Stability and compatibility of tegaserod from crushed tablets mixed in beverages and foods.

PURPOSE: The stability and compatibility of tegaserod from crushed tablets in selected beverages and foods were studied. METHODS: Suspensions of tegaserod maleate tablets containing 6 mg of the drug base were prepared by crushing the tablets and mixing the powder with tap water, apple juice, orange juice, milk, applesauce, yogurt, and chocolate-hazelnut spread. Drug stability, drug comparability, suspension homogeneity, and completeness of a dose were measured by high-performance liquid chromatography at intervals up to three days at 20-25 degrees C and 5 degrees C. In vitro dissolution profiles were determined for crushed tegaserod tablets in water, apple juice, orange juice, and applesauce. RESULTS: Tegaserod from crushed tablets was stable in and compatible with water, apple juice, orange juice, and applesauce, and the suspensions were homogeneous. The complete dose was delivered with these media. The dissolution profiles of crushed tegaserod tablets in water and in apple juice were comparable to those of intact tablets; the dissolution profiles in orange juice and applesauce were not comparable with those of intact tablets. The results with milk, yogurt, and chocolate-hazelnut spread as vehicles were inconclusive. The suspension in milk was not homogeneous, and the dose was incomplete. CONCLUSION: Tegaserod from crushed tablets was stable in and compatible with water, apple juice, orange juice, and applesauce, but the dissolution profile in orange juice or applesauce was not acceptable. Apple juice may be the preferred vehicle because it masks the drug's taste.     

Effects of cholestyramine and colestipol on the plasma concentrations of propranolol

The effect of equivalent hypolipidaemic doses of cholestyramine (8 g) or colestipol (10 g) on the plasma concentrations of propranolol and 4'-hydroxypropranolol was studied in 12 normal volunteers following the oral administration of 120 mg of normal release propranolol tablets. When two doses of either cholestyramine or colestipol were administered prior to the propranolol, the peak plasma concentrations and area under the curve for both propranolol and the metabolite 4'-hydroxypropranolol were reduced significantly (P less than 0.05). We conclude that the drug interaction between cholestyramine or colestipol and propranolol leads to significant reductions in plasma concentrations of propranolol and 4'-hydroxypropranolol which may cause a clinically diminished effect for a given dosage. Therefore, patients should be observed when either of these resins are added to or deleted from a therapeutic regimen.     

Relative bioavailability of deferasirox tablets administered without dispersion and dispersed in various drinks

Deferasirox (ExjadeA, ICL670) is a new, once-daily oral iron chelator, recently approved as first-line therapy in the treatment of iron overload resulting from blood transfusions. In registration studies, deferasirox tablets were dispersed in non-carbonated water prior to administration. In routine clinical practice, however, patients may prefer to take the tablet dispersed in a flavored drink rather than with water. OBJECTIVE: Stability and compatibility tests were performed to identify beverages suitable for the dispersion of tablets for further testing in man. This was followed by a pharmacokinetic study to assess the relative bioavailability of deferasirox tablets dispersed in two types of soft drinks, dispersed in water, and without dispersion. METHODS: An open-label, randomized, 4-period, crossover study was carried out with 28 healthy volunteers who received single 20 mg/kg oral doses of deferasirox without dispersion, dispersed in orange juice, dispersed in apple juice and dispersed in non-carbonated water (reference). Deferasirox and Fe-[deferasirox]2 were measured in plasma using liquid chromatography-mass spectrometry. Pharmacokinetic parameters were compared using standard bioequivalence tests. RESULTS: Mean deferasirox AUC0-t were 1,040 A+/- 530, 1,010 A+/- 278, 882 A+/- 252 and 996 A+/- 352 h x micromol/l when deferasirox tablets were administered without dispersion, dispersed in orange juice, dispersed in apple juice and dispersed in water, respectively, indicating that these forms of deferasirox administrations met bioequivalence criteria. Therefore, the oral bioavailability of deferasirox tablets was not affected neither by the degree of dispersion nor by the type of drink (orange or apple juice versus water) used for dispersion. CONCLUSIONS: This study shows that deferasirox bioavailability is unaltered when dispersed with orange or apple juice compared with dispersion in water. Thus, in addition to water, patients have the option of taking deferasirox tablets in orange or apple juice. The degree of dispersion did not affect deferasirox bioavailability. Therefore, deferasirox therapy will not be compromised if dispersion of the tablet is not fully complete; although the latter should be avoided.     

