Does using oral medication lubricants to swallow whole or crushed tablets alter drug absorption in vivo? A randomised, single-dose crossover bioequivalence study in healthy adults

Abstract

Tablets are often crushed and mixed with thick vehicles such as thickened fluids or medication lubricants to help people with swallowing difficulties to take their medications. In vitro dissolution tests indicate a highly significant reduction in drug dissolution rate when crushed tablets are mixed with vehicles classified as extremely thick (Level 4) according to the International Dysphagia Diet Standardisation Initiative (IDDSI) framework, leading to concerns that this practice may be having substantial impact on drug bioavailability and therapeutic effect. The aim of this study was to determine whether swallowing whole or crushed tablets with an IDDSI Level 4 medication lubricant causes the rate and extent of drug absorption to be significantly different to swallowing whole tablets with water. 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 was administered. Whole or crushed tablets were swallowed with water, or with the medication lubricants Gloup Forte or Gloup Family. Passive unstimulated saliva was collected at regular intervals from 5 min to 8 h after swallowing and analysed using HPLC-UV. Pharmacokinetic parameters were estimated using a standard non-compartmental approach. Co-administering whole tablets with medication lubricant was considered to be bioequivalent to swallowing whole tablets with water in terms of absorption rate and extent, though there was a short delay in reaching the maximum concentration of 12–18 min. Crushing the tablets caused maximum concentration of paracetamol to increase by 36 %, a reminder to avoid crushing tablets if possible. Using a medication lubricant instead of water reduced the crushing-induced dose-dump by 9–18 %. Concerns based on in vitro dissolution test results are not substantiated when tested in vivo, and, for immediate-release paracetamol tablets, we find no evidence for concern regarding the impact of medication lubricants on drug absorption. Assessment of other medication swallowing products and medications is recommended to establish whether these findings can be more widely generalised.