Preformulation: The use of FTIR in compatibility studies

Studies of active pharmaceutical ingredient (API) - excipient compatibility represent an important study in the preformulation stage of the development of new dosage forms. The potential physical and chemical interactions between an API and the excipients can affect the chemical nature, the stability and bioavailability of the former and, consequently, its therapeutic efficacy and safety. Solid dosage forms are generally less stable than their API components. Despite the importance of API-excipient compatibility testing, there is no universally accepted protocol to assess such interactions. Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Isothermal Stress Testing-Fourier Transform Infrared Spectroscopy (IST-FT-IR), Isothermal Stress Testing-High Performance Liquid Chromatography (IST-HPLC), are commonly used as screening techniques for assessing the compatibility of an active pharmaceutical ingredient (API) with some currently employed excipients. Through the assignment of spectral bands, FTIR provides information on chemical reactions taking place between the API and the excipient. Thus, this procedure gives formulation scientists information on which chemical groups to avoid in the excipients, favoring the development of more stable blends.Fil: Segall, Adriana Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

A Validated Reversed-Phase HPLC Method for the Determination of Atorvastatin Calcium in Tablets

A Reversed-Phase Liquid Chromatographic (RP-LC) assay method was developed for the quantitative determination of atorvastatin calcium in the presence of its degradation products. The assay involved an isocratic elution of atorvastatin calcium in a LiChroCARTR 250*4 mm HPLC Cartridge LiChrospherR 100 RP-18 (5 μm) column using a mobile phase consisting of 0.1% acetic acid solution: acetonitrile (45:55, v/v), pH = 3.8. The flow rate was 0.8 mL/min and the analytes monitored at 246 nm. The assay method was found to be linear from 8.13 to 23.77 μg/mL. All the validation parameters were within the acceptance range. The developed method was successfully applied to estimate the amount of atorvastatin calcium in tablets.Fil: Simionato, Laura Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Ferello, L.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Stamer. S.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Repetto, M. F.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Zubata, P. D.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Segall, Adriana Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Physicochemical Characterization of Physical Mixture and Solid Dispersion of Diclofenac Potassium with Mannitol

Diclofenac potassium is an anti-inflammatory agent classified as a class II drug as per the biopharmaceutical classification system (BCS). The poor dissolution rate of water-insoluble drugs is still a major problem confronting the pharmaceutical industry. There are several techniques to enhance the dissolution of poorly soluble drugs. Methods available include salt formation, micronization and addition of solvent or surface active agents. The objective of the present work is to improve the dissolution profile of diclofenac potassium by formation of a physical mixture and a solid dispersion with mannitol. The solid dispersion was prepared by solvent method using ethanol/water. As diclofenac potassium melts with decomposition, the compatibility study with mannitol was done with the acid form by differential scanning calorimetry (DSC). The dissolution properties and physicochemical properties of diclofenac potassium:mannitol physical mixture and solid dispersion were investigated by Powder X-ray Diffraction (PXRD), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and dissolution test. This study shows that the dissolution rate of diclofenac potassium can be enhanced considerably by formulating it with mannitol, as a physical mixture or as a solid dispersion although crystallinity was maintained.Fil: Han, Yong. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Laboratorio de Control de Calidad de Medicamentos; ArgentinaFil: Faudone, Sonia Nerina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Zitto, Gustavo. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Bonafede, Silvina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Laboratorio de Control de Calidad de Medicamentos; ArgentinaFil: Rosasco, María Ana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Laboratorio de Control de Calidad de Medicamentos; ArgentinaFil: Segall, Adriana Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Laboratorio de Control de Calidad de Medicamentos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Aspectos Históricos de los Protectores Solares

