Abstract Orally disintegrating films (ODFs) were prepared from hydroxypropyl methylcellulose (HPMC E6 1.5%, 2.0%, and 2.5%), plasticizers ((glycerin (Gly), propylene glycol (PP), or polyethylene glycol (PEG)), and isosorbide dinitrate using the solvent casting method. Design of experiments (DoE) was used considering the amount of film-forming agent (HPMC) and the nature of the plasticizers as independent variables and thickness, mechanical properties, disintegration time, and dissolution efficiency as dependent variables. The best formulation was selected based on the desirability function ( f D). Color analysis was performed using CIE- L a b coordinates. DSC curves and XRPD diffractograms showed ISDN amorphization, probably due to complexation with polymers (HPMC E6 and HPβCD). The polymer (HPMC E6) and plasticizer played a critical role in the mechanical and optical properties of the films; however, these factors had no significant effect on the dissolution efficiency of ISDN. Principal component analysis revealed a more defined distinction of the ODFs according to their chromatic characteristics. ODFs prepared with Gly and PEG 400 were translucent, whereas the other films were transparent. The dissolution efficiency values of the ODFs (F1-9) were higher than those observed for the reference product (88.35(0.01%), indicating increased solubility of ISDN, probably due to complexation with polymers (HPMC E6 and HPβCD). The maximum value obtained for desirability function ( f D ) was 0.86, which corresponded to the use of 1.5% to 2.0% polymer (HPMC E6) and Gly or PP as plasticizers. The F5 formulation showed adequate thickness (85.00(6.38 (m), elongation at break (4.82(0.01%), adhesiveness (0.23(0.09 mJ), dissolution efficiency (95.97(0.01%), and high transparency.

Abstract In this study, orodispersible films formed from hydroxypropyl methylcellulose (HPMC) E6 (2, 2.5, and 3%) and plasticizers ((glycerin (Gly), propylene glycol (PP), or polyethylene glycol (PEG)), containing doxazosin mesylate, were prepared by the solvent casting method and characterized. Design of experiments (DoE) was used as a statistical tool to facilitate the interpretation of the experimental data and allow the identification of optimal levels of factors for maximum formulation performance. Differential scanning calorimetry (DSC) curves and X-ray powder diffraction (XRPD) diffractograms showed doxazosin mesylate amorphization, probably due to complexation with the polymer (HPMC E6), and the glass transition temperature of the polymer was reduced by adding a plasticizer. Fourier transformed infrared (FTIR) spectroscopy results showed that the chemical structure of doxazosin mesylate was preserved when introduced into the polymer matrix, and the plasticizers, glycerin and PEG, affected the polymer matrix with high intensity. The addition of plasticizers increased the elongation at break and adhesiveness (Gly > PEG > PP), confirming the greater plasticizer effect of Gly observed in DSC and FTIR studies. Greater transparency was observed for the orodispersible films prepared using PP. The addition of citric acid as a pH modifier was fundamental for the release of doxazosin mesylate, and the desirability formulation had a release profile similar to that of the reference product.

Abstract Orally disintegrating films (ODFs) comprising hydroxypropyl methylcellulose (HPMC) E6 (2%, 2.5%, and 3%) and plasticizers (glycerin [Gly], propylene glycol [1], or polyethylene glycol [2]) containing CPT were prepared by the solvent casting method and characterized. The design of experiments (DoE) was used considering the amount of film-forming agent (HPMC) and the nature of the plasticizers as independent variables and thickness, mechanical properties, disintegration time, and dissolution efficiency as dependent variables. The best formulation was selected based on the desirability function (fD). Color analysis was performed using CIE-Lab coordinates. The films had a pH less than 4 and were thus suitable for maximum stability of CPT. The amount of HPMC E6 and the nature of the plasticizer play a critical role in the physical, mechanical, and physicochemical properties of the films. Principal component analysis and hierarchical cluster analysis revealed a more defined distinction of the ODFs according to their chromatic characteristics. ODFs prepared with Gly and PEG 400 were translucent, whereas the other films were transparent. DoE successfully facilitated the interpretation of the experimental data and allowed the identification of optimal values of the factors for maximum yield. The maximum value obtained for fD was 0.8520, corresponding to 2.0 - 2.5% of the polymer (HPMC E6), and PP as plasticizer. The best-fitting kinetics model for CPT release from the ODFs was the Korsmeyer-Peppas model. The results showed that orally disintegrating films can be a promising alternative for oral administration of captopril.

Abstract Development and validation of a simple and fast method of high-performance liquid chromatography with diode array detection (HPLC-DAD) for the simultaneously analysis of rutin, avobenzone, and octyl p-methoxycinnamate is presented. These substances were separated using a Kromasil C18 (250×4.6 mm, 5 μm) column, methanol: water (88:12 v/v) as the mobile phase, and a flow rate of 0.8 mL min−1. The experiment was performed at room temperature and elution was under isocratic conditions. Quantification was performed by external calibration at the wavelength of 325 nm. The validated parameters included linearity, selectivity, precision (repeatability), intermediate precision, accuracy, limit of detection, limit of quantification and robustness. The results of validation were statistically treated using the Action Stat version 3.5.152.34. The selectivity was also evaluated in the presence of two cyclodextrins (2-hydroxypropyl-β-cyclodextrin and β-cyclodextrin sulfobutyl ether sodium). The absence of parallelism between the curves of octyl p-methoxycinnamate in the absence and presence of the β-cyclodextrin sulfobutyl ether sodium in the mobile phase revealed interference from this matrix, thereby indicating the necessity of validating the method in the presence of this, and other matrices. The proposed method was selective, linear, precise, accurate, and robust for the simultaneous determination of rutin, avobenzone, and octyl p-methoxycinnamate.

Albendazole and fenbendazole are imidazole derivatives that exhibit broad spectrum activity against parasites, but the low solubility of these drugs considerably reduces their effectiveness. Complexation of albendazole and fenbendazole with cyclodextrins (β-cyclodextrin and hydroxypropyl-β-cyclodextrin) in both water and an aqueous solution of polyvinylpyrrolidone (PVP-k30) was studied to determine if it could increase the solubility and dissolution rate of the drugs. In an aqueous solution, β-cyclodextrin increased the solubility of albendazole from 0.4188 to ~93.47 µg mL-1 (223×), and of fenbendazole from 0.1054 to 45.56 µg mL-1 (432×); hydroxypropyl-β-cyclodextrin, on the other hand, increased solubility to ~443.06 µg mL-1 (1058×) for albendazole and ~159.36 μg mL-1 (1512×) for fenbendazole. The combination of hydroxypropyl-β-cyclodextrin and polyvinylpyrrolidone enabled a solubility increase of 1412× (~591.22 µg mL-1) for albendazole and 1373× (~144.66 µg mL-1) for fenbendazole. The dissolution rate of the drugs was significantly increased in binary and ternary systems, with hydroxypropyl-β-cyclodextrin proving to be more effective. The presence of the water-soluble PVP-k30 increased the dissolution rate and amorphization of the complexes. Analysis of the changes in displacement and the profile of the cyclodextrin bands in the 1H NMR spectra revealed a molecular interaction and pointed to an effective complexation in the drug/cyclodextrin systems. Monomeric forms and nanoclusters of cyclodextrins were observed in the drug/cyclodextrin systems, suggesting that the increase in solubility of the drugs in the presence of cyclodextrins should not be attributed only to the formation of inclusion complexes, but also to the formation of cyclodextrin aggregates.

The combined effect of hydroxypropyl-β-cyclodextrin (HPβCD) and polyvinylpyrrolidone (PVP) or sodium carboxymethylcellulose (CMC) on the solubility of pyrimethamine (PYR) was studied. Equimolar PYR-HPβCD solid systems, in the presence or the absence of 0.25% (w/v) PVP or 0.10% (w/v) CMC were prepared by coevaporation or freeze-drying, and characterized by differential scanning calorimetry, X-ray diffraction analysis and dissolution profile. Phase-solubility analysis was used to investigate the interactions in aqueous solution between PYR and HPβCD, in the absence or presence of polymers, which showed a linear increase of PYR solubility depending on the concentration of HPβCD. The presence of polymer did not alter the stoichiometry of the complexes. DSC results were indicative of complexation, due to the loss of the characteristic endothermic peak of PYR. X-ray diffraction analysis confirmed the DSC results. Binary and ternary complexes showed higher dissolution rate when compared with the pure drug.

In this work the evaluation of the dissolution profile of captopril-hydrochlorothiazide and zidovudine-lamivudine associations were carried out by multivariate spectroscopic method. The models were developed by partial least square regression from 20 synthetic mixtures using mean-centered spectral data. The external validation was accomplished with 5 synthetic mixtures shown mean prevision error of about 1%. Good agreement was observed in the analyses of commercial drugs (content uniformity and dissolution profile), considering the results obtained by the standard chromatographic method, with prevision error lower than 10%.

A ineficácia clínica de muitos medicamentos tem servido de alerta para estudos mais profundos sobre os componentes da formulação, processos empregados e características físico-químicas dos fármacos. O objetivo deste trabalho foi avaliar a liberação in vitro de comprimidos de fosfato de primaquina disponíveis no Brasil para tratamento da malária, e o desenvolvimento de novas formulações de liberação convencional. Embora os comprimidos de fosfato de primaquina estudados tenham sido aprovados pelos critérios propostos pela Farmacopéia Americana (2006) para o teste de dissolução, não apresentaram desempenho adequado para o perfil de dissolução, mostrando retenção do fármaco durante a liberação. Os resultados indicam a existência de problemas nos comprimidos de fosfato de primaquina analisados, podendo sugerir como um dos fatores responsáveis pelo aparecimento de resistência dos parasitas.

The clinical inefficacy of many medications has served to highlight the need for deeper studies on the formulation components, processes used and physicochemical characteristics of drugs. The objective of this study was to evaluate the in vitro release of primaquine phosphate from tablets available in Brazil for treating malaria, and the development of new formulations for conventional release. Although the primaquine phosphate tablets studied had been approved according to the criteria proposed by the United States Pharmacopoeia (2006) for the dissolution test, they did not present adequate dissolution performance characteristics, in that there was drug retention during the release process. The results indicate the existence of problems in the primaquine phosphate tablets analyzed, and it may suggest that this is one of the factors responsible for the appearance of parasite resistance.

A via transdérmica para a absorção de fármacos apresenta várias vantagens, porém a absorção através desta via não é fácil de ser obtida. A principal barreira encontrada é o estrato córneo e uma das estratégias encontradas para promover a permeação cutânea de fármacos é o uso de promotores de absorção. Há uma variedade de substâncias identificadas como promotores de absorção. Enquanto a lista de substâncias de promotores de absorção percutânea vem aumentando, na maioria dos casos, há uma correlação entre o efeito promotor e a toxicidade para a pele. O emprego destas substâncias depende, portanto, de estudos enfocando a toxicidade local e sistêmica, bem como o mecanismo de ação.

Transdermal applications of drugs present many advantages in terms of absorption, however this is not easily obtained through the transdermal route. The principle barrier is the stratum corneum and one of the strategies that have been found to promote cutaneous drug penetration is through the use of absorption enhancers. Many substances have been identified as absorption enhancers. Although the list of substances that promote absorption is growing, in most cases, there is a direct correlation between the effects of absorption enhancers and their skin toxicity. The use of these substances depends therefore on studies which focus on local and systemic toxicity, as well as action mechanisms.

Voltamogramas de redissolução catódica de cefaloglicina em meio ácido exibem uma única onda de redução em potenciais próximos da descarga do eletrólito (-1.0 V). Entretanto, o fármaco pode ser determinado indiretamente em meio alcalino (pH 10) através do complexo formado entre cefaloglicina e Hg(I) gerado na superfície do eletrodo sob potencial de acúmulo positivo (Eac= +0.20 V). Uma curva de calibração linear no intervalo de 0.122 a 1.22 mg/mL foi obtida para cefaloglicina em tampão B-R pH 10 utilizando-se tempo de acúmulo de 30 seg e potencial de acúmulo de +0.20 V. O método mostra alta reprodutibilidade e sensibilidade com desvio padrão relativo de 1,4 % para 5 determinações de 5x10-7 mol/L de cefaclor e limite de detecção de 5,17 ng/mL.

Cephaloglycin in B-R buffer pH < 4 is reduced at HMDE very close to the electrolyte discharge (-1.0 V). Nevertheless, in alkaline medium (pH 10) a peak at -0.6V is observed when cephaloglycin is accumulated at accumulation potentials close to +0.20V by formation of an adsorbed mercury complex. The accumulation of this complex is recommended for use in the indirect determination of cephaloglycin by cathodic stripping voltammetry in the range 0.122 to 1.22 mg/mL with pre-concentration for 30 sec at accumulation potential of +0.20V. The detection limit was calculated to be 5,17 ng/mL (n= 3). The relative standard deviation determined from five determinations at the 5x10-7 mol/L level was 1.4 %.