otapanje površine uzorka. Metoda anodnog uzorkovanja najčešće je povezana s tankoslojnom kromatografijom kao metodom kemijske analize. Cilj ovog rada bio je analiza slitine arheološke važnosti, pronađene u moru. Analiza kojoj je prethodilo anodno uzorkovanje, provedena je tankoslojnom kromatografijom. Uz samu analizu, određen je optimalni razvijač za razdvajanje komponenata olovnih legura, uvjeti anodnog uzorkovanja, elektrolit za uzorkovanje, te vrijeme nanošenja uzorka na kromatografsku podlogu. Analizom su određene glavne komponente legure, što se podudara s prethodno napravljenom destruktivnom, spektrometrijskom analizom sastava legure. U najvećoj mjeri sastoji se od olova i kositra. Spektrometrijska metoda daje točnije rezultate analize, no za razliku od tankoslojne kromatografije dugotrajna je s obzirom na pripremu uzorka i zahtjeva skuplju opremu. Tankoslojna kromatografija izvrsna je kao preliminarna metoda s glavnom prednosti anodnog uzorkovanja, no nije moguće odrediti sporedne komponente i elemente u tragovima.The analysis of alloys, as well as any other chemical analysis begins by sampling. Sampling methods of alloy mainly include destructive methods such as turning, boring and cutting, and obtained pieces of alloy dissolve in strong inorganic acids. Solutions of such samples are commonly analyzed by atomic absorption spectrometry (AAS) or optical emission spectrometry with inductively on coexcitation in the plasma (ICP-OES). In cases of limited amounts of samples of alloys or in situations where destructive sampling of the alloy is not desirable, we are reaching out to non-destructive methods of chemical analysis and sampling, and one of these methods is the method of anodic sampling or microdestructive anodic dissolution of the sample surface. A method of sampling an anode is usually associated with thin-layer chromatography as a method of chemical analysis. The aim of this study was to analyze alloy of archaeological significance, found in the sea. The analysis which was preceded by anodic sampling is carried out by thin-layer chromatography. In addition to the analysis, an optimum developer for the separation of the components of lead alloys was determined, such as sampling conditions anode, electrolyte for sampling, and time applying the sample to the chromatography medium. The analysis determined certain major components of the alloy, which is consistent with previously conducted destructive, spectrometric analysis of the alloy composition. For the most part it consists of lead and tin. Spectrometric method gives more accurate results of the analysis, but unlike the thin-layer chromatography takes more time due to the sample preparation and expensive equipment. Thin-layer chromatography is an excellent method as a preliminary with the main advantage of anodic sampling, but it is not possible to determine the minor component and trace elements

The micro scale study of granulation phenomenon using parameters of powder-binder interface

U ovome je radu sagledano granuliranje dviju pomoćnih tvari farmaceutske industrije u fluidiziranom sloju s taljenjem sa stajališta mikrorazine procesa. Testovi šaržnog granuliranja provedeni su prethodnim istraživanjem u procesnoj geometriji fluidiziranog sloja u laboratorijskom mjerilu. U fizičkoj pretvorbi tvari korišteno je vezivo, praškasti polietilen glikol koji taljenjem osigurava nužna kapljevita premoštenja. Mikrorazinski studij fenomena granuliranja usmjeren je k pronalaženju parametara međupovršine prašak-vezivo za sustave mikrokristalna celuloza/polietilen glikol i laktoza monohidrat/polietilen glikol. U karakterizaciji dviju međupovršina od značaja korištena je eksperimentalna tehnika mjerenja kontaktnog kuta goniometrom. Određeni su kontaktni kutovi triju testnih kapljevina poznatih energija površina na supstratima mikrokristalne celuloze, laktoze monohidrata i polietilen glikola. U kvantitativnom predviđanju interakcija korišteni su dvoparametarski modeli. Primjenom Owens-Wendtova i Wuova modela procijenjene su slobodne energije površina pojedinih faza, energije međupovršina od značaja te pripadajuće vrijednosti termodinamičkog rada adhezije i koeficijenta kvašenja. Parametri adhezije ukazuju na slabe interakcije između mikrokristalne celuloze i polietilen glikola te mogućnost odvajanja faza i posljedično na nemogućnost granuliranja ovog sustava. Dodatno, parametri međupovršine ukazuju na mogućnost uspostave značajnih interakcija između laktoze monohidrata i polietilen glikola.In this thesis, fluidized bed melt granulation of two pharmaceutical excipients is scrutinized from a micro scale level of scrutiny. Batch granulation tests were performed by previous research in process geometry of fluidized bed in a lab-scale. Binder, polyethylene glycol powder that provides necessary liquid bridges by melting, is used in physical conversion of a substance. The micro scale study of granulation phenomenon is focused towards detection of parameters of powder-binder interface for systems microcrystalline cellulose/polyethylene glycol and lactose monohydrate/polyethylene glycol. Experimental technique for measurement of contact angle using goniometer is used for characterization of two interfaces of interest. Contact angles of three test liquids with well known surface energies were determined on substrates of microcrystalline cellulose, lactose monohydrate and polyethylene glycol. Two parametric models were used for quantitative prediction of interactions. Surface free energies for each phase, interfacial energies of interest and corresponding values of thermodynamic work of adhesion and spreading coefficient were estimated using Owens-Wendt and Wu model. Adhesion parameters indicate weak interactions between microcrystalline cellulose and polyethylene glycol with possibility of phase dewetting and consequently on the inability for granulation of this system. Additionally, interface parameters indicate the possibility for establishment of considerable interactions between lactose monohydrate and polyethylene glycol

