Formulation Design of an HPMC-Based Sustained Release Tablet for Pyridostigmine Bromide as a Highly Hygroscopic Model Drug and its In Vivo In Vitro Dissolution Properties

• Published in: Drug development and industrial pharmacy 2007-11, Vol.33 (11), p.1183-1191
• Main Authors: Huang, Yuh-Tyng, Tsai, Tong-Rong, Cheng, Chun-Jen, Cham, Thau-Ming, Lai, Tsun-Fwu, Chuo, Wen-Ho
• Format: Article
• Language: English
• Subjects: Animals; Area Under Curve; Chemistry, Pharmaceutical; Delayed-Action Preparations; direct-compression method; Drug Stability; Excipients - chemistry; full factorial design; highly hygroscopic drug; Hypromellose Derivatives; in vitro-in vivo relationship; Methylcellulose - analogs & derivatives; Methylcellulose - chemistry; Pyridostigmine Bromide - administration & dosage; Pyridostigmine Bromide - chemistry; Pyridostigmine Bromide - pharmacokinetics; Rabbits; Solubility; sustained-release tablet; Tablets; zero-order mechanism
• ISSN: 0363-9045; 1520-5762
• DOI: 10.1080/03639040701377334

Pyridostigmine bromide (PB), a highly hygroscopic drug was selected as the model drug. A sustained-release (SR) tablet prepared by direct compression of wet-extruded and spheronized core pellets with HPMC excipients and exhibited a zero-order sustained release (SR) profile. The 23 full factorial design was utilized to search an optimal SR tablet formulation. This optimal formulation was followed zero-order mechanism and had specific release rate at different time intervals (released % of 1, 6, and 12 hr were 15.84, 58.56, and 93.10%). The results of moisture absorption by Karl Fischer meter showed the optimum SR tablet could improve the hygroscopic defect of the pure drug (PB). In the in vivo study, the results of the bioavailability data showed the Tmax was prolonged (from 0.65 ± 0.082 hr to 4.83 ± 1.60 hr) and AUC0-t (from 734.88 ± 230.68 ng ml.hr to 1153.34 ± 488.08 ng ml.hr) and was increased respectively for optimum PB-SR tablets when compared with commercial immediate release (IR) tablets. Furthermore, the percentages of in vitro dissolution and in vivo absorption in the rabbits have good correlation. We believe that PB-SR tablets designed in our study would improve defects of PB, decrease the frequency of administration and enhance the retention period of drug efficacy in vivo for personnel exposed to contamination situations in war or terrorist attacks in the future.