Predicting the human in vivo performance of different oral capsule shell types using a novel in vitro dynamic gastric model.

The disintegration of a capsule shell may determine the onset of drug dissolution from capsule formulations. In this study, the release of a rapidly dissolving model drug (paracetamol), from two hydroxypropyl methylcellulose capsules containing either carageenan (HPMC-C) or gellan gum (HPMC-G) and one hard gelatin (HG) capsule, were investigated using a conventional in vitro model, the USP dissolution apparatus I, and a novel in vitro model of the human gastric compartment, the dynamic gastric model (DGM). The results obtained in vitro were compared with in vivo gamma scintigraphy human data and in vivo gastric emptying profiles available in the literature. The drug release from HPMC-G capsules, observed with the USP dissolution apparatus I, was delayed with respect to the other two capsules, while the results obtained from the DGM in the fasted state were closer together, which was in agreement with data from the in vivo studies. In the fasted state, the capsule rupture times obtained from the DGM were similar to those observed by gamma scintigraphy in vivo studies. In the fed state, the 'apparent' rupture times observed with the DGM were delayed compared to fasted, and were even longer than those observed by scintigraphy in vivo for HPMC-G and HG capsules. However, these discrepancies can reasonably be explained by considering the impact of food upon dispersion of the capsule contents and the sampling from the DGM, when compared to the human scintigraphy experiments.

Changes in plasma carotenoid and vitamin E profile during supplementation with oil palm fruit carotenoids.

It has been hypothesized that supplementation with a single source of carotenoids causes perturbations in the plasma level of diet-derived carotenoids and that this may explain the lack of association between disease rates and the intake of carotenoid supplements. This article describes the effect of supplementation with an oil palm fruit extract, rich in beta-and alpha-carotene, on the plasma carotenoid profile of 15 healthy women volunteers. Volunteers were supplemented for 35 days with 15 mg/d of total carotenoids. Blood samples were taken at regular intervals during the supplementation period and analyzed for a range of carotenoids. Results indicate that the hydrocarbon carotenoid components of the supplement are absorbed and appear in the plasma disproportionately to the ratios in the supplement and that the plasma concentration of diet-derived lutein, a dihydroxy carotenoid ((3R,3S,6R)-beta,epsilon-carotene-3,3-diol), is depressed, whereas that of lycopene is unaffected. Plasma alpha-tocopherol concentrations were unaffected by supplementation. It is concluded that supplementation with carotenoids from a single source results in plasma carotenoid profile changes that are not predictable from a knowledge of supplement composition and that such changes should be monitored and considered when drawing conclusions as to the effect of carotenoid supplementation on health outcomes.

Splanchnic retention of intraduodenal and intrajejunal glucose in healthy adults.

Estimates of the spanchnic retention and appearance in the systemic circulation of orally administered glucose vary among laboratories even after recently identified sources of error have been accounted for [Livesey, G., P. D. G. Wilson, J. R. Dainty, J. C. Brown, R. M. Faulks, M. A. Roe, T. A. Newman, J. Eagles, F. A. Mellon, and R. Greenwood. Am. J. Physiol. 275 (Endocrinol. Metab. 38): E717-E728, 1998]. We questioned whether, in healthy humans, D-glucose delivered intraluminally to the midjejunum appeared systemically as extensively as that delivered intraduodenally. Subjects were infused over a period of 90 min with 50 g of glucose in 1 liter of isotonic saline (incorporating 0.5 g D-[13C6]glucose) per 70 kg of body weight. Infusions were via enteral tubes terminating approximately 15 and 100 cm postpylorus. The systemic appearance of glucose was monitored by means of a primed-continuous intravenous infusion of D-[6,6-2H2]glucose. Whereas 98 +/- 2% (n = 7) of the duodenally infused glucose appeared in the systemic circulation, only 35 +/- 9% (n = 7) of midjejunally infused glucose did so, implying that 65 +/- 9% was retained in the splanchnic bed. Either glucose was less efficiently absorbed at the midintestinal site or hepatic glucose sequestration was increased 10-fold, or both. The proximal intestine plays a key role in the delivery of glucose to the systemic circulation, and the distal intestine potentially delivers more glucose to the liver.

Simultaneous time-varying systemic appearance of oral and hepatic glucose in adults monitored with stable isotopes.

The rates (and extent) of appearance of glucose in arterialized plasma from an oral glucose load and from liver (RaO, RaH) can be estimated in humans using radioisotopes, but estimates vary among laboratories. We investigated the use of stable isotopes and undertook 22 primed intravenous infusions of D-[6,6-2H2]glucose with an oral load including D-[13C6]glucose in healthy humans. The effective glucose pool volume (VS) had a lower limit of 230 ml/kg body weight (cf. 130 ml/kg commonly assumed). This VS in Steele's one-compartment model of glucose kinetics gave a systemic appearance from a 50-g oral glucose load per 70 kg body weight of 96 +/- 3% of that ingested, which compared with a theoretical value of approximately 95%. Mari's two-compartment model gave 100 +/- 3%. The two models gave practically identical RaO and RaH at each point in time and a plateau in the cumulative RaO when absorption was complete. Less than 3% of 13C was recycled to [13C3]glucose, suggesting that recycling errors were practically negligible in this study. Causes of variation among laboratories are identified. We conclude that stable isotopes provide a reliable and safe alternative to radioactive isotopes in these studies.