The analysis of the alloy from the archaeological finding by thin-layer chromatography after anodic sampling

Analiza slitina, kao i svaka druga kemijska analiza započinje uzorkovanjem. Metode uzorkovanja slitina uglavnom uključuju destruktivne metode kao što su struganje, svrdlanje i rezanje, a dobiveni komadi slitina otapaju se u jakim anorganskim kiselinama. Otopine takvih uzoraka najčešće se analiziraju atomskom apsorpcijskom spektrometrijom (AAS) ili optičkom emisijskom spektrometrijom sa pobudom u induktivno spregnutoj plazmi (ICP – OES). U slučajevima ograničenih količina uzoraka slitine ili u situacijama kad destruktivno uzorkovanje slitine nije poželjno, poseže se za nedestruktivnim metodama uzorkovanja, a jedna je od tih metoda, metoda anodnog uzorkovanja, odnosno mikrodestruktivno anodno otapanje površine uzorka. Metoda anodnog uzorkovanja najčešće je povezana s tankoslojnom kromatografijom kao metodom kemijske analize. Cilj ovog rada bio je analiza slitine arheološke važnosti, pronađene u moru. Analiza kojoj je prethodilo anodno uzorkovanje, provedena je tankoslojnom kromatografijom. Uz samu analizu, određen je optimalni razvijač za razdvajanje komponenata olovnih legura, uvjeti anodnog uzorkovanja, elektrolit za uzorkovanje, te vrijeme nanošenja uzorka na kromatografsku podlogu. Analizom su određene glavne komponente legure, što se podudara s prethodno napravljenom destruktivnom, spektrometrijskom analizom sastava legure. U najvećoj mjeri sastoji se od olova i kositra. Spektrometrijska metoda daje točnije rezultate analize, no za razliku od tankoslojne kromatografije dugotrajna je s obzirom na pripremu uzorka i zahtjeva skuplju opremu. Tankoslojna kromatografija izvrsna je kao preliminarna metoda s glavnom prednosti anodnog uzorkovanja, no nije moguće odrediti sporedne komponente i elemente u tragovima.The analysis of alloys, as well as any other chemical analysis begins by sampling. Sampling methods of alloy mainly include destructive methods such as turning, boring and cutting, and obtained pieces of alloy dissolve in strong inorganic acids. Solutions of such samples are commonly analyzed by atomic absorption spectrometry (AAS) or optical emission spectrometry with inductively on coexcitation in the plasma (ICP-OES). In cases of limited amounts of samples of alloys or in situations where destructive sampling of the alloy is not desirable, we are reaching out to non-destructive methods of chemical analysis and sampling, and one of these methods is the method of anodic sampling or microdestructive anodic dissolution of the sample surface. A method of sampling an anode is usually associated with thin-layer chromatography as a method of chemical analysis. The aim of this study was to analyze alloy of archaeological significance, found in the sea. The analysis which was preceded by anodic sampling is carried out by thin-layer chromatography. In addition to the analysis, an optimum developer for the separation of the components of lead alloys was determined, such as sampling conditions anode, electrolyte for sampling, and time applying the sample to the chromatography medium. The analysis determined certain major components of the alloy, which is consistent with previously conducted destructive, spectrometric analysis of the alloy composition. For the most part it consists of lead and tin. Spectrometric method gives more accurate results of the analysis, but unlike the thin-layer chromatography takes more time due to the sample preparation and expensive equipment. Thin-layer chromatography is an excellent method as a preliminary with the main advantage of anodic sampling, but it is not possible to determine the minor component and trace elements

