Biomedical subjects

A Farinha

Publications and source records attributed to A Farinha.

8 recordsLinked to original sources

PubMed2005

Inter- and intralaboratory variation of in vitro diffusion cell measurements: an international multicenter study using quasi-standardized methods and materials.

In vitro measurements of skin absorption are an increasingly important aspect of regulatory studies, product support claims, and formulation screening. However, such measurements are significantly affected by skin variability. The purpose of this study was to determine inter- and intralaboratory variation in diffusion cell measurements caused by factors other than skin. This was attained through the use of an artificial (silicone rubber) rate-limiting membrane and the provision of materials including a standard penetrant, methyl paraben (MP), and a minimally prescriptive protocol to each of the 18 participating laboratories. "Standardized" calculations of MP flux were determined from the data submitted by each laboratory by applying a predefined mathematical model. This was deemed necessary to eliminate any interlaboratory variation caused by different methods of flux calculations. Average fluxes of MP calculated and reported by each laboratory (60 +/- 27 microg cm(-2) h(-1), n = 25, range 27-101) were in agreement with the standardized calculations of MP flux (60 +/- 21 microg cm(-2) h(-1), range 19-120). The coefficient of variation between laboratories was approximately 35% and was manifest as a fourfold difference between the lowest and highest average flux values and a sixfold difference between the lowest and highest individual flux values. Intralaboratory variation was lower, averaging 10% for five individuals using the same equipment within a single laboratory. Further studies should be performed to clarify the exact components responsible for nonskin-related variability in diffusion cell measurements. It is clear that further developments of in vitro methodologies for measuring skin absorption are required.

Clinical Laboratory Techniques↗

PubMed2000

Determination of clonixin in plasma and urine by reversed-phase high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method that enables the determination of clonixin in human plasma and urine samples is described. Recovery of the drug was over 87.6 and 80.7% for plasma and urine, respectively. The limit of quantitation of the method was established as 10 ng/ml in plasma and 20 ng/ml in urine samples, with RSDs of less than 11.1%. The applicability of the method was further assessed by determining the plasma concentrations time course of clonixin in six healthy volunteers after single oral dose administration of 150 and 300 mg of clonixin and Clonix.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

Improved bioavailability of a micronized megestrol acetate tablet formulation in humans.

Megestrol acetate, a progestogen widely used in the palliative treatment of endometrial carcinoma and breast cancer, is currently administered orally as a solid dosage form. Bioavailability of the drug following oral administration is closely related to the effectiveness and safety profile of the drug in formulation. Improved immediate-release formulations should allow improved drug delivery into the systemic circulation and, at the end, to the site of action. The micronization of drugs is one of the technological procedures to achieve such a purpose. This paper reports the design and results obtained in an in vivo study of the bioavailability of a micronized megestrol acetate tablet formulation compared to a conventional form. A significant increase in the drug bioavailability was observed, in either the rate or the extent of absorption. In vitro dissolution data of the two study formulations reflected the in vivo findings.

Adult↗

PubMed2000

Dissolution of omeprazole from delayed-release solid oral dosage forms.

The evaluation of the biopharmaceutical quality of omeprazole enteric-coated products (granules in capsules) with respect to its dissolution characteristics is not specifically regulated in any of the most common official pharmacopoeia. USP 23 includes a general monograph for enteric-coated products. This paper reports the evaluation of the medium pH effect on the dissolution rates of omeprazole from four omeprazole-containing products of different manufacturers. It is concluded that the USP 23 recommended dissolution procedure for enteric-coated products is not suitable due to the degradation of omeprazole under such conditions. Furthermore, the medium with pH 8.0 showed different dissolution rates not observed at pH 7.4, allowing discrimination between products of different manufacturers.

Administration, Oral↗

PubMed1999

Topical delivery of caffeine from some commercial formulations.

