The development of a stable, coated pellet formulation of a water-sensitive drug, a case study: development of a stable core formulation.
A development program has been carried out to provide a stable extrusion/spheronisation pellet formulation for a highly water-soluble drug, sitagliptin, which undergoes a change in physical form on processing and is subject to hydrolytic decomposition. A conventional extrusion/spheronization formulation resulted in significant degradation of the drug. The inclusion of glyceryl monostearate into the formulation was found to reduce the water levels required to such a level that there was no significant degradation of the drug during processing to form pellets. The use of a ram extruder to screen formulations with small quantities minimizes the need for the drug in the formulation-screening process, and the results from this method of extrusion were found to be translatable to the use of a screen extruder, which allowed scale-up of the process.
Fitzpatrick
Shaun
S
Development Laboratories, Merck Sharp and Dohme Ltd, Hoddesdon, Herts, UK. shaun_fitzpatrick@merck.com
Taylor
Scott
S
Booth
Steven W
SW
Newton
Michael J
MJ
D002626:Chemistry, Pharmaceutical / Q000379:methods; D020099:Coated Materials, Biocompatible; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D005989:Glycerides; D006868:Hydrolysis; D008863:Microspheres; D011719:Pyrazines / Q000008:administration & dosage; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000008:administration & dosage; D014867:Water
D020099:Coated Materials, Biocompatible; D005989:Glycerides; D011719:Pyrazines; D014230:Triazoles; D014867:Water; C048159:glyceryl monostearate; D000068900:Sitagliptin Phosphate