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Polymeric Materials for the Controlled Drug Delivery and Controlled Release of Active Substances
Chamradová, Ivana ; Kučerík, Jiří (referee) ; Lehocký,, Marián (referee) ; Vojtová, Lucy (advisor)
Literární rešerše předložené dizertační práce shrnuje poznatky jak o současně používaných biomateriálech, tak i o tzv. „chytrých“ biomedicínských materiálech mezi které patří termocitlivé kopolymery. Mezi tyto kopolymery, jejichž vodné roztoky gelují při teplotě lidského těla (37 °C), řadíme amfifilní triblokové kopolymery skládající se z hydrofobního laktidu, glykolidu a hydrofilního polyethylen glykolu (PLGA PEG PLGA). Komerčně dostupné termocitlivé kopolymery známé pod názvem ReGel or OncoGel jsou v současné době využívány jako injekčně aplikovatelné nosiče s postupným uvolňováním léčiv, zejména při léčbě cukrovky nebo onkologického onemocnění. Nicméně PLGA PEG PLGA triblokový kopolymer může být použit I jako polymerní nosič anorganického léčiva případně jako biodegradabilní implantát v dentálních či ortopedickýchých aplikacích. Z toho důvodu byl vybrán anorganický biokompatibilní hydroxyapatit (HAp) pro své majoritní zastoupení v tvrdých tkáních. Experimentální část je zaměřena na přípravu HAp/PLGA PEG PLGA kompozitů, ve kterých je HAp buď ve formě nano- (n-HAp) nebo „core-shell“ částic (CS). Nové CS částice, připravené dvouemulzní metodou, jsou složeny z „tuhého“ HAp jádra obaleného termocitlivým kopolymerem, který je navíc funkcionalizován kyselinou itakonovou (ITA/PLGA PEG PLGA/ITA). Funkcionalizace pomocí ITA vnáší do původní struktury kopolymeru jak síťovatelné dvojné vazby, tak i koncové karboxylové skupiny. Volné karboxylové skupiny na koncích ITA/PLGA PEG PLGA/ITA kopolymerního obalu byly dále zesíťovány za vzniku 3D chemické sítě (CS-x), jejíž životnost je řízena a kontrolována. ATR-FTIR spektroskopie prokázala přítomnost „nových“ esterových vazeb vzniklých karbodiimidovou reakcí –OH a –COOH skupin, kterým náleží adsorpční pásy ve vlnové délce 1021 cm-1.. n-HAp a CS-x částice byly přidány do kopolymerní termocitlivé matrice (PLGA PEG PLGA) za účelem charakterizace jejich reologického chování. Bylo zjištěno, že pokud bylo do polymerní matrice přidáno méně než 10 hm. % CS-x částic a jen 5 hm.% n-HAp kompozit si zachoval své termocitlivé vlastnosti. Na druhou stranu, přídavek vyššího množství HAp částic do polymerní matrice zajistil změnu vodného polymerního solu v permanentní gel při teplotě nad 37 °C. Analýza ICP-OES prokázala rychlejší uvolňování CS-x částic z 10 hm/obj. % PLGA PEG PLGA polymerní matrice do inkubačního média (6 % 9. den) než tomu bylo u n-HAp částic (jen 3 %), které jsou vázány více v micelární struktuře kopolymeru. Proto, kompozit na bázi n-HAP částic tvořící tuhý trvalý gel při tělesné teplotě, je vhodný více jako biologicky rozložitelné kostní lepidlo, zatímco kompozit z CS-x částic a termocitlivého kopolymeru je vhodný jako nosič léčiv pro injekční aplikace.
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Formulation of vancomycin loaded PLGA nanoparticles for local treatment of musculoskeletal infections II.
