Cromolyn sodium (CS) is a mast cell stabilizer which has been used to treat systemic mastocytosis, allergic- and exercise-induced asthma, and allergic reactions induced by atopic dermatitis. Presently, CS is administered orally and intranasally, and with a short half-life and poor absorption, 4 to 8 doses are required daily for treatment. Developing a transdermal product for CS would eliminate such drawbacks that lead to inconsistent patient dosing and provide sustained therapeutic effects when administered via skin. Our long-term goal is to determine the feasibility of delivering CS through skin. However, a prerequisite for evaluating the performance of any transdermal system is to have a sensitive analytical method that can selectively detect and quantify the drug without any interference from compounds that may leach from skin during permeation studies. Therefore, our preliminary goal was to develop and validate such a method that can be employed for transdermal studies. The optimized liquid chromatography-mass spectrometry (LC-MS) method utilized a chromatographic separation which involved an isocratic mobile phase (10mM ammonium bicarbonate, pH 8.0, 90% and acetonitrile, 10%) at a flow rate of 0.2500 mL/min. Detection involved direct MS/MS channels with m/z 467.0255 (precursor) and m/z 379.0517 (fragment) with argon as the collision gas. CS calibrants were prepared in phosphate-buffered saline (PBS), pH 7.4, for validation (0.1, 0.25, 0.5, 0.75, 1, and 2.5 μg/mL). To ensure no skin interference, dermatomed porcine ear skin was minced, placed in PBS, and shaken for 15 hours to extract any possible interfering components. The extract was filtered and analyzed with the optimized LC-MS conditions. Calibrants were also analyzed over 3 days with each day examining 6 injections (20 μL) of each sample. Peak areas determined by LC-MS were used to construct calibration curves for CS and to calculate % error and % RSD to elucidate accuracy and precision of the method. Results showed CS retention time to be around 4.4 minutes with no interfering peak from skin extract, and linearity was observed between 0.1-2.5 μg/mL. Inter- and intra-day accuracy and precision of the method were within the acceptable limit of ±20% at the lower limit of quantitation and ±15% at other concentrations. Future studies will involve using the validated method for quantification of CS in skin permeation studies to investigate our long-term goal.

A Oiss{!y'tation $uhm'itted in fulfilment of the r~;~airements, for' the degree of f·1aster· oi~'j Science at the University of the ~titwatersrand ' Juhanoasbul"g January 1991 / An attempt was made to separate ribosomal subunits by gel filtl'ation on Trisacryl GF2000 and Sepharose 4B. Trisacryl GP~2000,a sYllthet'ic gol, , separated rat .ljver rlbosonal subunits orl 'f~'135,em column with a resolution of ""Or3, resulting 'in <'1" 60 rJ impm''ity 'of each of the \~ subunits. subunits" were not resolved. Sepharose 4131 an agarose based gol, separated " the subunits by adsorpttcn chromatography rathr.r than 'i>.V () Q ':) At 4°C, the 405 .subunf ts were eluted with a kd () ruO,:~9( but the GOrf' $ubud"its adsorbed to th~.'g,~Jl and were eluted I; /) when the temperature of "the column was increas~d to 250C..3SoC. (' ,. ('-. This edsorpt ion phenonenon seems to b{~ tl propert~ of a 11 agllrose -: \') ~\:; based gels studied here, includ'ing Sepharose 2.B and .seph'ato~eoBt arid is exc 1us iva to !,mamm'i'lan r ibosOIntrt subuni ts • Anal,ys1S 0'(" the , u subunits by in vitro r14C]polypheny1alanine sy'nthes'is showed OCI " ,,'c. /\ I 7', " diff'erence 'in the act lvtt ies of dbosoma'J ~ubunH~ p~epdrf#d by ;/'/ ' grndient centrifugation or by 5epharos,e cni"OmatogNPPY;' Analy~ii ~~of " (~ (( the subunits by ~crylamidec'ugarose coU)po5it~) gs1s resulted ,in the '/ resolution ,.:n"f subunits isolated fr'oill lower organisms in o II non-denaturlnq !Jcl systems and SI,lbut1its from m«mm~nan'tissue in II /'\';1 Ga'! f'iltrat'ion does tyffer a 5t!i:l;~'ble metrKld'¥or the pr~p;n~¥tiol1of <::) . I \) \\ I) ribosoma 1 'subunits I but only' if 'the act~orption JH'OrJ&~"t'Jo,s of ,) (,) ':' o ,1) ,{

No description available.