Effects of resins and activated charcoal on the absorption of digoxin, carbamazepine and frusemide.

1. The interference of resins and activated charcoal with the absorption of digoxin, carbamazepine and frusemide was studied. 2. In a cross-over study consisting of four phases, single doses of colestipol hydrochloride (10 g), cholestyramine (8 g), activated charcoal (8 g) or water only were given to six healthy volunteers immediately after the simultaneous ingestion of digoxin (0.25 mg), carbamazepine (400 mg) and frusemide (40 mg). Plasma and urine concentrations of the test drugs and the urine volumes were determined up to 72 h. 3. The absorption of digoxin was not reduced by colestipol, moderately (30-40%, P less than 0.05) reduced by cholestyramine and greatly (96%) by charcoal. 4. The absorption of carbamazepine was not decreased by cholestyramine, slightly (10%) by colestipol and greatly (90%) by activated charcoal. 5. The absorption and the diuretic effect of frusemide were significantly diminished by all agents. The bioavailability was reduced by colestipol 80%, by cholestyramine 95% and by activated charcoal 99.5%. 6. The interference with the gastrointestinal absorption of most of the basic drugs by colestipol and cholestyramine seems to be minimal. On the other hand, the resins may seriously impair the absorption of certain acidic drugs, for example frusemide.     

Citric acid or orange juice for the 13C-urea breath test: the impact of pH and gastric emptying

BACKGROUND: There is an ongoing debate about the optimal test drink to be used in the 13C-urea breath test (13C-UBT). We recently reported that a citric acid solution is the optimal test drink in the 13C-UBT, because it provides a high 13CO2 recovery and the excellent accuracy of the test appears optimal compared to other test meals. Orange juice, because of a better taste, is also propagated as a test drink in the 13C-UBT. AIM: To compare the diagnostic accuracy of the 13C-UBT with either orange juice or citric acid solution as a test drink. Furthermore, the effect of these test drinks on the gastric emptying rate was determined. METHODS: H. pylori status was assessed by histology, rapid urease test and culture in 50 consecutive dyspeptic patients. A 13C-UBT was performed on two consecutive days by giving 75 mg of 13C-urea randomly dissolved in 200 mL 0.1 M citric acid solution or 200 mL orange juice. The 13CO2/12CO2 ratio was measured in breath samples taken before and 15, 30, 45 and 60 min after administration of the test drink. The gastric emptying rate of orange juice and citric acid solution was compared to that of water in 10 healthy subjects on three consecutive days by means of a 13C-sodium acetate breath test; 50 mg of 13C-sodium acetate was dissolved in 200 mL of each solution and breath samples were collected before and every 10 min for 90 min after administration of the test drink. RESULTS: Twenty-six out of 50 patients (52%) were infected with H. pylori. Significantly higher values over baseline (35.7+/-5.2 per thousand vs. 23.2+/-3.4 per thousand, P<0.001) and higher area under the curve (1507+/-198 vs. 927+/-128, P<0.001) were observed in H. pylori-positive patients when citric acid solution was administered compared with orange juice. Sensitivity of the 13C-UBT was 100% when citric acid was used as a test drink and 88% with orange juice. Specificity was 100% with both test drinks. Gastric emptying of citric acid solution (t1/2 = 60.9+/-3.5 min) was significantly slower than that of orange juice (t1/2 = 49.7+/-3.1 min, P<0.001). CONCLUSION: 13C-UBT loses diagnostic accuracy when orange juice instead of citric acid is used as a test drink. The faster gastric emptying of orange juice might be responsible for the lower diagnostic accuracy of the 13C-UBT.     

