The effects of xanthan gum and modified corn starch used in dysphagia diets on in vivo drug release

Swallowing of oral solid dosage forms without modification may be difficult or dangerous in patients with dysphagia. The most common method to facilitate drug administration in these patients is to mix the powdered drug with a small amount of thickened water, however little is known about the effects of this method on in vivo bioavailability of drugs. This study aimed to evaluate the impact of thickened fluids designed to use in dysphagia treatment on bioavailability of levetirasetam as a model drug. Powdered drugs were mixed with water thickened at three thickness levels (nectar, honey and pudding) with two commercial thickeners (modified maize starch, MS and xanthan gam, XG) in test groups and they were mixed with only deionized water in control groups during the study period. At the first stage, the effects of thickened water on in vitro drug release of 4 drugs (levetirasetam, carbamazepine, atenolol and cefixim) were tested by using dialysis membrane method. Addition of both thickeners significantly reduced the release of three drugs compared to the control group, except carbamazepine. Levetirasetam which showed the highest solubility was chosen as the model drug for in vivo experiments. New Zeland albino female rabbits (n=24) were divided into two groups as: control group (water+drug, n=6) and test group (thickened water+drug, n=18). Powdered drug was mixed with water thickened with XG (n=9) and MS (n=9) at 3 thickness levels, and administered to the rabbits. All of the samples were administered by an intragastric gavage, and blood samples were collected at 9 time points following administration. After two-weeks of wash-out, test groups were crossed over and sample collection was repeated. Blood samples were analysed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). The maximum observed concentration (Cmax) was lower and the time to reach Cmax (tmax) was relatively higher in test groups compared to control group. The lowest Cmax was detected at the highest thickness level, however, the differences between groups were not statistically significant (p=0.117 and p=0.495 for Cmax and tmax, respectively). No significant difference in total amount of levetirasetam absorbed (AUC) was found between groups (p=0.215 and p=0.183 for AUCinfinity and AUClast, respectively). The comparisions according to the type of thickener also revealed that pharmacokinetic parameters did not significantly differ between groups, except for a significantly lower Cmax when drug was mixed with MS-thickened water at nectar consistency compared to drug mixed with XG at the same thickness level (p=0.038). These results suggest that regardless of the thickness level, the administration of levetirasetam with two commercial thickening agents commonly used in dysphagia for safe swallowing, do not affect the pharmacokinetic efficiency and thus, the bioavailability of the drug.