PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
 
AAPS PharmSciTech. 2006 June; 7(2): E167–E175.
Published online 2006 June 16. doi:  10.1208/pt070255
PMCID: PMC2750282

Formulation and optimization of mouth dissolve tablets containing rofecoxib solid dispersion

Abstract

The purpose of the present investigation was to increase the solubility and dissolution rate of rofecoxib by the preparation of its solid dispersion with polyvinyl pyrrolidone K30 (PVP K30) using solvent evaporation method. Drug-polymer interactions were investigated using differential scanning calorimetry (DSC), x-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). For the preparation of rofecoxib mouth dissolve tablets, its 1[ratio]9 solid dispersion with PVP K30 was used with various disintegrants and sublimable materials. In an attempt to construct a statistical model for the prediction of disintegration time and percentage friability, a 32 randomized full and reduced factorial design was used to optimize the influence of the amounts of superdisintegrant and subliming agent. The obtained results showed that dispersion of the drug in the polymer considerably enhanced the dissolution rate. The drug-to-carrier ratio was the controlling factor for dissolution improvement. FTIR spectra revealed no chemical incompatibility between the drug and PVP K30. As indicated from XRD and DSC data, rofecoxib was in the amorphous form, which explains the better dissolution rate of the drug from its solid dispersions. Concerning the optimization study, the multiple regression analysis revealed that an optimum concentration of camphor and a higher percentage of crospovidone are required for obtaining rapidly disintegrating tablets. In conclusion, this investigation demonstrated the potential of experimental design in understanding the effect of the formulation variables on the quality of mouth dissolve tablets containing solid dispersion of a hydrophobic drug.

Keywords: rofecoxib, polyvinyl pyrrolidone K30, solid dispersion, solvent method, mouth dissolve tablets, factorial design

Full Text

The Full Text of this article is available as a PDF (316K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Van den Mooter G, Wuyts M, Blaton N, et al. Physical stabilisation of amorphous ketoconazole in solid dispersions with polyvinylpyrrolidone K25. Eur J Pharm Sci. 2001;12:261–269. doi: 10.1016/S0928-0987(00)00173-1. [PubMed] [Cross Ref]
2. Chiou WL, Riegelman S. Pharmaceutical applications of solid dispersions. J Pharm Sci. 1971;60:1281–1302. doi: 10.1002/jps.2600600902. [PubMed] [Cross Ref]
3. Esnaashari S, Javadzadeh Y, Batchelor HK, Conway BR. The use of microviscometry to study polymer dissolution from solid dispersion drug delivery systems. Int J Pharm. 2005;292:227–230. doi: 10.1016/j.ijpharm.2004.11.036. [PubMed] [Cross Ref]
4. Van den Mooter G, Augustijns P, Blaton N, Kinget R. Physico-chemical characterization of solid dispersions of temazepam with polyethylene glycol 6000 and PVP K30. Int J Pharm. 1998;164:67–80. doi: 10.1016/S0378-5173(97)00401-8. [Cross Ref]
5. Liu C, Desai KG. Characteristics of rofecoxib-polyethylene glycol 4000 solid dispersions and tablets based on solid dispersions. Pharm dev Technol. 2005;10:467–477. doi: 10.1080/10837450500299701. [PubMed] [Cross Ref]
6. Rawat S, Jain SK. Rofecoxib-beta-cyclodextrin inclusion complex for solubility enhancement. Pharmazie. 2003;58:639–641. [PubMed]
7. Masaki K. Orally disintegrating famotidine tablets; Tokyo, Japan: Academy of Pharmaceutical Science and Technology; 1997. pp. 79–84.
8. Corveleyn S, Remon JP. Formulation and production of rapidly disintegrating tablets by lyophilization using hydrochlorothiazide as a model drug. Int J Pharm. 1997;152:215–225. doi: 10.1016/S0378-5173(97)00092-6. [Cross Ref]
99. Roser BJ, Blair J, inventors. Rapidly soluble oral dosage forms, method of making some, and composition thereof. US patent 5 762 961. June 9, 1998.
10. Franco M, Trapani G, Latrofa A, et al. Dissolution properties and anticonvulsant activity of phenytoin-polyethylene glycol 6000 and-polyvinylpyrrolidone K-30 solid dispersions. Int J Pharm. 2001;225:63–73. doi: 10.1016/S0378-5173(01)00751-7. [PubMed] [Cross Ref]
11. Arias MJ, Gins JM, Moyano JR, Rabasco AM. Influence of the preparation method of solid dispersions on their dissolution rate: study of triamterene-D-mannitol system. Int J Pharm. 1995;123:25–31. doi: 10.1016/0378-5173(95)00026-F. [Cross Ref]
12. Higuchi T, Connors KA. Phase-solubility techniques. Adv Anal Chem Instrum. 1965;4:117–210.
13. Sethia S, Squillante E. Solid dispersion of carbamazepine in PVP K30 by conventional solvent evaporation and supercritical methods. Int J Pharm. 2006;272:1–10. doi: 10.1016/j.ijpharm.2003.11.025. [PubMed] [Cross Ref]
14. Gohel M, Patel M, Amin A, Agrawal R, Dave R, Bariya N. Formulation design and optimization of mouth dissolve tablets of nimesulide using vacuum drying technique. AAPS PharmSciTech. 2006;5:E36–E36. [PMC free article] [PubMed]
15. Seedher N, Bhatia S. Solubility enhancement of Cox-2 inhibitors using various solvent systems. AAPS PharmSciTech. 2003;4:E33–E33. doi: 10.1208/pt040333. [PMC free article] [PubMed] [Cross Ref]
16. Abdul-Fattah AM, Bhargava HN. Preparation and in vitro evaluation of solid dispersions of halofantrine. Int J Pharm. 2002;235:17–33. doi: 10.1016/S0378-5173(01)00941-3. [PubMed] [Cross Ref]
17. Torrado S, Torrado J, Cadorniga R. Preparation, dissolution and characterization of albendazole solid dispersions. Int J Pharm. 1996;140:247–250. doi: 10.1016/0378-5173(96)04586-3. [Cross Ref]
18. Torre P, Torrado S, Santiago T. Preparation, dissolution and characterization of praziquantel solid dispersions. Chem Pharm Bull (Tokyo) 1999;47:1629–1633.
19. Edward MR, editor. Remington’s pharmaceutical Science. Easton, PA: Mack Publishing; 2000. pp. 858–893.
20. Koizumi K, Watanabe Y, Morita K, Utoguchi N, Matsumoto M. New method of preparing high-porosity rapidly saliva soluble compressed tablets using mannitol with camphor, a subliming material. Int J Pharm. 1997;152:127–131. doi: 10.1016/S0378-5173(97)04924-7. [Cross Ref]
21. Mendenhall W, Sincich T, editors. A Second Course in Business Statistics: Regression Analysis. 3rd ed. San Francisco, CA: Dellen Publishing Co; 1989. pp. 141–226.

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