Microencapsulation of active ingredient

U farmaceutskoj industriji se velika pozornost počela obraćati na odgođeno otpuštanje lijeka. Većina aktivnih tvari se otpušta odmah iz lijeka te je njihovo djelovanje trenutno, zbog toga se nastoji pronaći formulacija koja će kontrolirano otpuštati aktivnu tvar i tako djelovati kroz duže vrijeme u tijelu. Bitno je i da je lijek stabilan i otpušta aktivnu tvar na točno određenom području. U ovom radu je ispitana djelotvornost mikroinkapsuliranja dronedaron hidroklorida s arapskom gumom kao i njegovo nanošenje na nosač, mikrokristalnu celulozu. Dronedaron hidroklorid je lijek za regulaciju srčane aritmije koji svoju komercijalnu primjenu pronalazi u tabletama Multaq 400 mg. Eksperimenti su provedeni u laboratorijskom sušioniku s raspršivanjem, Büchi B-290. Mijenjani su protoci zraka za raspršivanje od 30 do 60 %. Morfologija dobivenih uzoraka ispitana je pomoću pretražnog elektronskog mikroskopa (SEM). Kinetika otpuštanja je opisana pomoću matematičkih modela. Rezultati su pokazali da je iskorištenje dronedarona veće kod mikroinkapsuliranja arapskom gumom nego kod nanošenja na nosač. Najveće iskorištenje dronedarona dobiveno je za uzorke GA 40 i MCC 50. SEM mikrografije su potvrdile da su dobivene mikrokapsule dronedarona s arapskom gumom, a na uzorcima MCC vidljive su čestice dronedarona deponirane na površini. Otpuštanje dronedarona je vrlo brzo i neujednačeno u odnosu na komercijalnu tabletu. Najbolje rezultate daje uzorak s arapskom gumom koji je pripremljen pri protoku od 60 %. Za taj uzorak su dobivene vrlo sitne i sferične mikrokapsule.In recent years, pharmaceutical industry pays a great attention to the delayed drug release from different dosage forms. Most of the active substances are released immediately from the dosage form; therefore it is challenging to find a formulation for the controlled release as well as prolonged effectiveness in the body. It is important that the drug is stable and releases the active substance to a targeting area. This paper deals with microencapsulation efficiency of dronedarone hydrochloride with gum arabic, as well as the efficiency of his imobilization onto drug carrier, microcrystal cellulose. Dronedarone hydrochloride is a drug for regulation of cardiac arrhythmia, which finds its commercial application in Multaq 400 mg tablets. The experiments were performed in the laboratory spray-dryer, Büchi B-290. Flow rates of atomizing air were changed from 30 to 60 %. Scanning electron microscopy was used to characterize the morphology of prepared samples. Release kinetics is described by mathematical models. From the results it is evident that utilization is much higher in microencapsulation then in deposition onto carrier. Best results were obtained for GA 40 and MCC 50 samples. SEM micrographs confirmed that microcapsules of dronedarone and gum arabic were prepared. It was also confirmed that dronedarone was successfully deposited onto the surface of cellulose carrier. The release of the drug is very fast and uneven compared to the commercial tablet Multaq. Best results are obtained with microcapsules which have been prepared at an air flow of 60 %. Microcapsules obtained at those process conditions are very small and mostly spherical

