Ibuprofen melting

The physical states of the substances modeled differ at 298.15 K DSC measurements (see also Section 16.2.3.2) show that polymer Eudragit RS is amorphous without crystalline sections. In contrast, the plasticizers TEC, ATBC, and DBS are fluids. Furthermore, the drugs ibuprofen and theophylline are crystalline with ibuprofen melting within the hot-melt extrusion process, whereas theophylline stays solid. These differences were taken into account for the calculation of the solubility... 

The crystalline drug ibuprofen melts at 76°C, so the applied extrusion temperature allowed the incorporation of molten drug into the polymer matrix. Therefore, ibuprofen could be homogeneously dissolved up to values of w reading 20% (due to the high stickiness, no higher solid-state solutions could be produced). 

Fig. 4.12. DSC thermogram of non-solvated ibuprofen lysinate, illustrating the enantiotropic conversion of the metastable phase to the more stable phase (64°C endotherm) and subsequent melting of the stable form (181°C endotherm).

Supercooling has been observed in an extreme form in molten ibuprofen if the molten solid is allowed to cool from the melting point to room temperature without vibration in a smooth-lined container [48]. For instance, undisturbed rac-ibuprofen can exist as an oil phase for several hours to a few days. If disturbed, however, an exothermic recrystallization proceeds and bulk crystalline material rapidly grows vertically out of the oil phase so energetically that the system emits an audible cracking sound. 

Ibuprofen is known to form eutectics with excipients, resulting in loss of potency due to sublimation. Gordon et al. [47] in a DSC investigation of the compatibility of Ibuprofen with stearate lubricants were able to demonstrate that the melting point of Ibuprofen could be reduced by some 20-30°C, via the formation of eutectic mixtures (see Table 2.5). 

Passerini, N., B. Albertini, and M. L. Gonzalez-Rodriguez. 2002. Preparation and characterization of ibuprofen-poloxamer 188 granules obtained by melt granulaEanJ Pharm Scil5 71-78. 

An early example of Raman mapping by Breitenbach et al. [52] showed that when crystalline ibuprofen is formulated in a hot melt extrudate the API changes to the amorphous form. Ibuprofen is a sparingly water-soluble compound, so this formulation provides a route to better bioavailability via the more soluble amorphous form. Using confocal Raman mapping the form of the API was determined at the time of manufacture and under stress conditions and was used to assess the stability of the amorphous form. These studies also showed that the API was homogeneously distributed throughout the formulation based on the relative band intensities of the amorphous API and a formulation excipient, polyvinylpyrrolidone (PVP). 

Ibuprofen is available in liquid, sachet, capsule, melt and tablet form. The licensed age range for ibuprofen depends on the product formulation. Ibuprofen is only indicated for children over six months of age over the counter. It has additional anti-inflammatory properties which may be helpful in conditions such as otitis media. Ibuprofen has the potential to cause gastrointestinal disturbances, although if given with food this is unlikely. Note Caution if using in a child with history of severe asthma or renal disease. 

FIGURE 9.9 Melting point phase diagram obtained for the salt formed between racemic ibuprofen and the (S)-enantiomer of a-methylbenzylamine [H.G. Brittain, unpublished results]. 

The lack of any further Raman shifts during a stability study indicated that the ibuprofen in the melt extrudate is stable and that there were no crystallization processes that could affect the dissolution and bioavailability. Therefore, one use of confocal Raman spectroscopy could be to optimize various formulations and quickly determine their likely long-term stability. 

Polymorphism and pseudopolymorphism are known among chiral drugs. Whereas the enantiomers of chiral drugs may display ordinary polymorphism, the racemic species show a special type of polymorphism, namely conversion between the different types of racemate. For example, racemic sodium ibuprofen exhibits three polymorphs, the stable polymorph at room temperature being the conglomerate while the other two polymorphs, which are racemic compounds, are obtained by rapidly cooling the melt of the conglomerate [21]. 

Eutectic mixtures of ibuprofen and terpene penetration enhancers have also been studied. The eutectic mixture results in superior penetration compared to that of an aqueous solution when the skin was pre-treated with terpenes. In addition to these results with ibuprofen [13], screening by thermal analysis has shown a number of other drug classes, which because of the formation of eutectic mixtures or solid solutions and resulting melting point depression, may be suitable for enhanced drug delivery. These drugs include ACE inhibitors, P-blockers and other antiinflammatory drugs [14,15]. 

Kamble, R., Maheshwari, M., Paradkar, A., and S. Kadam. Melt solidification technique Incorporation of higher wax content in ibuprofen beads. AAPS Pharm Sci Technol, 5(4) (2004) 75-83. 

De Brabander, C., Vervaet, C., Bortel, L.V., Remon, J.P. Bioavailability of ibuprofen from hot-melt extruded mini-matrices. Int. J. Pharm. 2004, 271(1-2), 77-84. 

This is a particular case a low drying temperature must be applied because of the very low melting point of ibuprofen (76°C). The two drying conditions studied were 40°C for two hours or 60°C for two hours. 

Devise and perform an extraotion procedure fhat may be used to separate pure 2-(4 -isobutylphenyl)propionic acid (ibuprofen) from the over-the-counter medications Advil or Nuprin . Determine the melting point of the material you isolate to oonfirm its identity. 

Gryczke A, Schminke S, Manimzzaman M, Beck J, Douroumis D (2011) Development and evaluation of oraUy disintegrating tablets (ODTs) containing Ibuprofen granules prepared by hot melt extrusion. Colloids Surf B Biointerfaces 86(2) 275-84... 

Pharmaceutical formulators often meet the problem of low water solubility of the drugs. The water uptake [7] process of Ibuprofen, a non-steroid anti-inflammatory drug, after compression of the powder into a tablet and in the solid dispersion prepared by melting is shown in Fig. 1. 

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