Study on interaction between palladium(ІІ)-Linezolid chelate with eosin by resonance Rayleigh scattering, second order of scattering and frequency doubling scattering methods using Taguchi orthogonal array design.

Linezolid reacted with palladium to form 1:1 binary cationic chelate which further reacted with eosin dye to form 1:1 ternary ion association complex at pH 4 of Walpole's acetate buffer in the presence of methyl cellulose. As a result not only absorption spectra were changed but Resonance Rayleigh Scattering (RRS), Second-order Scattering (SOS) and Frequency Doubling Scattering (FDS) intensities were greatly enhanced. The analytical wavelengths of RRS, SOS and FDS (λex/λem) of ternary complex were located at 538 nm/538nm, 240 nm/480 nm and 660 nm/330 nm, respectively. The linearity range for RRS, SOS and FDS methods were 0.01-0.5 µg mL(-1), 0.1-2 µg mL(-1) and 0.2-1.8 µg mL(-1), respectively. The sensitivity order of three methods was as RRS>SOS>FDS. Accuracy of all methods were determined by recovery studies and showed recovery between 98% and 102%. Intraday and inter day precision were checked for all methods and %RSD was found to be less than 2 for all methods. The effects of foreign substances were tested on RRS method and it showed the method had good selectivity. For optimization of process parameter, Taguchi orthogonal array design L8(2(4)) was used and ANOVA was adopted to determine the statistically significant control factors that affect the scattering intensities of methods. The reaction mechanism, composition of ternary ion association complex and reasons for scattering intensity enhancement was discussed in this work.

A novel itraconazole bioadhesive film for vaginal delivery: design, optimization, and physicodynamic characterization.

The purpose of this work was to design and optimize a novel vaginal drug delivery system for more effective treatment against vaginal candidiasis. Itraconazole was formulated in bioadhesive film formulations that could be retained in the vagina for prolonged intervals. The polymeric films were prepared by solvent evaporation and optimized for various physicodynamic and aesthetic properties. In addition, percentage drug retained on vaginal mucosa was evaluated using a simulated dynamic vaginal system as function of time. A polymeric film containing 100 mg itraconazole per unit (2.5 cm x 2.5 cm) have been developed using generally regarded as safe listed excipients. The pH of vaginal film was found to be slightly acidic (4.90 +/- 0.04) in simulated vaginal fluid and alkaline (7.04 +/- 0.07) in water. The little moisture content (7.66 +/- 0.51% w/w) was present in the film, which helps them to remain stable and kept them from being completely dry and brittle. The mechanical properties, tensile strength, and percentage elongation at break (9.64 N/mm(2) and 67.56% for ITRF(65)) reveal that the formulations were found to be soft and tough. The films (ITRF(65)) contained solid dispersion of itraconazole (2.5)/hydroxypropyl cellulose (1)/polyethylene glycol 400 (0.5), which was found to be the optimal composition for a novel bioadhesive vaginal formulation, as they showed good peelability, relatively good swelling index, and moderate tensile strength and retained vaginal mucosa up to 8 h. Also, the film did not markedly affect normal vaginal flora (lactobacillus) and was noncytotoxic as indicated by the negligible decrease in cell viability.

A novel intravaginal delivery system for itraconazole: in vitro and in vivo evaluation.

The purpose of the present study was to formulate and systematically evaluate in vitro, ex vivo and in vivo performances of itraconazole containing bioadhesive vaginal film. We introduce here a novel intravaginal delivery system for itraconazole based on solid dispersion of itraconazole and hydroxypropyl methylcellulose E15 that improve drug solubility and produce bioadhesive system in presence of other ingredients. Solid dispersions of itraconazole were prepared with hydroxypropyl methylcellulose by a spray drying method and characterized by X-ray diffraction and differential scanning calorimetry. The film was prepared using a solvent evaporation technique. In the in vitro antimicrobial study, it was found that solid dispersion containing formulation improves antimicrobial action of itraconazole. From the ex vivo retention study, it was found that the bioadhesive polymers hold the film upto 7 hours on the vaginal mucosa. In vivo antifungal activity tested against Candida albicans vaginitis in female rats, was found to significantly improve the therapeutic benefit of the drug. At 6 days post-dose, the c.f.u. of Candida albicans was more than 10(3) fold decreased in film treated groups without affecting the morphology of vaginal mucosa. These studies suggested that bioadhesive vaginal film is a novel approach for delivery of itraconazole as topical drug delivery system for treating vaginal candidiasis.

