Chronotherapeutic drug delivery for early morning surge in blood pressure: a programmable delivery system.
The purpose of the study was to develop pulsatile capsule dosage form of valsartan for controlled delivery. In the majority of individuals blood pressure rises in the early morning hours, which lead to serious cardiovascular complications. Formulations with constant/programmable delivery rates make it possible to deliver drug at definite time or controlled rate in chronopharmacokinetic studies. The prepared system contained swellable polymer (l-hydroxypropyl cellulose (L-HPC), xanthan gum, polyethylene oxide or sodium alginate) together with drug tablet and erodible tablet (L-HPC or guar gum) in a pre-coated capsule. Various formulation factors were investigated through series of tests, in vitro dissolution and ex vivo continuous dissolution-absorption studies. We found that the type, amount of polymers and erodible tablet influenced the drug release. The formulation containing 200 mg sodium alginate and erodible tablet (150 mg) containing 50% guar gum and 46% lactose showed 5-6 h lag time and 10+/-2.1% drug release in initial 6 h following rapid release (99+/-1.7% release in 12 h) of drug was observed. The continuous dissolution-absorption study conducted using everted rat intestinal segment indicated delay in absorption of drug. Thus this approach can provide a useful means for timed release of valsartan and may be helpful for patients with morning surge.
Nayak
Usha Yogendra
UY
Manipal College of Pharmaceutical Sciences, Manipal University, Karnataka-576104, India. ushaynayak@gmail.com
Shavi
Gopal Venktesh
GV
Nayak
Yogendra
Y
Averinen
Ranjith Kumar
RK
Mutalik
Srinivas
S
Reddy
Sreenivasa Meka
SM
Gupta
Purshottam Das
PD
Udupa
Nayanabhirama
N
D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D055870:Drug Chronotherapy; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D012995:Solubility / Q000187:drug effects; D013608:Tablets, Enteric-Coated; D013777:Tetrazoles / Q000008:administration & dosage; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068756:Valsartan
D013608:Tablets, Enteric-Coated; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine