Preparation of ibuprofen/lipid composite microparticles by supercritical fluid technique

Abstract

Using the CO₂- and N₂-assisted atomization processes, the production of ibuprofen/lipid composite microparticles is investigated, in which the lipid includes myristic acid and tripalmitin. The produced composite particles show similar morphology to that of the pure lipids obtained by the same process. In the case of the N₂-assisted process, the average size of composite particles is slightly larger than that of the pure lipid particles due to the difficulty of solidification when using N₂. In the case of the CO₂-assisted process, the average size of composite particles is slightly smaller than that of the pure myristic acid particles, but slightly larger than that of the pure tripalmitin particles. The dissolution study reveals that the drug release from the ibuprofen/myristic acid particles is enhanced in comparison with that of the unprocessed ibuprofen. For the particles produced by the N₂-assisted process, the X-ray diffraction (XRD) patterns clearly indicate the encapsulation of ibuprofen into myristic acid. The obtained ibuprofen/tripalmitin composite particles with 5% or 20% of ibuprofen (in mass) evidently show the controlled drug release: only about 20% of the drug is released in 500 min from the ibuprofen/tripalmitin composite particles consisting of 20% ibuprofen prepared by the CO₂-assisted process, and the same release is obtained from the ibuprofen/tripalmitin composite particles containing 5% ibuprofen prepared by the N₂-assisted process.

References

1. Chen X Q, Yu H J, Yu W . Formation of fine ibuprofen particles by rapid expansionof supercritical solution. Chin J Pharm, 2002, 33: 227–228 (in Chinese)
2. Foster N R, Dehghani F, Charoenchaitrakool M, Warwick B . Application of dense gas techniques forthe production of fine particles. AAPSPharm Sci, 2003, 5: 105–111. doi:10.1208/ps050211
3. Charoenchaitrakool M, Dehghani F, Foster N R . Utilization of supercriticalcarbon dioxide for complex formation of ibuprofen and methyl-β-cyclodextrin. Int J Pharm, 2002, 239: 103–112. doi:10.1016/S0378-5173(02)00078-9
4. Türk M, Upper G, Steurenthaler M, Hussein K, Wahl M A . Complex formationof Ibuprofen and β-Cyclodextrinby controlled particle deposition (CPD) using SC-CO₂. J Supercrit Fluids, 2007, 39: 435–443. doi:10.1016/j.supflu.2006.02.009
5. Ambrogi V, Fardella G, Grandolini G, Perioli L . Intercalation compounds of hydrotalcite-like anionicclays with anti-inflammatory agents. I: Intercalation and in vitrorelease of ibuprofen. Int J Pharm, 2001, 220: 23–32.. doi: 10.1016/S0378-5173(01)00629-9
6. Kamble R, Maheshwari M, Paradkar A, Kadam S . Melt solidification technique: incorporation of higherwax content in ibuprofen beads. AAPS PharmSci Tech, 2004, 5(4): E61.. doi: 10.1208/pt050461
7. Thompson C J, Hansford D, Higgins S, Rostron C, Hutcheon G A, Munday D L . Evaluation of ibuprofen-loadedmicrospheres prepared from novel copolyesters. Int J Pharm, 2007, 329: 53–61. doi:10.1016/j.ijpharm.2006.08.019
8. Weidner E, Knez Z, Novak Z . WO9521688, 1995
9. Li J, Rodrigues M, Paiva A, Matos H, de Azevedo E G . Modeling of particle formation from a gas-saturated solution processes. AIChE J, 2005, 51: 2343–2357. doi:10.1002/aic.10478
10. Li J, Matos H, de Azevedo E G . Two-phase homogeneous modelfor particle formation from gas-saturated solution process. J Supercrit Fluids, 2004 : 32, 275–286. doi:10.1016/j.supflu.2004.01.004
11. Ghaderi R, Artursson P, Carlfor J . A new method for preparingbiodegradable microparticles and entrapment of hydrocortisone in DL-PLGmicroparticles using supercritical fluids. Eur J Pharm Sci, 2000 : 10, 1–9. doi:10.1016/S0928-0987(99)00079-2
12. Zhao L, Li J, Rodrigues M, Matos H, de Azevedo E G . Using N₂- or CO₂-assisted atomization process to producepolyethylene glycol microparticles. ChemEng Res & Design, 2007 : 7, 987–995. doi:10.1205/cherd06209
13. Zhao Y D, Su Y Z, Wang H T, Li J . N₂-assisted particle formation to micronize fatty acids. J Xiamen Univ, 2007, 1: 72–76 (in Chinese)
14. Chen H, Zhao L, Zhang H X, Su Y Z, Wang H T, Li J . Ibuprofen particle formation from gas-saturated solutions. In: Tong Z F. Chemicalengineering/biochemical technology and biomass energy. Beijing: Chemical Industry press, 2006 : 97–102 (in Chinese)
15. Chen H . Ibuprofen and MA microparticles and microcomposites generatedby particle formation from gas-saturated solutions. Dissertation for the Master Degree. Xiamen: Xiamen Univ, 2007, 30–49
16. Walsh R D B, Bradner M W, Fleischman S, Morales L A, Moulton B, Rodriguez-Hornedo N, Zaworotko M J . Crystal engineering of thecomposition of pharmaceutical phases. ChemCommun, 2003, 186–187