Abstract Natural cyclodextrins (CDs) and their chemically modified derivatives are used nowadays ... more Abstract Natural cyclodextrins (CDs) and their chemically modified derivatives are used nowadays as enabling pharmaceutical excipient capable to increase aqueous solubility of lipophilic drugs, enhance drug chemical stability, reduce volatility, mask unpleasant taste, reduce side effects, and enhance bioavailability, thereby further enabling therapeutic potential and the efficiency of drugs. This chapter provides a brief overview of the CDs chemistry, safety profile, and regulatory status. The mechanism of inclusion complex formation and its fate upon administration to the body is concisely described. The examples of CD-based products in clinical practice and development aimed for parenteral, ocular, nasal, oral, oromucosal, and (trans)dermal administration are presented, critically discussing the benefits and limitations related to CD application in the dosage form development. Finally the use of CDs as novel therapeutically active agents is presented.
Olive oil mill waste obtained after two-phase olive oil extraction process was subjected to conve... more Olive oil mill waste obtained after two-phase olive oil extraction process was subjected to conventional liquid solvent extraction under different pH/temperature/duration conditions using different types of food-grade solvents. The independent variables were: solvent type (ethanol percentage), extraction temperature (20-90 °C), extraction time (30 min-24 h) and pH (210.3) of extraction solvent while the response variables were total phenolic content and antioxidant activity of obtained extracts. The optimum solvent extraction conditions for phenols were 120 min at 70 °C using 60% ethanol as extraction solvent, at solvent to sample ratio 5:1 (v/w). For quantification of major bioactive olive polyphenols hydroxytyrosol, tyrosol and oleuropein in obtained extracts, fast and simple RP-HPLC-DAD method was developed and validated. Oleuropein was presented in highest amounts with average value of 115.14±0.19 mg/kg of fresh olive pomace.
Elimination of cariogenic bacteria from dental film is an important step in prevention and treatm... more Elimination of cariogenic bacteria from dental film is an important step in prevention and treatment of dental conditions and of related systemic diseases. Triclosan (TR), a broad spectrum antibacterial agent, is a possible candidate for this aim. However, to obtain effective TR levels in the oral cavity, there is the need of developing a suitable formulation allowing both a prolonged in situ residence and a controlled drug release. The design of such formulation is a particularly challenging issue for a poorly soluble drug as TR, due to the limited amount of saliva in the mouth, acting as dissolution medium. Based on these premises, we considered it worthy of interest to develop a TR mucoadhesive buccal formulation, by using pectin-Carbopol combinations as mucoadhesive matrix-forming polymer, and exploiting cyclodextrin (CD) complexation (with polymeric or native sCD) for improving drug solubility and optimising its release rate from the matrix. Phase-solubility studies were perfor...
Melatonin is a methoxyindole synthesized and secreted principally by the pineal gland in a circad... more Melatonin is a methoxyindole synthesized and secreted principally by the pineal gland in a circadian fashion. lt is also synthesized in other organs,
Ispitano je nastajanje inkluzijskih kompleksa lorazepama i risperidona s hidroksipropil-β-ciklode... more Ispitano je nastajanje inkluzijskih kompleksa lorazepama i risperidona s hidroksipropil-β-ciklodekstrinom (HP-β-CD) u otopini i u cvrstom stanju. U
The aim of this work was to develop pH-responsive microspheres of zaleplon (ZAL) with delayed dru... more The aim of this work was to develop pH-responsive microspheres of zaleplon (ZAL) with delayed drug release in the ileum, as a novel chronopharmaceutical drug delivery system, suitable for treatment of a specific type of insomnia characterised by premature awaking and inability to fall asleep again. ZAL is rapidly cleared from the body (t1/2=1h), therefore it would be suitable for development of such formulation [2]. Eudragit® L100 (EL100), a 1:1 methacrylatic acid/methylmethacrylate copolymer, with pH dependent solubility (pH>6) was used as the base of this formulation. Microparticles were prepared by spray-drying of ZAL/EL100 dispersion from ethanolic medium (MS1) or from 0.96% aqueous NH4HCO3 solution (MS2), transforming EL100 into soluble, thermolabile ammonium salt. In second case, after spray-drying procedure, EL100 was regenerated by thermal treatment at 85° for 3.5h, eliminating completely soluble ammonium salt from the microparticles, as confirmed by FTIR analysis. All mi...
Echinacea purpurea is used in herbal medicinal products for the prevention and treatment of the c... more Echinacea purpurea is used in herbal medicinal products for the prevention and treatment of the common cold, as well as for skin disorders and minor wounds. In this study, the efficiency of traditional maceration using water and ethanol was compared with the maceration using mixtures of water and glycerol, a non-toxic, biodegradable solvent from renewable sources. It was found that the glycerol–water mixtures were as effective as ethanol/water mixtures for the extraction of caffeic acid derivatives. All the prepared extracts demonstrated notable antiradical properties. Furthermore, an efficient ultrasound-assisted extraction using glycerol–water mixtures was developed using six independent variables. Their levels needed for the maximum extraction of caffeic acid derivatives were as follows: glycerol 90% (m/m), temperature 70 °C, ultrasound power 72 W, time 40 min, and ascorbic acid 0 mg/mL. Under the optimized conditions, ultrasound-assisted extraction was superior to maceration. It...