Microencapsulation of active ingredient

U farmaceutskoj industriji se velika pozornost počela obraćati na odgođeno otpuštanje lijeka. Većina aktivnih tvari se otpušta odmah iz lijeka te je njihovo djelovanje trenutno, zbog toga se nastoji pronaći formulacija koja će kontrolirano otpuštati aktivnu tvar i tako djelovati kroz duže vrijeme u tijelu. Bitno je i da je lijek stabilan i otpušta aktivnu tvar na točno određenom području. U ovom radu je ispitana djelotvornost mikroinkapsuliranja dronedaron hidroklorida s arapskom gumom kao i njegovo nanošenje na nosač, mikrokristalnu celulozu. Dronedaron hidroklorid je lijek za regulaciju srčane aritmije koji svoju komercijalnu primjenu pronalazi u tabletama Multaq 400 mg. Eksperimenti su provedeni u laboratorijskom sušioniku s raspršivanjem, Büchi B-290. Mijenjani su protoci zraka za raspršivanje od 30 do 60 %. Morfologija dobivenih uzoraka ispitana je pomoću pretražnog elektronskog mikroskopa (SEM). Kinetika otpuštanja je opisana pomoću matematičkih modela. Rezultati su pokazali da je iskorištenje dronedarona veće kod mikroinkapsuliranja arapskom gumom nego kod nanošenja na nosač. Najveće iskorištenje dronedarona dobiveno je za uzorke GA 40 i MCC 50. SEM mikrografije su potvrdile da su dobivene mikrokapsule dronedarona s arapskom gumom, a na uzorcima MCC vidljive su čestice dronedarona deponirane na površini. Otpuštanje dronedarona je vrlo brzo i neujednačeno u odnosu na komercijalnu tabletu. Najbolje rezultate daje uzorak s arapskom gumom koji je pripremljen pri protoku od 60 %. Za taj uzorak su dobivene vrlo sitne i sferične mikrokapsule.In recent years, pharmaceutical industry pays a great attention to the delayed drug release from different dosage forms. Most of the active substances are released immediately from the dosage form; therefore it is challenging to find a formulation for the controlled release as well as prolonged effectiveness in the body. It is important that the drug is stable and releases the active substance to a targeting area. This paper deals with microencapsulation efficiency of dronedarone hydrochloride with gum arabic, as well as the efficiency of his imobilization onto drug carrier, microcrystal cellulose. Dronedarone hydrochloride is a drug for regulation of cardiac arrhythmia, which finds its commercial application in Multaq 400 mg tablets. The experiments were performed in the laboratory spray-dryer, Büchi B-290. Flow rates of atomizing air were changed from 30 to 60 %. Scanning electron microscopy was used to characterize the morphology of prepared samples. Release kinetics is described by mathematical models. From the results it is evident that utilization is much higher in microencapsulation then in deposition onto carrier. Best results were obtained for GA 40 and MCC 50 samples. SEM micrographs confirmed that microcapsules of dronedarone and gum arabic were prepared. It was also confirmed that dronedarone was successfully deposited onto the surface of cellulose carrier. The release of the drug is very fast and uneven compared to the commercial tablet Multaq. Best results are obtained with microcapsules which have been prepared at an air flow of 60 %. Microcapsules obtained at those process conditions are very small and mostly spherical

The micro scale study of granulation phenomenon using parameters of powder-binder interface

U ovome je radu sagledano granuliranje dviju pomoćnih tvari farmaceutske industrije u fluidiziranom sloju s taljenjem sa stajališta mikrorazine procesa. Testovi šaržnog granuliranja provedeni su prethodnim istraživanjem u procesnoj geometriji fluidiziranog sloja u laboratorijskom mjerilu. U fizičkoj pretvorbi tvari korišteno je vezivo, praškasti polietilen glikol koji taljenjem osigurava nužna kapljevita premoštenja. Mikrorazinski studij fenomena granuliranja usmjeren je k pronalaženju parametara međupovršine prašak-vezivo za sustave mikrokristalna celuloza/polietilen glikol i laktoza monohidrat/polietilen glikol. U karakterizaciji dviju međupovršina od značaja korištena je eksperimentalna tehnika mjerenja kontaktnog kuta goniometrom. Određeni su kontaktni kutovi triju testnih kapljevina poznatih energija površina na supstratima mikrokristalne celuloze, laktoze monohidrata i polietilen glikola. U kvantitativnom predviđanju interakcija korišteni su dvoparametarski modeli. Primjenom Owens-Wendtova i Wuova modela procijenjene su slobodne energije površina pojedinih faza, energije međupovršina od značaja te pripadajuće vrijednosti termodinamičkog rada adhezije i koeficijenta kvašenja. Parametri adhezije ukazuju na slabe interakcije između mikrokristalne celuloze i polietilen glikola te mogućnost odvajanja faza i posljedično na nemogućnost granuliranja ovog sustava. Dodatno, parametri međupovršine ukazuju na mogućnost uspostave značajnih interakcija između laktoze monohidrata i polietilen glikola.In this thesis, fluidized bed melt granulation of two pharmaceutical excipients is scrutinized from a micro scale level of scrutiny. Batch granulation tests were performed by previous research in process geometry of fluidized bed in a lab-scale. Binder, polyethylene glycol powder that provides necessary liquid bridges by melting, is used in physical conversion of a substance. The micro scale study of granulation phenomenon is focused towards detection of parameters of powder-binder interface for systems microcrystalline cellulose/polyethylene glycol and lactose monohydrate/polyethylene glycol. Experimental technique for measurement of contact angle using goniometer is used for characterization of two interfaces of interest. Contact angles of three test liquids with well known surface energies were determined on substrates of microcrystalline cellulose, lactose monohydrate and polyethylene glycol. Two parametric models were used for quantitative prediction of interactions. Surface free energies for each phase, interfacial energies of interest and corresponding values of thermodynamic work of adhesion and spreading coefficient were estimated using Owens-Wendt and Wu model. Adhesion parameters indicate weak interactions between microcrystalline cellulose and polyethylene glycol with possibility of phase dewetting and consequently on the inability for granulation of this system. Additionally, interface parameters indicate the possibility for establishment of considerable interactions between lactose monohydrate and polyethylene glycol