Simultaneous determination of salbutamol sulphate, bromhexine hydrochloride and etofylline in pharmaceutical formulations with the use of four rapid derivative spectrophotometric methods.

Four simple, rapid, accurate, precise, reliable and economical spectrophotometric methods have been proposed for simultaneous determination of salbutamol sulphate (SS), bromhexine hydrochloride (BH) and etofylline (ET) in pure and commercial formulations without any prior separation or purification. They were first derivative zero crossing spectrophotometry (method 1), simultaneous equation method (method 2), derivative ratio spectra zero crossing method (method 3) and double divisor ratio spectra derivative method (method 4). The ranges for SS, BH and ET were found to be 1-35 microg mL(-1), 4-40 microg mL(-1) and 5-80 microg mL(-1). For methods 1 and 2, the values of limit of detection (LOD) were 0.2314 microg mL(-1), 0.4865 microg mL(-1) and 0.2766 microg mL(-1) and the values of limit of quantitation (LOQ) were 0.7712 microg mL(-1), 1.6217 microg mL(-1) and 0.9221 microg mL(-1) for SS, BH and ET, respectively. For method 3, LOD values were 0.3297 microg mL(-1), 0.2784 microg mL(-1) and 0.7906 microg mL(-1) and LOQ values were 0.9325 microg mL(-1), 0.9282 microg mL(-1) and 2.6352 microg mL(-1) for SS, BH and ET, respectively. For method 4, LOD values were 0.3161 microg mL(-1), 0.2495 microg mL(-1) and 0.2064 microg mL(-1) and LOQ values were 0.9869 microg mL(-1), 0.8317 microg mL(-1) and 0.6879 microg mL(-1) for SS, BH and ET. The precision values were less then 2% R.S.D. for all four methods. The common excipients and additives did not interfere in their determinations. The results obtained by the proposed methods have been statistically compared by means of Student t-test and by the variance ratio F-test.

Pepsina capturada en gránulos gelificados de k-carragenato reticulados mediante actividad ionotrópica para una mejora de la estabilidad: Optimización y caracterización fisicoquímica mediante el diseño de Box-Behnken / Ionotropically cross-linked k-carrageenan gel beads of pepsin for stability improvement: optimization and physicochemical characterization using Box-Behnken design

En este trabajo se examina la infl uencia de los parámetros de proceso, particularmente la concentración de k-carragenato, la concentración de cloruro potásico y el tiempo de endurecimiento, en pepsinas capturadas en gránulos de k-carragenato reticulados mediante actividad ionotrópica para la mejora de su estabilidad mediante la metodología de superficie de respuesta. Se utilizó un diseño de Box-Behnken para investigar el efecto de las variables de proceso en la captura, el tiempo necesario para la liberación del 50% de las enzimas (T50), el tiempo necesario para la liberación del 90% de las enzimas (T90) y el tamaño de partícula. Los gránulos se prepararon mediante el vertido de gotas de k-carragenato con pepsina en una solución de cloruro potásico agitada magnéticamente. El perfil de liberación enzimática in vitro de los gránulos se ajustó a varios modelos cinéticos de liberación para comprender el mecanismo de liberación. La caracterización topográfica se realizó mediante microscopía electrónica de barrido (SEM) y la captura se confirmó a través de espectrometría infrarroja por transformada de Fourier (FTIR) y calorimetría diferencial de barrido (DSC). La prueba de estabilidad se realizó según las indicaciones de ICH para las zonas III y IV. Una matriz polimérica preparada con un 3,0% p/v de k-carragenato y 0,3 M de cloruro potásico mediante el método de gelificación ionotrópica, con un tiempo de endurecimiento de 10 minutos provocó la producción de gránulos caracterizados por un disco esférico con un centro aplanado, una ausencia de agregados, una captura de más del 80% y un valor T90 inferior a 40 minutos. Se observó que la vida de almacenamiento de los gránulos cargados con pepsina aumentó hasta los 3,24 años en comparación con los 0,97 años de la formulación convencional. Se puede concluir que la metodología propuesta se puede utilizar para preparar gránulos de k-carragenato cargados de pepsina para la mejora de la estabilidad. Además, se concluyó que la selección adecuada de la concentración de carragenato con control de la velocidad de liberación y su potencial interactivo para la reticulación es importante, y determinará el tamaño y la forma general de los gránulos, la duración y el patrón de los perfiles de disolución y la capacidad de carga de la enzima

