Systemic Review of Screening the Shapes of Ibuprofen Particles in Different Solvents

Md Abdur Rashid

doi:10.9734/jpri/2021/v33i29a31567

Abstract

Ibuprofen is a very popular analgesic which is mostly available in the market as tablet dosage form. The ibuprofen molecule possesses a chiral center in the propionic acid group. So, there are two enantiomers (R and S), whose chemical properties are similar, but which have optical rotations of opposite sign. The (-) form (l- or laevo-) is the R (-) enantiomer whereas the (+) form (d or dextro-) is referred to as S (+) – ibuprofen. The R (-) isomer is biologically inactive while the S (+) isomer is active. The R (-) form however is slowly converted to the S (+) active form during metabolism in the human body by the presence of the enzyme isomerase (2-arylpropionyl-CoA epimerase). Thus, a large difference in the body potency between the two enantiomers is not found. During manufacturing of tablet, ibuprofen particle plays a significant role in flowability and compressibility etc. Theoretically particle size and shape have great impact on those sorts of mechanical properties of tablets. The morphology can influence physical properties such as packing density, bulk density, agglomeration, and dissolution behaviour as well as the mechanical strength and wet ability. Furthermore, crystal shapes have also been found to have an effect on the bioavailability of the resulting APIs. Commercial ibuprofen typically has a needle shaped morphology with rough surfaces and show poor flowability, poor compaction behavior and a tendency to stick to the tablet punches. To overcome these problems, a suitable size and shape of ibuprofen crystal is desirable that could be directly compressed with fewer operation steps but still having good product stability and therapeutic efficacy, but it can be changed through recrystallization or other methods such as spray drying, etc. Ibuprofen crystallized from solvents with a high hydrogen bonding ability like methanol will form chunky crystals and low hydrogen bonding solvents like hexane will form needle like crystals. Therefore, it was necessary to review the shapes of ibuprofen particles in different solvents. This review paper has covered a comprehensive studies of ibuprofen particle shapes in different solvents and cosolvents.

Highlights

This article reviews the relevant background knowledge of ibuprofen, in particular its crystallization behavior in different industrially used solvents and the mixture of solvents
Ibuprofen crystallized from solvents with a high hydrogen bonding ability like methanol will form chunky crystals and low hydrogen bonding solvents like hexane will form needle like crystals
The prior literature on the properties of ibuprofen, and its crystal growth will be reviewed in this paper

Summary

INTRODUCTION

This article reviews the relevant background knowledge of ibuprofen, in particular its crystallization behavior in different industrially used solvents and the mixture of solvents. The Boots’ synthesis of ibuprofen is a five-step process (Fig. 4) and results in large quantities of waste chemical by-products that must be disposed of or otherwise managed. Inactive enantiomer of ibuprofen (chiral) flat achiral enol biologically active enantiomer of ibuprofen (chiral) In this process, only small amounts of unwanted byproducts are produced. Compared to the Boots’ process, the Hoechst process is more eco-friendly and cheaper Ibuprofen, which is commercially available as colorless, needle like (acicular) shaped crystals has a melting point in the rage of 75 - 77oC. It is insoluble in water but soluble in most organic solvents [9,1]. The density of racemic ibuprofen is 1.110 g/ml [15]

Crystal Structure of Ibuprofen

Polymorphism

Effect of Super Saturation and Temperature on Ibuprofen Crystals

CONCLUSIONS