La presente tesis consta de dos vertientes interrelacionadas. La primera se centra en intentar cuantificar experimentalmente la contribución energética en disolución de la interacción anión-, mediante el uso de calix[4]pirroles aril substituidos en las posiciones meso- como moléculas modelo. El trabajo realizado muestra que la interacción anión- es repulsiva para anillos con valores de ESP negativos y a medida que el efecto electrón atrayente de los sustituyentes aumenta la interacción se vuelve menos repulsiva, hasta que, cuando el valor de ESP en el centro del anillo aromático es positivo la interacción se vuelve ligeramente atractiva. La segunda en el uso de estos receptores simples para obtener arquitecturas supramoleculares más complejas, y su autoensamblaje en capsulas. Los estudios muestran que calix[4]pirroles sustituidos con grupos urea en sus anillos aromáticos se autoemsamblan en capsulas diméricas en presencia de un huesped adecuado como los N-óxidos de alquil aminas y piridinas en disolventes apolares. / This thesis consists of two interrelated aspects. The first one pretends to quantify experimentally the energetic contribution in solution of the anion- interaction, using aryl extended calix[4] pyrroles substituted in their meso- positions as a model system. The work performed shows that the anion- interaction is repulsive for aromatic rings with negative ESP values, as the electron withdrawing character of the substituent increases the interaction becomes less repulsive, until eventually, when the ESP value in the center of the aromatic ring is positive the interaction turns into slightly attractive.The second one is based on the use of these simple receptors as scaffolds to obtain complex structures and their self-assembly into capsules. The studies performed show that aryl extended calix[4]pyrroles substituted with urea functions on their upper rim self-assemble into dimeric capsules in the presence of a suitable guest like the N-oxides of alkyl amines and pyridines in non-polar solvents.

Krūties piktybiniai navikai – viena svarbiausių sveikatos apsaugos problemų visame pasaulyje. Vėžiu ar kita piktybine liga sergantį pacientą turi nuolat stebėti gydytojas onkologas, o lygiagrečiai galima taikyti ir augalų terapiją, kadangi tai padidina chemoterapijos efektyvumą ir padeda sumažinti nepageidaujamą jos pašalinį poveikį. „Onkofit M“ receptūrą pasiūlė Prof. Dr. V. F. Korsun. Darbe aprašomas „Onkofit M“ preparatų (vaistažolių arbatos ir kietųjų kapsulių su sausaisiais augaliniais ekstraktais) technologijos kūrimas ir pateikti vaistinių augalinių žaliavų, įeinančių į “Onkofit M” sudėtį, aprašymai, farmakologiniai poveikiai, cheminės sudėtys, kurie pagrindžia pasirinkimą. Nustatyta, kad sausųjų augalinių ekstraktų mišinio technologinės savybės nepalankios kapsuliavimui, todėl jos suteiktos modeliuojant pagalbines medžiagas bei jų kiekius. Parinkta „Onkofit M“ kapsuliuojamos masės sudėtis. Teisingas mišinio sudėties parinkimas patvirtintas UAB „Aconitum“ – pagaminta eksperimentinė serija pilotiniam tyrimui. Patikrintas eksperimentinės serijos „Onkofit M“ kapsulių stabilumas. Parinkta placebo kapsuliuojamos masės sudėtis ir pagamintos pilotiniam tyrimui reikalingos placebo kapsulės. Paruoštas ir supakuotas į popierinius maišelius vaistažolių mišinys arbatai, vertintas jo stabilumas. / Malignant breast tumours – one of the most important health care issues in the world. A patient who is having a cancer must be constantly monitored by an oncologist and at the same type fitotherapy may be applied as well that can improve the efficiency of chemotherapy and reduce its side effects. The formula of “Onkofit M” has been introduced by V. F. Korsun. The development of the technology of “Onkofit M” preparations (herbal teas and solid capsules with dry extracts) description of herbal ingredients, pharmacological effects, chemical composition that validate the choice of certain components, are represented in this study. It has been identified that technological properties of dry plant extracts mixture are not suitable for capsulation; therefore they have been improved while varying types and amounts of additives. The proper composition of “Onkofit M” was selected and it was approved by UAB “Aconitum” – the experimental batch was manufactured for the pilot research. The stability of the experimental batch of “Onkofit M” capsules was tested. The composition of placebo capsules was determed and batch of such capsules was also manufactured for the pilot research. Herbal tea was prepared and packaged in paper bags; stability tests were performed as well.