No / This study investigated and characterised transdermal permeation of bioactive agents from a topically applied Arnica montana tincture. Permeation experiments conducted over 48 h used polydimethylsiloxane (silastic) and human epidermal membranes mounted in Franz-type diffusion cells with a methanol-water (50:50 v/v) receptor fluid. A commercially available tincture of A. montana L. derived from dried Spanish flower heads was a donor solution. Further donor solutions prepared from this stock tincture concentrated the tincture constituents 1, 2 and 10 fold and its sesquiterpene lactones 10 fold. Permeants were assayed using a high-performance liquid chromatography method. Five components permeated through silastic membranes providing peaks with relative retention factors to an internal standard (santonin) of 0.28, 1.18, 1.45, 1.98 and 2.76, respectively. No permeant was detected within 12 h of applying the Arnica tincture onto human epidermal membranes. However, after 12 h, the first two of these components were detected. These were shown by Zimmermann reagent reaction to be sesquiterpene lactones and liquid chromatography/diode array detection/mass spectrometry indicated that these two permeants were 11,13-dihydrohelenalin (DH) analogues (methacrylate and tiglate esters). The same two components were also detected within 3 h of topical application of the 10-fold concentrated tincture and the concentrated sesquiterpene lactone extract.

Die vorliegende Arbeit befasst sich mit dem Einfluss von Formulierungsparametern auf die nasale In-vitro-Verfügbarkeit der Arzneistoffe Oxymetazolinhydrochlorid (OXY), Xylometazolinhydrochlorid (XYLO) und Natriumcromoglicat (DSCG) und untersucht das Permeationsverhalten von ausgewählten Fertigpräparaten und Eigenrezepturen an exzidierter Rindernasenmukosa sowie deren Wechselwirkungen mit einer Mucinmodelldispersion. Der Vergleich der strukturanalogen Sympathomimetika XYLO und OXY gegeneinander und mit dem Antiallergikum DSCG sollte hinsichtlich der Einfluss nehmenden Parameter den Bezug zur molekularen Struktur und den physikalisch-chemischen Eigenschaften der Arzneistoffe ermöglichen. Eine mit DSCG durchgeführte In-vivo-Studie (Kaninchen) sollte klären, inwieweit die In-vitro-Daten und -Einflussparameter mit dem In-vivo-Verhalten korrelieren. Während im Resümee dieser Arbeit für XYLO und OXY Zusammenhänge zwischen ihren physikochemischen Eigenschaften, ihrer In-vitro-Permeabilität und den getesteten Formulierungsparametern aufgezeigt werden konnten, war dies für DSCG nicht möglich und ein Querbezug nicht gegeben. DSCG zeigt aufgrund seiner nachgewiesenen konzentrationsabhängigen Selbstassoziationstendenz substanzspezifisches Verhalten und reagiert sensibel auf eine Variation der Formulierungsparameter. Sowohl an der isolierten Mukosa als auch mit der Mucinmodelldispersion resultierten ausgeprägte Wechselwirkungen. Eine Kombination von DSCG mit dem Polymer Natriumhyaluronat erwies sich dabei als vorteilhaft, da sich die Mukoadhäsivität in vivo bestätigte. Eine entsprechende Formulierung scheint geeignet die Dosierungshäufigkeit von Natriumcromoglicat zu reduzieren und damit die Patientencompliance zu verbessern. Da die nasale Verfügbarkeit eines Pharmakons das Resultat eines komplexen Wechselspiels zwischen dem Wirkstoff, den vielfältigen Faktoren der applizierten Arzneiformulierung und den physiologischen Gegebenheiten ist, sind Verallgemeinerungen der Zusammenhänge schwierig und isolierte Effekte kaum zu erfassen. Die vorliegenden Resultate verdeutlichen jedoch, wie eminent wichtig die separate Betrachtung jedes Wirkstoffpräparates ist. / This thesis presents the formulation parameter's influence on the nasal in vitro availability of the model drugs xylometazoline hydrochlorid (XYLO), oxymetazoline hydrochlorid (OXY) and disodium cromoglycate (DSCG). The nasal availability has been studied using excised nasal bovine mucosa to capture the drug's in vitro permeation behaviour and a mucin model dispersion to determine the drug's interactions with the nasal mucus glycoproteins. The aim of this thesis was to determine the influence of different additionals on the nasal availability using commercial and test preparations of the model drugs. Comparing the results of the sympathomimetic XYLO, its hydroxy derivative OXY and the mast cell stabilizer DSCG with regard to the exerting formulation parameters should facilitate a relation between the drugs' molecular structure and physical-chemical properties. In the case of DSCG a concluding in vivo study on rabbits should clarify if influences established in vitro result in a altered availability in vivo too. Whereas for XYLO and its hydroxy derivative OXY connections between their physicalchemical properties, the in vitro permeation behaviour and the investigated formulation parameters excist but not for DSCG is a link between the three drugs not possible. DSCG possesses a strong substance specific component due to its concentartion dependent selfassoziation which reacts sensitively to altered formulation parameters. DSCG interacts with the isolated absorptive mucosa as well as with mucin modell dispersion in a marked extent. The combination of DSCG with the polymer sodium hyaluronate possesses in vivo an in vitro clear mucoadhesive properties which seem to be suitable to reduce DSCG's application frequency and improve thereby the patients' compliance. A drug's nasal availability results on a complex interplay of its physical-chemical properties, diverse formulation parameters and physiological conditions. Generalizations between the determined connections are difficult and isolated effects are hardly ascertainable. Additionally to the numerous formulation parameters with an impact on a drug's nasal availability it is nessecary to look at every drug formulation separatly.

