Alfonso del Pozo

Studies on the reliability of a bihyperbolic functional absorption model. I. Ring-substituted anilines

The present study reviews and checks the rearranged master lines of the functional bihyperbolic absorption model proposed by Plá-Delfina and Moreno, by examining the correlations between absorption rate constants experimentally found in the small intestine and in the colon of the rat, and two types of partition constants for a series of ring-substituted anilines, of low to medium molecular weight. Evidence is given which demonstrates the reliability of the bihyperbolic equation for the small intestine data, showing the importance of the type of substitution in the absorption rate of compounds; for the colonic data, the collapsed, monohyperbolic form of this equation (i.e., the Wagner-Sedman equilibrium model) applies, independent of the nature and position of the group substituents in the aniline molecule. This means that, as the bihyperbolic model equation predicts, aqueous pore diffusion is a crucial factor, as important as membrane permeation, in absorption in the small intestine, whereas in the colon only this latter route is operative. The perspectives opened by the application of the model to gastrointestinal absorption studies are also discussed.

Use of ultrasound to prepare lipid emulsions of lorazepam for intravenous injection.

Lipid emulsions can be used as a vehicle for the production of low-volume injectable preparations with minimally water-soluble active ingredients. First, we focus on the galenic and technological conditions established by ultrasound techniques. A 2(5) factorial design was used to optimize the carrier emulsion. The study then deals with the development of a parenteral emulsion formulation for lorazepam (1 mg/ml), which is compared with the highest concentration (0.05 mg/ml) achieved in the optimal aqueous diluent for lorazepam (dextrose 5% in water). The physical and chemical stability of lorazepam in the emulsion was examined for 7 months.

Calculation of the gastric absorption rate constants of 5-substituted barbiturates through theRm values or substituent ΔRm constants in reversed-phase partition chromatography

A linear correlation between the logarithm of the in situgastric absorption rate constants (ka)of 5-substituted barbiturates and their Rmvalues in selected reversed-phase partition chromatographic systems is demonstrated, as well as between the Δlog kaand the ΔRmderived parameters. On the basis of the chromatographic behavior of 14 closely related compounds of this series, the substituent ΔRmconstants for the main functional groups are calculated, so that the gastric absorption constants of nontested barbiturates can be predicted with close approximation. Predicted Rmand log kavalues show an excellent correlation with log 1/C values taken from pharmacological literature data. The migration mechanisms involved in reversed-phase partition chromatography are discussed in connection with the results obtained with other types of partition systems and with bulk-phase solvents. The possible relationships between chromatographic parameters and absorption rate constants found from absorption sites other than the stomach are outlined; as well as the advantages and limitations of the procedure.

Use of chromatographicRm values as a possible approach to calculation of the absorption rate constants for some related drugs

A possible correlation between the logarithm of the absorption rate constants (kaof closely chemically related drugs consistent with the pH-partition theory and their Rm values in partition chromatograms is reported. The theoretical basis for the existence of this relationship is briefly outlined. On the basis of the data reported in the available literature for gastric absorption rate constants of several barbiturates and their Rm values in seven paper Chromatographic partition systems, correlations ranging from good to excellent were found.

An experimental assessment of the Wagner-Sedman extraction theory for the intestinal absorption of antibacterial sulfonamides

The chromatographic parameters in a reverse-phase partition system and the rat gut in situabsorption rate constants for 18 antibacterial sulfonamides are highly correlated values. The correlation is logarithmic-logistic in nature, being in accordance with the Wagner-Sedman extraction theory for a constant pH value. Parabolic correlations did not satisfactorily fit the experimental data. This behavior, not frequently reported in regard to the intestinal absorption of drugs, is discussed in connection with other apparently contradictory available data.

Pharmaceutical design of a new lactose-free coprocessed excipient: application of hydrochlorothiazide as a low solubility drug model

Most co-processed excipients used in direct-compression tablets contain lactose, which prevents lactose-intolerant patients from taking such tablets. Therefore, a novel lactose-free co-processed excipient for direct compression tablets has been prepared. Microcrystalline cellulose and dicalcium phosphate dehydrate were used as primary excipients which underwent a wet granulation process and factorial experiment in order to ascertain the best prototype. Finally, the best two prototypes were added to hydrochlorothiazide, which has chosen as the model drug because of its low solubility. An extensive characterization of the new excipient as well as the drug loaded tablets is reported. Our results show adequate parameters (rheological and compression behavior, uniformity of weight, disintegration, friability, crushing force and cohesion index). Moreover, the biopharmaceutical profile was evaluated; the tablets exhibits a Weibull kinetic function and fast drug release.Most co-processed excipients used in direct-compression tablets contain lactose, which prevents lactose-intolerant patients from taking such tablets. Therefore, a novel lactose-free co-processed excipient for direct compression tablets has been prepared. Microcrystalline cellulose and dicalcium phosphate dehydrate were used as primary excipients which underwent a wet granulation process and factorial experiment in order to ascertain the best prototype. Finally, the best two prototypes were added to hydrochlorothiazide, which has chosen as the model drug because of its low solubility. An extensive characterization of the new excipient as well as the drug loaded tablets is reported. Our results show adequate parameters (rheological and compression behavior, uniformity of weight, disintegration, friability, crushing force and cohesion index). Moreover, the biopharmaceutical profile was evaluated; the tablets exhibits a Weibull kinetic function and fast drug release.

Sorption–desorption test for functional assessment of skin treated with a lipid system that mimics epidermal lamellar bodies

Many skin diseases are associated with either increases or decreases in lamellar body secretion, or dysfunctional lamellar bodies. Consequently, diseased skin is characterized by reduced barrier function and altered lipid composition and organization. Human skin is commonly evaluated in vivo with non‐invasive biophysical techniques. The dynamic functions of the skin are evaluated with repeat measurements such as the sorption–desorption test (SDT).