Physicochemical stability of captopril and enalapril extemporaneous formulations for pediatric patients.

The prevalence of hypertension among children has been increasing. Community and Hospital Pharmacists are often challenged to provide an oral liquid extemporaneous formulation for pediatric patients, because there are no appropriate dosage drugs to the specific needs of the child. The objective of this study is to choose and develop suitable pediatric extemporaneous formulations for captopril and enalapril maleate and to determine their physicochemical stability. A survey was carried out to evaluate the extent of dispensation of these drugs in Hospitals in Spain. Stability studies of formulations have been studied according to ICH normative at 5, 25 and 40 °C. Three samples from each temperature were withdrawn and assessed for stability on days 0, 15, 30, 50 and 90 using a high-performance liquid chromatography (HPLC) mass spectrometer assay. Rheological studies were carried out to ensure the maintenance of the physical characteristics of these non-Newtonian fluids. Captopril and enalapril maleate formulations used the pure drug and were stable during 50 days at 5 °C. We have developed easy antihypertensive oral liquid extemporaneous formulations for pediatric patients with physical and chemical stability higher than those provided by the majority of Hospitals.

Drug diffusion from disperse systems with a hydrophobically modified polysaccharide: Enhancer vs Franz cells.

This study assesses the capacity of a new hydrophobically modified polysaccharide -hydroxypropyl cellulose-methyl methacrylate - to control drug release in semisolid formulations. The dispersed systems contain the new polymer, Igepal CO520 as surfactant and theophylline as model drug at three concentrations (0.5, 1 and 1.5%, w/w). Drug release study shows that the systems containing 0.5% (w/w) of drug have faster release and higher diffusion coefficient than the other two concentrations. These results can be explained by two different structures ("relaxed" and "structured") found from a rheological point of view. Also, this paper compares two different devices for testing drug release and diffusion. It has been obtained more reliable and reproducible results with Enhancer Cell respect to Franz diffusion cell. In both cases, Fickian diffusion was the mechanism predominant for all systems. Finally, the utility of this polymer has been demonstrated to make three-dimensional gel structure and control theophylline release from systems in topical application.

Surface tension and rheology of aqueous dispersed systems containing a new hydrophobically modified polymer and surfactants.

This article reports data supporting that the hydroxypropyl cellulose-methyl methacrylate (HCMMA) hydrophobically modified polymer studied is surface-active at the air-water interface due to its amphiphilic nature. Surface tension measurements of diluted solutions point to the formation of a complex between this copolymer and a polyoxyethylene nonylphenyl ether non-ionic surfactant of high HLB. Conversely, no indications of specific interactions were found either with a polyoxyethylene nonylphenyl ether non-ionic surfactant of intermediate HLB or with an anionic surfactant such as sodium dodecyl sulfate (SDS). The physical stability of such dispersions depended on the surfactant used. The HCMMA/SDS systems studied showed phase separation shortly after preparation, while the dispersions with the non-ionic surfactant of higher HLB exhibited at least short-term stability and Newtonian behaviour. Foam-like dispersions of HCMMA-surfactant systems with intermediate HLB presented long-term stability, underlying the important role of hydrophobic interactions in these systems. One of the latter dispersions and the corresponding continuous phase were rheologically characterised by small amplitude oscillatory shear and flow curve experiments and exhibited a high Newtonian viscosity up to a critical shear stress followed by a shear thinning as well as weak-gel viscoelastic properties. The results obtained support that (a) the continuous phase presents a complex microstructure, which required the use of a serrated sensor system to avoid the occurrence of wall depletion phenomena, (b) it controls the rheology of the whole dispersion and (c) the latter showed both physical stability and rheological properties suitable for applications as controlled release systems in pharmacy or cosmetics.

Determination of foscarnet (trisodium phosphonoformate) in pharmaceutical preparations by high-performance liquid chromatography with ultraviolet detection.

An isocratic high-performance liquid chromatographic method with UV detection has been developed and validated for the quantitative determination of foscarnet in isoosmotic sodium chloride aqueous solution. The mobile phase consisted of mixture of methanol:water (30:70 v/v), containing 1 mm tetrahexylammonium hydrogen sulphate at pH 5.80. The analyte was separated on a reversed-phase C(18) column packed with 4 microm spherical particles of octadecylsilane. Hydrochlorothiazide was used as internal standard. UV detection at 232 nm allowed a quantification limit of 50 microg/mL. The assay was linear from 50 to 4000 microg/mL. The coefficient of variation was < or =2.52% for intra-assay precision and < or =3.49% for inter-assay precision. The deviation from the nominal value ranged from -0.57 to 0.47% for the same-day accuracy and from -0.75 to 3.06% for day-to-day accuracy.