Evaluation of sustained release suppositories prepared with fatty base including solid fats with high melting points.
To prepare the sustained release suppositories, solid fats such as polyglycerol ester of fatty acids (PGEFs) or beeswax were utilized with a fatty suppository base, Witepsol H15. PGEFs such as decaglycerol heptabehenate (HB750) and hexaglycerol pentastearate (PS500), and beeswax have relatively high melting points. The addition of PGEFs or beeswax to Witepsol H15 increased the apparent viscosity of suppository bases at 37 degrees C without any large change in the melting point of Witepsol H15. Moreover, the apparent viscosity of a mixed base with HB750, PS500 or beeswax at 37 degrees C was significantly correlated with the amount of each solid fat in a mixed base. The release of acetaminophen (AAP), a model drug, from suppositories was delayed by HB750, PS500 or beeswax, and an excellent correlation was observed between the apparent viscosity of these mixed bases and Higuchi's rate constants in each mixed base suppository, suggesting that these solid fats could regulate the drug release from the mixed base suppositories by changing their viscosity. In the in vivo absorption study in rats, several suppositories made from Witepsol H15-HB750 or Witepsol H15-beeswax mixed bases prolonged the rectal absorption of AAP without reducing AUC. In conclusion, by using solid fats such as HB750 and beeswax with relatively high melting points, it is possible to control the rate of drug release from fatty base suppositories for maintaining the plasma concentration of drugs for longer time periods.
Takatori
Toshihito
T
Pharmaceutical Research and Technology Center, Dainippon Pharmaceutical Co. Ltd., 1-5-51 Ebie, Fukushima-ku, Osaka 553-0001, Japan.
Shimono
Norihito
N
Higaki
Kazutaka
K
Kimura
Toshikiro
T
D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D005990:Glycerol / Q000031:analogs & derivatives* / Q000737:chemistry*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013488:Suppositories / Q000737:chemistry*; D044366:Transition Temperature; D014280:Triglycerides / Q000737:chemistry*; D014783:Viscosity; D014885:Waxes / Q000737:chemistry*
D003692:Delayed-Action Preparations; D013488:Suppositories; D014280:Triglycerides; D014885:Waxes; C009683:witepsol; C038228:beeswax; D000082:Acetaminophen; D005990:Glycerol