Absorption of all-trans and 9-cis beta-carotene in human ileostomy volunteers.

1. Mass balance studies were carried out in fasted ileostomy subjects (n = 5) given an oral physiological dose (10 mg) of beta-carotene [all-trans: 9-cis, 84:16 (w/w)] dispersed in vegetable oil. Blood and ileal effluent samples were collected and analysed for beta-carotene. 2. Results showed that 90% (range 97.0-74.3%) of the total beta-carotene was absorbed without measurable perturbation of plasma total beta-carotene concentration, or change in the all-trans: 9-cis beta-carotene ratio. Peak loss of beta-carotene in ileal effluent occurred at 4.9 h (range 2.9-8.4 h) postingestion, and no further loss was detected after 5.4-12.4 h, depending upon the individual. Comparison of the ratio of all trans-beta-carotene to 9 cis-beta-carotene in the test meal and effluent indicated that isomerization did not occur during passage through the gastrointestinal tract and that both isomers were similarly absorbed. However, the all-trans: 9-cis beta-carotene ratio of the plasma did not change. Reasoned assumptions allowed the construction of a mathematical model of plasma beta-carotene disposal. 3. It is concluded that physiological doses of isolated all-trans and 9-cis beta-carotene are well absorbed without necessarily causing detectable excursions in plasma beta-carotene concentrations, or altering the ratio of all-trans to 9-cis beta-carotene. Isomerization of beta-carotene does not occur during passage through the gastrointestinal tract. Absorbed beta-carotene is rapidly cleared from the plasma to an unobservable pool at a rate similar to that of chylomicron triacylglycerol.

Circadian patterns of total 24-h hydrogen and methane excretion in humans ingesting nonstarch polysaccharide (NSP) diets and the implications for indirect calorimetric and D2 18O methodologies.

OBJECTIVES: To quantify the relationship between substrate fermentation and total 24-h H2 and CH4 excretion on mixed diets and to assess errors incurred in the calculation of energy expenditure and fuel selection by the exclusion of these gases from standard calculations. DESIGN AND SUBJECTS: Twelve healthy, lean men were studied over two consecutive dietary periods of 3 weeks. Measurements of total H2 and CH4 excretion were made during 24h within a whole body calorimeter. Subjects were fed a diet containing 16 g or 38 g of nonstarch polysaccharide (NSP) and 16 g or 19 g resistant starch (RS). Colonic fermentation was measured by balance techniques during the two dietary treatments. RESULTS: There was an inverse non-linear relationship between H2 and CH4 excretion on both diets (r2 = 0.53; P < 0.001), but absolute excretion did not increase significantly as the intake of NSP and RS (from 28 +/- 3 and 48 +/- 4 g/day) increased. No relationship was found between daytime and 24-h measurements of H2 and CH4. H2 and CH4 excretion introduces an error of less than 0.2% and 1% in calculations of energy expenditure and CO2 production from the standard human equations used in indirect calorimetric (IC) and doubly labelled water (DLW) methodologies respectively, and less than 2% in fuel utilisation calculated as % non-protein energy expenditure from IC. CONCLUSIONS: This study provides evidence that neither daytime nor total 24-h rates of H2 or CH4 excretion accurately predict degree of fermentation of NSP+RS in either individual subjects or groups of subjects, probably because of changes in the stochiometry of the fermentation process.

Physiological effects of retrograded, alpha-amylase-resistant cornstarch in rats.

Retrograded amylose was prepared by gelatinization of high amylose cornstarch, followed by storage at 1 degrees C for 48 h. The insoluble residue, which resisted hydrolysis with porcine amylase, was dried and fed to male Wistar rats for 14 d in powdered semisynthetic diet. Control rats received a similar diet containing sucrose in place of resistant starch. Fecal collections were performed throughout the feeding period. After 14 d the animals were killed. The small intestine and cecum were removed for morphological examination, measurement of small intestinal crypt cell production rate (CCPR) and analysis of luminal carbohydrate content. Blood samples were collected for analysis of cholesterol, glucagon, and enteroglucagon. In the starch-fed rats, fecal bulk and excretion of starch were higher than in the controls, but they declined markedly over the feeding period. Cecal size and contents were also greater in the starch-fed rats, and cecal pH was significantly lower. The CCPR was 66% higher in the ileum of the starch-fed rats (P less than 0.001), but there was no difference in the jejunum. There were no differences in serum cholesterol or enteroglucagon levels. We conclude that retrograded amylose is partially degraded in the alimentary tract of rats, but it contributes significantly to fecal bulk.

