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Biomedical subjects

O I Corrigan

Publications and source records attributed to O I Corrigan.

At least 37 records · Page 2Linked to original sources
PubMed1991

A comparison of the effect of synthetic and naturally occurring surfactants on the solubility and absorption of clofazimine (B 663).

All simple micellar systems investigated, containing both naturally occurring and synthetic surfactants, enhanced the solubility of clofazimine. The incorporation of fatty acid to form mixed micelles, brought about a further enhancement in drug solubility in the case of naturally occurring surfactants, in contrast, with synthetic surfactants this enhancement decreased. The most effective absorption promoter was a synthetic surfactant: fatty acid mixed micellar system. The results indicate an optimum surfactant: fatty acid ratio at which the solubility and membrane effects of the surfactant system are balanced.

Absorption↗
PubMed1991

Controlled delivery of oestradiol-17-b from silastic implants: in vitro and in vivo evaluation.

Oestradiol-17-b release from silastic implants of different length was determined in vitro over periods of up to 511 days. Sink conditions were provided by either Sodium lauryl sulphate (1%) or polyethylene glycol 400 (50%) in aqueous based media. Drug release profiles were fitted to the kinetic expression for matrix controlled release from a cylindrical delivery system, thus allowing prediction of both the rate and extent of release with time. A linear relationship was found between the cumulative amount of drug released in vitro and that released in vivo; the latter being measured from implants recovered from animals slaughtered in the period 96-515 days post implantation. A linear relationship was also obtained between serum oestradiol concentrations in the period 14 to 84 days post implantation and the in vitro release rate.

Animals↗
PubMed1989

Transdermal delivery of nicotine in normal human volunteers: a single dose and multiple dose study.

The absorption of nicotine delivered by a transdermal delivery system (TDS) was investigated in two separate studies, (A) a dose proportionality study and (B) a multiple dose study. In the dose range of 15-60 mg nicotine, the AUC and Cmax values were proportional to the dose. The levels achieved were in the same range as reported in smokers, following absorption from nicotine chewing gum. The TDS used in the present study produced sustained levels of nicotine for 24 h. No significant accumulation of nicotine was evident as a result of multiple dose administration using a 30-mg nicotine patch. Absorption of nicotine from the TDS was 80-90% and the rate of delivery was similar during both studies.

Administration, Cutaneous↗
PubMed1987

Physicochemical investigations of dipolar aprotic solvents as potential cholelitholytic agents.

A number of dipolar aprotic solvents have been examined as potential co-solvents for gallstone dissolution. The power of these agents to solubilize such gallstone components as cholesterol, calcium carbonate, calcium palmitate and palmitic acid was determined and compared with that of monooctanoin (Capmul), using the synthetic solubility method. The solubilities of cholesterol and palmitic acid were greater in the N-methyl, N-ethyl and N-butylpyrrolidone derivatives than in monooctanoin. In contrast, the solubilities of the calcium salts were very low (less than 0.25% w/w) in all solvents examined. The influence of N-methylpyrrolidone (NMP) on both the in-vitro dissolution of cholesterol from gallstones and the decrease in stone weight with time was determined. NMP proved to be a better solvent than monooctanoin for human stones. NMP, which is miscible with water and monooctanoin, may have potential as a co-solvent in the design of solvent systems for gallstones.

Calcium Carbonate↗
PubMed1986

Mechanism of dissolution of cholesterol-calcium bilirubinate compressed discs in monooctanoin.

The dissolution of cholesterol monohydrate and calcium bilirubinate (neutral salt) mixtures in monooctanoin was investigated using the static disc method. The intrinsic dissolution rate of calcium bilirubinate was orders of magnitude (approximately 1000 fold) lower than that of cholesterol. Cholesterol release decreased as its weight fraction in the solid decreased. In model systems containing below 50% cholesterol dissolution became negligible. The release profiles deviated from the classical model for dissolution from two component mixtures. The observed dissolution profiles of both components were greater than predicted by theory. Anomalous positive curvatures in dissolution profiles suggested that calcium bilirubinate initially reduced the surface area available for cholesterol dissolution. A model, taking into account the change in surface area, was used to fit the cholesterol dissolution data. The results were consistent with the reported relationship between human gallbladder stone cholesterol content and average stone weight loss.

Bilirubin↗
PubMed1984

Amorphous spray-dried hydroflumethiazide-polyvinylpyrrolidone systems: physiochemical properties.