Content of CYP3A4 inhibitors, naringin, naringenin and bergapten in grapefruit and grapefruit juice products

The flavonoids, naringin and naringenin and the furanocoumarin, bergapten (5-methoxypsoralen), were detected in some fresh grapefruit and commercial grapefruit juices but were not detected in other fruit juices tested (orange; orange with apple base; dark grape; orange and mango with apple base; orange, peach, passion fruit juice). The contents of these three grapefruit constituents in commercial juice and fresh grapefruit varied from brand to brand and also from lot to lot. Juice was prepared from the fresh fruit via different methods (by hand, squeezer or blender). The naringin content, after hand-squeeze, ranged from 115 to 384 mg/l. With hand-squeeze juice production, bergapten was not detected (less than 0.5 mg/l) in two varieties of grapefruit, and naringenin was usually not in detectable levels (less than 2 mg/l) in three varieties. All three constituents were present in New Zealand grapefruit preparations (including juice by hand-squeeze) and different lots showed variation in content (1.5-, 2.3- and 4.7-fold for naringin, naringenin and bergapten, respectively). Differences in the concentrations of these three constituents, which have potential for drug interaction, may contribute to the variability in pharmacokinetics of CYP3A4 drugs and some contradictory results of drug interaction studies with grapefruit juice.     

Relationship of components of an alcohol interoceptive stimulus to induction of desire for alcohol in social drinkers.

The ability of a low (0.2 g/kg) oral dose of ethanol to provide a drug discriminative stimulus was studied in young healthy human volunteers, who were social drinkers. Seventeen of 24 subjects acquired the discrimination following 10 trials in which they received aliquots of ethanol or of placebo drink (tonic water mixed with Tabasco sauce). In generalization studies, in which the dose of ethanol was varied, discrimination performance was dose dependent; doses greater than 0.05 g/kg gave rise to significant ethanol-appropriate responding. Concurrent estimates of the subjective effects of doses administered as discriminative stimuli revealed that two factors--taste and light-headedness--were associated with discrimination: at the training dose, 0.2 g/kg, although both the factors taste and light-headedness were significantly increased, only taste predicted discrimination performance. At lower doses, taste did not contribute to discrimination, but the subjective rating light-headedness correlated significantly with discrimination accuracy. Post hoc analyses of the influence of the amount of alcohol regularly drunk by the volunteers, on discrimination performance suggested light-headedness correlated with discriminative performance only in social drinkers drinking more than 20 units per week. In a second experiment, groups of "high" (mean 40 units per week) and "low" (mean 10 units per week) social drinkers were prospectively identified. Discrimination performance of 0.2 g/kg ethanol in orange juice vs. orange juice vehicle indicated that both groups were able to perform the discrimination following a single training trial, and that generalization curves over the range 0.05-0.2 g/kg were dose dependent, and not different between the groups. At the lowest dose, discrimination performance was predicted by taste, stimulation, and light-headedness in the "high" group, but not in the "low" group. The ability of these ethanol doses to induce feelings of craving for ethanol were assessed in parallel, using the Desire for Alcohol Questionnaire (DAQ). "High" drinkers showed higher desire for ethanol on all factors of the DAQ except the "positive negative reinforcement" factor, and sampling ethanol tended to increase desire in these measures. However, at each dose, the induction of feelings of desire for ethanol showed a negative correlation with discrimination performance. These findings are discussed in the context of the ability of animals and humans to use several components of drug-induced stimuli in the performance of drug discrimination, and the role of such discriminative stimuli in priming of ethanol drinking.     

Impaired absorption of tetracycline by colestipol is not reversed by orange juice

Nine volunteers received a 500 mg oral dose of tetracycline hydrochloride in three trials: A: With 180 ml water; B: With 30 gm colestipol in 180 ml water; C: With 30 gm colestipol in 180 ml orange juice. Tetracycline concentrations in multiple urine samples collected during 48 hours after each dose were determined by high pressure liquid chromatography. The three trials did not differ significantly in 48 hour cumulative urine volume (3086 vs 3207 vs 3194 ml for Trials A, B, and C). However, the three trials differed significantly in 48 hour excretion of tetracycline (F = 28.2; P less than .001). During Trial A, mean excretion was 237 mg; this was significantly (P less than .05) reduced to 109 mg in Trial B and 104 mg in Trial C. However, Trials B and C were not different. Thus, coadministration of tetracycline with colestipol significantly impairs tetracycline absorption by more than 50%. Mixing colestipol with orange juice does not alter colestipol-induced impairment of tetracycline absorption.     

