Effect of hydroxypropylmethylcellulose (HPMC) on the release profiles and bioavailability of a poorly water-soluble drug from tablets prepared using macrogol and HPMC.
The aim of the present study was to investigate the effect of hydroxypropylmethylcellulose (HPMC-2208), used as an excipient for controlled release of drug, on the release profiles and bioavailability of the poorly water-soluble nifedipine (NP) from a tablet prepared using macrogol 6000 (PEG) and HPMC. The crushing tolerance of the NP tablet prepared using PEG and HPMC (NP-PEG-HPMC tablet) was markedly increased with increasing compression force used during the preparation from 20 to 200 MPa. The values reached their maximal levels (approximately 13 kg for the NP-PEG-HPMC tablet and 8 kg for the PEG tablet) at the compression force of 100 MPa. Although NP is a poorly water-soluble drug, it was rapidly dissolved from the NP-PEG tablet (without HPMC) due to the improvement of its dissolution rate in the presence of PEG. NP dissolution was complete at the latest within 1 h. On the other hand, dissolution of NP from the NP-PEG-HPMC tablet was significantly delayed with an increase in the concentration of HPMC in the tablet. The dissolution of NP from the NP-PEG-HPMC tablet containing 50% HPMC-2208 was markedly delayed as the viscosity of HPMC also increased. Interestingly, the same peak plasma NP concentration (C(max)) and the area under the plasma NP concentration-time curve (AUC(0-10)) were observed for both the NP-PEG tablet and NP-PEG-HPMC tablets, however, the time to C(max) (t(max)) for the NP-PEG-HPMC tablet was significantly higher when the NP-PEG-HPMC tablet was orally administered to rabbits. We describe here a preparation method of a new sustained-release NP-PEG-HPMC tablet using a mixture of NP-PEG granules (prepared with PEG) and HPMC.
Ishikawa
T
T
Department of Pharmaceutics, Showa Pharmaceutical University, 3-3165, Higashi-Tamagawagakuen, Machida-shi, Tokyo, 194-8543 Japan.
Watanabe
Y
Y
Takayama
K
K
Endo
H
H
Matsumoto
M
M
D000284:Administration, Oral; D000818:Animals; D002121:Calcium Channel Blockers / Q000097:blood / Q000493:pharmacokinetics*; D005079:Excipients / Q000493:pharmacokinetics; D007785:Lactose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009543:Nifedipine / Q000097:blood / Q000493:pharmacokinetics*; D010078:Oxazines; D011208:Powders; D011817:Rabbits; D051381:Rats; D013607:Tablets
D002121:Calcium Channel Blockers; D005079:Excipients; D010078:Oxazines; D011208:Powders; D013607:Tablets; D008747:Methylcellulose; C071191:MK 458; D009543:Nifedipine; D007785:Lactose