RAMAN AND THERMAL ANALYSIS OF IBUPROFEN-ISOMALT SYSTEMS

Ultrasound-assisted compaction of pharmaceutical powders is still a rather novel technique and literature reports extend only over the last years. However, the lack of systematic knowledge and fundamental understanding of the underlying physics of the ultrasound-assisted compression of powders have prevented large applications. Applications of high-intensity ultrasonic energy are based upon the mechanical effects which result from particle motion: various mechanisms may be activated by the ultrasonic energy to promote the effect on media, even though mechanisms involved are not always known or understood, such as heat, stirring, chemical and mechanical effects. The main aim of this paper was to formulate ibuprofen and isomalt (an artificial sugar substitute, multifunctional excipient, poorly hygroscopic and anticaking agent) and obtain a taste masking of the drug through a US assisted compaction coupled to an improvement of the dissolution rate to be obtained both through the amorphousness of drug and/or excipient and dehydration of excipient. Experimental methods 600 mg of the material required for each round, flat-faced tablet was separately weighed and manually loaded into the die. Tabletting was then carried out on a US assisted pharmaceutical tabletting machine and the experimental conditions were as reported (a). Physical mixtures were prepared containing 10, 20 and 30% w/w ibuprofen and hydrate and dehydrated isomalt and compacted either by a traditional or ultrasound assisted machine. The systems were analysed by means of differential scanning calorimetry (DSC) and thermogravimetric (TGA) and FT-IR techniques. Result and Discussion SEM Analysis - At SEM particles of pure compounds appear with a morphology very different. While isomalt contains agglomerated spherical particles shape with rounded margins and an irregular and rough surface (A), ibuprofen particles have a crystalline habit with agglomerates formed by hexagonal plates stacked together (B). In fragments of a tablet traditionally compacted, single component regions are clearly evident at (even optical) microscope, assembled together with only deformed edge, following the pressure of the die (C). On the contrary tablets, compacted under US, leave, after fracture, particles with sharp edges, compact texture (D) and fairly smooth surface (E, F). Considering the texture it can be hypothesized that mixture components underwent thermal events during US compression. Thermal Analysis - Since two endotherms (melting of ibuprofen and dehydration of isomalt) partially overlap, occurring at temperature close together, determination of the melting heat is unsuitable. Therefore the same measurements were repeated using isomalt previously dehydrated in oven at 70° for 2 days. Thermograms of all the mixtures thus appear more regular and two different endotherms (for the drug and excipient) are present, suitably separated and calculation carried out in these last systems let us to draw some partial conclusions. Thermal parameters of ibuprofen and isomalt do not change when they are in mixture, suggesting the absence of any interaction; DH of isomalt appears about 10% higher for samples dehydrated in oven, than for the hydrated compound: possibly dehydration process leave the mass partially amorphous; crystallinity cannot be rapidly recovered, at least at least at the scanning rate of 10°C/min (as in all measurements); also ibuprofen amorphises during the cooling after the melting: crystallinity appears not to be recovered during a normal thermal cycle (at 10°C/min). Raman Analysis - – Scanning was performed up to 3500 cm-1 and spectra of both compounds are riche of narrow and well defined peaks, whose position in the range of wave numbers considered, can be employed to identify each compound, when in mixture. It was chosen to consider the following peaks to check the presence of ibuprofen in the mixtures: 745, 782, 1608 cm-1, which can be found in the spec...