Formulation and optimization of alkaline extracted ispaghula husk microparticles of isoniazid – in vitro and in vivo assessment

Abstract

Microparticles containing isoniazid were prepared by the emulsification internal ionic gelation method using a novel, alkaline extracted ispaghula husk as a wall forming material. A four-factor three-level Box–Behnken design was employed to study the effect of independent variables on dependent variables. Sodium alginate concentration (X₁), alkaline extraction of ispaghula husk (AEISP) concentration (X₂), concentration of cross-linking agents (X₃) and stirring speed (X₄) were four independent variables considered in the preparation of microparticles, while the particle size (Y₁) and entrapment efficiency (Y₂) were dependent variables. Optimized microparticles exhibited 83.43% drug entrapment and 51.53 µm particle size with 97.80% and 96.37% validity, respectively, at the following conditions – sodium alginate (3.55% w/v), alkaline extracted ispaghula husk (3.60% w/v), cross-linker concentration (7.82% w/v) and stirring speed (1200 rpm). The optimized formulation showed controlled drug release for more than 12 h by following Higuchi kinetics via non-Fickian diffusion. The gamma scintigraphy of the optimized formulation in Wistar rats showed that microparticles could be observed in the intestinal lumen after 1 h and were detectable in the intestine up to 12 h, with decreased percentage of radioactivity (t_1/2 of ^99mTc 4–5 h).

• isoniazid
• Box–Behnken design
• alkaline extracted ispaghula husk
• mucoadhesion
• gamma scintigraphy