Production of extended release mini-tablets using directly compressible grades of HPMC.
BACKGROUND
Hypromellose (HPMC) has been previously used to control drug release from mini-tablets. However, owing to poor flow, production of mini-tablets containing high HPMC levels is challenging. Directly compressible (DC) HPMC grades have been developed by Dow Chemical Company.


OBJECTIVE
To compare the properties of HPMC DC (METHOCEL™ K4M and K100M) with regular (REG) HPMC grades.


METHODS
Particle size distribution and flowability of HPMC REG and DC were evaluated. 3 mm mini-tablets, containing hydrocortisone or theophylline as model drugs and 40% w/w HPMC DC or REG were produced. Mini-tablets containing HPMC DC grades were manufactured using a rotary press simulator at forces between 2-4 kN and speeds of 5, 10, 15 or 20 rpm. Mini-tablets containing HPMC REG were produced manually.


CONCLUSIONS
The improved flowability of HPMC DC grades, which have a narrower particle size distribution and larger particle sizes, meant that simulated large scale production of mini-tablets with good weight uniformity (CV 1.79-4.65%) was feasible. It was not possible to automatically manufacture mini-tablets containing HPMC REG due to the poor flowability of the formulations. Drug release from mini-tablets comprising HPMC DC and REG were comparable. Mini-tablets containing HPMC DC illustrated a higher tensile strength compared to mini-tablets made with HPMC REG. Mini-tablets produced with HPMC DC at different compression speeds had similar drug release profiles.


CONCLUSIONS
Production of extended release mini-tablets was successfully achieved when HPMC DC was used. Drug release rate was not influenced by the different HPMC DC grades (K4M or K100M) or production speed.
School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University , Liverpool , UK.
Faiezah A A
FA
Mohamed
Matthew
M
Roberts
Linda
L
Seton
James L
JL
Ford
Marina
M
Levina
Ali R
AR
Rajabi-Siahboomi
D000893:Anti-Inflammatory Agents / Q000032:analysis / Q000737:chemistry*; D001993:Bronchodilator Agents / Q000032:analysis / Q000737:chemistry*; D055598:Chemical Phenomena; D003692:Delayed-Action Preparations / Q000737:chemistry; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D006854:Hydrocortisone / Q000032:analysis / Q000737:chemistry*; D065347:Hypromellose Derivatives; D007700:Kinetics; D055595:Mechanical Phenomena; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008958:Models, Molecular; D010316:Particle Size; D011786:Quality Control; D012995:Solubility; D013499:Surface Properties; D013607:Tablets; D013718:Tensile Strength; D013806:Theophylline / Q000032:analysis / Q000737:chemistry*
D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D005079:Excipients; D013607:Tablets; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D013806:Theophylline; D006854:Hydrocortisone