[Studies on nimodipine sustained-release tablet capable of floating on gastric fluid with prolonged gastric resident time].
Nimodipine was incorporated into poloxamer 188 solid dispersion before formulation, then mixed excipient and solid dispersion were directly compressed into nimodipine floating sustained-release tablet(NM-FSRT). Formulations were optimized using uniform design and variables affecting nimodipine release from matrix were studied. Preliminary in vivo evaluation was carried out in healthy volunteers. Results showed that the optimized formulation could remain floating on gastric fluid for over 10 hours. In vitro release(0.15-6 h) conformed to zero-order kinetics. Hydroxypropylmethylcellulose(HPMC) and polyethylene glycol 6000(PEG 6000) showed the biggest effect on in vitro drug release. Increasing HPMC content and decreasing PEG 6000 content led to decrease of nimodipine release in vitro. NM-FSRT did remain floating on gastric fluid with prolonged gastric resident time(GRT) of 5 hours under fed condition, while GRT was only 3 hours under fasted condition. GRT of nimodipine conventional tablet(NM-CT) under fed and fasted conditions was 3 and 2 hours, respectively. Relative bioavailability of NM-FSRT was 391.46% and MRT was over twice that of NM-CT. NM-FSRT appeared to have prolonged GRT and improved bioavailability.
Wu
W
W
Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai 200433.
Zhou
Q
Q
Zhang
H B
HB
Ma
G D
GD
Fu
C D
CD
D001682:Biological Availability; D003692:Delayed-Action Preparations; D005750:Gastric Juice / Q000378:metabolism; D006801:Humans; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives*; D009553:Nimodipine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013607:Tablets
D003692:Delayed-Action Preparations; D013607:Tablets; D065347:Hypromellose Derivatives; D009553:Nimodipine; D008747:Methylcellulose