Effect of Granules Properties on the In-vitro and In-vivo Performance of Ibuprofen Sustained Release Matrix Tablets

M S Shubair

doi:10.3797/scipharm.aut-04-27

Abstract

The impact of variations in the wet granulation step during the manufacturing process on the in-vitro and in-vivo performance of ibuprofen sustained release matrix tablets was investigated. Two batches were produced under different wet granulation conditions. The granules of the first batch (T1) were characterized by having a lower bulk density (0.56 g/ml), a higher percentage of fines (56.7% w/w) and a smaller geometric mean diameter (dg), 600 µm. While the granules of batch (T2) were characterized by having a more coherent properties, a higher bulk density (0.66 g/ml), a lower percentage of fines (36.9% w/w) and a larger dg, 720 µm. Three large scale production batches (B1, B2, B3) were manufactured similarly to T2 and found to have granules possessing similar properties. In-vitro tests showed that tablets of T1 had a statistically significant higher release rate constant than tablets of either T2, B1 ,B2 or B3. In-vivo tests were done using T1 and T2 tablets. Although T1 and T2 were bioequivalent with respect to Cmax and AUC, T2 exhibited a statistically significant longer sustained release characteristics than T1 (P<0.05).

Highlights

Ibuprofen (IB) is a propionic acid derivative of a non-steroidal antiinflammatory drug (NSAID) widely used for the treatment of rheumatoid arthritis and as an analgesic and antipyretic agent [I]
For a short biological half life NSAIDs, a sustained release dosage forms are desirable in order to allow twice or once daily administration of the drug to reduce side effects due to high plasma
Different sustained release dosage forms for ibuprofen were proposed [2-71.One of the designs, which was successful in the formulation of sustained release IB dosage form, was the bimodal drug release pattern [8, 91

Summary

Introduction

Ibuprofen (IB) is a propionic acid derivative of a non-steroidal antiinflammatory drug (NSAID) widely used for the treatment of rheumatoid arthritis and as an analgesic and antipyretic agent [I]. For a short biological half life NSAIDs, a sustained release dosage forms are desirable in order to allow twice or once daily administration of the drug to reduce side effects due to high plasma. Different sustained release dosage forms for ibuprofen were proposed [2-71.One of the designs, which was successful in the formulation of sustained release IB dosage form, was the bimodal drug release pattern [8, 91. The bimodal design aimed at delivering a proportion of IB at colon, and a high morning drug plasma concentration might be achieved [8].The benefit of a high early morning levels of drug in plasma is to overcome morning stiffness symptom of rheumatoid disease. The aim of this study was to investigate the effect of variation in granules properties on the in-vitro and in-vivo performance of IB sustained release matrix tablets

Results and Discussion

Granules properties Micoroscopical and Density Propetties of granules

Experimental Materials