Energy balance and energy values of alpha-amylase (EC 3.2.1.1)-resistant maize and pea (Pisum sativum) starches in the rat.

Apparent and partial digestible energy values for alpha-amylase (EC 3.2.1.1)-resistant, retrograde starches, isolated from cooked maize and pea starches (RMS and RPS respectively), were determined in male Wistar rats (about 180 g) during a 28-29 d balance period with ten animals per treatment. The starches were provided as supplements (100 g/kg diet) to a semi-synthetic basal diet (B), and their effects on the apparent digestibilities of nitrogen and fat, and on gains of live weight, fat and lean tissue were examined. Diet B alone was the control; sucrose (Su) and Solka-floc cellulose (SFC) were also examined for reference. Apparent digestibilities for Su, SFC, RMS and RPS were 1.0, 0.16, 0.98 and 0.89 respectively. Whereas the apparent digestibilities of gross energy, N and fat in the diet were unaffected by supplementation with Su, each was decreased by supplementation with SFC, RMS and RPS. Partial digestible energy values calculated from the intakes and faecal losses of energy in the basal and supplemented diets were 15, 12.4 and 0.8 kJ/g for RMS, RPS and SFC respectively. These values were smaller than corresponding apparent digestible energy values calculated from the apparent digestibility of the supplement and its gross energy value. Only the Su and starch supplements increased the intake of apparent digestible energy and the gain of live weight. Both starches and Su increased total energy (and fat) deposition to almost similar extents. It is concluded that the resistant starches contribute significant dietary energy, enhance growth and elevate fat deposition to extents almost similar to Su.

Utilization of alpha-amylase (EC 3.2.1.1) resistant maize and pea (Pisum sativum) starch in the rat.

1. The extent of utilization of alpha-amylase (EC 3.2.1.1)-resistant retrograded starches in vivo was assessed in male Wistar rats (about 100 g body-weight). All animals were given a fibre-free semi-synthetic basal diet (SS) containing sucrose as the only carbohydrate source, ad lib., for 13 d. On day 14, after an overnight fast, rats were allocated to one of five dietary treatments (n 30):1, fibre-free basal SS diet; 2-5, basal SS diet supplemented with 100 g sucrose, Solka floc (cellulose), resistant maize starch (RCS) or resistant pea (Pisum sativum) starch (RPS)/kg diet. Animals allocated to each dietary treatment were divided into three groups of ten rats which were given the appropriate diet for 8 or 9, 17 or 18 and 29 or 30 d (8/9, 17/18 or 29/30 d groups respectively). Rats were fed on 12 g diet/d (treatment 1) or 13.2 g diet/d (treatments 2-5) for the first 20 d, and 14 or 15.4 g/d respectively until the end of the experiment. Rats fed on the supplemented basal diets were thus given 10% more food to allow for the addition of the test carbohydrate. Faecal carbohydrate excretion was determined at intervals in the 17/18 d groups. At the end of each experimental period animals were killed after consuming their daily food ration and small intestinal length, weight of caecal and ileal contents and tissue, and pH of caecal contents measured. The amount of carbohydrate in the caecal and ileal contents from the 8/9 and 17/18 d groups was determined. 2. Weights of ileal and caecal contents, caecal tissue and faecal output were significantly greater at all time points for rats fed on the resistant starches compared with those fed on basal and sucrose-supplemented diets. Values were higher for RPS-fed rats than for RCS-fed rats. 3. The quantity of carbohydrate recovered from ileal and caecal contents showed that both RCS and RPS were partially digested and absorbed as carbohydrate, but that RPS was digested to a lesser extent. 4. The concentration of carbohydrate decreased between the ileal and caecal sites when RPS and RCS were given but was essentially unchanged when cellulose was given. This is consistent with rapid fermentation of a fraction of these starches. 5. Faecal carbohydrate elimination in the 17/18 d groups fed on RCS and RPS declined with time, which suggested an adaptive response resulting in increased utilization of the starches. This adaptive response was slower in the RPS-fed rats than the RCS-fed rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Validity of calculating fatty acid intake from mixed diets.

One hundred and seventy six weighed duplicate diets were collected over 16 consecutive days from 11 subjects. Analyses of their fatty acid composition were used to asses the validity of food composition tables. Four different calculating techniques were employed. Using the published data produced correlation coefficients of 0.29 between analysed and calculated polyunsaturated/saturated fatty acid ratios, whilst the addition of new analytical data and recoding fried foods produced a correlation coefficient of 0.56. The latter method also decreased the mean difference between analysed and calculated polyunsaturated/saturated consumption, when compared with the standard procedure.

An abbreviated food table using food groups for the calculation of energy, protein and fat intake.

A method of estimating the energy, protein and fat composition of diets is described, based on 84 food groups. Data from 3 dietary studies are used to compare intake calculated using the food groups and detailed food composition tables, with analyses of duplicate diets. For even small groups of people the mean differences and correlation coefficients between calculated and analysed results are similar for both methods of calculation. This approach could be used as a rapid coding method, or where skilled manpower is not available.