This work examines the influence of process parameters, namely k-carrageenan concentration, potassium chloride concentration, and hardening time, on pepsin entrapped in ionotropically crosslinked k-carrageenan beads for improvement of its stability using response surface methodology. A Box-Behnken design was employed to investigate the effect of process variables on the entrapment, time required for 50% enzyme release (T50), time required for 90% enzyme release (T90), and particle size. The beads were prepared by dropping the k-carrageenan containing pepsin into a magnetically stirred potassium chloride solution. In vitro enzyme release profi le of the beads was fitted to various release kinetics models in order to understand the release mechanism. Topographical characterization was carried out by SEM, and entrapment was confirmed by FTIR and DSC. Stability testing was carried out according to the ICH guidelines for zones III and IV. A polymeric matrix prepared by 3.0% w/v k-carrageenan and 0.3 M potassium chloride using the ionotropic gelatin method, with a hardening time of 10 min resulted in the production of beads characterized by a spherical disk shaped with a collapsed center, an absence of aggregates, an entrapment of more than 80%, and a T90 of less than 40 min. The shelf-life of the pepsin-loaded beads was found to increase to 3.24 years compared with 0.97 years for the conventional formulation. It can be inferred that the proposed methodology can be used to prepare pepsinloaded k-carrageenan beads for stability improvement. In addition, the proper selection of rate-controlling carrageenan concentration and their interactive potential for crosslinking is important, and will determine the overall size and shape of beads, the duration and pattern of dissolution profiles, and the enzyme loading capacity

Determinación por cromatografía de líquidos y estudio farmacocinético del sulfato de salbutamol en el plasma de conejo / Liquid chromatographic determination and pharmacokinetics study of salbutamol sulphate in rabbit plasma

Desarrollar y validar un método de cromatografía de líquidos de alto rendimiento (HPLC) exacto, preciso, específico y sencillo con detección de UV para la determinación de sulfato de salbutamol en el plasma de conejo. Se agregó estándar interno (cloramfenicol) a 0,5 ml de plasma de conejo. Se extrajeron sulfato de salbutamol y cloramfenicol en 5 ml de di(2-etilhexil) fosfato 0,1 M en cloroformo. La fase de cloroformo se trató con ácido clorhídrico 0,5 M y se analizó una alícuota de fase acídica mediante un sistema de HPLC de fase inversa equipado con una columna analítica C18 de 4,6 × 250 mm i. d. y detección de UV (landa = 276 nm). La fase móvil consistió en agua (70%), metanol (20%) y acetonitrilo (10%), y su velocidad de flujo fue de 1,2 ml/min. No se detectaron picos de interferencia de componentes endógenos en los cromatogramas de plasma sin aditivos. El fármaco y el estándar interno se elucionaron a 3,0 y 15,4 minutos, respectivamente. La proporción del área pico fármaco/estándar fue lineal frente a la relación de concentración del fármaco que resultó ser lineal (r=0,992) sobre 100-1500 ng/ml. La eficacia de la extracción fue superior al 80,00% y la concentración de cuantifi cación mínima fue 100 ng/ml (CV<10%) basada en 500 ìl de plasma. El coeficiente intradía de variación (CV) osciló entre el 1,9 y el 6,2%, y el interdía osciló entre el 1,1 y el 8,9%. El porcentaje de recuperación de sulfato de salbutamol en plasma osciló entre el 98,97 y el 102,41%. El ensayo fue sencillo, sensible, preciso y exacto para su uso en estudios farmacocinéticos del sulfato de salbutamol en conejos. El método mencionado se utilizó para estudiar la farmacocinética de los comprimidos convencionales, los comprimidos de disolución rápida y el recubrimiento de sulfato de salbutamol de disolución rápida después de la administración oral a conejos

