Studies on the preparation, characterization and pharmacological evaluation of tolterodine PLGA microspheres.
In this study, poly(d,l-lactide-co-glycolide) (PLGA) microspheres of tolterodine depot formulation were prepared using oil in water (o/w) method to investigate their potential pharmacokinetic and pharmacodynamic advantages over tolterodine l-tartrate tablets. Morphological studies of the microspheres showed a spherical shape and smooth surface with mean size of 50.69-83.01 microm, and the encapsulation efficiency was improved from 62.55 to 79.10% when the polymer concentration increased from 180 to 230 mg/ml. The addition of stearic or palmitic acids could significantly raise the drug entrapment efficiency but only slightly affected the in vitro release. A low initial burst followed by a proximately constant release of tolterodine was noticed in the in vitro release profiles. The in vivo study was carried out by intramuscular (i.m.) administration of tolterodine-loaded microspheres on beagle dogs, and a sustained release of drug from the PLGA microspheres was achieved until the 18th day with a low initial burst. Since the absence of hepatic first pass metabolism, only a single active compound-tolterodine was detected in the plasma. This avoided the coexistence of two active compounds in plasma in the case of oral administration of tolterodine, which may lead to a difficulty in dose control due to the different metabolic capacity of patients. In the pharmacodynamic study, the influence of tolterodine PLGA microspheres on the inhibition of carbachol-induced rat urinary bladder contraction was more significant than that of tolterodine l-tartrate tablets. There were invisible changes in rat bladder slices between tolterodine-loaded PLGA microspheres group and tolterodine l-tartrate tablets group. These results indicate that the continuous inhibition of muscarinic receptor may offer an alternative therapy of urge incontinence.
Sun
Fengying
F
College of Life Science, Jilin University, 2699 Qianjin Street, Changchun, Jilin 130012, China.
Sui
Cheng
C
Teng
Lesheng
L
Liu
Ximing
X
Teng
Lirong
L
Meng
Qingfan
Q
Li
Youxin
Y
D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics* / Q000494:pharmacology; D003408:Cresols / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics* / Q000494:pharmacology; D003692:Delayed-Action Preparations; D004285:Dogs; D004339:Drug Compounding; D005260:Female; D019344:Lactic Acid; D008863:Microspheres; D009821:Oils; D010316:Particle Size; D010665:Phenylpropanolamine / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics* / Q000494:pharmacology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013607:Tablets; D000068737:Tolterodine Tartrate; D014867:Water
D001559:Benzhydryl Compounds; D003408:Cresols; D003692:Delayed-Action Preparations; D009821:Oils; D011108:Polymers; D013607:Tablets; D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D010665:Phenylpropanolamine; D019344:Lactic Acid; D000068737:Tolterodine Tartrate