Hydroflumethiazide was spray-dried with polyvinylpyrrolidone (PVP) to produce products containing 0-30% PVP. These systems were amorphous and differed from previously prepared coprecipitates of similar composition. Differential scanning calorimetry (DSC) suggested that at low PVP weight fractions both amorphous drug and an amorphous drug-PVP complex can be present in spray-dried systems. The apparent solubility of hydroflumethiazide in spray-dried products increased with increasing PVP content reaching a plateau value approximately four times that of the pure crystalline drug. The estimated free energy and entropy of the spray-dried drug were greater than that of crystalline drug and also increased with increasing PVP content. Dissolution studies with compressed discs supported the apparent solubility data. The results suggest that amorphous phases having different orders of organization are formed in spray-dried systems with increasing PVP content.

Chemical Phenomena↗
PubMed1982

Mechanism of drug dissolution rate enhancement from beta-cyclodextrin-drug systems.

The influence of beta-cyclodextrin on the physicochemical properties of bendrofluazide, chlorothiazide, hydrochlorothiazide and hydroflumethiazide was investigated using solubility, X-ray powder diffraction, differential scanning calorimetry (DSC) and intrinsic dissolution rate methods. The solubility of each drug was enhanced in the presence of beta-cyclodextrin, the effect being greatest with bendrofluazide. X-ray diffraction data on equimolar freeze dried systems indicated the formation of solid state inclusion complex only in the case of bendrofluazide. The relative increase in initial dissolution rate of drug from freeze dried systems varied from sixty fold for bendrofluazide to three fold for hydroflumethiazide. The observed dissolution rates were intermediate between those predicted by the classical two component soluble complex model and a carrier controlled model. It was concluded that the enhanced drug dissolution rates, which are above those predicted by the soluble complex model, are due to an extension of carrier phase dissolution control to higher drug weight fractions than predicted by the soluble complex model and that this was a consequence of the disparate solubilities of the carrier and drug.

Bendroflumethiazide↗
PubMed1980

The effect of dosage on the bioavailability of chlorothiazide administered in solution.

Chlorothiazide in solution was administered at four dose levels to three healthy male volunteers under controlled conditions. Excretion data indicated that the drug was poorly absorbed from the gastrointestinal tract. The 24 h recovery of the drug from urine fell from 33 to 6% as the dose was increased from 0.21 to 1.75 g per 70 kg of body weight. The cumulative amount of sodium excreted could be correlated with the cumulative amount of drug excreted, rather than with the dose administered. The electrolyte excretion response intensity could also be correlated with the amount of drug excreted. There was a poor linear relationship between response intensity and drug excretion rate. After higher doses the data suggested that the response was in the non-linear section of the dose response curve.

Biological Availability↗
PubMed1976

The influence of polyvinylpyrrolidone on the solution and bioavailability of hydrochlorothiazide.

The dissolution properties of hydrochlorothiazide-PVP 10 000 mechanical mix and coprecipitate systems were qualitatively similar to those previously reported using hydroflumethiazide. Quantitative differences were dependent on the proportion of PVP present, its molecular weight and method of incorporation. Cumulative urinary excretion data from test capsule preparations showed that bioavailability was enhanced by the presence of PVP. However, the degree of enhancement was less than that expected from constant surface area disc rate studies. Dissolution tests on the capsule formulations, using the U.S.P. basket stirrer assembly, did not correlate with in vivo results. Using the Levy beaker method and a stirring speed of 40 rev min-1, good correlation between amount dissolved in 30 min and amount excreted in urine after 24 h was obtained. The dissolution tests revealed that PVP retards the initial dissolution from capsule dosage forms, probably by retarding deaggregation and dispersion of drug particles.

Adult↗
PubMed1975

The influence of polyvinylpyrrolidone on the dissolution properties of hydroflumethiazide.

The incorporation of hydroflumethiazide with polyvinylpyrrolidone (PVP) was found to retard and to enhance the dissolution of the drug from compressed discs, the magnitude of the effect being dependent on the proportion of PVP present and its method of incorporation. The most active system dissolved sixteen times faster than pure hydroflumethiazide. Low concentrations of PVP were also found to decrease the apparent solubility of hydroflumethiazide while at high concentrations solubility was enhanced. X-ray and infrared analysis of systems suggested the presence of an amorphous form of hydroflumethiazide in coprecipitate systems. The dissolution data were consistent with a physical model which takes account of the roles played by crystalline and amorphous hydroflumethiazide together with the complexing and crystal growth inhibiting effect of PVP on hydroflumethiazide.

Chemical Precipitation↗