To develop and validate a simple, specifi c, precise and accurate HPLC method with UV detection for the determination of salbutamol sulphate in rabbit plasma. To 0.5 ml of rabbit plasma internal standard (chloramphenicol) was added. Salbutamol sulphate and chloramphenicol were extracted to 5 ml of 0.1 M-bis-(2 ethyl hexyl) phosphate in chloroform. The chloroform phase was treated with 0.5 M hydrochloric acid and an aliquot of the acidic phase was analyzed by a reverse phase HPLC system equipped with 4.6 × 250 mm i. d. C18 analytical column and UV detection landa = 276 nm). Mobile phase consisted of water (70%), methanol (20%) and acetonitrile (10%) and its fl ow rate was 1.2 ml/min. There were no interfering peaks from endogenous components in blank plasma chromatograms. The drug and internal standard eluted at 3.0 and 15.4 min, respectively. The peak drug/IS area ratio was linear versus drug concentration relationship was linear (r=0.992) over 100-1500ng/ml. The extraction efficiency was greater than 80.00% and minimum quantification concentration was 100 ng/ml (CV<10%) based on 500ìl of plasma. The intraday coefficient of variation (CV) ranged from 1.9 to 6.2% and interday varied from 1.1 to 8.9 %. The % recovery of salbutamol sulphate in plasma range from 98.97 to 102.41%. The assay was simple, sensitive, precise and accurate for the use in pharmacokinetic studies of salbutamol sulphate in the rabbit. The mentioned method was used to study the pharmacokinetics of conventional tablets, fast dissolving tablets and fast dissolving film of salbutamol sulphate after oral administration in rabbits

Preparación de comprimidos de desintegración rápida de clorhidrato de ondansetrón mediante el método de compresión directa / Preparation of rapidly disintegrating tablets of ondansetron hydrochloride by direct compression method

Para elaborar comprimidos de desintegración rápida con un contenido de 8 mg de clorhidrato de ondansetrón, con sufi ciente integridad mecánica y buen sabor, se preparó una formulación de celulosa microcristalina (CM), lactosa anhidra, manitol y croscarmelosa. Los comprimidos se elaboraron mediante el método de compresión directa. Se determinaron propiedades tales como la resistencia a la fractura, el tiempo de desintegración, el tiempo de humidifi cación y la friabilidad. Para la preparación de los primeros lotes se utilizó el diseño experimental de compuesto de segundo orden esférico de dos factores, y para su optimización se empleó la función de deseabilidad. Para la preparación de los comprimidos de desintegración rápida se utilizó un diseño en retículos simple con restricciones en la proporción de los excipientes. En un diseño posterior, se seleccionaron como variables independientes la resistencia a la fractura y la concentración de celulosa microcristalina, de lactosa anhidra y de manitol. Para relacionar las variables independientes con la resistencia a la fractura y el tiempo de desintegración, se utilizaron ecuaciones matemáticas y representaciones gráfi cas. Además, para optimizar la formulación, se calculó el índice sintético que considera una desviación positiva o negativa a partir de un valor ideal. Se superpusieron las representaciones gráfi cas de la resistencia a la fractura y el tiempo de desintegración para encontrar la región optimizada en la que se pueden producir comprimidos con resistencia al aplastamiento y tiempos de desintegración aceptables. Para demostrar la similitud de la disolución en agua destilada y saliva simulada (pH 6,8) se utilizó el concepto de los factores de similitud f2 y Sd. Se podrían preparar comprimidos de desintegración rápida con una estructura duradera y un sabor agradable si se selecciona el nivel adecuado de CM, lactosa anhidra, manitol, croscarmelosa y fuerza de compresión

