Formulation Design of a Highly Hygroscopic Drug (Pyridostigmine Bromide) for its Hygroscopic Character Improvement and Investigation of In Vitro/In Vivo Dissolution Properties

ABSTRACT

Pyridostigmine bromide (PB) sustained-release (SR) pellets were developed by extrusion-spheronization and fluid-bed methods using Taguchi experimental and 2³ full factorial design. In vitro studies, the 2³ 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°C/60% RH, 30°C/65% RH, and 40°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 T_max (from 0.65 ± 0.082 hr–4.82 ± 2.12 hr) and AUC_{0–30 hr} (from 734.88 ± 230.68 ng/mL.hr–1454.86 ± 319.28 ng/mL.hr) were prolonged and increased, as well as C_max (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.

KEYWORDS:

• Sustained release pellets
• Taguchi experimental design
• 2³ full factorial design
• Zero-order mechanism
• In vitro-in vivo relationship
• Hygroscopic character