<p>In conclusion, the results obtained firstly indicated that the BP, EMEA and WHO were in fairly good agreement on the criteria and specifications that can be used to assesses the pharmaceutical quality of a traditional plant medicine such as Phela. Secondly, the Phela plant powders were found to have acceptable pharmaceutical properties that did not complicate or adversely affected the capsule manufacture. Thirdly, the Phela capsules produced were generally of acceptable pharmacopoeial standard. Fourthly, HPLC fingerprinting and pattern recognition analysis proved useful to examine the chemical stability of selected marker compounds of Phela and indicated that the capsules had no practical shelf life under elevated temperature and humid conditions. Overall, the Phela capsules should thus be suitable for use in a short time clinical trial, but for use in a long period trial the long term stability of the Phela capsules under ambient conditions must still be confirmed.</p>

Kauno gamybinėse vaistinėse dozuoti milteliai yra dažnai gaminama vaisto forma ir sudaro 11,58 proc. ekstemporalių kartinių vaistų. Miltelių gamyba, pakuojant į popierines kapsules, nėra pakankamai racionali. Pacientų atžvilgiu – tai nesandari laikyti ir nepatogi vartoti vaisto forma, todėl miltelius racionaliau yra pakuoti į kietąsias, skrandyje suyrančias kapsules. Šio darbo tikslas - nustatyti ir įvertinti dažniausiai vaistinėse pasitaikančių miltelių kapsuliavimo sąlygas. Tyrimo objektai yra sudėtiniai milteliai ir jais užpildytos kapsulės. Taikyti tyrimų metodai: miltelių technologinių savybių nustatymo metodai (Carr indeksas, Hausner koeficientas, kūgio kampas), kapsulių masės vienodumo ir stabilumo nustatymo – gravimetriniai metodai. Atrinktos dažniausiai vaistinėse gaminamos ekstemporalių kartinių miltelių sudėtys. Aspkaičiavus papildomus pagalbinių medžiagų kiekius atrinktoms miltelių sudėtims, jie pritaikyti pakuoti į kietąsias skrandyje suyrančias kapsules. Įvertinta papildomos pagalbinės medžiagos kiekio įtaka technologinėms miltelių mišinių savybėms ir dozavimo tikslumui. Atlikti užpildytų kapsulių kokybės ir stabilumo tyrimai stebint kapsulių masės vienodumą, turinio drėgmės kiekį ir kapsulių suirimo laiką. Parinkus dažniausiai vaistinėse gaminamų ekstemporalių kartinių miltelių receptūras, modeliuojant papildomus pagalbinės medžiagos kiekius, miltelių mišinys pritaikytas kapsuliavimui. Naudotos rankinės kapsulių pildymo mašinėlės “Capsuline – 15”, “Capsuline... [toliau žr. visą tekstą] / Powder is often produce drug form in Kaunas industrial pharmacy and consists of 11,58 per cent. Powder manufacture, packing in paper caps are not rational enough. An attitude of patient, this formulation is leaking and inconvenient to use. Powder is more rational packed in solid gastro - soluble capsules. The aim of this research is to set the encapsulation conditions of commonly occurring powder mixtures. The study objects are composite powders and hard gelatin capsules filled them. Research methods have been applied in this study: methods for determining powder technological properties (Carr index, Hausner ratio, angle of reponse), capsule mass uniformity and stability tests. Commonly produced extemporaneous powder mixtures in pharmacies were selected. Estimated an additional content of adjuvant substances for powder compositions and applied to the encapsulation of hard gelatin capsules. Evaluated influence of the estimated content of adjuvant substances on the technological properties of the powder mixture and dosing accuracy. Perform filled capsules quality and stability studies monitoring of moisture content in capsules, mass uniformity and disintegration time of capsules. Modeling of adjuvant substances quantities, powder mixture applied for capsulation. Manual capsule filling machines “Capsuline – 15”, “Capsuline – 60” and semi-automatic capsule filling machine “Feton Fastlock 100” were used. The uniformity of capsules mass and stability studies of produced... [to full text]