To make rapidly disintegrating tablets containing 8 mg ondansetron hydrochloride with suffi cient mechanical integrity as well as a pleasant taste, microcrystalline cellulose (MCC), lactose anhydrous, mannitol and croscarmellose were formulated. Tablets were prepared by a direct compression method. Tablets properties such as tensile strength, disintegration time, wetting time and friability were determined. The two-factor spherical second order composite experimental design was used for the preparation of preliminary batches and the desirability function was employed for the optimization of preliminary batches. For preparation of the rapidly disintegrating tablets, simplex lattice design with constraints on the proportion of excipients was utilized. In later design, tensile strength and disintegration time were selected as dependent variables and concentration of microcrystalline cellulose, concentration of lactose anhydrous and concentration of mannitol were selected as controlling factors. Mathematical equations and contour plots were used to relate independent variables with tensile strength and disintegration time. Furthermore, the composite index which considers a positive or negative deviation from an ideal value was calculated for the optimization of the formulation. Contour plots of tensile strength and disintegration time were superimposed to fi nd out the optimized region at which tablets with an acceptable crushing strength and disintegration time can be produced. The concept of similarity factors f2 and Sd were used to prove similarity of dissolution in distilled water and simulated saliva (pH 6.8). Rapidly disintegrating tablets with durable structure and desirable taste could be prepared by selecting proper level of MCC, lactose anhydrous, mannitol, croscarmellose and compression force

Método de cromatografía líquida de alta resolución para la determinación simultánea de fosinopril sódico e hidroclorotiazida en formulaciones de comprimidos / High performance liquid chromatographic method for simultaneous determination of fosinopril sodium and hydrochlorothiazide in tablets formulation

Se ha desarrollado un método HPLC de fase inversa con detección de UV sencillo, específi co, exacto y preciso para la determinación de fosinopril sódico e hidroclorotiazida en formulaciones farmacéuticas. La solución de fármaco se preparó en fase móvil y se inyectó en una columna C18 con detección de UV a 208 nm. La fase móvil era una mezcla de 0,2% p/v de ácido fosfórico en agua y acetonitrilo (30:70) añadida a una velocidad de fl ujo de 0,5 ml/min a 29 0C. Los gráfi cos de calibración fueron lineales en el rango de 10-50 μg/ml (r2 > 0,99) para el fosinopril sódico y de 6,25-31,35 μg/ml para la hidroclorotiazida (r2 > 0,99). El límite de detección fue de 0,5 μg/ml para el fosinopril sódico y de 1,0 μg/ml para la hidroclorotiazida, con un límite de cuantifi cación de 10 μg/ml y 6,25 μg/ml para el fosinopril sódico y la hidroclorotiazida, respectivamente. La evaluación estadística del método se examinó mediante calibración intradía (n=5) e interdía (n=5) y resultó satisfactoria, con una exactitud y precisión elevadas. El método sugerido se aplicó con éxito en la determinación simultánea de fosinopril sódico e hidroclorotiazida en formulaciones de comprimidos, con un elevado porcentaje de recuperación, buena exactitud y precisión

