Formulation design of a highly hygroscopic drug (pyridostigmine bromide) for its hygroscopic character improvement and investigation of in vitro/in vivo dissolution properties.
Pyridostigmine bromide (PB) sustained-release (SR) pellets were developed by extrusion-spheronization and fluid-bed methods using Taguchi experimental and 2(3) full factorial design. In vitro studies, the 2(3) full factorial design was utilized to search for the optimal SR pellets with specific release rate at different time intervals (release percent of 2, 6, 12, and 24 hr were 6.24, 33.48, 75.18, and 95.26%, respectively) which followed a zero-order mechanism (n=0.93). The results of moisture absorption by Karl Fischer has shown the optimum SR pellets at 25 degrees C/60% RH, 30 degrees C/65% RH, and 40 degrees C/75% RH chambers from 1 hr-4 weeks, attributing that the moisture absorption was not significantly increased. In the in vivo study, the results of the bioavailability data showed the Tmax (from 0.65+/-0.082 hr-4.82+/-2.12 hr) and AUC0-30 hr (from 734.88+/-230.68 ng/mL.hr-1454.86+/-319.28 ng/mL.hr) were prolonged and increased, as well as Cmax (from 251.87+/-27.51 ng/mL-115.08+/-14.87 ng/mL) was decreased for optimum SR-PB pellets when compared with commercial immediate-release (IR) tablets. Furthermore, a good linear regression relationship (r=0.9943) was observed between the fraction dissolution and fraction absorption for the optimum SR pellets. In this study, the formulation design not only improved the hygroscopic character of PB but also achieved the SR effect.
Huang
Yuh-Tyng
YT
Graduate Institute of Pharmaceutical Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C.
Tsai
Tong-Rong
TR
Cheng
Chun-Jen
CJ
Cham
Thau-Ming
TM
Lai
Tsun-Fwu
TF
Chuo
Wen-Ho
WH
D000042:Absorption; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D004355:Drug Stability; D004356:Drug Storage; D006813:Humidity; D007700:Kinetics; D016014:Linear Models; D008297:Male; D008855:Microscopy, Electron, Scanning; D011729:Pyridostigmine Bromide / Q000737:chemistry / Q000493:pharmacokinetics*; D011817:Rabbits; D012995:Solubility; D013678:Technology, Pharmaceutical
D002800:Cholinesterase Inhibitors; D003692:Delayed-Action Preparations; D011729:Pyridostigmine Bromide