Ptáčková, Karolína ; Šnejdrová, Eva (advisor) ; Zbytovská, Jarmila (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Karolína Ptáčková Title of thesis: Formulation of vancomycin loaded PLGA nanoparticles for local treatment of musculoskeletal infections II. Supervisor: PharmDr. Eva Šnejdrová, Ph.D. Consultant: Mgr. Vladislav Frolov The aim of the work was to formulate vancomycin hydrochloride (Van-HCl) loaded PLGA nanoparticles (NPs) using a double emulsion method for the local treatment of musculoskeletal infections. During preparation, selected critical formulation factors were modified and their influence on the characteristics of nanoparticles was studied. The size of the NPs determined by the DLS method ranged from 200 to 800 nm, the PDI was lower than 0.2 in most batches. The encapsulation efficiency (EE) determined by the direct method ranged from 2 % to 9 %. Glycerol monostearate at a concentration of 15 mg/ml proved to be a suitable primary emulsion stabilizer. The optimal concentration of PVA for stabilizing the nanosuspension was 30 mg/ml. The size of the NPs was influenced by the intensity of homogenization and the concentration of PVA. The concentration of Van-HCl, the organic solvent used and the intensity of homogenization led to an increase in EE. The DSC method confirmed that Van-HCl remains...
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Formulation of vancomycin loaded PLGA nanoparticles for local treatment of musculoskeletal infections I.
Petrášová, Ivana ; Šnejdrová, Eva (advisor) ; Smékalová, Monika (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Pharmaceutical Technology Author: Ivana Petrášová Title of thesis: Formulation of PLGA nanoparticles with vancomycin for local treatment of musculoskeletal infections I Supervisor: PharmDr. Eva Šnejdrová, Ph.D. The treatment of musculoskeletal infections requires the presence of high antibiotics concentration at the infection site. However, high doses of orally administered drugs cause the risk of increased systemic toxicity and serious adverse effects. Targeted drug delivery, currently one of the main areas of pharmaceutical research, represents a suitable option of a treatment without excessive burden on the organism. This diploma thesis focuses on the formulation of a therapeutic system for the local treatment of musculoskeletal infections in the form of polymer nanoparticles containing the antibiotic vancomycin. Due to the need of incorporation of a hydrophilic antimicrobial substance into them, the suspension-emulsion method of their preparation was used. Different concentrations of polyvinyl alcohol stabilizer and tripentaerythritol branched hydrophobic polymer poly(D,L- lactide-co-glycolide) were used for the preparation. Within the study the size of nanoparticles, polydispersity, zeta potential, encapsulation efficiency...
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Formulation and characterization of w/o emulsions for local treatment of musculoskeletal infections
Vedralová, Štěpánka ; Šnejdrová, Eva (advisor) ; Mužíková, Jitka (referee)
CHARLES UNIVERSITY Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical technology Author: Štěpánka Vedralová Title of diploma thesis: Formulation and characterization of w/o emulsions for local treatment of musculoskeletal infections Supervisor: PharmDr. Eva Šnejdrová, Ph.D. The aim of the diploma thesis was to formulate a depot dosage form for the prevention and local treatment of musculoskeletal infections. A water-in-oil emulsions have been formulated which, due to the partition coefficient between the outer and inner phases, can provide sustained drug release. Oils with different viscosities were tested as oil phases. Tricaprin was chosen for the preparation of emulsions, due to the highest stability of the prepared emulsion. Lecithin and sorbitan monooleate or polyglyceryl-3-polyricinooleate (PGPR) and magnesium stearate were used as emulsifiers. The aqueous phase was a solution of vancomycin hydrochloride and gentamicin sulphate. The flow properties on a rotational rheometer were evaluated. The influence of the emulsion composition and the homogenization method on the coefficient of consistency and the index of flow behaviour of the emulsions was studied. The emulsions stabilized with lecithin have a higher viscosity and a structure more sensitive to changes in composition...