A simple, specifi c, accurate and precise reversed phase HPLC method with UV detection for the simultaneous determination of fosinopril sodium and hydrohclorthiazide in pharmaceutical formulations was developed. The drug solution was prepared in mobile phase and was injected into a C18 column with UV detection at 208 nm. The mobile phase was a mixture of 0.2%w/v phosphoric acid in water and acetonitrile (30:70) delivered at a fl ow rate of 0.5 ml/min at 29 0C. The calibration graphs were linear in the range of 10-50 μg/ml (r2 > 0.99) for fosinopril sodium and 6.25- 31.35 μg/ml for hydrochlorthiazide (r2 > 0.99). The detection limit was 0.5μg/ml for fosinopril sodium and 1.0 μg/ml for hydrochlorthiazide with quantitation limit of 10 μg/ml and 6.25 μg/ml for fosinopril sodium and hydrochlorthiazide, respectively. The statistical evaluation of the method was examined by performing intra-day (n=5) and inter-day calibration (n=5) and was found to be satisfactory, with high accuracy, and precision results. Application of the suggested method was successfully applied to the simultaneous determination of fosinopril sodium and hydrochlorthiazide in tablets formulation, with high percentage of recovery, good accuracy with precision

Effect of pH on in vitro permeation of ondansetron hydrochloride across porcine buccal mucosa.

The influence of drug concentration, pH in donor chamber, and 1-octanol/buffer partition coefficient on transbuccal permeation of ondansetron hydrochloride (pKa, 7.4) across porcine buccal mucosa was studied by using an in-line Franz type diffusion cell at 37 degrees C. The pH was adjusted to several values and the solubility of the drug in different pH was measured. Solubility of ondansetron hydrochloride decreases with increasing pH. The permeability of the drug was evaluated at different donor pH and drug concentrations. Permeability of un-ionized (Pu) and ionized (Pi) species of drug was calculated by fitting the data to a mathematical model. The steady state flux increased linearly with the donor concentration (r2 = 0.9843) at pH 7.4. The permeability coefficient and the partition coefficient of the drug increased with increasing pH. The values of Pu and Pi were 4.86 x 10(-6) cm/sec and 7.18 x 10(-7) (c)m/sec, respectively. The observed permeability coefficients and the permeability coefficients calculated from the mathematical model at various pH showed good linearity (r2 = 0.9799). The total permeability coefficient increased with increasing the fraction of un-ionized form of the drug. The drug permeated through buccal mucosa by a passive diffusion process. The non-ionized species of drug penetrated well through buccal mucosa and the permeation was a function of pH. Transbuccal delivery is a potential route for the administration of ondansetron hydrochloride.

Development and evaluation of fast-dissolving film of salbutamol sulphate.

The objective of this work was to prepare and optimize the fast-dissolving film of salbutamol sulphate, which can be useful in an acute attack of asthma. The film was prepared using a solvent evaporation technique and is taken through the sublingual route. The film contains polyvinyl alcohol as a polymer, glycerol as a plasticizer, and mannitol as filler. A 33 full factorial design was utilized for the optimization of the effect of independent variables such as amount of polyvinyl alcohol, amount of glycerol, amount of mannitol on the mechanical properties, and % drug release of film. The multiple regression analysis of the results led to equations that adequately describe the influence of the independent variables on the selected responses. Polynomial regression equations and contour plots were used to relate the dependent and independent variables. The experimental results indicated that polymer concentration, plasticizer concentration, and filler concentration had complex effects on film mechanical behavior and % drug release. Furthermore, the desirability function was employed in order to determine the best batch out of all 27 batches of the factorial design. The % relative error was calculated, which showed that observed responses were in close agreement with the predicted values calculated from the generated regression equations. It was found that the optimum values of the responses for fast release film could be obtained at medium levels of polyvinyl alcohol and glycerol, and a high level of mannitol. The prepared film was clear, transparent, and had a smooth surface. The concept of similarity factors Sd was used to prove similarity of dissolution between distilled water and simulated saliva (pH 6.8) or simulated gastric fluid (pH 1.2).

