Development and evaluation of wafer loaded with sertaconazole solid dispersion for the treatment of oral candidiasis

Abstract Candidiasis is one of the most common fungal infections of oral cavity in humans, causing great oral discomfort, pain and aversion to food. To develop more effective antifungal systems for the treatment of oral candidiasis, an oral mucoadhesive wafer containing sertaconazole solid dispersion (STZ-SD) was developed in this study. Dispersion of STZ in Soluplus® as a solubility enhancement excipient was done by melting, solvent evaporation and freeze drying method at various STZ to Soluplus® ratios. The optimized STZ-SD was then incorporated in the sodium carboxymethyl cellulose (SCMC) gel, xanthan gum gel, or their combination to prepare the lyophilized wafers. The swelling capacity, porosity, and mechanical, release and mucoadhesive properties of the wafers, together with their antifungal activity, were then evaluated. The melting method sample with the ratio of 8:1 showed the best results in terms of saturation solubility and dissolution rate. The STZ-SD-composite wafer exhibited higher hardness and mucoadhesion, as compared to those made of the SCMC polymer. The STZ-SD-wafer also exhibited a greater antifungal effect when compared to the STZ-wafer. The present study, thus, suggested that the STZ-SD-wafer could serve as a novel effective delivery system for oral candidiasis treatment.

Solubility and dissolution enhancement of flurbiprofen by solid dispersion using hydrophilic carriers

ABSTRACT The intent of the current work is to study the effect of polyethylene glycol 8000 and polyethylene glycol 10000 as hydrophilic carriers on dissolution behaviour of flurbiprofen. In the present study, solvent evaporation method was used to prepare flurbiprofen solid dispersions and evaluated for physico-chemical properties, drug-carrier compatibility studies and dissolution behaviour of drug. Solubility studies showed more solubility in higher pH values and formulations SD4 and SD8 were selected to prepare the fast dissolving tablets. FTIR and DSC study showed no interaction and drug was dispersed molecularly in hydrophilic carrier. XRD studies revealed that there was change in the crystallinity of the drug. The results of In vitro studies showed SD8 formulation confer significant improvement (p<0.05) in drug release, Q20 was 99.08±1.35% compared to conventional and marketed tablets (47.31±0.74% and 56.86±1.91%). The mean dissolution time (MDT) was reduced to 8.79 min compared to conventional and marketed tablets (25.76 and 22.22 min.) indicating faster drug release. The DE (% dissolution efficiency) was increased by 2.5 folds (61.63%) compared to conventional tablets (23.71%). From the results, it is evident that polyethylene glycol solid dispersions in less carrier ratio may enhance the solubility and there by improve the dissolution rate of flurbiprofen.

Dissolution efficiency and bioequivalence study using urine data from healthy volunteers: a comparison between two tablet formulations of cephalexin / Eficiência de dissolução e estudo de bioequivalência utilizando dados de urina de voluntários saudáveis: uma comparação entre duas formulações de comprimidos de cefalexina

The aim of the present study was to assess the bioequivalence of two cephalexin tablet formulations available in the Brazilian market (product A as reference formulation and product B as test formulation). Dissolution efficiency (DE%) was calculated for both formulations to evaluate their in vitrobiopharmaceutical features. The oral bioequivalence study was performed in twenty-four healthy volunteers in a crossover design. Single oral dose (tablet containing 500 mg of cephalexin) of each product was administered with two weeks of washout period. Urinary concentrations of cephalexin were measured by high-performance liquid chromatography (HPLC) method and pharmacokinetics parameters were estimated by urinary excretion data. The bioequivalence was determined by the following parameters: the cumulative amount of cephalexin excreted in the urine, the total amount of cephalexin excreted in the urine and the maximum urinary excretion rate of cephalexin. DE values of immediate-release cephalexin tablets (500 mg) were 68.69±4.18% for product A and 71.03±6.63% for product B. Regarding the dissolution test of the two brands (A and B) analysed, both were in compliance with the official pharmacopeial specifications, since the dissolution of both formulations was superior to 80% of the amount declared in the label after 45 minutes of test (A=92.09%±1.84; B=92.84%±1.08). The results obtained indicated that the products A and B are pharmaceutical equivalents. Confidence intervals for the pharmacokinetic parameters were in compliance with the international standards, indicating that products A and B can be considered bioequivalents and, therefore, interchangeable...