The report deals with the study of the resistence of the nonporous polymer materiále against permeation of the selected TICs, with the analysis of the running difussion processes and utilization of the acquired results for the selection of suitable barrier materials for the protective means.

Muitas estratégias são indicadas a fim de suplantar a baixa permeabilidade de fármacos através da epiderme, umas delas, a de incluir promotores de penetração em formulações farmacêuticas e/ou cosméticas, formulados em sistemas terapêuticos transdérmicos (TTS). Estas substâncias são passíveis de modificar os domínios proteicos da epiderme e removerem provisoriamente a resistência da barreira do estrato córneo, permitindo o acesso dos fármacos aos tecidos viáveis através da circulação sistêmica. A natureza do veículo tópico é conhecida por desempenhar um papel importante na promoção da absorção dentro e através da pele. Os veículos tópicos convencionais, como pomadas, cremes ou géis, exercem predominantemente seus efeitos ao liberar o medicamento na superfície, e as moléculas dos fármacos, então, se difundem através de suas camadas. Os hidrogéis foram obtidos a partir de material polimérico reticulado por processo de radiação ionizante. A cafeína foi escolhida como substância modelo de permeação dérmica, por ser hidrofílica. Entretanto, para que a molécula penetre na barreira cutânea, deve ser associada a promotores de absorção cutânea. A papaína tem sido aplicada na pele íntegra como agente promotor de penetração e absorção cutânea. As enzimas interferem na absorção percutânea de fármacos por duas formas: como um potencializador de penetração e retardador de absorção. Neste trabalho, foram sintetizadas membranas de hidrogéis com poli (N-2- vinil - pirolidona) (PVP), poli (etilenoglicol) (PEG), poli (etilenoglicol diacrilato) (PEG-DA), cafeína e gel de papaína formado de polímero sintético pré-neutralizado para estudo da cinética de permeação cutânea, utilizando ecdise de cobra (Boa Constrictor) como membrana modelo de permeação. As membranas de hidrogel preparadas, foram caracterizadas por análise de termogravimetria (TG), calorimetria exploratória diferencial (DSC), intumescimento, fração gel, microscopia eletrônica de varredura (MEV), e realizados ensaios de permeação dérmica em células de Franz e tomografia de coerência óptica (OCT). O teste de permeação \"in vitro\" desses hidrogéis na ecdise foram satisfatórios, comprovando a eficácia da papaína como promotora de permeação dérmica e contribuindo, assim, para futuros trabalhos que possam explorar ainda mais essa área de entrega de fármacos. / Many strategies are indicated for supplanting the low permeability of pharmaceuticals through the epidermis, one of them to include developers of access in cosmetics formulations, produced in Transdermal Drug Systems. Those substances are capable of modifying the protein dominates of the epidermis and temporarily remove the resistant barrier of the stratum cornea, allowing this way, the access to the pharmaceutical to the viable fabric through the systemic circulation. The nature of the topic vehicle is known for developing an important role of the absorption inside and through the skin. The conventional ways, as ointments, creams or gels, predominated theirs effects by liberating the medication in the superficies, so the pharmaceutical molecules defund beyond their layers. The hydrogels were got from the polymeric reticulate material for ionizing radiation process. The caffeine was chosen as a substance model of the dermis permeation, due to be hydrophilic. Moreover, for the molecule access, it is necessary to the developers of dermal absorption. The papain has been applied in the integra skin as agent promoter of access and dermal absorption. The enzymes interfere in the dermal absorption of the pharmaceutical in two forms: as optimizing, as well as, retarding absorption. This essay we could synthesized hydrogel membranes as Poly (N -2 - vinyl-pirolidon) (PVP), Poly(ethylene glycol) (PEG), Poly (ethylene glycol) diacrylate (PEG-DA), caffeine and papain gel formed by polymeric synthetic pre-neutralized for the studies of kinetic of dermal access for using ecdysis of a snake (Boa constrictor) as a membrane model of access. The membranes of hydrogel prepared for this essay were characterized by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), swelling, gel fraction, scanning electron microscopy (SEM), and rehearsal of dermal access in Franz cells and optical coherence tomography (OCT). The test of permeation in vitro was satisfactory evidencing the efficacies of papain as a developer of dermal permeation, as well as, contributing for the future work that can explore even more this area of pharmaceutical delivery.