Administración transbucal del sulfato de salbutamol: determinación in vitro de las rutas de transporte bucal / Transbuccal delivery of salbutamol sulphate: in vitro determination of routes of buccal transport

Se estudió la influencia de la concentración de fármaco, el pH del compartimento dador y el coeficiente de partición 1-octanol/tampón en la permeación transbucal del sulfato de salbutamol (pKa1 = 9,3; pKa2 = 10,3) a través de mucosa bucal porcina utilizando una célula de difusión de Franz en línea a 37 ºC. El pH se ajustó a varios valores y la solubilidad del fármaco se midió en distintos pH. La solubilidad del sulfato de salbutamol descendió al aumentar el pH. Se evaluó la permeabilidad del fármaco a diferentes concentraciones de fármaco y pH dador. Se calculó la permeabilidad de especies ionizadas (Pi) y no ionizadas (Pu) del fármaco. El flujo de estado estable aumentó de forma lineal con la concentración dadora (r2=0,9683) con pH 7,4. El coeficiente de partición y permeabilidad aumentaron al aumentar el pH. Los valores de Pu y Pi del sulfato de salbutamol fueron 8,89 · 10-6 cm·s-1 y 2,49 · 10-6 cm·s-1, respectivamente. El coeficiente de permeabilidad total aumentó al aumentar la fracción de la forma no ionizada del fármaco. El fármaco penetró a través de la mucosa bucal mediante un proceso de difusión pasivo. El coeficiente de partición y la dependencia del pH de la permeabilidad del fármaco indicaron que el sulfato de salbutamol se transportó principalmente a través de la ruta paracelular mediante un mecanismo de partición

The influence of drug concentration, pH in donor chamber, and 1-octanol/buffer partition coefficient on transbuccal permeation of salbutamol sulphate (pKa1 = 9.3, pKa2 = 10.3) across porcine buccal mucosa was studied by using in-line franz type diffusion cell at 37ºC. The pH was adjusted to several values, and the solubility of the drug in different pH was measured. Solubility of salbutamol sulphate decreased with increasing the pH. The permeability of the drug was evaluated at different donor pH and drug concentrations. Permeability of unionized (Pu) and ionized (Pi) species of drug was calculated. The steady state flux increased linearly with the donor concentration (r2=0.9683) at pH 7.4. The permeability and the partition coefficient increased with increasing pH. The value of Pu and Pi of salbutamol sulphate were 8.89 · 10-6 cm·s-1 and 2.49 · 10-6 cm·s-1 respectively. The total permeability coefficient increased with increasing the fraction of unionized form of the drug. The drug permeated through buccal mucosa by a passive diffusion process. The partition coefficient and pH dependency of drug permeability indicated that salbutamol sulphate was transported mainly via the paracellular route by a partition mechanism

Evaluación y optimización simultánea de papaína inmovilizada en gránulos de alginato entrecruzado mediante un diseño factorial 3x3 y la función de deseabilidad / Evaluation and simultaneous optimization of papain entrapped in crosslinked alginate beads using 33 factorial design and the desirability function

En este artículo se investiga el entrecruzamiento del alginato sódico con iones de calcio a través de la gelación ionotrópica para capturar la papaína mediante disolventes "benignos para el entorno". Se empleó un diseño factorial completo 3x3 para investigar el efecto de las tres variables del proceso, que son la concentración de alginato sódico, la concentración de cloruro cálcico y el tiempo de endurecimiento sobre el porcentaje de captura, el tiempo necesario para la liberación de un 50 por ciento (T50) y un 90 por ciento (T90) de la enzima, la distribución y el ángulo de reposo. Los gránulos se prepararon mediante el uso de un dispositivo de goteo para el vertido de gotas de solución de alginato sódico que contiene la enzima en la solución de cloruro cálcico agitada magnéticamente. Además, se empleó la función de deseabilidad para optimizar el proceso sometido a estudio. Se demostró que los valores óptimos de las respuestas se pueden obtener en los niveles inferiores de las tres variables del proceso. La caracterización topográfica se realizó mediante microscopía electrónica de barrido (SEM) y la captura se confirmó a través de una calorimetría diferencial de barrido (DSC). Se concluyó que la selección adecuada de concentración de alginato con control de la velocidad de liberación y su potencial interactivo para el entrecruzamiento es importante y determina el tamaño y la forma general de los gránulos, los perfiles de patrón de disolución y duración, la sensibilidad al pH y la capacidad de carga de la enzima (AU)