Comparative in vitro evaluation of the antacid capacity of Rennie alginate suspension and Gaviscon suspension
The in vitro acid-neutralizing capacity (ANC) of a single dose (10 mL) of Rennie alginate suspension (per 10 mL: calcium carbonate 1200 mg, magnesium carbonate 140 mg and sodium alginate 300 mg) was compared with that of a single dose (10 mL) of Gaviscon Liquid suspension (Reckitt Benckiser, Slough, UK) (per 10 mL: sodium alginate 500 mg, sodium bicarbonate 267 mg, calcium carbonate 160 mg) using a method adapted from Van Dop and Overvliet4 and Rosset and Rice.5 A Mettler DL70ES titrator (Mettler Toledo Inc., Colombus, OH, USA) was used to evaluate the quantity of acid, expressed in mmol (mmol H+), required to titrate a single dose of either product to pH 2.5. The choice of pH 2.5 was chosen arbitrarily as an in vitro evaluation point and was a compromise between representative values of pH 3.5,6 3.05, 7 and 2.0.4
Rennie alginate is manufactured by Bayer Consumer Care and marketed under various brand names (Belgium: Rennie Algin Liquid; the Netherlands: Rennie Refluxine; Turkey: Rennie Duo; UK: Rennie Liquid Relief). Gaviscon Liquid suspension is manufactured and marketed by Reckitt Benckiser, GSK Consumer Healthcare or Novartis Italy, depending on the country.
A 300 mL beaker containing 50 mL of 0.1 m HCl was incubated at 37 ± 1 °C in a water bath and a magnetic stirrer in the beaker was set to produce a constant stirring rate of 200 ± 20 rpm. A single dose of 10 mL alginate suspension was then added to the beaker, at which point titration with 0.2 mmol HCl/min was initiated. Changes in the pH of the solution in response to the addition of HCl were recorded using a standardized combination pH electrode until the pH of the solution decreased to 2.5.
In vitro evaluation of the acid dependency of raft formation from Rennie alginate suspension or Gaviscon suspension
In order to determine whether the ANC of Rennie alginate suspension impacts upon the raft-forming properties of this product, the quantity of acid (expressed in mmol H+) required to produce a floating gel from a single dose of either Rennie alginate suspension (composition as above) or Gaviscon suspension (composition as above) was determined. Solutions of pH 1.0–1.7 were made up by adding 20, 40, 60, 80 or 100 mL of 0.1 m HCl to 150 mL glass beakers and adding purified water (where required) to a final volume of 100 mL. A single 10 mL dose of each product was then added to each of these 100 mL solutions. Fifteen minutes after adding either Rennie alginate or Gaviscon suspension, the gel formed was collected, placed on filter paper (No. 4) for a further 15 min and then weighed. The weight of gel formed by each of the two products at each pH was recorded.
This experiment was conducted under blinded conditions in order to prevent bias and the Rennie alginate and Gaviscon suspensions also looked similar.
In vivo antacid activity of Rennie alginate suspension compared with placebo
This was a double-blind, placebo-controlled, randomized crossover study, the primary objective of which was to compare the antacid activity of Rennie alginate suspension (composition as above) with that of placebo (Rennie alginate excipients without sodium bicarbonate) using continuous intragastric pH monitoring in 12 healthy, fasting volunteers. Secondary objectives were to determine tolerance and acceptability. The study protocol was approved by the local ethics committee and the trial was conducted in accordance with the principles of the Declaration of Helsinki and its amendments.
Randomization was conducted by computer-generated random numbers, treatment allocation was blinded and both the Rennie and the placebo treatments looked identical.
Subjects were men or women between 18 and 40 years of age, whose cigarette consumption was <6 per day and who were able to abstain from smoking throughout the study. Subjects who had past or present symptoms of an oesophageal, gastrointestinal or bowel habit disorder, who had undergone gastrointestinal tract surgery other than appendectomy, who were taking drugs (other than oral contraceptives) <2 weeks before the start of the study, who consumed more than three cups of tea, coffee or cola, or who regularly consumed alcohol were excluded from the study. All patients provided written informed consent. Subjects were recruited by and at the Unité de Recherches Thérapeutiques (Hôpital Lariboisière, Paris). All volunteers participated in the study after providing written informed consent and provided they met the selection criteria based on a detailed clinical examination.
After an overnight fast, subjects attended the study centre at 08:15 hours on each of two mornings not <3 days apart. Intragastric basal pH was recorded from 08:30 hours for 30 min, following which a 10 mL sachet of Rennie alginate suspension (ANC 31 mmol H+ by titration to pH 2.5) or 10 mL placebo suspension (ANC 0 mmol H+ by titration to pH 2.5) were administered at 09:00 hours according to randomized order. Intragastric pH was then monitored for a further 3 h after dosing. Tolerance and acceptability of the study medications were also recorded.
Changes in gastric pH were measured using a combined glass electrode (miniature pH-glass electrode Ag/AgCl Type 440-M3 Ingold; Urdorf, Switzerland), and were recorded using a portable pH meter (GPD & pH monitor Proxima, ABS, Saint-Dié, France) according to a standard procedure. The specific characteristics of the electrode were determined before the start of and after the study by two-point calibration with buffer solutions at pH 1 and 7 (Merck Eurolab, Paris, France). With the volunteer seated, the probe was introduced transnasally and pushed down to the gastro-oesophageal junction, i.e. the site at which a sharp drop in pH from 6 to 4 arises. The probe was then placed 10 cm below the gastro-oesophageal junction and fixed to the cheek with a piece of adhesive tape. After use, the probe was immersed in an aqueous solution of glutaraldehyde 2% for 30 min.
Baseline pH in each individual was calculated as the median of 100 values taken in the 15 min prior to administration of the test product. The pH recordings were then used to determine the onset of antacid action (lag-time to reach pH 3), peak gastric pH, time to reach peak gastric pH and the duration of pH spent above baseline. Acceptability of treatment taste was also evaluated in response to the question ‘What do you think of the taste of the product’ using a visual analogue scale (VAS) of 0–100 mm, where 0 = very unacceptable and 100 =very acceptable.
Results were analysed in accordance with the randomized, crossover trial study design, using anova for repeated measures (crossover study), including two factors (treatment and period) and their interaction. The taste and acceptability of the medications for the two groups were compared using a Wilcoxon test. Statistical significance was defined as P ≤ 0.05.