Application of melt granulation technology to enhance stability of a moisture sensitive immediate-release drug product.
The preparation of tablets by the melt granulation process was investigated to enhance chemical stability of a highly water-soluble drug substance, dipeptidylpeptidase IV (DPP-IV) inhibitor (Compound I), that is susceptible to degradation in presence of moisture. Melt granulation with a lipophilic binder (hydrogenated castor oil; Cutina HR) improved the stability of the drug, while still maintaining immediate-release characteristics of the drug product. The drug to binder ratio was shown to impact the degradation behavior of the drug product. With higher binder levels, the sensitivity of the drug to degradation under humidity conditions decreased. It is postulated that the lipophilic binder coated drug particles at the surface protecting them from the influence of moisture. The granules had good flow properties and good compressibility and tablets prepared from them exhibited low weight variation and low friability.
Kowalski
James
J
Pharmaceutical and Analytical Development Department, Novartis Pharmaceuticals Corp., East Hanover, NJ 07936, United States.
Kalb
Oskar
O
Joshi
Yatindra M
YM
Serajuddin
Abu T M
AT
D000631:Aminopyridines / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002368:Castor Oil / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D044367:Phase Transition; D011759:Pyrrolidines / Q000737:chemistry*; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry; D013607:Tablets / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors; D017186:Titrimetry; D014867:Water / Q000032:analysis
C546230:1-(2-(5-cyano-2-pyridinylamino)ethylamino)acetyl-2-pyrrolidinecarbonitrile; D000631:Aminopyridines; D005079:Excipients; D011759:Pyrrolidines; D013229:Stearic Acids; D013607:Tablets; D014867:Water; D002368:Castor Oil