Modification of crystal habit of ibuprofen using the phase partition technique: effect of aerosil and tween 80 in binding solvent.
A ternary diagram, representing the solubility of binding solvent (chloroform) in a mixture of ethanol and water, was constructed. For this study, the solvent mixture that gave the best ibuprofen pellets (IPs) was composed of chloroform.ethanol:water at a ratio of 1.5%:8%:90.5%. The suitable agitator speed, temperature, and mixing time were found to be 1,500 rpm, 25 degrees C +/- 2 degrees C, and 20 min, respectively. In addition, suitable stirring time when the phase partition process of IPs began was 15 min. IPs obtained from these conditions were small and round, approximately 1 mm; surface determination by scanning electron microscopy (SEM) indicated that the IPs were composed of drug microcrystals rearranged on the surface. For the dissolution, IPs showed lower drug release when compared with pure ibuprofen crystal (IC) (f2 analysis). An attempt to modify the dissolution property of IP by incorporating various concentrations of Aerosil and Tween 80 in the binding solvent was made. Microscopic appearance showed that both Aerosil and Tween 80 gave less spherical pellets when compared with the use of binding solvent alone. For both the Aerosil and Tween 80 employed, the results indicated a change in rearrangement of drug microcrystals and a change in crystal habit. However, Tween 80 gave more change of the crystallographic direction of drug microcrystals than Aerosil. In term of dissolution, the results showed that employing Tween 80 at 1.2% gave the highest drug release compared to the use of Aerosil and IC alone (f2 analysis). These pellets had a good flow property, as indicated by Carr's compressibility, flow rate, and angle of repose, and they can be compressed into a tablet, encapsulated by suitable polymer, or pulverized to obtain micronized crystals. In the case of compression into tablets, the dissolution profiles of these tablets compared with those of commercial product meet the USP 24 requirement (Q > or = 80% at 60 min).
Umprayn
K
K
Department of Manufacturing Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Luengtummuen
A
A
Kitiyadisai
C
C
Pornpiputsakul
T
T
D003460:Crystallization; D004339:Drug Compounding / Q000379:methods*; D004343:Drug Implants; D005079:Excipients / Q000737:chemistry*; D007052:Ibuprofen / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D011136:Polysorbates / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013607:Tablets
D004343:Drug Implants; D005079:Excipients; D011136:Polysorbates; D012997:Solvents; D013607:Tablets; D012822:Silicon Dioxide; D007052:Ibuprofen