Quellfähige natürliche Schichtsilicate können nach vorheriger Modifizierung als nanoskalige Barrierefüllstoffe für hybridpolymere Beschichtungen eingesetzt werden. Durch Ionenaustausch nach der „Onium-Methode“ wurden aus natürlichem Montmorillonit unterschiedlich modifizierte organophile Schichtsilicate hergestellt, die mit thermisch oder strahlenhärtenden Barrierelacken verträglich sind. Als Modifizierungsreagenzien kamen neben aliphatischen auch olefinische und alkoxysilylfunktionelle Ammonium-Verbindungen zum Einsatz. Beschichtungen aus den modifizierten Barrierelacken zeigten teilweise deutlich verbesserte Sauerstoffbarriereeigenschaften. Ein signifikanter Einfluß auf die Wasserdampfbarriere war bei diesem Füllstoffanteil nicht festellbar. Die optische Transparenz der hybridpolymeren Barriereschichten wird auch durch Anteile von bis zu 5 Gew. % an Schichtsilicat nicht nennenswert beeinflusst. Dies belegen UV-VIS-Spektren.Aufgrund der deutlichen Steigerung der Sauerstoffbarrierewirkung unter Beibehaltung der optischen Transparenz der Beschichtung stellt die Kombination von modifizierten Schichtsilicaten mit hybridpolymeren Barrierelacken daher eine interessante Alternative zu den bisher eingesetzten Barrieresystemen ohne Füllstoff dar. Der Einfluss von Lacklagerung, Lackkomponenten und Härtungsbedingungen im Hinblick auf die Struktur und Sperrwirkung von Hybridpolymerschichten wurde im zweiten Teil dieser Arbeit untersucht. Dabei wurden die Ergebnisse struktureller Untersuchungen durch 29Si, 13C- und 27Al-NMR-Spektroskopie mit Barrieremessungen korreliert. Der letzte Teil der Arbeit befasst sich mit der Optimierung von Migrationsschutzschichten. Hybridpolymere bieten neben einer Barrierewirkung gegenüber Gasen und Dämpfen auch einen wirksamen Schutz gegen die Migration weiterer chemischer Substanzen, wie z.B. Weichmachern. Am Beispiel eines strahlenhärtenden hybridpolymeren Lackes wurde über die Formulierung des Lackes eine Korrelation zwischen Migrations- und Sauerstoffbarrierewirkung hergestellt. / Hydrophilic swelling layered silicate clay minerals such as Montmorillonite have to be modified first in order to integrate them on nanoscale into inorganic-organic barrier coatings. Using an ionic-exchange technique, natural Montmorillonite was converted into organophilic clay, which is compatible with several types of inorganic-organic barrier lacquers. As modifying agents different types of aliphatic as well as olefinic and alkoxysilane ammonia compounds were used. Coatings of clay modified inorganic-organic polymers showed improved gas barrier properties while keeping the water vapor transmission rate at a constant low level. Although barriere coatings with up to 5 percent on weight of modified clay were made, the coatings maintained their full optical transparency which was proven by UV-VIS-Spectroscopy.Due to the high improvement in the oxygen barrier properties while not affecting optical properties, modified clay minerals are well suited fillers for inorganic-organic barrier coatings. The influence of lacquer storage, lacquer compounds and curing conditions on the structure and barrier properties of inorganic-organic coatings was investigated in the second part of this thesis. A correlation was done between barrier properties and structural datas determined by 29Si-, 13C- und 27Al-NMR-spectroscopic investigations. The last part of the thesis deals with the optimization of migration barrier coatings. In addition to the barrier properties against water vapor and oxygen, inorganic-organic polymers can also function as protection layers against unwanted migration of chemical substances like softeners. Based on modifications on a photocurable lacquer a correlation between migration and oxygen barrier properties was made.

by Wong Dart-man. / Bibliography: leaves 107-114 / Thesis (M.Phil.)--Chinese University of Hong Kong, 1982

No description available.