O objetivo deste trabalho foi o desenvolvimento e validação de métodos analíticos para determinação do bromidrato de darifenacina (DF) em comprimidos de liberação modificada. Na fase de identificação, a matéria-prima do fármaco (substância química de referência) foi analisada e caracterizada utilizando-se de medidas físicas (ponto de fusão, polarimetria, solubilidade), espectroscopia (infravermelho, ultravioleta-visível, massas) e técnicas cromatográficas (cromatografia a líquido de alta eficiência, cromatografia em camada delgada). Nos estágios posteriores, os experimentos para quantificação do comprimido foram realizados utilizando-se de desenhos experimentais (fatoriais completes, desenhos de composto central, fatoriais fracionados). O método de CLAE foi validado e um produto de degradação foi obtido na condição de estresse oxidativo (H2O2 13%, 72h). Para o método espectrofotométrico, a interferência de excipientes foi verificada e a técnica de derivada (método zero-crossing) foi utilizada para quantificação. Ambos os métodos foram comparados e não demonstram diferença significativa quando aplicados ao doseamento do comprimido. / The aim of this study was the development and validation of the analytical methods to the determination of darifenacin hydrobromide (DF) in extended-release tablet. In the identification stage, the bulk drug was analyzed and characterized using physical measures (melting point, polarimetry, solubility), spectroscopy (infrared and ultraviolet-visible) and chromatographic techniques (high performance liquid chromatographic, HPLC, and thin-layer chromatography, TLC). In the subsequent stages, the experiments to quantification for the DF tablet were performed using experimental designs (full factorial designs, central composite designs and fractional factorial designs). The HPLC method was validated and a degradation product was obtained in oxidation stress condition (H2O2 13%, 72h). For the spectrophotometric method, excipient interference was observed and derivative technique (zero-crossing method) was employed to quantification. Both the methods were compared showing no signficative difference to tablet assay.

O objetivo deste trabalho foi o desenvolvimento e validação de métodos analíticos para determinação do bromidrato de darifenacina (DF) em comprimidos de liberação modificada. Na fase de identificação, a matéria-prima do fármaco (substância química de referência) foi analisada e caracterizada utilizando-se de medidas físicas (ponto de fusão, polarimetria, solubilidade), espectroscopia (infravermelho, ultravioleta-visível, massas) e técnicas cromatográficas (cromatografia a líquido de alta eficiência, cromatografia em camada delgada). Nos estágios posteriores, os experimentos para quantificação do comprimido foram realizados utilizando-se de desenhos experimentais (fatoriais completes, desenhos de composto central, fatoriais fracionados). O método de CLAE foi validado e um produto de degradação foi obtido na condição de estresse oxidativo (H2O2 13%, 72h). Para o método espectrofotométrico, a interferência de excipientes foi verificada e a técnica de derivada (método zero-crossing) foi utilizada para quantificação. Ambos os métodos foram comparados e não demonstram diferença significativa quando aplicados ao doseamento do comprimido. / The aim of this study was the development and validation of the analytical methods to the determination of darifenacin hydrobromide (DF) in extended-release tablet. In the identification stage, the bulk drug was analyzed and characterized using physical measures (melting point, polarimetry, solubility), spectroscopy (infrared and ultraviolet-visible) and chromatographic techniques (high performance liquid chromatographic, HPLC, and thin-layer chromatography, TLC). In the subsequent stages, the experiments to quantification for the DF tablet were performed using experimental designs (full factorial designs, central composite designs and fractional factorial designs). The HPLC method was validated and a degradation product was obtained in oxidation stress condition (H2O2 13%, 72h). For the spectrophotometric method, excipient interference was observed and derivative technique (zero-crossing method) was employed to quantification. Both the methods were compared showing no signficative difference to tablet assay.

<p>While eye drops are a well-accepted and convenient method for ocular drug delivery, they exhibit significant limitations such as poor drug bioavailability, low ocular residence time, pulsatile delivery profiles in the tear fluid as well as the need for patient compliance. Silicone hydrogel (SH) contact lenses have been proposed as alternative ocular drug delivery systems due to their potential for targeted delivery to the corneal surface and high oxygen permeability. The ability of novel hyaluronic acid (HA)-containing silicone hydrogel materials to release timolol maleate (TM), an antiglaucoma drug, or ketotifen fumarate (KF), an anti-histamine administered for ocular allergies, was examined.</p> <p>The releasable wetting and the therapeutic agent were added to the pre-polymer mixture of the SH during synthesis through direct entrapment, while the reaction was performed by UV induced free-radical. The impact of the wetting agent on the swellability, surface wettability, optical transparency and <em>in vitro </em>drug release was studied.</p> <p>Simultaneous drug and wetting agent incorporation resulted in modified SH materials with slightly increased water content and significantly improved surface wettability. In addition, the optical transparency of these materials was not affected by drug loading. However, direct entrapment of HA decreased their optical clarity. <em>In vitro</em> release showed that TM was released over a 14 day period, whereas KF release lasted up to 36 days. For both therapeutic agents used in the current research, non-covalent entrapment of wetting agent and its MW did not significantly change the release kinetics, however the release rate of TM was slowed and controlled by the release of the HA, due to electrostatic interactions between the protonated TM and the anionic HA.</p> <p>The development of SH materials capable of simultaneously releasing a therapeutic and a wetting agent for an extended period of time and in a sustained manner can have a significant potential as extended drug delivery systems for the treatment of front of the eye diseases while also possibly providing comfort during wear.</p> / Master of Applied Science (MASc)

Identification of predictors of treatment response in patients with major depressive disorder (MDD) may facilitate improved disease management. Data were pooled from two 6-week, double-blind, placebo-controlled studies of extended-release quetiapine (quetiapine XR; 150 or 300 mg/day) as adjunct to ongoing antidepressant therapy. Effects of psychiatric history and baseline demographic and disease characteristics on efficacy outcomes (Week 6 Montgomery Åsberg Depression Rating Scale [MADRS] total score reduction) were evaluated in population subgroups (quetiapine XR both doses pooled, n = 616; placebo, n = 303). Baseline Clinical Global Impressions-Severity (CGI-S) score and previous depressive episodes on Week 6 MADRS total score change, and baseline MADRS individual item scores on Week 6 change in CGI-Improvement score, were also evaluated. No major differences between responders and non-responders to quetiapine XR were observed for patient characteristics or demographic and disease characteristics. No suggestion of a predictive association was found between baseline CGI-S score, number of depressive episodes, and baseline MADRS item scores and efficacy outcomes. These analyses showed no major differences between responders and non-responders, and no predictive association between the parameters assessed and efficacy outcomes for adjunct quetiapine XR in patients with MDD and an inadequate response to prior antidepressant therapy.