Effect of colestipol,a new bile acid sequestrant,on the absorption of phenprocoumon in man

Summary The effect of colestipol, a basic anion-exchange resin, which lowers the serum cholesterol level, has been examined on the absorption of phenprocoumon in four human volunteers,in vivo. Plasma concentrations of phenprocoumon were determined after the simultaneous ingestion either of 8 g colestipol or 4 g placebo (microcrystalline cellulose) and 12 mg phenprocoumon according to a randomized crossover repetition design. The plasma levels were not affected by colestipol, suggesting that it had no effect on the absorption of phenprocoumon. —In vitro, the phenprocoumon-binding capacity of colestipol was the same as that of cholestyramine, except in buffers at pH 5 when there was a marked decrease in the colestipol binding.     

Effect of Anions on Adsorption of Bile Salts by Colestipol Hydrochloride

The Langmuir affinity constant and adsorptive capacity for the adsorption of citrate anion or cholate anion by colestipol hydrochloride at pH 7.5, 37°C, were similar. Prior exposure of colestipol hydrochloride to citrate anion caused the adsorption of cholate anion to decrease slightly in comparison to a control utilizing only cholate anion. The concentration of citrate anion was found to be directly related to the decrease in cholate anion adsorption. Simultaneous exposure of colestipol hydrochloride to citrate and cholate anions at pH 7.5, 37°C, resulted in the same adsorption of cholate anion as sequential exposure to citrate anion followed by cholate anion. Sequential exposure of colestipol hydrochloride to simulated gastric fluid and simulated intestinal fluid containing cholate anion resulted in a small decrease in cholate adsorption which was attributed to competition with phosphate anion in simulated intestinal fluid. Pepsin in the simulated gastric fluid did not affect adsorption of cholate anion from simulated intestinal fluid. Preexposure to components of tomato juice and orange juice also slightly reduced the adsorption of cholate anion by colestipol hydrochloride.     

The effect of colestipol and cholestyramine on the systemic clearance of intravenous ibuprofen in rabbits

Abstract— The effect of oral administration of the non-absorbable anion-exchange resins cholestyramine and colestipol on the systemic clearance and other pharmacokinetic parameters of intravenously administered ibuprofen (25 mg kg^?1) was studied in rabbits. Single doses of colestipol hydrochloride (0·4 g kg^?1) or cholestyramine (0·17 g kg^?1) were given 30 min before ibuprofen administration. In cholestyramine-treated rabbits a significant reduction in ibuprofen plasma concentration was observed compared with both control (water only) and colestipol-treated rabbits. Cholestyramine treatment resulted in a significant decrease in the terminal elimination half-life and the mean residence time. Furthermore, a 31% increase in the systemic clearance and 23% decrease in the area under the plasma concentration-time curve were also observed in cholestyramine-treated rabbits. Colestipol treatment did not change these parameters. The volume of distribution parameters (Vd_ss and Vd_area) did not change following either treatment. The changes in the pharmacokinetic parameters are compatible with an acceleration of ibuprofen elimination induced by oral administration of cholestyramine and not by colestipol. This effect is thought to be due to augmentation of net biliary excretion through enteric binding.     

Inhibitory effects of green tea and grape juice on the phenol sulfotransferase activity of mouse intestines and human colon carcinoma cell line, Caco-2

Tea and fruit juices are beverages consumed daily all over the world. The present study reports the inhibitory effects of these beverages on the activity of mammalian intestinal phenol sulfotransferases (P-STs). Green tea strongly inhibited the E. coli-expressed mouse intestinal P-ST activity in vitro. (-)-Epigallocatechin gallate (EGCG) was found to be the most potent inhibitor among the catechins tested (IC50=0.93 microM). (-)EGCG also inhibited the P-ST activity of the human colon carcinoma cell line, Caco-2. Kinetic analysis showed that the inhibition was competitive. Among fruit juices examined (apple, grape, grapefruit and orange), grape juice exhibited the most potent inhibitory action on the P-ST activity of mouse intestines and human colon carcinoma cells. The inhibitory activity of grape juice was located mainly in the skin and seeds. Flavonols, such as quercetin and kaempferol, inhibited the P-ST activity at low concentrations. These observations suggest the possible inhibition of P-ST activity in human intestines by green tea or grape juice.     