Darbo tikslas – parengti augalinės žaliavos granuliavimo ir kapsuliavimo technologiją, atlikti biofarmacinius tyrimus ir panaudojus gautus rezultatus pagaminti eksperimentinę kapsuliuoto produkto seriją. Darbo uždaviniai: Įvertinti karčiojo kiečio augalinių miltelių technologines savybes; Parinkti ir pritaikyti tinkamą granuliavimo technologiją; Atlikti granulių kokybės vertinimą; Pritaikyti augalinės žaliavos kapsuliavimo technologiją; Atlikti kapsulių kokybės vertinimą ir biofarmacinius tyrimus, palyginti ir įvertinti laboratorijoje ir pusiau pramoniniu būdu pagamintų kapsulių kokybės rodiklius. Tyrimo objektas – karčiojo kiečio milteliai ir jų pagrindu pagaminti produktai. Metodai: atliktas karčiojo kiečio miltelių vertinimas, nustatant miltelių birumą, kūgio kampą ir suberiamąjį tankį. Drėgnos granuliacijos būdu pagamintoms granulėms nustatytas procentinis drėgmės kiekis, atliktas suberiamojo tankio nustatymas, išmatuotas granulių dydis. Įvertinta vidutinė kapsulių masė, nustatytas kapsulių suirimo laikas ir bendras fenolinių junginių kiekis išsiskiriantis iš vienos kapsulės. Rezultatai: karčiojo kiečio milteliai yra nebirūs, įsielektrinę, vidutinis dalelių dydis – 22,15 µm, jos nelygiais kraštais. Atlikus drėgną granuliaciją miltelių dalelės tapo lygesniais kraštais, vidutinis dydis – 16,67 µm. Daugeliu atveju suberiamasis tankis viršijo 0,3 g/cm3, išskyrus 2 proc. želatinos tirpalą ir 64 proc. cukraus sirupo tirpalą. Didžiausią kapsulės svorį pasiekėme su 5 proc... [toliau žr. visą tekstą] / Objective of work: to prepare plant material granulation and encapsulation technology to perform biopharmaceutical research and use the results to produce a series of experimental encapsulated product. Tasks: Evaluate wormwood plant powder technological features; Select and apply appropriate granulation technology; Perform pellet quality; Adapt plant material encapsulation technology; Perform quality assessment capsules and biopharmaceutical research, compare , and evaluate laboratory and semi- industrial scale capsules made of quality indicators. The object of investigation – wormwood powder and products based on this material. Method: wormwood powder biopharmaceutical evaluation set pourability, cone angle and tapped density. Wet granulation extruded pellets fixed percentage of moisture carried tapped density of measured grain size. The estimated average weight of capsules set time capsule disintegration and total phenolic compounds, different from one capsule. Results: wormwood powder is non – bulk, charged an average particle size – 22.15 μm, it’s rough edges. After a wet granulation powder particles become more even edges, the average size – 16.67 μm. In most cases, tapped density over 0.3 g/cm3, with the exception of 2 percent gelatin solution and 64 percent sugar syrup solution. The greatest weight of the capsule reached the 5 percent gelatine, 5 percent. methylcellulose and 64 percent granulate sugar syrup. The hardest part was filled in capsules granulate made with... [to full text]

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Alabama at Birmingham, 2007. / Title from first page of PDF file (viewed Feb. 18, 2009). Includes bibliographical references.

Thesis (Ph. D.)--University of Alabama at Birmingham, 2007. / Title from first page of PDF file (viewed June 23, 2008). Includes bibliographical references.