Wet granulation of pharmaceutical excipient in fluidized bed

Ovim istraživanjem sagledano je mokro granuliranje mikrokristalne celuloze u fluidiziranom sloju s raspršivanjem kao nužan procesni korak u osiguravanju željene funkcionalnosti mješavine za tabletiranje. Dodatne ulazne struje materijala u procesu su zrak i vezivo, otopina polivinilpirolidona čiji je kolektiv kapljica dodavan različitim geometrijama raspršivanja. Studij fenomena okrupnjavanja u laboratorijskom mjerilu usmjeren je k pronalaženju uvjeta provedbe procesa, geometrije raspršivanja i svojstava ulaznih struja materijala koji će sinergističkim djelovanjem upravljati mikro- i mezorazinskim događajima na povoljan i željeni način te time rezultirati kolektivom postojanih okrupnjenih jedinki, granula mikrokristalne celuloze. Detektirane promjene svojstva kolektiva jedinki, raspodjele veličina čestica s vremenom granuliranja ukazuju na odmak fizičke pretvorbe mikrokristalne celuloze u procesu granuliranja. Proces fizičke pretvorbe mikrokristalne celuloze modeliran je mehanističkim pristupom, primjenom populacijske bilance. Pristup modeliranja populacijskom bilancom u ovome radu podrazumijeva ispitivanje mogućnosti primjene 1-D populacijske bilance u diskretiziranom obliku te Size-Independent Kernel (SIK) modela koalescencije u predviđanju stvarnih promjena u svojstvu partikulskog sustava (raspodjeli veličina čestica) tijekom procesa fizičke pretvorbe tvari. Primijenjeni pristup ukazuje u određenoj mjeri na zastupljenost pojedinih mehanizama u procesu granuliranja. Metodom optimizacije, očitovanom u minimiziranju ukupne sume kvadrata odstupanja, procijenjen je karakterističan procesni parametar, konstanta brzine koalescencije. Time je kvantificirana kinetika fizičke pretvorbe mikrokristalne celuloze u stohastičkom okruženju fluidiziranog sloja.With this study, wet fluid-bed spray granulation of microcrystalline cellulose (MCC) is scrutinized as an essential process path for achieving required functionality of a compression mix. Additional inlet process streams are air and binder, solution of polyvinylpyrrolidone whose droplet population is added using various spraying geometries. Study of the enlargement phenomenon in a lab-scale is focused towards detection of process conditions, spraying geometry and formulation properties that will synergically drive micro- and meso-scale events in a favourable and desired way and therewith result in a collective of stable enlarged entities, MCC granules. Detected temporal changes of the property of a group of entities, particle size distribution (PSD) point to the progress of physical conversion of microcrystalline cellulose within granulation process. Process of physical conversion of microcrystalline cellulose is modelled with mechanistic approach using population balance. Such modelling approach in this paper implies testing the applicability of a 1-D discretized population balance with Size-Independent Kernel (SIK) coalescence model for simulating real temporal changes of the property of MCC particulate system (particle size distribution) during complex transformation path of powder. Used approach might indicate the contributions of underlying mechanisms in the net granulation process and identify the dominant granulation mechanism as well. Optimization method that connotes minimizing the overall sum of squared errors is used for estimation of characteristic process parameter, coalescence rate constant. Thus, kinetic of physical conversion of MCC powder in a stochastic fluid-bed environment is quantified

