A formulation approach for development of HPMC-based sustained release tablets for tolterodine tartrate with a low release variation.
OBJECTIVE
The purpose of this study was to develop hydroxypropylmethylcellulose (HPMC)-based sustained release (SR) tablets for tolterodine tartrate with a low drug release variation.


METHODS
The SR tablets were prepared by formulating a combination of different grades of HPMC as the gelling agents. The comparative dissolution study for the HPMC-based SR tablet as a test and Detrusitol SR capsule as a reference was carried out, and the bioequivalence study of the two products was also conducted in human volunteers.


RESULTS
The amount of HPMC, the grade of HPMC and the combination ratio of different grades of HPMC had remarkable effects on drug release from the SR tablets. Both the test and reference products had no significant difference in terms of comparative dissolution patterns in four different media (f₂ > 50). Furthermore, the dissolution method and rotation speed showed no effects on the drug release from the two products. The 90% confidence intervals of the AUC(0-36) and C(max) ratios for the test and reference products were within the acceptable bioequivalence intervals of log0.8-log1.25.


CONCLUSIONS
A HPMC-based SR tablet for tolterodine tartrate with a low release variation was successfully developed, which was bioequivalent to Detrusitol® SR capsule.
College of Pharmaceutical Science, Soochow University , Suzhou , PR China.
Qing-Ri
QR
Cao
Jae-Seung
JS
Choi
Yan
Y
Liu
Wei-Juan
WJ
Xu
Mingshi
M
Yang
Beom-Jin
BJ
Lee
Jing-Hao
JH
Cui
D000328:Adult; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D002214:Capsules; D055598:Chemical Phenomena; D003408:Cresols / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D005782:Gels; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D010665:Phenylpropanolamine / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D013499:Surface Properties; D013607:Tablets; D013810:Therapeutic Equivalency; D000068737:Tolterodine Tartrate; D064804:Urological Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D014783:Viscosity; D055815:Young Adult
D001559:Benzhydryl Compounds; D002214:Capsules; D003408:Cresols; D003692:Delayed-Action Preparations; D005079:Excipients; D005782:Gels; D018727:Muscarinic Antagonists; D013607:Tablets; D064804:Urological Agents; D010665:Phenylpropanolamine; D065347:Hypromellose Derivatives; D000068737:Tolterodine Tartrate; D008747:Methylcellulose