Permeation of caffeine through human skin and artificial membranes (mounted in modified Franz type diffusion cells) was evaluated, either from saturated solutions or from commercially available topical formulations (all containing 3% caffeine). Data interpretation of the caffeine diffusion through human skin does not implicate transfer through pores despite caffeine being a relatively polar molecule. No correlation was found between transfer though the synthetic membranes (cellulose acetate impregnated with isopropyl myristate and silicone rubber soaked in isopropyl myristate) and that observed through skin. The synthetic membranes can be used for assessing product performance in quality assurance but will give little indication of its performance in vivo. The study investigated the percutaneous permeation of caffeine through human skin in order to obtain a mechanistic interpretation of its route of permeation. Synthetic membranes were also examined to determine if they could be used as models for human skin. Different commercial formulations investigated to determine the significance of enhancement strategies.

Administration, Topical↗

PubMed1999

Bioequivalence evaluation of two omeprazole enteric-coated formulations in humans.

Omeprazole, a proton pump inhibitor, effectively suppresses the gastric acid secretion in the parietal cells of the stomach. Several previously published papers focus on the pharmacokinetics of the drug and its interactions with physiological aspects or with other drugs. The increasing number of omeprazole containing products available in the market, raises questions of therapeutic equivalence and/or generic substitution. The bioequivalence evaluation between two or more formulations provides information about in vivo performance. In a favorable decision regarding bioequivalence, the products are considered to have a similar therapeutic efficacy when used under the same therapeutic conditions. This paper reports the design, results and some important aspects involved in a bioequivalence study between two solid oral formulations from different manufacturers. Some important findings were the high intra-subject variability observed for Cmax and the variability observed between subject profiles, probably caused by the multi-unit type of formulations studied.

Adult↗

PubMed1998

Uniformity of dosage units--comparative study of methods and specifications between Eur. Pharm. 3rd and USP 23.

Methods and specifications of Eur. Ph. 3rd Ed. and USP 23 for the evaluation of the uniformity of dosage units were compared, in relation to: (i) allowed dispersion of the sample; and (ii) adequability to control the individual contents of active ingredient in relation to the labelled amount. Using the characteristics of the normal distribution curve, we calculate: (1) the highest dispersion allowable, represented by the relative standard deviation of the uniformity of mass of single-dose preparations of Eur. Ph. 3rd Ed., (results were 3.4, 5.1 and 6.8% for L1 = 5, L = 7.5 and L = 10, respectively); and (2) for all the methods studied the allowable units frequency for different intervals of the labelled amount. Differences between the tests of Eur. Ph. 3rd Ed. and USP 23 can lead to acceptance samples with very different individual contents variability, namely if the limit specifications for the strength was +/- 10%. The main reasons for that are: (1) in Eur. Ph. 3rd Ed., the limits are set with reference to the average content of the sample, and in USP 23, they are set with reference to the labelled amount of the active ingredient; and (2), the USP 23 calculates the content of active ingredient in each tablet from the result of the assay, when the weight variation method was used. Taking +/- 5% of label claim as the specification for the strength of the product, according EEC requirements, the maximum percentage of units outside the range 95-105% of label claim allowed by Eur. Ph. 3rd Ed. and USP 23 tests are similar.

Chemistry, Pharmaceutical↗

PubMedDate not supplied

Chronic headaches and sleep disorders.

BACKGROUND: Headaches and sleep problems are common complaints in the daily practice of the general practitioner. Since the relationship between headaches and sleep complaints is complex, clear models of interaction are needed for adequate diagnosis and treatment. METHODS: All subjects, successively seen in a headache clinic during a defined period, were subdivided based on the time of onset of cephalalgia. Subjects who reported onset of headache on a long-term basis, during the nocturnal or early morning (before final awakening) period, were systematically studied by a headache clinic and a sleep disorders center. This subgroup represented 17% of the total headache group. RESULTS: Although the results of the headache clinic study did not differentiate this subgroup from the other patients, the sleep disorders center's interviews and questionnaires demonstrated a significant impact of the sleep disorders on headache and daytime function. Nocturnal monitoring during sleep identified specific sleep disorders in 55% of the subjects with onset of headache during the nocturnal sleep period. Follow-up after treatment of the sleep disorder showed that all subjects with an identifiable sleep disorder reported either an improvement or absence of their headache. The subjects identified with periodic limb movement syndrome were mostly those who reported only an improvement in their sleep and still needed treatment for their headaches. The question of the interaction and association of sleep-related headache and periodic limb movement syndrome is unresolved. CONCLUSION: Headaches occurring during the night or early morning are often related to a sleep disturbance.

Adult↗