physicochemical characteristics of ibuprofen

Study the physicochemical characteristics of ibuprofen and evaluate the solid dispersion formulation of ibuprofen by using different molecular weight of PEG

1. Study the physicochemical characteristics of ibuprofen and evaluate the solid dispersion formulation of ibuprofen by using different molecular weight of PEG Presented by:- Hadeia Mashaqbeh

2. introduction Is a nonsteroidal anti-inflammatory drug that is widely used as an analgesic It is a non-selective inhibitor of cyclo-oxygenase-1 (COX-1) and Cyclooxygenase-2 (COX-2) Used to reduce fever and treat pain or inflammation caused by many conditions such as headache, back pain, arthritis, chronic laryngitis and bronchiolitis

3. Ibuprofen 2-(4-isobutylphenyl)- propionic acid Ibuprofen is Crystalline stable solid with characteristic odor. It melts at about 75-78 °C

4. its application in the pharmaceutical field is limited by its: low aqueous solubility bad taste bad manufacturing behavior; the flow properties are poor and it has a high tendency to stick to the punches increasing risk of serious effects on the stomach and intestines.

5. solubility class II drug according to the BCS classification Ibuprofen is readily soluble in most organic solvents, very soluble in alcohol and is almost insoluble in water ( 21 mg/L at 25 °C).

6. Solubility enhancement includes : both conventional techniques as inclusion complexation , solid dispersions, salt formation etc. As well as relatively newer techniques such as selfemulsifying systems, micro emulsion, nanosizing and supercritical fluid processing.

7. Solid dispersions Solid dispersion is one of the most promising approaches for solubility enhancement . Solid dispersion of Ibuprofen was prepared with Poloxamer 407, PVP K12, PEG 4000 and PEG 6000 solid dispersions using PEG 8000 Solid dispersions of ibuprofen were prepared using polyethylene glycol 20000 by physical mixing and solvent evaporation method.

8. polymorphism two phases form a monotropic set: Phase I is the more stable phase at all temperatures lower than its melting at Tm I = 348 K. Metastable phase II may exist up to its melting point at Tm II= 0 290 K.

9. Experimental work Preparation of Ibuprofen Solid Dispersion . Ibuprofen and PEG (4000, 6000 and 20000) in 1:10 proportions were prepared by melt method. Each carrier, PEG 4000, 6000 and 20000 was first melted separately at a temperature of 65 °C in a water bath. The Ibuprofen was incorporated to each melt of PEG 4000, 6000, 20000 and kept in room temperature for cooling. The solidified mass was scrapped and then crushed Preparation of Ibuprofen Physical Mixtures Physical mixtures of ibuprofen were prepared by mixing ibuprofen with PEG 4000, 6000 and 20000 each at once in combination and individually in a glass mortar by trituration . The ratio of Ibuprofen and PEG was 1:10.

10. Solid dispersions Solid dispersions were characterized by differential scanning calorimetry (DSC), Thermal Gravimetric Analysis (TGA) , fourier transform infrared spectroscopy (FTIR) and x-ray diffraction Also evaluated for equilibrium solubility

11. DSC The endothermic peak at 79.4 °C and the absence of loss of mass in the TGA indicate that it is the melting point of ibuprofen which is the charcteristics of racemic ibuprofen.

12. TGA The decomposition at 255 °C results in a loss of mass with the release of CO2 and hydrogen from the carboxylic acid chain

13. Ibuprofen Carboxylic group 3000-3400 cm -1 Methyl group stretching 2955 cm -1 Stretching of carbonyl group 1720 cm -1 C-C stretching 1231cm -1 CH 2 rocking vibration 779 cm −1

14. X-ray for ibuprofen

15. UV Spectrophotometry The UV spectra of ibuprofen were presented. The absorption maxima was observed at 222 nm.

16. Evaluate The Solubility Of Ibuprofen With Physical Mix and Solid Dispersion Formulation By Using PEGs With Molecular Weight 4000, 6000 and 20000.

17. Solubility results

18. the increase in the solubility of the drug when it is physically mixed with PEG is probably due to a wettability improvement and a local solubilization effect by the carrier. In the case of the solid dispersion it can be concluded that higher drug saturated solubility may only related to the presence of polymeric carrier in the medium, but not associated to the drug status in the solid dispersion system (neither polymorphic change nor reduction in particle size ).

19. Najib , N.M. and Sheikh Salem, M.A., 1987. Release of Ibuprofen from Polyethylene glycol solid dispersions:-Equilibrium solubility approach. Drug Development and Industrial Pharmacy , 13 (12), pp.2263-2275.

20. ftir

21. Physical mixture vs solid dispersion

22. The new endothermic peaks appeared at nearly 60 c related to the melting point of PEG .

23. X-ray

24. Result Decreased by increasing both the polymer molecular weight and concentrations. At a very high polymer concentration, a prevailing viscosity delaying effect was observed, solubilization effect will decrease due to the decrease of the affinity of polymer toward the drug

25. Comparison between 1:1 and 1:10 As the molecular weight of PEG and concentration increase solubilization effect will decrease due to the decrease of the affinity of polymer toward the drug

26. Conclusions Solubility studies showed enhancement in solubility in the presence of PEG in solid dispersions but physical mixture gives higher ranges of solubility This study indicating compatibility between PEGs and Ibuprofen As the molecular weight of PEG and concentration increase solubilization effect will decrease due to the decrease of the affinity of polymer toward the drug . According to these result solid dispersion of ibuprofen should prepared with higher drug :polymer ratio or with lower molecular weight PEG