Comparison of ease of swallowing of dietary supplement products for age-related eye disease.

OBJECTIVE: To examine patients' perceptions on the relative importance of the physical characteristics and appearance of dietary supplements, and to evaluate two supplements with the same combination of vitamins and minerals used in the Age-Related Eye Disease Study (AREDS) with respect to ease of swallowing and other features in elderly patients. DESIGN: A single-site, single-visit, crossover design, subject-masked comparison of two dietary supplements (ICaps AREDS Formula--Alcon; Ocuvite PreserVision-Bausch & Lomb). SETTING: Ophthalmology practice. PATIENTS: 50 patients aged 50 years or older. INTERVENTIONS: Patients ranked the importance of eight physical characteristics of a vitamin tablet or capsule (ease of swallowing, size, shape, color, smell, coating, texture, and taste) irrespective of the test products used in the study and then took both test products randomly and were asked to indicate which product they preferred based on the same eight characteristics. MAIN OUTCOME MEASURES: Overall patient preference and preference for swallowing two tablets at once. RESULTS: The highest rated (most important) characteristic in a vitamin supplement was ease of swallowing, with a median score of 9.0 on a 0-10 visual analogue scale. The characteristic of least importance was tablet color, with the lowest median score of 1.0. Statistically significant differences were detected between the products with regard to preferences for ease of swallowing, swallowing two tablets at once, size, and coating (P < or = .0001). Significantly more patients preferred the ICaps AREDS formula to Ocuvite PreserVision with respect to these characteristics and overall preference (P < .001). Age, gender, and previous vitamin use were contributing factors in the rating of physical characteristics and tablet preferences. CONCLUSION: Based on the results of this study, ease of swallowing is the most important characteristic of dietary supplement tablets for elderly patients, followed by taste, size, and smell. Significant differences in preference exist between the study products, which contain similar formulations but have different physical characteristics.     

In Vitro Stability and Recovery Studies of Pimavanserin in Water and in Different Vehicles Orally Administered

Background and objectiveSwallowing difficulties (i.e., dysphagia) occur in up to 40% of the adult general population, particularly among the elderly prescribed solid oral dosage forms. Pimavanserin is approved for the treatment of hallucinations and delusions in patients with Parkinson’s disease psychosis (PDP) as a 34-mg capsule formulation. Patients with PDP may be at-risk for dysphagia that could affect administration of intact pimavanserin capsules. The stability of oral pimavanserin was evaluated in different liquid/soft food vehicles.MethodsThe stability of pimavanserin intended for oral administration was assessed by sprinkling the contents of 1 pimavanserin 34-mg capsule into water (40 mL), applesauce (40 g), vanilla Ensure (60 mL), or non-pulp orange juice (60 mL).ResultsThe stability study demonstrated >95% recovery within 24 hours after contents of a 34-mg pimavanserin capsule were dispersed in applesauce, vanilla Ensure®, orange juice, or water. Assay values at 24 h for individual capsules were within 5% of time zero, and no significant change in the impurity profile was observed in any vehicle. Pimavanserin degradation products recovered from various food vehicles for individual and total degradation products were < 0.5% at all time points. In addition, the impurity profile of compatibility samples matched that obtained for a control sample. ConclusionThese results support the ability of pimavanserin to be given orally by emptying the capsule contents into soft foods or liquids in accordance with the product label.     

Orange and apple juice greatly reduce the plasma concentrations of the OATP2B1 substrate aliskiren

AIM

The aim of this study was to investigate the effects of orange juice and apple juice on the pharmacokinetics and pharmacodynamics of aliskiren.