A biodisponibilidade é uma característica decisiva para a eficácia dos medicamentos, podendo sua intensidade ser estimada através da cedência "in vitro". Vários fatores são capazes de influenciá-la, entre eles a composição quali e quantitativa dos adjuvantes, assim como as características da substância ativa e da forma farmacêutica. A hidroclorotiazida é um diurético de amplo emprego, que apresenta problemas de biodisponibilidade e bioequivalência devido a sua baixa hidrossolubilidade. Através de planejamento fatorial 2 3 foram preparadas formulações de cápsulas de gelatina dura contendo 50 mg de hidroclorotiazida. Foi analisada a influência dos fatores material de enchimento (lactose e celulose microcristalina), reguladores de fluxo (dióxido de silício altamente disperso e estearato de magnésio) e hidrofilizante (polissorbato 80) sobre as características de qualidade dos complexos farmacêuticos e das cápsulas. O regulador de fluxo ou a interação entre este e o material de enchimento foram os fatores determinantes nas características de fluxo dos complexos farmacêuticos, analisadas através do ângulo de repouso e do índice de compressibilidade. A cedência "in vitro" das cápsulas, determinada com auxílio de aparelho de célula de fluxo e parametrizada pela eficiência de dissolução, foi influenciada preponderantemente pelo regulador de fluxo. Foram comparados os perfis de cedência "in vitro" entre as cápsulas e comprimido do mercado. O comportamento intermediário demonstrado pelo comprimido indica a necessidade de avaliação comparativa entre medicamentos contendo hidroclorotiazida a fim de assegurar sua bioequivalência. / The bioavailability is a decisive characteristic to drugs efficacy that can be predict by different "in vitro" dissolution methods. The bioavailability has been shown to be dependent on factors such as the drug, the dosage forms, type and quality of adjuvants. Hydrochlorothiazide is a widely used diuretic. Due to its limited aqueous solubility, this drug has potencial bioavailability problems. Eight differents hydrochlorothiazide hard gelatin capsules, containing 50 mg of the drug, were prepared according to a 2 3 factorial design. The influence of fillers (lactose or microcrystaline cellulose), glidants (magnesium stearate or coloidal silicon dioxide) and surfactant (polysorbate 80) on the pharmaceutical characteristics of powder mixtures and capsules were evaluated. The powder mixtures flow characteristics were evaluated through repose angle and compressibility index. It was determined that the glidant and its interaction with filler influenced this characteristic. The "in vitro" release of hydrochlorothiazide from capsules was carried out by a open flow-though dissolution method. The dissolution efficiency was the selected parameter to express the drug release. The glidant was the determinant factor. The dissolution profile of these capsules and marketed tablets was compared. The results evidenced the importance of comparative evaluation of hydrochlorothiazide dosage forms to assure their bioequivalence.

The use of minocycline for the treatment of a broad range of systemic infections and for severe acne has been associated with vestibular side effects. The severity of side effects may lead to poor adherence to therapy by patients. The use of sustained release formulations of minocycline that display slow dissolution of minocycline following administration may be beneficial in reducing the incidence and severity of side effects. Therefore, sustained release capsule dosage forms containing 100 mg minocycline (base) were manufactured and assessed for use as sustained release oral dosage forms of minocycline. Minocycline sustained release capsules were manufactured based on matrix technologies using hydroxypropylmethyl cellulose (HPMC) and Compritol® as release retarding polymers. The rate and extent of minocycline release from the capsules was evaluated using USP Apparatus 1 and samples were analysed using a validated High Performance Liquid Chromatographic (HPLC) method with ultraviolet (UV) detection. Differences in the rate and extent of minocycline release from formulations manufactured using HPMC or Compritol® were influenced by the concentration of polymer used in the formulations. The rate and extent of minocycline release was faster and greater when low concentrations of polymer were used in formulations. The effect of different excipients on the release pattern(s) of minocycline and particularly their potential to optimise minocycline release from experimental formulations was investigated. The use of diluents such as lactose and microcrystalline cellulose (MCC) revealed that lactose facilitated minocycline release when HPMC was used as the polymer matrix. In contrast, the use of lactose as diluent resulted in slower release of minocycline from Compritol® based formulations. The addition of sodium starch glycolate to HPMC based formulations resulted in slower release of minocycline than when no sodium starch glycolate was used. Compritol® based formulations were observed to release minocycline faster following addition of sodium starch glycolate and Poloxamer 188 to experimental formulations. In vitro dissolution profiles were compared to a target or reference profile using the difference and similarity factors, ƒ1 and ƒ2 , and a one way analysis of variance (ANOVA). In addition, the mechanism of minocycline release was elucidated following fitting of dissolution data to the Korsmeyer-Peppas, Higuchi and Zero order models. Minocycline release kinetics were best described by the Korsmeyer-Peppas model and the values of the release exponent, n (italics), revealed that drug release was a result of the combined effects of minocycline diffusion through matrices and erosion of the matrices. These in vitro dissolution profiles were better fit to the Higuchi model than to the Zero order model. Two formulations that displayed a fit to the Zero order model were identified for further studies as potential dosage forms for sustained release minocycline.