Farmaceutsko-tehnološki aspekti preparata za prevenciju i lečenje poremećaja venske cirkulacije

The main purposes of pharmacotherapy in deep and superficial venous thrombosis are prevention and therapy of acute and chronic venous insufficiency as well as complications such as pulmonary embolism, dermatoses, venous ulcers and infection. The main therapeutics are: thrombolytics (streptokinase, alteplase), anticoagulants (heparin, enoxaparin, reviparin, dalteparin, nadroparin, fondaparinux, warfarin, acenocumarol, dabigatran etexilate, rivaroxaban) and vasoprotectives for oral administration (calcium dobesilate, bioflavonoids and plant extracts with vasoprotective activity), cutaneous application (heparin, heparinoids, aescin, troxerutin) and rectal administration (heparin in combination with corticosteroides, local anesthetics, epithelization agents and/or adstringents). Marketed pharmaceutical preparations for prevention and therapy of venous disorders are conventional dosage forms for: parenteral administration of antithrombotics (powder for solution for i.v. injection/infusion, solution for i.v. injection/infusion, solution for s.c. injection), oral administration of anticoagulants and vasoprotectives (tablets, film-coated tablets, hard capsules), cutaneous application (creams, hydrogels, ointments, pastes) and rectal administration (suppositories, rectal ointments, rectal foams). With suitable selection of the active substance form (low-molecular weight heparins, pro-drug dabigatran etexilate), technological processing (micronisation, nanonisation, recrystallization, peletization), excipients (e.g., solubilizers, absorption enhancers or percutaneous penetration/permeation enhancers), as well as by incorporation of the active substance into an appropriate vehicle/basis or by drug carrier encapsulation (e.g., liposomes), the improvements of biopharmaceutical profile, adherence, therapeutic efficacy and safety of such pharmaceutical preparations are achievable.Farmakoterapija dubokih i superficijalnih venskih tromboza sprovodi se u cilju ublažavanja simptoma, prevencije ili lečenja akutne i hronične venske insuficijencije i komplikacija kao što su plućna embolija i varikozni ulkusi. Osnovu terapije čine: trombolitici (streptokinaza, alteplaza), antikoagulansi (heparin, heparini male molekulske mase, fondaparinuks, varfarin, acenokumarol, dabigatraneteksilat, rivaroksaban) i vazoprotektivi za oralnu upotrebu (kalcijum-dobesilat, bioflavonoidi i biljni ekstrakti sa vazoprotektivnim delovanjem), primenu na koži (heparin, heparinodi, escin, trokserutin) i rektalnoj sluzokoži (heparin u kombinaciji sa kortikosteroidima, lokalnim anesteticima, epitelizansima i/ili adstringensima). Registrovani su preparati za parenteralnu primenu antitrombotičkih sredstava (u obliku praškova za rastvore i rastvora za i.v. injekcije/infuzije ili rastvora za s.c. injekcije), peroralnu primenu antikoagulanasa i vazoprotektiva (u obliku neobloženih tableta, film tableta i tvrdih kapsula), kao i preparati sa vazoprotektivnim delovanjem za primenu na koži (u obliku kremova, hidrofilnih gelova, masti i pasta) i rektalnu primenu (u obliku supozitorija, rektalnih masti i rektalnih pena). Odgovarajućim izborom oblika aktivne supstance (niskomolekularne frakcije heparina, pro-lek dabigatraneteksilat), postupaka tehnološke obrade (mikronizacija, nanonizacija, rekristalizacija, peletizacija), korišćenjem pomoćnih supstanci kao što su solubilizatori i inhenseri apsorpcije ili perkutane penetracije/permeacije, inkorporiranjem aktivne supstance u odgovarajući vehikulum/podlogu/bazu i/ili inkapsulacijom u pogodan nosač (npr. liposomi), mogu se unaprediti biofarmaceutski profil preparata, adherenca, efikasnost i bezbednost terapije

Primena perkolacione teorije u formulaciji farmaceutskih oblika - hidrofilne matriks tablete