O objetivo do presente estudo foi avaliar a bioequivalência de duas formulações de cefalexina disponíveis no mercado brasileiro (produto A como formulação referência e produto B como formulação teste). A eficiência de dissolução (DE%) foi calculada para ambas as formulações para avaliar suas características biofarmacêuticas. O estudo de bioequivalência oral foi realizado em vinte e quatro voluntários sadios utilizando um desenho cruzado. Uma dose oral única (comprimido contendo 500 mg de cefalexina) de cada produto foi administrada com um período de washout de duas semanas. Concentrações urinárias de cefalexina foram mensuradas por método de cromatografia líquida de alta eficiência (CLAE) e os parâmetros farmacocinéticos foram estimados por dados de excreção urinária. A bioequivalência foi determinada pelos seguintes parâmetros: quantidade acumulada da cefalexina excretada na urina, quantidade total da cefalexina excretada na urina e a taxa de excreção máxima da cefalexina. Os valores de DE dos comprimidos de liberação imediata de cefalexina (500 mg) foram 68,69±4,18% para o produto A e de 71,03±6,63% para o produto B. Com relação ao teste de dissolução das duas marcas analisadas (A e B), ambas apresentaram-se de acordo com as especificações farmacopéicas, uma vez que a dissolução de ambas formulações foi superior a 80% da quantidade declarada após 45 minutos de teste (A=92,09%±1,84; B=92,84% ±1,08). Os resultados obtidos indicaram que os produtos A e B são equivalentes farmacêuticos. Os intervalos de confiança para os parâmetros farmacocinéticos estavam de acordo com os padrões internacionais, demonstrando que os produtos A e B podem ser considerados bioequivalentes e, portanto, intercambiáveis...

Preparation, Characterization and Optimization of Poloxamer Solid Dispersions of a Poorly Water Soluble Drug Aprepitant.

Aim: The aim of the present investigation was to enhance the dissolution rate of a poorly water soluble drug, aprepitant, by preparation of solid dispersion with hydrophilic carrier, poloxamer 188, using solvent evaporation method. Place and Duration of Study: Department of Pharmaceutical Sciences and Department of Emerging Life Sciences, Guru Nanak Dev University, Amritsar, Punjab, between August 2012 and July 2013. Study Design: Designs of experiments were carried out with two input variables, drug to carrier ratio (X1) and amount of solvent (X2). A total of 7 experiments were performed (4 factorial runs and 3 centre points) as per full factorial design. Percent dissolution efficiency at 60 min (DE60) was selected as the response variable. Pareto chart along with half probability plot were studied for determining the most significant process variables, which were modelled using ANOVA. Methodology: Solid dispersions of aprepitant with poloxamer 188 were prepared using the solvent evaporation method and studied systematically using an optimization technique. A 22 full factorial design approach was used for the optimization of process variables on dissolution characteristics. The optimized solid dispersion was characterized by dissolution studies, Fourier Transform Infrared Spectroscopy, Differential Scanning Calorimetry, X-ray powder Diffraction studies and Scanning Electron Microscopy. Results: The results of the experimental study confirm that the factors like drug to carrier ratio and solvent amount significantly influence the dependent variable DE60. A high level of drug to carrier ratio and low level of solvent amount were found to be suitable for maximum DE60. The use of factorial design approach helped in the optimization of the solid dispersion. The characterization of optimized solid dispersion (F5) demonstrated that the decrease in crystallinity of aprepitant and poloxamer 188 might be responsible for the enhanced dissolution rate. Analysis of dissolution data indicated the best fitting with firstorder model. Conclusion: Dissolution enhancement of aprepitant was successfully obtained by preparing its solid dispersion with poloxamer 188 using solid evaporation method.

Formulation and in vitro evaluation of flurbiprofen-polyethylene glycol 20000 solid dispersions.