Poor technological properties of raw olive pomace extracts (OPE) significantly limits its utiliza... more Poor technological properties of raw olive pomace extracts (OPE) significantly limits its utilization as nutraceutical and functional food ingredient. Increasing the share of the main olive pomace biophenols (OPB) and improving physical properties of crude OPE are prerequisites for obtaining a usable extract. To achieve that, we examined encapsulation of OPE with different types and amounts of cyclodextrins (CDs). To determine physical parameters of freeze-dried OPE, CIE LAB color and particle size distribution were analyzed. Stability of crude OPE was examined under accelerated degradation conditions (60 °C, 75% humidity, 45 days). Stability parameters were: 1) total phenolic content; 2) antiradical potential; 3) the amount of OPB determined with HPLC-FLD. In comparison to the native sample (no CD), all the samples containing CDs were significantly lighter, redder, and yellower. It was impossible to carry out particle size analysis for the native sample due to the loss of its powder properties soon after the exposure to the air (the sample absorbed moisture and turned into gummy consistency). The studied stability parameters revealed that randomly methylated β-CD (RAMEB) and hydroxypropyl β-CD (HPB) provided the greatest protection from extracts' disintegration. The examined CDs significantly improved the technological properties of OPE. RAMEB and HPB could be considered as the most appropriate encapsulating agents.
• Hipnotici ne lijece nesanicu, ali kratkorocno mogu ublažiti simptome. • Prije pocetka uzimanja ... more • Hipnotici ne lijece nesanicu, ali kratkorocno mogu ublažiti simptome. • Prije pocetka uzimanja terapije, potrebno je utvrditi uzrok nesanice te ga odgovarajuce lijeciti, kada je to moguce. • Hipnotici bi se trebali koristiti samo kratkorocno (2-4 tjedna) ; dugorocna redovita primjena dovodi do razvoja tolerancije, ovisnosti i ostalih nuspojava. • Higijena spavanja, tehnike opustanja i psiholoske metode su u pacijenata s nesanicom dugorocno ucinkovitije od hipnotika. • Nebenzodiazepinski hipnotici ('Z-lijekovi') poput zopiklona, zolpidema i zaleplona imaju slicna farmakoloska svojstva i profil nuspojava kao i benzodiazepini, ne nude mnoge prednosti te su skuplji od benzodiazepina.
Abstract Natural cyclodextrins (CDs) and their chemically modified derivatives are used nowadays ... more Abstract Natural cyclodextrins (CDs) and their chemically modified derivatives are used nowadays as enabling pharmaceutical excipient capable to increase aqueous solubility of lipophilic drugs, enhance drug chemical stability, reduce volatility, mask unpleasant taste, reduce side effects, and enhance bioavailability, thereby further enabling therapeutic potential and the efficiency of drugs. This chapter provides a brief overview of the CDs chemistry, safety profile, and regulatory status. The mechanism of inclusion complex formation and its fate upon administration to the body is concisely described. The examples of CD-based products in clinical practice and development aimed for parenteral, ocular, nasal, oral, oromucosal, and (trans)dermal administration are presented, critically discussing the benefits and limitations related to CD application in the dosage form development. Finally the use of CDs as novel therapeutically active agents is presented.
Olive oil mill waste obtained after two-phase olive oil extraction process was subjected to conve... more Olive oil mill waste obtained after two-phase olive oil extraction process was subjected to conventional liquid solvent extraction under different pH/temperature/duration conditions using different types of food-grade solvents. The independent variables were: solvent type (ethanol percentage), extraction temperature (20-90 °C), extraction time (30 min-24 h) and pH (210.3) of extraction solvent while the response variables were total phenolic content and antioxidant activity of obtained extracts. The optimum solvent extraction conditions for phenols were 120 min at 70 °C using 60% ethanol as extraction solvent, at solvent to sample ratio 5:1 (v/w). For quantification of major bioactive olive polyphenols hydroxytyrosol, tyrosol and oleuropein in obtained extracts, fast and simple RP-HPLC-DAD method was developed and validated. Oleuropein was presented in highest amounts with average value of 115.14±0.19 mg/kg of fresh olive pomace.
Elimination of cariogenic bacteria from dental film is an important step in prevention and treatm... more Elimination of cariogenic bacteria from dental film is an important step in prevention and treatment of dental conditions and of related systemic diseases. Triclosan (TR), a broad spectrum antibacterial agent, is a possible candidate for this aim. However, to obtain effective TR levels in the oral cavity, there is the need of developing a suitable formulation allowing both a prolonged in situ residence and a controlled drug release. The design of such formulation is a particularly challenging issue for a poorly soluble drug as TR, due to the limited amount of saliva in the mouth, acting as dissolution medium. Based on these premises, we considered it worthy of interest to develop a TR mucoadhesive buccal formulation, by using pectin-Carbopol combinations as mucoadhesive matrix-forming polymer, and exploiting cyclodextrin (CD) complexation (with polymeric or native sCD) for improving drug solubility and optimising its release rate from the matrix. Phase-solubility studies were perfor...
