Development and optimization of fluoxetine orally disintegrating tablets using Box-Behnken design

Bahaa E Ali,Gamal A Gabr,Ramadan Al-Shdefat,Mohammad Khalid Anwer,Abdullah K Rabba,Mohamed H Fayed,Mohammad Javed Ansari,Khalid M El-Say

doi:10.4314/tjpr.v15i4.1

Abstract

Purpose : To develop and optimise some variables that influence fluoxetine orally disintegrating tablets (ODTs) formulation. Methods : 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 (X 1 ), lubricant mixing time (X 2 ), and compression force (X 3 ) and then their effect was monitored on tablet weight (Y 1 ), thickness (Y 2 ), hardness (Y 3 ), % friability (Y 4 ), and disintegration time (Y 5 ). Results : All powder blends showed acceptable flow properties, ranging from good to excellent. The disintegration time (Y 5 ) was affected directly by lubricant concentration (X 1 ). Lubricant mixing time (X 2 ) had a direct effect on tablet thickness (Y 2 ) and hardness (Y 3 ), while compression force (X 3 ) had a direct impact on tablet hardness (Y 3 ), % friability (Y 4 ) and disintegration time (Y 5 ). Accordingly, Box-Behnken design suggested an optimized formula of 0.86 mg (X 1 ), 15.3 min (X 2 ), and 10.6 KN (X 3 ). Finally, the prediction error percentage responses of Y 1 , Y 2 , Y 3 , Y 4 , and Y 5 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. Conclusion : Fluoxetine ODT formulation has been developed and optimized successfully using Box- Behnken design and has also been manufactured efficiently using direct compression technique. Keywords : Box-Behnken experimental design, Orally disintegrating tablets, Direct compression, Antidepressant, Magnesium stearate, Mixing time

Highlights

Up to one-third of people in all age groups have experienced swallowing issues during their lifetime [1]
Optimizing the amount of magnesium stearate and mixing time is critical in the manufacturing of orally disintegrating tablets (ODTs) [5]
All the ODT formulations met the United States pharmacopoeia requirements concerning the homogeneity of weight

Summary

Introduction

Up to one-third of people in all age groups have experienced swallowing issues during their lifetime [1]. ODTs greatly improve patients’ compliance as it is taken without the need of water. It provides very rapid onset of action for patients in which it promote pregastric absorption of the drug molecules through buccal, sublingual, oropharyngeal, and esophageal membranes. It avoids the first-pass hepatic metabolism leads to elevate bioavailability and reduces drug side effects [3]. Lubrication is a critical element in tablet formulation. Optimizing the amount of magnesium stearate and mixing time is critical in the manufacturing of ODTs [5]

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Results

Discussion

Conclusion