Physical characterization and kinetic modelling of matrix tablets of ketorolac tromethamol formulated with polymers and waxes

Gülgün Yener,Melike Üner,Evin Ayçiçek,Ebru Altuntaş

doi:10.4314/tjpr.v15i12.3

Abstract

Purpose: To design controlled release ketorolac tromethamol (KT) matrix tablets for increased drug bioavailability. Methods: Waxes (Compritol ® ATO 888, Precirol ® ATO 5 and stearic acid - SA) and polymers (hydroxypropyl methylcellulose - HPMC and xanthan gum - XG) were used in the preparation of the matrix tablets at various excipient concentrations for controlled drug delivery. The physical properties of the formulations were determined. Drug release profiles from the tablets were obtained and their drug release mechanisms were characterized by kinetic modeling. Analytical quantification method of KT in dissolution media was also validated by certain performance criteria. Results: KT matrix tablets prepared individually with Compritol and HPMC at 30 and 40 % concentrations, respectively, displayed the best tablet compression properties. The tablets prepared with HPMC and XG displayed slower drug release profiles compared to the tablets prepared with waxes in general ( p 0.05). However, drug release from the tablets containing 40 % XG was faster than tablets prepared with HPMC (30 and 40 %) and XG (30 %) at pH 7.2 ( p < 0.05). Drug release mechanisms from the tablets prepared with wax and polymers were non-Fickian, indicating coupled diffusion/erosion and diffusion/polymer relaxation, respectively. Conclusion: KT matrix tablets have been successfully formulated by direct compression method. The findings demonstrate that both the desired physical characteristics and drug release profiles were obtained for matrix tablets prepared with HPMC. Keywords: Ketorolac tromethamol, Controlled release, Matrix tablets, Oral drug delivery, Waxes, Polymers

Highlights

Ketorolac tromethamol (KT) [(±) - 5-benzoyl - 2, 3 - dihydro - 1H – pyrrolizine - 1 -carboxylic acid compound with 2 - amino - 2 - 1, 3 – propanediol (1:1)] is a non-steroidal antiinflammatory drug (NSAID) of heterocyclic acetic acid derivatives which has a pKa of 3.54 [1,2]
Because of the risk of possible serious side effects, it is not suitable for long-term therapy [3,4] related to gastrointestinal system, vascular and cardiovascular systems, urinary system
“Poor” or “very poor” characteristics were observed with decrease in wax or polymer concentrations in general

Summary

Introduction

Ketorolac tromethamol (KT) [(±) - 5-benzoyl - 2, 3 - dihydro - 1H – pyrrolizine - 1 -carboxylic acid compound with 2 - amino - 2 - (hydroxymethyl) 1, 3 – propanediol (1:1)] is a non-steroidal antiinflammatory drug (NSAID) of heterocyclic acetic acid derivatives which has a pKa of 3.54 [1,2] It is used for short-term management of moderately severe acute and/or postoperative pain to reduce postoperative narcotic requirements. Its recommended initial dose is 10 mg followed by 10 - 30 mg every 4 - 6 h. It is prescribed for not more than 5 days for adults and as a single dose for children. Because of the risk of possible serious side effects, it is not suitable for long-term therapy [3,4] related to gastrointestinal system (ulceration, bleeding and/or perforation of the stomach or intestines), vascular (cerebrovascular bleeding) and cardiovascular systems (cardiovascular thrombosis, myocardial infarction and stroke), urinary system (renal impairment)

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