Valvejet Technology for the Production of a Personalised Fixed Dose Combination of Ramipril and Glimepiride: an Investigative Study on the Stability of Ramipril

Pharm Res. 2018 Jul 27;35(9):181. doi: 10.1007/s11095-018-2465-7.


Purpose: To use valvejet technology for printing a fixed dose combination of ramipril and glimepiride, and to investigate the stability profile of ramipril, which is susceptible to a range of processing and storage conditions.

Methods: Inks of ramipril and glimepiride were formulated and printed on to HPMC film and the films were evaluated for the chemical and solid-state integrity of the APIs using HPLC and XRPD. The stability of the APIs in the inks and in the printed samples was investigated using Raman and NMR techniques.

Results: The printed samples demonstrated excellent precision and accuracy in the doses of APIs deposited. Both drugs were chemically intact in the freshly printed samples and ramipril was found to be in its amorphous form. Ramipril in the printed samples has transformed into ramipril diketopiperazine when stored at 40°C with 75% RH, but remained stable when stored in a desiccator. Results from the stability study of ramipril ink show that the API has undergone degradation when stored both at room temperature and at 40°C but remained stable when stored in a refrigerator.

Conclusion: An FDC of ramipril and glimepiride was successfully printed using valvejet technology. The significance of inkjet printing in producing amorphous dosage forms from solution based inks and personalised dosage forms of drugs susceptible to processing conditions was demonstrated using ramipril. This study illustrates the significance of examining the stability of the APIs in the inks and the importance of appropriate storing of both the inks and printed samples.

Keywords: fixed dose combination; glimepiride; personalised medicine; ramipril; valvejet technology.

MeSH terms

  • Antihypertensive Agents / chemistry*
  • Crystallization
  • Drug Combinations
  • Drug Compounding / instrumentation*
  • Drug Stability
  • Drug Storage
  • Excipients / chemistry
  • Hypoglycemic Agents / chemistry*
  • Hypromellose Derivatives / chemistry
  • Printing / instrumentation*
  • Ramipril / chemistry*
  • Sulfonylurea Compounds / chemistry*
  • Viscosity


  • Antihypertensive Agents
  • Drug Combinations
  • Excipients
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • Hypromellose Derivatives
  • glimepiride
  • Ramipril