Existe poca literatura acerca de cómo se protegió la gente del sol en la antigüedad. Durante milenios, la vestimenta estuvo relacionada con el clima local. Aproximadamente 5000 años antes de Cristo se descubrió el tejido, y en Egipto el algodón, la lana y el lino se utilizaron en vestimenta. En la India, se utilizó en mayor medida el algodón. Existe evidencia a través de lo que demuestran las pinturas, que en los países tropicales, solo algunas partes del cuerpo eran cubiertas por vestimenta (por ej dhoti, la falda de los Egipcios) aunque también existían extensas vestimentas, particularmente los “sari” de las mujeres y las “togas” de los hombres. Con respecto a la cabeza, existían sombreros de paja, turbantes y pelucas en las diversas culturas. Las tribus desérticas, como los beduinos, llevaban trajes sueltos, flojos y en Egipto proveía protección una vestimenta similar voluminosa (djellaba) o un vestido (haik). Los Tuareg, en el norte de África, cubrían su cara con un velo azul. Los paraguas también datan de la antigüedad. En el antiguo Egipto, Mesopotamia,  China e India se utilizaban para proteger del sol a la gente importante. Estos paraguas eran muy grandes y eran llevados por portadores como una marca de honor y autoridad. Una variante era el baldaquino, un pabellón fijo y llevado sobre una persona o un lugar importante. En el siglo XXVIII, el uso de un pequeño paraguas (o parasol) se convirtió en una moda sobre todo para que las mujeres se protegieran del sol. Los estilos de las vestimentas variaban según la casta, la ocupación y el sexo, aún en la antigua Grecia y Egipto, la piel pálida era un ideal entre las mujeres. Es sabido, que el deseo de mantener la piel pálida fue uno de los orígenes de los cosméticos: el polvo blanco (generalmente sales de arsénico) fue uno de los materiales cosméticos más antiguos. Se utilizaron muchas formas de protección física: Celsus (en el siglo I antes de Cristo), recomendaba cubrir la cabeza y frotar la piel con aceite.  Los Tibetanos utilizaban como protectores solares una combinación de alquitranes y hierbas. Los indígenas de Guyana decoraban su piel con una variedad de extractos de plantas, probablemente por razones cosméticas, pero que también servían como protectores solares.Fil: Segall, Adriana Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Actualización en Protección Solar

Fil: Segall, Adriana Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Fotoestabilidad de Avobenzona utilizando diferentes antioxidantes

En la actualidad, existe la necesidad de desarrollar protectores solares efectivos para asegurar una óptima fotoprotección. La Avobenzona (Butyl methoxydibenzoylmethane) es uno de los filtros UVA más comúnmente utilizado en protectores solares y es fotoinestable. Su fotoestabilidad es altamente dependiente de la polaridad y de la capacidad de cesión de protones de los solventes. En la industria cosmética son comúnmente utilizados los antioxidantes para reducir el envejecimiento de la piel provocado por la radiación ultravioleta, previniendo o reduciendo las especies reactivas generadas. El propósito del presente trabajo es evaluar la foto degradación de la Avobenzona luego de su exposición a radiación UV simulada en solventes de diferente polaridad tales como: isopropanol, metanol, acetato de etilo, dimetilsulfóxido, hexanol, etanol y propilenglicol. Se determinó la degradación de la Avobenzona en estos solventes, y se seleccionaron hexano, metanol, etanol y propilenglicol. A la Avobenzona se le agregaron los antioxidantes: derivados de la vitamina C: fosfato de ascorbilo y magnesio, fosfato sódico de ascorbilo, palmitato de ascorbilo y por otro lado el acetato de Vitamina E y se evaluó su foto estabilidad. De los antioxidantes probados, el que mejor protegió a la Avobenzona fue el fosfato sódico de ascorbilo.Currently, there is a need to develop effective sunscreens to ensure optimal photo protection. The Avobenzone (Butyl methoxydibenzoylmethane) is one of the most commonly used UV filters in sunscreens and photo unstable. Their photo stability is highly dependent on the polarity and the proton transfer capability of the solvent. In cosmetics industry antioxidants are commonly used to reduce skin aging induced by ultraviolet radiation, preventing or reducing the generated reactive species. The purpose of this study is to evaluate the photo-degradation of Avobenzone after exposure to UV radiations simulated in different polarity solvents such as isopropanol, methanol, ethyl acetate, dimethyl sulfoxide, hexanol, ethanol and propylene glycol. Avobenzone degradation was determined in hexane, methanol, ethanol and propylene glycol. The antioxidants added Avobenzone: vitamin C derivates: magnesium ascorbyl phosphate, sodium ascorbyl, phosphate, ascorbyl palmitate and secondly Vitamin E acetate and photo stability was evaluated. Among the antioxidants tested which better protected the Avobenzone was sodium ascorbyl phosphate.Fil: Asero, Marta. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Segall, Adriana Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentin

Validation of a Stability indicating RP-HPLC Method for the Determination of Gatifloxacin in eye drops