Solid dispersion is one of the most widely used methods to enhance the solubility and dissolution rate of poor water soluble drugs. In the present study, flurbiprofen solid dispersions were prepared using solvent evaporation method by incorporating polyethylene glycol 20000 and evaluated for solubility studies, drug-carrier compatibility studies and in vitro dissolution studies. From the solubility studies, formulations F4 were selected to prepare in the form of tablets and compared with control tablets (conventional tablets using pure drug). From the results of in vitro dissolution study, tablets containing polyethylene glycol 20000 showed almost complete drug release within the 15 min. The percent drug release in 15 min (Q15) and initial dissolution rate for formulation F4 was 99.26±1.12%, 6.62%/min. These were very much higher compared to control tablets (34.95±1.29%, 2.33%/min). The relative dissolution rate was found to be 2.84 and dissolution efficiency was found to be 57.48 and it is increased by 3.5 fold with F4 formulation compared to control tablets (17.91). From the above results, it is concluded that the formulation of solid dispersions using polyethylene glycol 20000 is a suitable approach to improve the solubility and dissolution rate of flurbiprofen.

Formulation, Evaluation and Pharmacokinetics of Flurbiprofen Fast Dissolving Tablets.

Aim: The intent of present study is to formulate fast dissolving tablets of flurbiprofen using different superdisintegrants to improve the dissolution and bioavailability. Place and Duration of Study: Jyothishmathi Institute of Pharmaceutical Sciences, Karimnagar, Andhra Pradesh, India, between January 2011 and December 2012. Methodology: Flurbiprofen fast dissolving tablets were prepared using different superdisintegrants and characterized for different physical parameters, DSC, FTIR studies, in vitro dissolution studies and in vivo pharmacokinetics to prove the enhancement of bioavailability. Results: From the in vitro dissolution studies, the percent drug release in 15 min (Q15) was found to be 91.46±1.42% in case of optimized formulation where as the conventional tablets prepared by similar manner showed 22.92±0.47% in 15 min. The initial dissolution rate and dissolution efficiency for optimized formulation was 6.10%/min and 53.44 but it was 1.53%/min and 10.96 in conventional tablets. They increased by 4.0 folds when compared to conventional tablets. From the pharmacokinetic evaluation, the optimized fast dissolving tablets produced peak plasma concentration (Cmax) as 11433.32 ng/ml at 2 h Tmax, but they were found to be 8792.64 ng/ml at 3 h Tmax, in case of conventional tablets. The area under the curve for the optimized fast dissolving and conventional tablets were found to be 42691.23 and 30727.14 ng-h/ml. Conclusion: In summary, formulation of fast dissolving tablets using superdisintegrants was a good approach to enhance the dissolution and absorption rates of flurbiprofen.

Síntesis, caracterización fisicoquímica y del estado sólido de asparaginatos de cobre, magnesio, manganeso y zinc / Synthesis, physiochemical and solid state characterization of copper, magnesium, manganese and zinc asparaginates

Introducción: la deficiencia de minerales en la población está asociada a enfermedades metabólicas, hormonales e inmunológicas. Usualmente, los minerales son suplementados en el organismo en forma de sales inorgánicas, las cuales pueden causar molestias gástricas y baja absorción en dependencia del tipo de sal empleado. Estudios previos muestran una adecuada absorción y ausencia de efectos gástricos cuando los minerales están asociados a ligandos orgánicos como enzimas, proteínas y particularmente aminoácidos. Objetivo: determinar mediante un estudio de preformulación la viabilidad de utilizar asparaginatos de cobre, magnesio, manganeso y zinc en suplementos nutricionales. Métodos: se realizó la síntesis y la verificación de formación de los complejos por espectroscopia infrarroja por transformada de Fourier y difracción de rayos X de polvos. Se evaluó la solubilidad, la constante de disociación, la eficiencia de la disolución y las propiedades físicas del estado sólido (morfología, distribución y tamaño de partícula, índice de Haussner, porosidad y compresibilidad) de los complejos. Se determinó la compatibilidad de los complejos con excipientes. Resultados: en los espectros infrarrojos se observó la participación del grupo carboxilo de la asparagina en la formación del enlace de coordinación de los complejos. En los difractogramas de rayos X se mostró la ausencia de los materiales de partida y la cristalinidad en los complejos. La solubilidad, la constante de disociación y la eficiencia de la disolución de los complejos, establecieron su carácter anfótero. Conclusiones: los resultados en las propiedades físicas del estado sólido, la humedad y la compatibilidad con excipientes, establecen que las formulaciones de los aparaginatos de cobre, magnesio, manganeso y zinc tienen propiedades reológicas adecuadas para propósitos farmacéuticos.