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Formulation and characterization of hydrogels for local treatment of musculoskeletal infections
Drdová, Pavlína ; Šnejdrová, Eva (advisor) ; Vraníková, Barbora (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Pharmaceutical Technology Author: Pavlína Drdová Title of thesis: Formulation and characterization of hydrogels for local treatement of musculoskeletal infection Supervisor: PharmDr. Eva Šnejdrová, Ph.D. Local anti-infective therapy for musculoskeletal infections eliminates systemic drug toxicity. By selecting a suitable drug delivery system, higher drug concentrations at the site of infection and sustained release can be achieved. Such a system may be gels, formulated and tested in the submitted diploma thesis. The theoretical part of the work was devoted to the description of musculoskeletal infections and their treatment, characterization of gels and their use in parenteral administration. Hydrophilic gels based on hypromellose, carrageenan, gelatin and fish gelatin containing vamcomycin hydrochloride and gentamicin sulfate were formulated. Flow and viscoelastic properties were tested on a rotational rheometer. The analysis of flow curves by the Power law model proved a non-Newtonian type of flow. The most sensitive to applied stress is a 3 % hypromellose gel, the least a dispersion of iota-carrageenan with povidone 25. Viscoelastic properties were evaluated based on elastic, viscous and complex modulus, phase angle and yield...
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Formulation and characterization of w/o emulsions for local treatment of musculoskeletal infections
Vedralová, Štěpánka ; Šnejdrová, Eva (advisor) ; Mužíková, Jitka (referee)
CHARLES UNIVERSITY Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical technology Author: Štěpánka Vedralová Title of diploma thesis: Formulation and characterization of w/o emulsions for local treatment of musculoskeletal infections Supervisor: PharmDr. Eva Šnejdrová, Ph.D. The aim of the diploma thesis was to formulate a depot dosage form for the prevention and local treatment of musculoskeletal infections. A water-in-oil emulsions have been formulated which, due to the partition coefficient between the outer and inner phases, can provide sustained drug release. Oils with different viscosities were tested as oil phases. Tricaprin was chosen for the preparation of emulsions, due to the highest stability of the prepared emulsion. Lecithin and sorbitan monooleate or polyglyceryl-3-polyricinooleate (PGPR) and magnesium stearate were used as emulsifiers. The aqueous phase was a solution of vancomycin hydrochloride and gentamicin sulphate. The flow properties on a rotational rheometer were evaluated. The influence of the emulsion composition and the homogenization method on the coefficient of consistency and the index of flow behaviour of the emulsions was studied. The emulsions stabilized with lecithin have a higher viscosity and a structure more sensitive to changes in composition...
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Formulation and characterization of hydrogels for local treatment of musculoskeletal infections
Drdová, Pavlína ; Šnejdrová, Eva (advisor) ; Vraníková, Barbora (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Pharmaceutical Technology Author: Pavlína Drdová Title of thesis: Formulation and characterization of hydrogels for local treatement of musculoskeletal infection Supervisor: PharmDr. Eva Šnejdrová, Ph.D. Local anti-infective therapy for musculoskeletal infections eliminates systemic drug toxicity. By selecting a suitable drug delivery system, higher drug concentrations at the site of infection and sustained release can be achieved. Such a system may be gels, formulated and tested in the submitted diploma thesis. The theoretical part of the work was devoted to the description of musculoskeletal infections and their treatment, characterization of gels and their use in parenteral administration. Hydrophilic gels based on hypromellose, carrageenan, gelatin and fish gelatin containing vamcomycin hydrochloride and gentamicin sulfate were formulated. Flow and viscoelastic properties were tested on a rotational rheometer. The analysis of flow curves by the Power law model proved a non-Newtonian type of flow. The most sensitive to applied stress is a 3 % hypromellose gel, the least a dispersion of iota-carrageenan with povidone 25. Viscoelastic properties were evaluated based on elastic, viscous and complex modulus, phase angle and yield...
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Influence of formulation factors on the characteristics of terbinafine loaded nanoparticles.
