Does Swallowing Tablets With An Extremely Thick (iddsi Level 4) Medication Lubricant Alter Drug Absorption? A Randomised, Single-dose Crossover Study In Healthy Adults

• By: ABU MALOUH, Marwa (The University Of Queensland, Australia)
• Co-author(s): Ms Marwa Abu Malouh (Postgraduate Student, School of Pharmacy, The University of Queensland. , Brisbane, Australia)
  Dr Julie Cichero (: Honorary Senior Fellow, School of Pharmacy, The University of Queensland; , Brisbane, Australia)
  Associate Prof Stephanie Reuter (Senior Research Fellow at University of South Australia School of Pharmacy & Medical Sciences, University of South Australia, Adelaide, Australia)
  Ms Min-Tz Weng (Postgraduate Student, School of Pharmacy, The University of Queensland. , Brisbane, Australia)
  Dr Esther Lau (Course Coordinator and Lecturer, Discipline of Pharmacy, School of Clinical Sciences, Queensland University of Technology, Brisbane, Australia)
  Prof Lisa Nissen (Associate Professor, School of Pharmacy, The University of Queensland; , Brisbane, Australia)
  Dr Kathryn Steadman (Professorial Research Fellow and Pr Centre for the Business and Economics of Health Faculty of Business, Economics and Law, Brisbane, Australia)
  
• Abstract:

  
  Background: People who find it difficult to swallow whole tablets with water will commonly crush them and mix them with a food/fluid. Medication lubricants are a commercial pharmaceutical product designed to replace the food/fluid, providing a reproducible swallowing and dissolution environment for the medicine. These products are useful in aged care and hospital facilities where there can be a high proportion of patients requiring help to swallow medications. Results from in vitro-dissolution testing using medication lubricants and other thickening products indicates a highly significant reduction in dissolution rate of a of range drugs from crushed tablets, particularly noticeable with fluids classified as extremely thick (Level 4) using the International Dysphagia Diet Standardisation Initiative (IDDSI) framework.
  Purpose: To determine whether swallowing whole or crushed tablets with an IDDSI Level 4 medication lubricant, Gloup Forte, causes the rate and extent of drug absorption to be significantly different to swallowing whole tablets with water.
  Method: An open-label, randomised, single-dose crossover study in 19 healthy adults was performed, in which a standard oral dose of immediate-release paracetamol tablets prepared in six different ways was administered. Whole or crushed tablets were swallowed with water, or with the medication lubricant Gloup Forte vanilla or Gloup Forte lemon, both assessed as being IDDSI Level 4 thickness. Participants rinsed their mouth with water (and swallowed), and then brushed using an electric toothbrush for 4 minutes to remove residual paracetamol. Passive unstimulated saliva was collected at regular intervals from 5 minutes to 8 hours after swallowing and analysed using HPLC-UV. Pharmacokinetic parameters were estimated using a standard non-compartmental approach. A linear mixed-effects analysis of variance (ANOVA) model was used to perform statistical comparisons of Ln-transformed pharmacokinetic data (Cmax, AUClast) between treatment groups. The residual mean error was used to construct the 90% confidence intervals for the ratio of treatment means.
  Results: For the whole tablets, co-administration with Gloup Forte was found to have no significant impact on paracetamol pharmacokinetics, with the 90% confidence intervals for AUClast and Cmax contained within the standard 80-125% limits. Administering crushed tablets with water or Gloup Forte had minimal impact on total paracetamol exposure (AUClast 90% CI: 89.7 – 113%, 79.7 - 99.9% and 88.0 - 110% for water, Gloup Forte/vanilla and Gloup Forte/lemon, respectively). However, crushing paracetamol tablets and caused a 35% increase in the maximal concentrations when administered with water (Cmax 90% CI: 109 – 170) and ~ 20-25% increase when administered with Gloup Forte (Cmax 90% CI: 95.3 - 147% and 102 - 157% for Gloup Forte/vanilla and Gloup Forte/lemon, respectively).
  Conclusion: These IDDDSI Level 4 medication lubricants, Gloup Forte/vanilla and Gloup Forte/lemon, do not have a significant effect on paracetamol exposure when used by healthy adults to swallow whole or crushed paracetamol tablets. However, crushing tablets causes a significant increase in the rate of absorption, which is tempered by the use of Gloup Forte instead of water. These findings do not align with in vitro-dissolution test results, and we find no evidence that these products delay or reduce drug absorption.