Introduction: the mineral deficiency in the human population has been associated with metabolic, hormonal and immunological disorders. These minerals are generally supplemented with inorganic salts in the body, but they might cause gastric distress and low absorption problems depending on the type of salt used. Previous studies demonstrated adequate absorption and absence of gastric effects when minerals were associated with organic ligands such as enzymes, proteins and particularly amino acids. Objective: to determine the viability of copper, magnesium, manganese and zinc asparaginates as nutritional supplements in a preformulation study. Methods: the synthesis and verification of the formation of complexes were carried out by Fourier transformed infrared spectroscopy and X-ray diffraction of powders. The solubility, the dissociation constant, the dissolution efficiency and the physical solid state properties (morphology, particle distribution and size, Haussner´s index, porosity and compressibility) of these complexes were evaluated. The compatibility of the complex with excipients was determined. Results: the involvement of the asparagine carboxyl group in the formation of the coordination bond of the complex was observed in the infrared spectra. the absence of starting materials and the crystallinity in the complexes were evidenced in the X-ray diffraction of powders. The solubility, the dissociation constant and the dissolution efficiency of the complexes established their amphoteric character. Conclusions: the results achieved in the physical solid state properties, the level of moisture and the compatibility with the formulation excipients indicate that copper, magnesium, manganese and zinc asparaginates have suitable rheological properties for pharmaceutical purposes.

Using fluid bed granulation to improve the dissolution of poorly water-soluble drugs

In this study, fluid bed granulation was applied to improve the dissolution of nimodipine and spironolactone, two very poorly water-soluble drugs. Granules were obtained with different amounts of sodium dodecyl sulfate and croscarmellose sodium and then compressed into tablets. The dissolution behavior of the tablets was studied by comparing their dissolution profiles and dissolution efficiency with those obtained from physical mixtures of the drug and excipients subjected to similar conditions. Statistical analysis of the results demonstrated that the fluid bed granulation process improves the dissolution efficiency of both nimodipine and spironolactone tablets. The addition of either the surfactant or the disintegrant employed in the study proved to have a lower impact on this improvement in dissolution than the fluid bed granulation process.

Comparative in vitro dissolution study of Aceclofenac Marketed Tablets in Two Different Dissolution Media by Validated Analytical Method.

In this study five marketed brands of aceclofenac 100 mg tablets have been evaluated using dissolution test in two different media with the aim to assess bioequivalence and to select a proper dissolution medium. Other general quality parameters of these tablets like weight variation, hardness, friability, disintegration time were also determined according to established protocols. All the brands complied with the official specification for friability, uniformity of weight, disintegration time and drug content. UV spectroscopic and RP-HPLC methods were validated for the parameters like linearity, accuracy, precision and robustness. Potency was determined by using these two methods. Potency obtained from UV method and HPLC methods were found similar with paired t test. Dissolution test results were subjected to further analysis by difference factor (f1), similarity factor (f2) and dissolution efficiency (% DE). Higher drug release was found in phosphate buffer pH 6.8 than in 0.05% sodium lauryl sulphate solution. All brands were found similar in respect of drug release in phosphate buffer pH 6.8 but they differ in respect of drug release in 0.5% sodium lauryl sulphate. So phosphate buffer pH 6.8 may be a suitable media for dissolution study of aceclofenac tablets.

Solubility enhancement of ibuprofen in the presence of hydrophilic polymer and surfactant.

Solid dispersions of ibuprofen (IBU) were prepared by solvent evaporation method using polyvinyl pyrrolidone (PVP) and/or sodium lauryl sulphate (SLS). Physicochemical properties of the various solid dispersion systems were determined by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. The results from dissolution studies indicated that ternary solid dispersion systems were more efficacious than the corresponding binary ones. The increase in the dissolution rate of ibuprofen from its solid dispersions with the PVP and/or SLS used in this study could be attributed to several factors such as improved wettability, local solubilisation, and drug particle size reduction. The most effective solid dispersion was the 20:180:10 w/w IBUPVP- SLS ternary system, which allowed dissolution of 85 % drug after only 9.15 minutes (in comparison with 94.61 minutes for drug alone and 17.92 minutes for the binary system).