Percolation theory is a mathematical tool that enables insight into characteristics of geometrically complex systems. Geometrical transition of solid dosage forms is followed by sudden changes in certain tablet characteristics (mechanical properties, drug release rate). The aim of the presented study is implementation of percolation theory concepts in hydrophilic matrix tablets characterization, by determination of the percolaction thresholds for key mechanical properties of matrix tablets as well as for drug release profiles. Hydrophilic matrix tablets have been formulated using polyethylene oxide polymers as matrix forming substances, diclofenac sodium as the model drug substance, as well as mycrocristaline cellulose as a tablet filler. Varying the excipient weight ratio and applied compression force, 18 formulations have been prepared using direct compression method. Compressibility and compactibility of the excipients hava been investigated, followed by characterization of matrix tablets tensile strenght. Dissolution test for diclofenac sodium matrix tablets has been conducted using rotating paddles method, and obtained drug release profiles have been analyzed using mathematical model. In order to estimate percolation thresholds changes in matrix tablets tensile strength and kinetic parameters of dissolution profiles were studied in aspect to changes in matrix tablets relative density i.e. volumetric ratio of matrix forming substance and initial porosity of matrix tablets. Obtained values for percolation thresholds, i.e. critical porosities for tensile strenghts are 22,57 % and 50,63 % for PEO WSR 1105 and PEO WSR Coagulant hydrophilic matrix tablets respectively. Percolation threshold for kinetic parameters of diclofenac sodium release profiles for PEO WSR 1105 matrix tablets is 20,86%. Obtained results indicate that percolation thresholds can be identified as critical formulations that are susceptible to sudden changes in mechanical properties and/or characteristics in drug release profiles following minor changes in formulation composition or process parameters.Perkolaciona teorija je matematička alatka koja omogućava uvid u karakteristike geometrijski složenih sistema. Geometrijska tranzicija u čvrstim farmaceutskim oblicima je povezana sa naglim promenama određenih karakteristika tableta (mehaničke karakteristike, brzina rastvaranja lekovite supstance). Cilj rada je implementacija koncepata perkolacione teorije u karakterizaciji hidrofilnih matriks tableta, određivanjem perkolacionih pragova za ključne mehaničke karakteristike matriks tableta kao i za profile brzine rastvaranja lekovite supstance. Hidrofilne matriks tablete su izrađene sa polietilen oksidnim polimerima kao matriks-formirajućim materijalima, diklofenak-natrijumom kao lekovitom supstancom i mikrokristalnom celulozom kao sredstvom za dopunjavanje. Izrađeno je 18 formulacija variranjem masenog udela ekscipijenasa i primenjene sile kompresije, pri čemu su matriks tablete izrađene metodom direktne kompresije. Ispitana je kompresibilnost i kompaktibilnost ekscipijenasa, kao i zatezna čvrstoća izrađenih matriks tableta. Brzina rastvaranja diklofenak-natrijuma iz matriks tableta je ispitana u aparaturi sa rotirajućom lopaticom, a dobijeni profili su analizirani primenom matematičkog modela. Perkolacioni pragovi su određeni praćenjem promena u zateznoj čvrstoći matriks tableta i kinetičkim parametrima profila brzine rastvaranja lekovite supstance, u funkciji relativne gustine matriks tableta odnosno zapreminskog udela matriks-formirajuće supstance i poroziteta matriks tableta. Dobijene vrednosti perkolacionih pragova, tj. kritičnih poroziteta za zateznu čvrstoću iznose 22,57% odnosno 50,63% za PEO WSR 1105 i PEO WSR Coagulant hidrofilne matriks tablete. Perkolacioni prag za kinetičke parametre profila brzine rastvaranja diklofenak-natrijuma za PEO WSR 1105 hidrofilne matriks tablete iznosi 20,86 %. Dobijeni rezultati ukazuju na mogućnost identifikacije perkolacionih pragova kao kritičnih formulacija koje podležu naglim promenama karakteristika matriks tableta sa manjim promenama u sastavu formulacija ili parametara procesa izrade

Release Rate Enhancement of Lurasidone Hydrochloride from Orally Disintegrating Tablets using Lyophilisation

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. Ovo djelo je dano na korištenje pod licencom Creative Commons Imenovanje 4.0 međunarodna.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. This work is licensed under a Creative Commons Attribution 4.0 International License