title: Evaluation of crushed ticagrelor tablet doses: recovery following crushing and naso-gastric tube passage ex vivo.
abstract: BACKGROUND
  Orally available ticagrelor in combination with low-dose aspirin (75-100 mg/day) is indicated for adult patients with acute coronary syndromes. However, patients with swallowing difficulties may be unable to consume the currently available 90-mg tablet. It is hypothesized that ticagrelor could be given to this patient cohort as a crushed dose administered either orally or via a naso-gastric (NG) tube.
  
  
  OBJECTIVE
  To investigate the potential use of crushed ticagrelor tablets (90- and 180-mg doses) for oral dose or NG tube administration.
  
  
  METHODS
  Ticagrelor tablets (90 or 180 mg [two 90-mg tablets]) were prepared to emulate oral and NG tube administration by similar methods. For the oral dose, ticagrelor tablets were crushed using a mortar and pestle and transferred to a dosing cup. 100 mL of water was added to the mortar, stirred, and the contents were transferred to the dosing cup and stirred to form a suspension. At this stage, where the suspension would normally be administered to a patient, it was collected for high performance liquid chromatography (HPLC) analysis. The mortar was then flushed with 100 mL of water, and the contents were again transferred to the dosing cup, stirred, and collected for HPLC analysis. For the NG dose, polyvinylchloride, polyurethane, and silicone size CH10 NG tubes were used. The tablets were crushed using a mortar and pestle, diluted with 50 mL of water, and stirred. At this stage, where the suspension would normally be administered to a patient through an NG tube using a syringe, it was collected for HPLC analysis. The mortar was then flushed with two additional 50 mL aliquots of water and the contents were passed through the NG tube. HPLC analysis examined the recoverability of ticagrelor in each of the dose suspensions and flushes and the stability of the suspension when held in a syringe for up to 2 h.
  
  
  RESULTS
  One or two crushed 90-mg ticagrelor tablets, prepared for either oral or NG tube administration, delivers a mean dose of ≥97% of the original tablet. No degradation of the suspensions was detected after ticagrelor had been held in the syringe for up to 2 h.
  
  
  CONCLUSIONS
  Although not an approved method of administration, these results suggest that ticagrelor tablets can be crushed and prepared for oral administration or for administration via an NG tube. From a clinical perspective, a syringe hold-time of up to 2 h should allow for enough time between preparation and administration (orally or via an NG tube) of the dispersed tablets to the patient. Future studies are required to test the effect of crushed dosing on pharmacokinetic and pharmacodynamic parameters.
authors.affiliation: AstraZeneca, Research & Development, Pharmaceutical Development, Silk Road Business Park, Charter Way, Hurdsfield Industrial Estate, Macclesfield SK10 2NA, UK. barry.crean@astrazeneca.com
authors.forename: Barry
authors.initials: B
authors.lastname: Crean
authors.forename: Cindy
authors.initials: C
authors.lastname: Finnie
authors.forename: Anna
authors.initials: A
authors.lastname: Crosby
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis; D000284:Administration, Oral; D004355:Drug Stability; D007441:Intubation, Gastrointestinal; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage / Q000032:analysis*; D013535:Suspensions; D013607:Tablets; D000077486:Ticagrelor
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D013535:Suspensions; D013607:Tablets; D000077486:Ticagrelor; D000241:Adenosine