METHODS

In a randomized crossover study, 12 healthy volunteers ingested 200 ml of orange juice, apple juice or water three times daily for 5 days. On day 3, they ingested a single 150-mg dose of aliskiren. Plasma aliskiren concentrations were measured up to 72 h, its excretion into urine up to 12 h and plasma renin activity up to 24 h.

RESULTS

Orange and apple juice reduced aliskiren peak plasma concentrations by 80% (95% CI 63%, 89%, P < 0.001) and 84% (95% CI 72%, 91%, P < 0.001), and the area under the plasma aliskiren concentration–time curve (AUC) by 62% (95% CI 47%, 72%, P < 0.001) and 63% (95% CI 46%, 74%, P < 0.001), respectively, but had no significant effect on its elimination half-life or renal clearance. The decreases in aliskiren AUC by orange and apple juice correlated with aliskiren AUC during the water phase (r = 0.98, P < 0.001). Plasma renin activity was 87% and 67% higher at 24 h after aliskiren during the orange juice and apple juice phases, respectively, than during the water phase (P < 0.05).

CONCLUSIONS

Orange juice and apple juice greatly reduce the plasma concentrations and renin-inhibiting effect of aliskiren, probably by inhibiting its OATP2B1-mediated influx in the small intestine. Concomitant intake of aliskiren with orange or apple juice is best avoided.     

Stability, Dose Uniformity, and Palatability of Three Counterterrorism Drugs—Human Subject and Electronic Tongue Studies

Purpose These studies evaluated the ability of common household food and drink products to mask the bitter taste of three selected anti-terrorism drugs. Methods Three anti-terrorism drugs (doxycycline, ciprofloxacin hydrochloride, and potassium iodide) were mixed with a variety of common household food and drinks, and healthy adult volunteers evaluated the resulting taste and aftertaste. In parallel, the ASTREE Electronic Tongue was used to evaluate taste combinations. Stability of the mixtures over time was monitored, as was the dosage uniformity across preparations. Results Foods and drinks were identified that satisfactorily masked the bitter flavor of each drug. Dose uniformity and stability were also acceptable over the range studied, although some combinations were significantly less stable than others. The electronic tongue was able to differentiate between tastes, but ranked masking agents in a different order than human volunteers. Conclusions Doxycycline, potassium iodide, and ciprofloxacin, which are stockpiled in solid tablet form, can conveniently be prepared into more palatable formulations, using common household foods and drinks. The electronic tongue can be used to perform an initial screening for palatability.     

Sorption of fluoroacetate (compound 1080) by Colestipol, activated charcoal and anion-exchange in resins in vitro and gastrointestinal decontamination in rats

The sorption of sodium fluoroacetate (FA) by activated charcoal (AC) and 5 anion exchange resins (AERs) was tested in 2 simulated gastrointestinal (GI) fluids. Each sorbent was incubated with FA in a shaker-water-bath at 37 C for 24 h. Supernatant was removed and filtered, and the concentration of FA was determined by gas chromatographic detection of the dichloroaniline derivative. Under simulated gastric conditions (0.1 M HCl at approximately pH 1.5), the sorbents removed the following proportions of FA from solution: Carbosorb AC, 87 +/- 2%; cholestyramine, 28 +/- 7%; colestipol, 96 +/- 0%; Amberlite IRA-96, 70 +/- 2%; DEAE-Sephadex, 7 +/- 4%; Chitosan, 66 +/- 2%. Under simulated intestinal conditions (0.05 M sodium phosphate at approximately pH 7.4), binding was as follows: Carbosorb AC, 68 +/- 4%; cholestyramine, 53 +/- 5%; colestipol, 46 +/- 2%; AmberliteIRA-96, 10 +/- 20%; DEAE-Sephadex, 64 +/- 7%; Chitosan, 5 +/- 2%. All findings differed significantly from control, with the exception of Amberlite IRA-96 and Chitosan in phosphate buffer, and DEAE-Sephadex in HCI. In a second study, rats were given 5 mg FA/kg, and then gavaged with 2 g/kg Carbosorb AC, colestipol or bentonite. Over 4 h, the area under the curve of serum FA versus time (AUC) decreased by 39% in the rats treated with colestipol and 42% in those treated with bentonite. In contrast, Carbosorb AC did not affect the AUC,yet increased Tmax In another study, mortality was assessed 96 h after rats were orally dosed with 5 mg FA/kg followed by gavage with 2 g/kg Carbosorb AC, colestipol or water immediatey or 30 min after dosing. When the sorbents were given immediately, mortality was the same as control (75%). Surprisingiy, the 30-min delay resulted in lower mortality in colestipol-treated rats, (approximately 38%) compared to 100% in the group treated with Carbosorb AC. Before any recommendation can be made regarding the use of colestipol as a GI decontaminant, the latter findings require confirmation in an intensive care setting. The potential for synergistic effects with 2 or more sorbents also warrant investigating.     