Barák, Vlastimil ; Šnejdrová, Eva (advisor) ; Dittrich, Milan (referee)
CHARLES UNIVERSITY FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY Author: Vlastimil Barák Title of Diploma thesis The influence of formulation factors on the characteristics of terbinafine loaded nanoparticles Supervisor: PharmDr. Eva Šnejdrová, Ph.D. Consultant: Mgr. Juraj Martiška The diploma thesis is focused on biodegradable polymer nanoparticles loaded by terbinafine based on the copolymer of glycolic and lactic acid branched on polyacrylic acid. The nanoprecipitation method was employed, and the influence of formulation factors on nanoparticle characteristics was studied. The following formulation factors were the concentration of the polymer, the amount of terbinafine, and the concentration of surfactant. Nanoparticles of 120 nm to 300 nm were obtained depending on the preparation conditions. The nanoparticle polydispersity was in all cases from 0.080 to 0.230. The prepared nanoparticles were stable, as evidenced by zeta potential values above 38 mV. A positive zeta potential is desirable for dermal and mucosal adhesion in the topical and ocular application of nanoparticles with terbinafine. The amount of polymer used to form nanoparticles has the greatest effect on particle size. With increasing polyester concentration in the internal phase, the size of the...
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Terbinafine-loaded biodegradable polymeric systems for topical administration
Pokorná, Tereza ; Šnejdrová, Eva (advisor) ; Dittrich, Milan (referee)
CHARLES UNIVERSITY FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY Author: Tereza Pokorná Title of Diploma thesis Terbinafine-loaded biodegradable polymeric systems for topical administration Supervisor: PharmDr. Eva Šnejdrová, Ph.D. In the diploma thesis the released properties of solid dispersions with terbinafine, based on polyesters of D,L-lactic acid and glycol acid, branched with pentaerythritol and tripentaerythritol are studied. The theoretical part deals with solid dispersions, their classification and methods of preparation, methods of drug dissolution testing, properties, effect, use of terbinafine and preparations containing terbinafine. In the experimental part, solid dispersions were prepared by the melting method. The drug was incorporated into the polyester in the form of a hydrochloride or a base in a concentration of 10 % or 20 %. Some systems were plasticized with 30% triethyl citrate. Thin layers were formulated from solid dispersions, and drug dissolution tests were performed on phosphate buffer pH 7.4 at 37 řC. Assay of terbinafine released was performed spectrophotometrically at 223 nm and ultra-high performance liquid chromatography. Based on the results of this diploma thesis, it can be clearly stated that the suitable carrier of terbinafine...
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Influence of formulation factors on the characteristics of terbinafine loaded nanoparticles.
Barák, Vlastimil ; Šnejdrová, Eva (advisor) ; Dittrich, Milan (referee)
CHARLES UNIVERSITY FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY Author: Vlastimil Barák Title of Diploma thesis The influence of formulation factors on the characteristics of terbinafine loaded nanoparticles Supervisor: PharmDr. Eva Šnejdrová, Ph.D. Consultant: Mgr. Juraj Martiška The diploma thesis is focused on biodegradable polymer nanoparticles loaded by terbinafine based on the copolymer of glycolic and lactic acid branched on polyacrylic acid. The nanoprecipitation method was employed, and the influence of formulation factors on nanoparticle characteristics was studied. The following formulation factors were the concentration of the polymer, the amount of terbinafine, and the concentration of surfactant. Nanoparticles of 120 nm to 300 nm were obtained depending on the preparation conditions. The nanoparticle polydispersity was in all cases from 0.080 to 0.230. The prepared nanoparticles were stable, as evidenced by zeta potential values above 38 mV. A positive zeta potential is desirable for dermal and mucosal adhesion in the topical and ocular application of nanoparticles with terbinafine. The amount of polymer used to form nanoparticles has the greatest effect on particle size. With increasing polyester concentration in the internal phase, the size of the...
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