Search tips
Search criteria 


Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
AAPS PharmSciTech. 2003 December; 4(4): 514–522.
Published online 2003 October 9. doi:  10.1208/pt040465
PMCID: PMC2750658

Preparation and characterization of flurbiprofen beads by melt solidification technique


Amelt solidification technique has been developed to obtain sustained-release waxy beads of flurbiprofen. Low glass transition temperature (tg) and shear-induced crystallization of flurbiprofen made it a suitable candidate for melt solidification technique. The process involved emulsification and solidification of flurbiprofen-cetyl alcohol melt at significantly low temperature (5°C). The effect of variables, namely, the amount of cetyl alcohol and the speed of agitation, was studied using 32 factorial design. The technique and the beads were evaluated on the basis of process and desired yield, surface topography, Fourier-transform infrared (FT-IR), differential scanning calorimetry (DSC), particle size distribution, crushing strength, and drug release. Average values for process and desired yields were 97% wt/wt and 26% wt/wt, respectively. No interaction was observed between drug and excipient. Multiple regression analysis was carried out, and response surfaces were obtained. A curvilinear relationship was observed between percentage of desired yield and the amount of cetyl alcohol. Linear decrease in crushing strength was observed with increase in the amount of cetyl alcohol. Drug released from the beads followed zero order kinetics. Burst release was shown to a greater extent in beads containing a lower amount of cetyl alcohol. Response surfaces of time required for certain percentage of drug (tD%) showed that after critical concentration of about 20% of cetyl alcohol (400 mg/batch), no significant release retardant effect was observed.

Keywords: flurbiprofen, melt solidification technique, factorial design, cetyl alcohol, response surface methodology, zero order kinetics

Full Text

The Full Text of this article is available as a PDF (793K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Bodmeier R, Wang J, Bhagwatwar H. Process and formulation variables in the preparation of wax microparticles by melt dispersion technique for water insoluble drugs. J Microcapsul. 1992;9:89–98. doi: 10.3109/02652049209021226. [PubMed] [Cross Ref]
2. Schaefer T, Holm P, Kristensen HG. Melt granulation in a laboratory scale high shear mixer. Drug Dev Ind Pharm. 1990;16:1249–1277. doi: 10.3109/03639049009115960. [Cross Ref]
3. Nadia P, Beatrice A, Cristina C, Lorenzo R. Preparation and characterisation of iburprofen-poloxamer 188 granules obtained by melt granulation. Eur J Pharm Sci. 2002;15:71–78. doi: 10.1016/S0928-0987(01)00210-X. [PubMed] [Cross Ref]
4. Gokonda SR, Hileman GA, Upadrastha SM. Development of matrix controlled release beads by extrusion-spheronozation techniques technology using a statistical screening design. Drug Dev Ind Pharm. 1994;20:279–292. doi: 10.3109/03639049409050183. [Cross Ref]
5. Kim JW, Ulrich J. Prediction of degree of deformation and crystallization time of molten droplets in pastillations process. Int J Pharm. 2003;257:205–215. doi: 10.1016/S0378-5173(03)00141-8. [PubMed] [Cross Ref]
6. Barthelemy P, Laforet JP, Farah N, Joachim J. Compritol 888 ATO: an innovative hot melt coating agent for prolonged drug formulations. Eur J Pharm Biopharm. 1999;47:87–90. doi: 10.1016/S0939-6411(98)00088-5. [PubMed] [Cross Ref]
7. Adeyeye CM, Price JC. Development and evaluation of sustained release ibuprofen-wax microspheres I: effect of formulation variables on physical characteristics. Pharm Res. 1991;8:1377–1383. doi: 10.1023/A:1015845022112. [PubMed] [Cross Ref]
8. Adeyeye CM, Price JC. Development and evaluation of sustained release ibuprofen-wax microspheres II: in vitro dissolution studies. Pharm Res. 1994;11:575–579. doi: 10.1023/A:1018931002991. [PubMed] [Cross Ref]
9. Paradkar AR, Maheshwari M, Ketkar AR, Chauhan B. Preparation and evaluation of ibuprofen beads by melt solidification techniques. Int J Pharm. 2003;255:33–42. doi: 10.1016/S0378-5173(03)00081-4. [PubMed] [Cross Ref]
10. Maheshwari M, Ketkar AR, Chauhan B, Patil VB, Paradkar AR. Preparation and characterization of ibuprofen-cetyl alcohol beads by melt solidification technique: effect of variables. Int J Pharm. 2003;261:57–67. doi: 10.1016/S0378-5173(03)00292-8. [PubMed] [Cross Ref]
11. Gilman AG, Rall TW, Taylor P. Goodman and Gillman's the Pharmacological Basis of Therapeutics. New York, NY: Pergamon Press; 1990.
12. Jarosz PJ, Parrott EJ. Comparison of granule strength and tablet strength. J Pharm Sci. 1983;72:530–535. doi: 10.1002/jps.2600720513. [PubMed] [Cross Ref]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists