Two series of cycloalkyl analogues of Antergan have been synthesized and analyzed. The compounds of the first series have the basic structure of N, N-dimethyl-N¹-phenyl-N¹ -(cycloalkylmethyl)-ethylenediamine in which the alkyl group was a propyl-, butyl-, pentyl-, hexyl-, or heptyl- ring structure. The second series of dicycloalkyl analogues has the general formula of N, N-dimethyl-N¹-cycloalkyl-N¹-(cycloalkylmethyl)-ethylenediamine in which both alkyl groups of propyl-, pentyl-, hexyl-, or heptyl- were the same ring size. Hydrochloride, picrate, and methyl iodide salts were prepared for these diamines, and for a number of the intermediates. In both series, the general reaction sequence followed was to start with the appropriate cycloalkyl carboxylic acid and build up to a secondary amine via an acid chloride and amide. The desired amine was then condensed with β-dimethylaminoethylbromide hydrobromide to form the tertiary diamine analogue. Two compounds, the dicyclohexyl- and dicycloheptyl-analogues, were formed by condensing the cycloalkylcarbonyl chloride with a substituted secondary ethylenediamine, and then reducing the amide with lithium aluminum hydride. Attempts to synthesize a sufficient quantity of the cyclo-octanecarboxanilide intermediate were unsuccessful. Difficulty was also encountered in preparing a stable and pure salt derivative for a number of the dicycloalkyl analogues. Signature of Examiners / Pharmaceutical Sciences, Faculty of / Graduate

Thesis (Ph. D.)--Virginia Polytechnic Institute and State University, 1990. / Vita. Abstract. Includes bibliographical references (leaves 181-196). Also available via the Internet.

Two series of diphenhydramine analogues have been prepared. In the first series, one phenyl ring in the benzhydryl nucleus has been substituted with a cycloalkyl ring containing three to seven carbon atoms inclusive. In the second series both phenyl rings have been replaced by two rings containing three, five and six carbon atoms. The following amines have been prepared: 2-(α -cyclopropylbenzyloxy)-N,N-dimethylethylamine, 2-(α -cyclobutylbenzyloxy) -N,N-dimethylethylamine, 2-(α-cyclopentylbenzyloxy)-N,N-dimethylethylamine, 2- (α -cyclohexylbenzyloxy) -N, N-dimethylethylamine, 2-(α-cycloheptylbenzyloxy)-N,N-dimethylethylamine, 2-(dicyclopropylmethoxy)-N,N-dimethylethylamine, 2-(dicyclopentylmethoxy)-N,N-dimethylethylamine and 2-(dicyclohexylraethoxy)-N,N,-dimethylethylamine. These compounds have been characterized by their infrared spectra and, where possible, by elemental analyses of the chloroplatinates. The reaction scheme involved a Grignard reaction of the cycloalkylbromide on benzaldehyde to yield the cycloalkyl-phenylcarbinol for the first series, and reaction on ethyl formate to yield the dicycloalkylcarbinol for the second series. Cyclobutylphenylcarbinol was obtained through a Friedel-Crafts reaction of cyclobutanecarboxyl chloride on benzene using aluminum chloride as the catalyst and subsequent reduction of the cyclobutylphenylketone with lithium aluminum hydride. These secondary carbinols were then condensed with 2-dimethylaminoethylbromide hydrobromide in the presence of sodium amide. An alternate condensation reaction in the second series involved reaction of the dicycloalkylmethylbromide with 2-dimethylaminoethanol using sodamide as the condensing agent. The major problems in the syntheses of the carbinols are the presence of carbonyl contaminants in some of the products, particularly in the cycloheptyl and cyclooctyl compounds, and the low yields of addition products obtained. It appears that better results would be achieved if the amount of Grignard reagent in the solution is estimated by a standard method to determine the amount of aldehyde or ester required for the reaction. In the condensation reactions, difficulty was encountered in formation of the sodium derivative. This reaction required a finely-divided form of the condensing agent and sufficient warming time for the reaction to proceed. However, too lengthy a period of heating appears to alter the carbinol molecule so that no product could be obtained. The second phase of the condensation reaction also proceeds slowly, and a sufficient period of refluxing is necessary for the reaction to go to completion. The alternate procedure which was also employed in the second series of compounds did not appear to improve the yields of products. Signature of Examiners / Pharmaceutical Sciences, Faculty of / Graduate

The main objective of the present study was to determine the feasibility of obtaining aqueous polymer-coated pellet formulations using EudragitR NE 30 D dispersion and chlorpheniramine maleate as the model drug. Many factors influence the rate of drug release from coated beads including, the substrate, the coating formulation and the coating process. A drug release profile that was comparable to that of the reference standard, DykatussR Capsules was obtained with a formulation employing 8.3% EudragitR NE 30 D, 0.5% talc and 1% polyethylene glycol. In vitro dissolution tests on this formulation showed drug release to be predictable, reproducible and independent of the dissolution methods or media. Short term storage confirmed the stability at room temperature (20°C) and low temperature (5C). Scanning electron micrographs of pellets stored at elevated temperatures i.e. 37°C with 80% relative humidity and 40°C illustrated the phenomenon of 'further gradual coalescence' which corresponded to the decrease in release of drug from the pellets. / Thesis (M.Sc.)-University of Natal, Durban, Westville, 1991.

No description available.

Thesis (M.S.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "May 2007" Includes bibliographical references.

Thesis (M.S.)--Virginia Polytechnic Institute and State University, 1990. / Vita. Abstract. Includes bibliographical references (leaves 67-73). Also available via the Internet.

Triprolidine hydrochloride (C₁₉H₂₂N₂.HCl.H₂O) (TPH) is a well-known antihistamine drug. It melts between 118°C and 122°C and the amount of water present is 4.5 mass percent. TPH is reported as being photosensitive and must be stored in sealed, light-tight containers. The thermal stabilities of TPH and of 1:1 molar and 1:1 mass ratio physical mixtures of TPH with beta-cyclodextrin (BCD) and with glucose have been examined using DSC, TG and TG-FTIR, complemented by X-ray powder diffraction (XRD) and infrared spectroscopic (IR) studies. Thermal studies of the solid TPH/BCD mixtures indicated that interaction between the components occurs and it is possible that the TPH molecule may be least partially accommodated in the cavity of the BCD host molecule. XRD results support this indication of inclusion. The results for mixtures of TPH/glucose also suggest that there is interaction between the two components. The results of molecular modelling suggest that TPH is most likely to be accommodated in the BCD cavity as a neutral triprolidine molecule with the toluene portion of the molecule entering first. There is also an indication that the Z-isomer should be accommodated slightly more readily than the E-isomer. Photostability studies were done by irradiating thin layers of solid samples of TPH and its mixtures for various times at 40°C using an Atlas Sun test CPS lamp operating at 550 W h m⁻². An analytical method using HPLC was developed and validated to determine the amounts of any photodegradants. DSC, TG, FTIR, XRD and IR were also used examine the irradiated samples. XRD results showed that changes in the TPH crystal structure occurred during irradiation and that these changes increased with the time of irradiation. Irradiation for 20 hours with UV or exposure to sunlight showed the presence of degradants. The results obtained illustrate the general stability of TPH, especially in the solid state. Although the potential for isomerization to the pharmaceutically inactive Z-isomer exists, this transformation would require extreme light conditions. The study has also shown TPH to be compatible with both glucose and BCD, which are potential excipients both in solid and liquid dosage forms. The presents of these excipients in dosage forms will thus not adversely affect the stability and the therapeutic efficacy of TPH. . An analytical method using HPLC was developed and validated to determine the amounts of any photodegradants. DSC, TG, FTIR, XRD and IR were also used examine the irradiated samples. XRD results showed that changes in the TPH crystal structure occurred during irradiation and that these changes increased with the time of irradiation. Irradiation for 20 hours with UV or exposure to sunlight showed the presence of degradants.

This thesis describes the synthesis of a series of dialkylaminoalkoxy derivatives of methyl p-nitrophenylacetate for testing as anti-histamine or hay fever drugs.

Controlled and sustained release dosage forms are the focus of worldwide research. These dosage forms facilitate patient compliance by simplifying the dosage regimen, and decrease the risk of adverse effects by reducing large fluctuations in the plasma concentration of the drug. The objective of this study was to formulate a repeat-action tablet to provide a sustained release dose of pseudoephedrine sulfate (PSS), and an immediate release dose of both PSS and loratadine. The release profile was compared to that of a commercially available preparation, Clarityne-D®. This formulation developed presents a novel mechanism of sustaining the release of PSS. The prototype tablet consisted of a sustained release core coated with an ethylcellulose dispersion to introduce a lag phase into the release profile and a second outer film coat incorporating PSS and loratadine. The core comprised an ethylcellulose granulation of PSS compressed into a hydroxypropyl methylcellulose matrix. The release of PSS from prototypes was assessed using USP Apparatus 3, as this apparatus was more representative of in vivo conditions and discriminated more effectively between the different tablet compositions produced during development. All dissolution samples were analysed for PSS and loratadine using validated highperformance liquid chromatographic methods. The prototype sustained release cores were found to be more resistant than the reference product to elevated temperature and humidity (40°C/87% RH) with fewer observed changes to the release profiles following storage for up to six months. This study was a feasibility study to obtain proof of concept. The release profile obtained from the prototype tablets was similar (f₂ = 50.0) to that of the reference product. Further development and optimisation of this dosage form is necessary, including evaluation of the choice of hydrophobic polymer, the effect of compression force and tablet geometry and characterisation of the release mechanism from the coated matrix. Assessment of these factors is necessary in order to optimise the formulation with respect to the desired therapeutic objectives.