Akihiro Tada

Preparation and Evaluation of Hollow-type Suppositories Containing Morphine Hydrochloride Powder or Solution.

The bioavailability of morphine following rectal administration of a hollow-type suppository containing morphine hydrochloride (10mg) in different-added forms was evaluated in patients under general anesthesia during operation. The hollow-type suppositories were prepared using Witepsol H-15, a suppository containing 1% morphine solution (morphine solution, 10mg/ml) or 10% morphine powder diluted with lactose (morphine powder, 100mg) in its cavity. The plasma concentration of morphine and its metabolite, morphine-3-glucuronide (M-3-G), were determined.The mean Cmax and AUC of morphine following rectal administration of the hollow-type suppository containing morphine solution were higher than those obtained from the suppository containing morphine powder, whereas the mean Cmax and AUC of M-3-G were lower than those following administration of the suppository containing morphine powder. The mean AUC ratio. of M-3-G to morphine following administration of the morphine-powder containing suppository was three times larger than that of the suppository containing morphine solution. The hollow type suppository containing morphine solution or powder could thus be useful for the pain control of patients with cancer.These findings suggest that the hollow-type suppository containing morphine powder or solution, which could be adjusted to specific individual dosages, constitutes a useful clinical application for the cancer patient from the viewpoint of enhancing the quality of life.

Application of Hollow Type Suppository to Pharmaceutical Preparation in Hospital. II. Morphine Hydrochloride Suppository.

The evaluation of morphine hydrochloride (MOR) hollow type suppository was carried out by a comparison between rectal and intravenous administrations of MOR in rabbits.The hollow type suppository containing three doses of MOR (1mg/kg, 3mg/kg, 10mg/kg) was used for the rectal administration, and the aqueous solution of MOR (20mg/ml) was used for the intravenous administration (3mg/kg).The serum concentration of MOR was measured with gas chromatography-mass spectrometer by selected ion monitoring method.The absorption constant of MOR from suppository had dose-dependent characteristics, although the peak serum concentrations (1mg/kg;38.8ng/ml, 3mg/kg;61.9ng/ml, 10mg/kg;137.1ng/ml) were reached within 0.4 hours, respectively The area under the curve of serum concentration (AUC) after rectal administration were compaired with the AUC after intravenous administration.The bioavailability (AUCrectl/AUCiv×Doseiv/Doserectal×100) were 90%(1mg/kg), 62%(3mg/kg) and 53%(10mg/kg), respectively.These data suggested that the absorption of MOR had dose-dependency. We used hollow type supporitory of MOR for the pain control of patients with cancer for 6 years.It was required to administer every 4-6 hours for pain control.Thus, it was concluded that MOR hollow type suppository could be useful for the pain control of patients with cancer, especially for the patients who were not able to ingest the oral preparations and the patients who need individual dosage adjustment.