Flavor and taste of lansoprazole strawberry-flavored delayed-release oral suspension preferred over ranitidine peppermint-flavored oral syrup: in children aged between 5-11 years

OBJECTIVE: To compare the flavor and taste preference of two acid-inhibitory therapies in healthy children aged between 5-11 years. METHODS: A single-site, single-blind, taste test trial was conducted in which 111 children participated after parental consent. One teaspoonful (5 mL) of lansoprazole delayed-release oral suspension (strawberry-flavored) and ranitidine oral syrup (peppermint-flavored) were provided to each child with a 10-minute break between samples. Children tasted the sample, swished it in their mouth for 10 seconds, and then expectorated the sample. Spring water and crackers were used to clear the palate between samples. After each sampling, children were observed for facial expressions and asked to rate their degree of liking of each sample based on a 5-point facial hedonic scale (5=like it very much, 1=dislike it very much). Likes, dislikes, and product preference were recorded. RESULTS: Of the 56 female and 54 male children who tasted both samples, 95% (105/110) preferred lansoprazole. Taste and flavor were the most often cited reasons for preferring lansoprazole (61 and 17 children, respectively) while three children preferred the flavor of ranitidine oral syrup. Lansoprazole received a higher mean liking rating compared with ranitidine (mean liking scores of 4.1 and 2.2, respectively). There was no significant difference in the preference for lansoprazole between age groups and gender with the degree of liking scores ranging between 3.5-4.4. Forty-two children disliked the texture of the lansoprazole oral suspension, citing the granules (31/110), thickness (7/110), or consistency/texture (4/110), specifically. CONCLUSION: After sampling both products, 95% of children preferred the flavor and taste of the strawberry-flavored lansoprazole delayed-release oral suspension compared with the peppermint-flavored ranitidine oral syrup.     

Polymeric sorbents for bile acids. I: Comparison between cholestyramine and colestipol.

Isotherms for the sorption of bile acids at 20 degrees C, in tris(hydroxymethyl)aminomethane.HCl(tris) and KH2PO4-NaOH (phosphate) buffers (pH 7.4), indicate that the binding by cholestyramine and colestipol is mainly through ionic linkages, although hydrophobic interactions are also of importance. Cholestyramine has a higher sorption capacity for bile acids, in both buffers, than colestipol. The chloride form of cholestyramine has a higher capacity for cholate in tris buffer than the iodide form. Increased ionic strength of the medium leads to decreased amounts of sorption.     

Effect of Competing Anions on Binding of Bile Salts by Cholestyramine

The binding of bile salts by cholestyramine may be influenced by other anions, as the Langmuir adsorption coefficients for three bile salts tested were similar to the model anion, citrate. However, the selectivity coefficient indicated preferential binding of cholate anion in comparison to citrate anion. Binding experiments confirmed cholestyramine's preference for bile salts as the presence of other anions reduced but did not prevent the binding of cholate anion. Binding of cholate anion was reduced in direct relationship to the citrate anion concentration. Prior exposure of cholestyramine to citrate anion caused the binding of cholate anion to decrease slightly. Sequential exposure of cholestyramine to simulated gastric fluid and simulated intestinal fluid containing cholate anion resulted in a decrease in cholate binding which was attributed to competition with anions present in the gastrointestinal fluids. Components of tomato juice and orange juice, fluids commonly used to enhance ingestion of cholestyramine, also reduced the binding of cholate anion.