Melatonin is a methoxyindole synthesized and secreted principally by the pineal gland in a circad... more Melatonin is a methoxyindole synthesized and secreted principally by the pineal gland in a circadian fashion. lt is also synthesized in other organs,
Ispitano je nastajanje inkluzijskih kompleksa lorazepama i risperidona s hidroksipropil-β-ciklode... more Ispitano je nastajanje inkluzijskih kompleksa lorazepama i risperidona s hidroksipropil-β-ciklodekstrinom (HP-β-CD) u otopini i u cvrstom stanju. U
The aim of this work was to develop pH-responsive microspheres of zaleplon (ZAL) with delayed dru... more The aim of this work was to develop pH-responsive microspheres of zaleplon (ZAL) with delayed drug release in the ileum, as a novel chronopharmaceutical drug delivery system, suitable for treatment of a specific type of insomnia characterised by premature awaking and inability to fall asleep again. ZAL is rapidly cleared from the body (t1/2=1h), therefore it would be suitable for development of such formulation [2]. Eudragit® L100 (EL100), a 1:1 methacrylatic acid/methylmethacrylate copolymer, with pH dependent solubility (pH>6) was used as the base of this formulation. Microparticles were prepared by spray-drying of ZAL/EL100 dispersion from ethanolic medium (MS1) or from 0.96% aqueous NH4HCO3 solution (MS2), transforming EL100 into soluble, thermolabile ammonium salt. In second case, after spray-drying procedure, EL100 was regenerated by thermal treatment at 85° for 3.5h, eliminating completely soluble ammonium salt from the microparticles, as confirmed by FTIR analysis. All mi...
Echinacea purpurea is used in herbal medicinal products for the prevention and treatment of the c... more Echinacea purpurea is used in herbal medicinal products for the prevention and treatment of the common cold, as well as for skin disorders and minor wounds. In this study, the efficiency of traditional maceration using water and ethanol was compared with the maceration using mixtures of water and glycerol, a non-toxic, biodegradable solvent from renewable sources. It was found that the glycerol–water mixtures were as effective as ethanol/water mixtures for the extraction of caffeic acid derivatives. All the prepared extracts demonstrated notable antiradical properties. Furthermore, an efficient ultrasound-assisted extraction using glycerol–water mixtures was developed using six independent variables. Their levels needed for the maximum extraction of caffeic acid derivatives were as follows: glycerol 90% (m/m), temperature 70 °C, ultrasound power 72 W, time 40 min, and ascorbic acid 0 mg/mL. Under the optimized conditions, ultrasound-assisted extraction was superior to maceration. It...
Poor technological properties of raw olive pomace extracts (OPE) significantly limits its utiliza... more Poor technological properties of raw olive pomace extracts (OPE) significantly limits its utilization as nutraceutical and functional food ingredient. Increasing the share of the main olive pomace biophenols (OPB) and improving physical properties of crude OPE are prerequisites for obtaining a usable extract. To achieve that, we examined encapsulation of OPE with different types and amounts of cyclodextrins (CDs). To determine physical parameters of freeze-dried OPE, CIE LAB color and particle size distribution were analyzed. Stability of crude OPE was examined under accelerated degradation conditions (60 °C, 75% humidity, 45 days). Stability parameters were: 1) total phenolic content; 2) antiradical potential; 3) the amount of OPB determined with HPLC-FLD. In comparison to the native sample (no CD), all the samples containing CDs were significantly lighter, redder, and yellower. It was impossible to carry out particle size analysis for the native sample due to the loss of its powder properties soon after the exposure to the air (the sample absorbed moisture and turned into gummy consistency). The studied stability parameters revealed that randomly methylated β-CD (RAMEB) and hydroxypropyl β-CD (HPB) provided the greatest protection from extracts' disintegration. The examined CDs significantly improved the technological properties of OPE. RAMEB and HPB could be considered as the most appropriate encapsulating agents.
• Hipnotici ne lijece nesanicu, ali kratkorocno mogu ublažiti simptome. • Prije pocetka uzimanja ... more • Hipnotici ne lijece nesanicu, ali kratkorocno mogu ublažiti simptome. • Prije pocetka uzimanja terapije, potrebno je utvrditi uzrok nesanice te ga odgovarajuce lijeciti, kada je to moguce. • Hipnotici bi se trebali koristiti samo kratkorocno (2-4 tjedna) ; dugorocna redovita primjena dovodi do razvoja tolerancije, ovisnosti i ostalih nuspojava. • Higijena spavanja, tehnike opustanja i psiholoske metode su u pacijenata s nesanicom dugorocno ucinkovitije od hipnotika. • Nebenzodiazepinski hipnotici ('Z-lijekovi') poput zopiklona, zolpidema i zaleplona imaju slicna farmakoloska svojstva i profil nuspojava kao i benzodiazepini, ne nude mnoge prednosti te su skuplji od benzodiazepina.
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