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