A reversed-phase liquid chromatography (RP-LC) method was validated for the determination of gatifloxacin in eye drops. The LC method was carried out on a Phenomenex LiChrosphere 5 µm RP-18 100 Ǻ 125 x 4.6 mm maintained at room temperature. The mobile phase consisted of water:acetonitrile:triethylamine (80:20:3 v/v/v), pH adjusted to 3.3 using phosphoric acid, run at a flow rate of 1 mL/min and using ultraviolet detection at 293 nm. The chromatographic separation was obtained with a retention time of 3.6 min and was linear in the range of 30-70 µg/mL (r2 = 0.9991). The specificity and stability indicating the capability of the method was proven through forced degradation studies, which also showed that there was no interference of the excipients. The accuracy was 100.63% with RSD = 1.65. Method validation demonstrates satisfactory results for precision and robustness. The proposed method was applied for the analysis of marketed eye drops, for improving the quality control and to assure the therapeutic efficacy.Fil: Han, Yong K.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Tecnologia Farmaceutica; Argentina;Fil: Segall, Adriana Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina

Vitamin A palmitate and α-lipoic acid stability in o/w emulsions for cosmetic application

Skin becomes thin, dry, pale, and fi nely wrinkled with age. Retinoids are a large class of compounds that are important in modern therapy for dermatological treatment of wrinkled skin. Of the retinoids, retinol and vitamin A palmitate are thought to induce thickening of the epidermis and to be effective for treatment of skin diseases. Accordingly, α-lipoic acid or the reduced form, dihydrolipoate, are potent scavengers of hydroxyl radicals, superoxide radicals, peroxyl radicals, singlet oxygen, and nitric oxide with anti-infl ammatory properties (1). Cosmetic ingredient stability prediction relies on kinetic quantitative chemical analysis of active components at different temperatures. Vitamin A palmitate and α-lipoic acid, are known to be unstable to light or heat (2). The aims of this study were to evaluate the stability of α-lipoic acid and vitamin A palmitate in the presence of vitamin E (acetate) and other antioxidants in lipophilic/hydrophilic medium (O/W emulsions) at pH 3.0, 5.0, and 7.0. The formulations that were investigated contained 0.12% (w/w) vitamin A palmitate, 0.4% (w/w) vitamin E acetate, and 0.5 % α-lipoic acid (formulation A), supplemented with ascorbyl palmitate, magnesium ascorbyl phosphate, and vitamin C (formulation B) or with butylhydroxytoluene (BHT, formulation C) or ascorbyl palmitate (formulation D). The chemical analyses of α-lipoic acid and vitamin A palmitate were carried out by HPLC. Formulations C and D at pH 7.0 were selected as the most stable for these components. The purpose of this paper is the selection of the most stable formulations for their application in in vivo studies.Fil: Moyano, M. A.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Segall, Adriana Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

A Validated Specific Stability-Indicating RP-HPLC Assay Method for the Determination of Loteprednol Etabonate in Eye Drops

A new stability-indicating RP-HPLC assay method was developed and validated for quantitative determination of loteprednol etabonate in bulk drugs and in ophthalmic suspensions in the presence of degradation products generated from forced degradation studies. The system consisted of Agilent Technologies Zorbax Eclipse XDB-Phenyl 5 µm 4.6 × 250 mm, and detection was performed at 244 nm. The mobile phase consisted of water–acetonitrile–acetic acid (34.5:65.0:0.5, v/v/v) run at a flow rate of 1 mL/min and maintained at room temperature. The calibration curve was linear from 30 to 70 µg/mL with r > 0.999. Accuracy (mean recovery 100.78%) and precision were found to be satisfactory. Stress conditions including acid and alkali hydrolysis, water stress, oxidation, photolysis and heat were applied. The degradation products did not interfere with the detection of loteprednol etabonate, thus the method can be considered as a stability-indicating method. The proposed method can be used for quality control assay of loteprednol etabonate in bulk drug and in ophthalmic suspensions and for stability studies as a result of the ability of the method to separate loteprednol etabonate from its degradation products and excipients.Fil: Han, Yong Ki. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Segall, Adriana Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Thermal analysis of lipoic acid and evaluation of the compatibility with excipients

Differential scanning calorimetry (DSC) was used as a screening technique for assessing the compatibility of lipoic acid with some currently employed cosmetic excipients. In the first phase of the study DSC was used as a tool to detect any interaction. Based on the DSC results alone, methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, butylated hydroxytoluene, non ionic self emulsifying wax, propylene glycol and acetylated lanolin were found to exhibit interaction with lipoic acid. Stressed binary mixtures (stored at 50 °C for 1 week) of lipoic acid and excipients were evaluated by HPLC. Binary mixtures were evaluated by IR spectroscopy.Fil: Moyano, María A.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Broussalis, Adriana M.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacognosia; ArgentinaFil: Segall, Adriana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin