[Studies on heart-protecting musk pH-dependent gradient-release pellets].
OBJECTIVE
To prepare heart-protecting musk pH-dependent gradient-release pellets and investigate the drug release in vitro and in vivo.


METHODS
The pH-dependent gradient-release pellet system was prepared by using HPMC, Eudragit L-30D-55 and Eudragit L100-Eudragit S100 (1:5) combinations as coater. The release of borneol and total ginsenoside from pH-dependent gradient-release pellets were determined according to the method of Pharmacopoeia of the People's Republic of China (2000) in the simulated gastrointestinal pH conditions. The gastrointestinal transit and disintegration of pellets was investigated by using gamma-scintigraphic trace in volunteers. The pharmacokinetics of borneol of heart-protecting musk pH-dependent gradient-release pellets was studied in 6 healthy volunteers by GC methods.


RESULTS
The f2 value of release data of borneol and total ginsenoside of the heart-protecting musk pH-dependent gradient-release pellets was 79.6 in the simulated gastrointestinal pH conditions. The gamma-scintigraphic trace evaluation demonstrated that the pellets coated with HPMC, Eudragit L-30D-55 or Eudragit L100-Eudragit S100 (1:5) combinations can disintegrate in stomach, duodenum and jejunum or ileum. The gastrointestinal transit time of pellets was about 5 hours in fasted state and about 6 hours in fed state. The concentration-time curves of borneol of heart-protecting musk pills fit in two-compartment model. The pharmacokinetics data showed that borneol had a short time of absorption and elimination. The mean residence time (MRT) of borneol of heart-protecting musk pills was 2.61 hours. The plasma concentration of borneol of heart-protecting musk sustained-release capsule which consisted of three kinds of pellets coated with HPMC, Eudragit L-30D-55 or Eudragit L100-Eudragit S100 (1:5) combinations was steadier than those of heart-protecting musk pills, its Cmax was lower than and Tmax was near to those of heart-protecting musk pills, its MRT was 4.0 hours, and its relative bioavailability was 96%.


CONCLUSIONS
The lipidsoluble borneol and watersoluble total ginsenoside of heart-protecting musk pH-dependent gradient-release pellets can release simultaneously while sustained-releasing in vitro. The heart-protecting musk pH-dependent gradient-release pellets had the characteristics of pH-dependent gradient-releasing and disintegration while transiting in gastrointestinal tract. A characteristic of gradient sustained-release was shown in the concentration-time curves of borneol of heart-protecting musk sustained-release capsule in volunteers.
Song
Hong-tao
HT
Department of Pharmacy, Shenyang Military General Hospital, Shenyang 110016, China. sohoto@sohu.com
Guo
Tao
T
Zhang
Ru-hua
RH
Ma
Yan
Y
Li
Xian
X
Bi
Kai-shun
KS
D000328:Adult; D001892:Camphanes / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage*; D005772:Gastrointestinal Transit; D036145:Ginsenosides / Q000493:pharmacokinetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007785:Lactose / Q000031:analogs & derivatives*; D008297:Male; D008419:Materia Medica / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008747:Methylcellulose / Q000031:analogs & derivatives*; D010078:Oxazines; D011109:Polymethacrylic Acids; D011897:Random Allocation
D001892:Camphanes; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D005229:Fatty Acids, Monounsaturated; D036145:Ginsenosides; D008419:Materia Medica; D010078:Oxazines; D011109:Polymethacrylic Acids; C008563:musk; C038300:methylmethacrylate-methacrylic acid copolymer; D008747:Methylcellulose; C071191:MK 458; D007785:Lactose; C022871:isoborneol