The single-pass perfused rabbit ear as a model for studying percutaneous absorption of clonazepam. II. Influence of hydrogel-borne propylene glycol and skin pretreatment with lauryl alcohol.

Enhancers of the percutaneous diffusion of clonazepam in the isolated single-pass perfused rabbit ear were evaluated and included propylene glycol (PG), polyethylene glycols (PEGs) of different molecular weight, as well as skin pretreatment with lauryl alcohol (LA). PG caused a concentration-dependent increase in the diffusion of clonazepam, due partly to the increased solubility of the active principle in the hydrogel. PEGs of molecular weight up to 3,000 Daltons added to the PG hydrogel showed a simple additive effect on percutaneous diffusion enhancement induced by PG. Transdermal delivery of clonazepam also increased as a function of exposure time following pretreatment with LA.

The single-pass perfused rabbit ear as a model for studying percutaneous absorption of clonazepam. I. General characteristics.

A single-pass perfused rabbit ear was employed as the model for studying percutaneous absorption of clonazepam in an open perfusion system. Clonazepam at 1.5% concentration (w/w) was suspended in a gel containing 1% (w/w) neutralized Carbopol 934 vehicled by a 50% water solution of propylene glycol and applied to the skin, in a thermostatically controlled chamber, after 10 min pretreatment with a lauryl alcohol enhancer. At 32 degrees C, the amount of clonazepam which diffused into the effluent after a 3 h lag phase was constant for 3 h and the flux averaged 0.486 mcg/h/cm2, whereas at 25 degrees C, the flux averaged 0.424 mcg/h/cm2. The amount of drug diffusing into the effluent was a function of the contact surface area and was independent of the rate of perfusion up to values of 1 ml/min. The apparent diffusion coefficient, Ds, and the partition coefficient, KM, were 2.75/10(6)/cm/h and 5.21, respectively.

Thin layer densitometry in the quantitative assay of drugs. Note V--Assay of reserpine and chlorthalidone in the presence of the potential impurities of their solid pharmaceutical forms.

Densitometric detection of compounds separated by thin layer was applied to the assay of a mixture of reserpine and chlorthalidone and their possible impurities. The method of analysis gave satisfactory results in the quality control of pharmaceutical preparations. Good results were obtained in urine tests for the detection of chlorthalidone, reserpine and methylreserpate. The times for the development of fluorescence in reserpine and methylreserpate directly in the chromatographic plate, are also described.

In vitro study of clonazepam diffusion kinetics from solutions or hydrophilic gel.

Preliminary studies were conducted to evaluate the influence of temperature, pH and ionic strength of the donor and receptor medium on the solubility, partition coefficient and diffusion rate of clonazepam across a lipophilic artificial membrane, in view of future setting up of transdermal formulation of this drug. The in vitro release of clonazepam from a carbopol hydrogel was also investigated.

Thin-layer chromatography and densitometry in drug assay: comparison of methods for monitoring valproic acid in plasma.

A thin-layer chromatographic (TLC) method is described for the assay of the anti-epileptic drug, valproic acid, in plasma. The use of high-performance (HPTLC) plates gave sensitive detection limits (4.87 micrograms ml-1) for derivatives of valproic acid and the reproducibility on the same or different plates was good. Comparison with high-performance liquid chromatography showed a similar performance of plate and column.

Formulation factors influencing the release of clonazepam from a carbopol hydrogel.

A study of formulation factors influencing the release of clonazepam from a Carbopol hydrogel through a cellulose nitrate membrane impregnated with lauryl alcohol was performed using two diffusion cell assemblies. The formulation variables were the cosolvent effects of propylene glycol and polyethylene glycol of different molecular weights in aqueous solutions of various composition. The gel formulation phenomenologically behaves as a zero-order release system, although the diffusion controlled mechanism may also be operative. The results showed that both methods were practically equivalent in terms of drug release profile and total drug released allowing the best formulation to be found.

Drug analysis by near-infra-red reflectance spectroscopy. Determination of the active ingredient and water content in antibiotic powders.

Near-infra-red reflectance spectroscopy is used to determine the active ingredient concentration and water content of an antibiotic powder (ceftazidime pentahydrate). The validity of predictive models for active ingredient concentrations and water content, constructed by means of the multiple linear regression technique is discussed. A procedure is devised for the analysis of production samples, which, on account of the very limited range of concentrations, prove a difficult fit to the above-mentioned model. The results obtained in testing formulation samples from 1 year's industrial production are used to illustrate the potential of the technique.

[Densitometric control of the degradation products of vitamin B1 and calculating activation factors]. / Contrôle densitométrique des produits de dégradation de la vitamine B1 et calcul des facteurs d'activation.

The authors perfect a TLC method with densitometric detection for the determination of vitamin B1 in the presence of its hydrolytic and oxidation products. The decomposition process and the proportions of products formed in the ampoules under different conditions of temperature/time treatment are also investigated and the activation factors (z and FO) of thiamine thermical decomposition, for their application in sterilization processes.

Application of NIRS to the quantity control of pharmaceuticals ketoprofen assay in different pharmaceutical formulae.

The possibility of using reflectance NIRS to assay 2-(benzoylphenyl)-propionic acid (Ketoprofen) in solid-state and gel preparations is investigated. The number of samples and amplitude of the percentage content distribution of the samples is examined in order to define the best possible calibration system.