Development and optimization of fluoxetine orally disintegrating tablets using Box-Behnken design|
Ali, Bahaa E.; Rabba, Abdullah K.; Fayed, Mohamed H.; El-Say, Khalid M.; Anwer, Mohammad Khalid; Ansari, Mohammad Javed; Al-Shdefat, Ramadan & Gabr, Gamal A.
To develop and optimise some variables that influence fluoxetine orally disintegrating tablets
Fluoxetine ODTs tablets were prepared using direct compression method. Three-factor, 3-
level Box-Behnken design was used to optimize and develop fluoxetine ODT formulation. The design
suggested 15 formulations of different lubricant concentration (X1), lubricant mixing time (X2), and
compression force (X3) and then their effect was monitored on tablet weight (Y1), thickness (Y2),
hardness (Y3), % friability (Y4), and disintegration time (Y5).
All powder blends showed acceptable flow properties, ranging from good to excellent. The
disintegration time (Y5) was affected directly by lubricant concentration (X1). Lubricant mixing time (X2)
had a direct effect on tablet thickness (Y2) and hardness (Y3), while compression force (X3) had a direct
impact on tablet hardness (Y3), % friability (Y4) and disintegration time (Y5). Accordingly, Box-Behnken
design suggested an optimized formula of 0.86 mg (X1), 15.3 min (X2), and 10.6 KN (X3). Finally, the
prediction error percentage responses of Y1, Y2, Y3, Y4, and Y5 were 0.31, 0.52, 2.13, 3.92 and 3.75 %,
respectively. Formula 4 and 8 achieved 90 % of drug release within the first 5 min of dissolution test.
Fluoxetine ODT formulation has been developed and optimized successfully using Box-
Behnken design and has also been manufactured efficiently using direct compression technique.
Box-Behnken experimental design; Direct compression; Magnesium stearate; Orally disintegrating tablets; Antidepressant; Mixing time