Characteristics of rofecoxib-polyethylene glycol 4000 solid dispersions and tablets based on solid dispersions.
The aim of this work was to report the properties of rofecoxib-PEG 4000 solid dispersions and tablets prepared using rofecoxib solid dispersions. Rofecoxib is a poorly water soluble nonsteroidal anti-inflammatory drug with a poor dissolution profile. This work investigated the possibility of developing rofecoxib tablets, allowing fast, reproducible, and complete rofecoxib dissolution, by using rofecoxib solid dispersion in polyethylene glycol (PEG) 4000. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to characterize the solid state of solid dispersions. The effect of PEG 4000 concentration on the dissolution rate of rofecoxib from its solid dispersions was investigated. The dissolution rate of rofecoxib from its solid dispersions increased with an increasing amount of PEG 4000. The extent of dissolution rate enhancement was estimated by calculating the mean dissolution time (MDT) values. The MDT of rofecoxib decreased significantly after preparing its solid dispersions with PEG 4000. The FTIR spectroscopic studies showed the stability of rofecoxib and absence of well-defined rofecoxib-PEG 4000 interaction. The DSC and XRD studies indicated the amorphous state of rofecoxib in solid dispersions of rofecoxib with PEG 4000. SEM pictures showed the formation of effective solid dispersions of rofecoxib with PEG 4000 since well-defined change in the surface nature of rofecoxib and solid dispersions were observed. Solid dispersions formulation with highest drug dissolution rate (rofecoxib: PEG 4000 1:10 ratio) was used for the preparation of solid dispersion-based rofecoxib tablets by the direct compression method. Solid dispersion-based rofecoxib tablets obtained by direct compression, with a hardness of 8.1 Kp exhibited rapid drug dissolution and produced quick anti-inflammatory activity when compared to conventional tablets containing pure rofecoxib at the same drug dosage. This indicated that the improved dissolution rate and quick anti-inflammatory activity of rofecoxib can be obtained from its solid dispersion-based oral tablets.
Liu
Chengsheng
C
Life Science College, Ocean University of China, Qingdao, China.
Desai
Kashappa Goud
KG
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000627:therapeutic use; D002152:Calorimetry, Differential Scanning; D004487:Edema / Q000188:drug therapy; D005260:Female; D007700:Kinetics; D007783:Lactones / Q000737:chemistry* / Q000627:therapeutic use; D008297:Male; D008855:Microscopy, Electron, Scanning; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013450:Sulfones / Q000737:chemistry* / Q000627:therapeutic use; D013607:Tablets; D013997:Time Factors; D014961:X-Ray Diffraction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007783:Lactones; D013450:Sulfones; D013607:Tablets; C116926:rofecoxib; D011092:Polyethylene Glycols