ABSTRACT
The incorporation of a drug in a carrier by either solvent evaporation or melt embedding may result in either a solid solution or a solid suspension of the active ingredient within the carrier material. Consequently, solid dispersions [SD] of rofecoxib containing varying concentrations of either polyethylene glycol [PEG] 35000 or urea were prepared in an attempt to improve the solubility and dissolution rate of rofecoxib. Moreover, the influence of the PEG chain length on the dissolution characteristics of the drug was also investigated. The physical characteristics of rofecoxib, physical mixtures iPM] and SDs were investigated by a variety of analytical methods including fourier transform infrarrd spectroscopy [FTIR], powder X-ray diffraction [XRD] and differential scanning calorimetry [DSC]. For testing the applicability to formulate in a solid dosage form, 1:9 rofecoxib SD with PEG 3500C was formulated in the form of hard gelatin capsules. The obtained results showed that the dissolution rates of PMs were higher than that of pure drug. However, SDs exhibited higher dissolution rates than those of PMs. compared to urea, PEG 35000 had the most influential effect on enhancing the rate and extent of rofecoxib dissolution from their systems. The drug to carrier ratio in the prepared SDs was one of the main influences on the performance of a SD. In addition, it was found at the fusion method was more efficient than the solvent method in improving the dissolution of the drug from the investigated SDs. Regarding the effect of the pH of the dissolution medium, it was found that the pH change had negligible effect on the release of the drug from its dispersions with PEG 35000. The FTIR spectra revealed an interaction between rofecoxib and PEG 35000. Besides, the amorphous form of rofecoxib found in powdered SDs, as demonstrated by XRD and DSC, may explain the better dissolution rate from SD
ABSTRACT
Suppositories of one gram each containing 50mg, tramadol HCI were prepared using different bases, namely cacao butter, witepsol HI5, witepsol E76, suppocire D, emulcire, PEG [three different formulations] and glycerogelatin. The suppositories were stored for six months at room temperature, in a refrigerator and in an incubator at 37.5 +/- 1 degree C. Quality control for both fresh and stored suppositories was investigated. It was found that several signs of aging have occurred during storage conditions. The most stable formulation was witepsol H15 stored in a refrigerator. In-vitro release of tramadol HCI from fresh suppositories was studied in Sorensen's phosphate buffer pH7.4 at 37 +/- 0.5 degree C. The release of tramadol HCI from different suppository bases could be arranged as follows: Witepsol HI5 > PEG formula 1 > Cacao butter >PEG formula 3 > PEG formula 2 > glycerogelatin > suppocire D >emulcire > witepsol E76. It is obvious that the release rate was most rapid from oleaginous bases due to the hydrophilic nature of tramadol HCI. In-vitro release of stored tramadol HCI suppositories was studied in Sorensen's phosphate buffer pH 7.4 at 37 +/- 0.5 degree C. The release of tramadol HCI from different bases was affected greatly by the stability of the bases. It was obvious that witepsol H15 base stored in refrigerator for six months gave the most proper release, formulations that showed the highest release of tramadol HCI in-vitro were selected for in vivo study namely: witepsol HIS. cacao butter and PEG I bases. The drug plasma levels were compared to those obtained after oral administration of the same dose of tramadol hydrochloride. The Cmax of tramadol HCI was 920 +/- 77ng/ml, 639 +/- 51ng/ml and 415 +/- 5.3 ng/ml one hour after the administration of oral solution, witepsol HI5 and cacao butter suppositories, respectively while in the case of PEG 1 it was 370 +/- 24ng/ml after half an hour of administration