Formulation Validation

Used as preservatives in many topical pharmaceutical products, paraben esters have been found to exhibit estrogenic effects that have been linked to breast cancer. This has led to requiranents for their rapid and quantitative detection. Traditional methods of analysis are slow and tedious. For gas chromatographic methods, derivatization as silyl- or fluoroacetyl derivatives followed by extraction and sample cleanup complicate the process, while liquid chromatographic methods require extraction and long chromatographic run times. To increase speed and decrease complexity, solid phase microextraction with ion mobility spectrometry (SPME-IMS) was used for the determination of parabens in pharmaceutical formulations.  

Other SPME-IMS methods that have been reported for application to pharmaceutical or related samples include those for analysis of ephedrine in urine, meth-amphetamines in human serum, and captopril in human plasma and pharmaceutical preparations. In a method similar to SPME-IMS, testosterone was collected with a molecular imprinted polymer from urine and desorbed into an IMS. The method was validated with HPLC and determined to have a detection limit of 0.9 ng/mL with a linear dynamic range from 10 to 250 ng/mL.  

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Sanger-van de Griend, C. E., Wahlstrom, H., Groningsson, K., and Widahl-Nasman, M. (1997). A chiral capillary electrophoresis method for ropivacaine hydrochloride in pharmaceutical formulations validation and comparison with chiral liquid chromatography. /. Pharm. Biomed. Anal. 15(8), 1051-1061. 

It is easily seen that the incompressible model formulation contains less covariance terms than the model equations for compressible flows (3.401). For this reason the compressible formulation is seldom used, instead the formulation valid for incompressible flows is often used for weakly compressible systems as well. 

Validation of clinical trial formulations Validation of in vitro tests on solid dosage forms Experimental strategy for validation of industrial processes Optimization of industrial processes by evolutionary operation (EVOP)... 

Parameters for critical processing steps should be clearly specified. For example, for microdose products critical parameters include mixing time, sequence of additions, and mixing equipment (see Microdose Formulations— Validation and Control). 

The Boltzmann equation is considered valid as long as the density of the gas is sufficiently low and the gas properties are sufficiently uniform in space. Although an exact solution is only achieved for a gas at equilibrium for which the Maxwell velocity distribution is supposed to be valid, one can still obtain approximate solutions for gases near equilibrium states. However, it is evident that the range of densities for which a formal mathematical theory of transport processes can be deduced from Boltzmann s equation is limited to dilute gases, since this relation is reflecting an asymptotic formulation valid in the limit of no coUisional transfer fluxes and restricted to binary collisions only. Hence, this theory cannot without ad hoc modifications be applied to dense gases and liquids. 

A solvent free, fast and environmentally friendly near infrared-based methodology was developed for the determination and quality control of 11 pesticides in commercially available formulations. This methodology was based on the direct measurement of the diffuse reflectance spectra of solid samples inside glass vials and a multivariate calibration model to determine the active principle concentration in agrochemicals. The proposed PLS model was made using 11 known commercial and 22 doped samples (11 under and 11 over dosed) for calibration and 22 different formulations as the validation set. For Buprofezin, Chlorsulfuron, Cyromazine, Daminozide, Diuron and Iprodione determination, the information in the spectral range between 1618 and 2630 nm of the reflectance spectra was employed. On the other hand, for Bensulfuron, Fenoxycarb, Metalaxyl, Procymidone and Tricyclazole determination, the first order derivative spectra in the range between 1618 and 2630 nm was used. In both cases, a linear remove correction was applied. Mean accuracy errors between 0.5 and 3.1% were obtained for the validation set. 

Validation studies in manufacturing businesses and discussion with experts led to the view that knowledge used to define p, gp, tp and. Vp, could be structured such that may be formulated as ... 

The basic elements and considerations for assay development, validation, and specification assignment are reviewed briefly. Assay development produces a method that requires validation for the analysis and release of materials (bulk or formulated finished product) for use in clinical development. The cumulative analysis of materials and stability considerations is then used to established specifications for internal and regulatory submission. 

While significant amounts of experimental data are available on the side-chain tautomerism of the functionalized azoles, most are of qualitative character and not fully systematic. No accurate structural correlations which would allow rehable predictions of the energy preferences of a specific tautomer or the state of a tautomeric equilibrium at given conditions have been developed. Nevertheless, trends can be discerned, some of which have previously been formulated [76AHC(S1), pp. 386-391, 443-446]. More recent studies discussed in this section have confirmed the validity of the following ... 

The miracle of the appropriateness of the language of mathematics for the formulation of the laws of physics is a wonderful gift which we neither understand nor deserve. We should be grateful for it and hope that it will remain valid in future research and that it will extend, for better or for worse, to our pleasure even though perhaps also to our bafflement, to wide branches of learning. ... 

Relations (2.46) and (2.47) are equivalent formulations of the fact that, in a dense medium, increase in frequency of collisions retards molecular reorientation. As this fact was established by Hubbard within Langevin phenomenology [30] it is compatible with any sort of molecule-neighbourhood interaction (binary or collective) that results in diffusion of angular momentum. In the gas phase it is related to weak collisions only. On the other hand, the perturbation theory derivation of the Hubbard relation shows that it is valid for dense media but only for collisions of arbitrary strength. Hence the Hubbard relation has a more general and universal character than that originally accredited to it. 

No, this would be a violation of the 2nd Law of Thermodynamics. The value of A is restricted between -1 and 1 for reactions with AG>0. Thus with reactions with AG>0 the original formulation of Faraday s 1st law is always valid. 

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