J. Leino et al., DEVELOPMENT OF RECTALLY ADMINISTERED PROLONGED-RELEASE HARD GELATIN CAPSULES USING DIFFERENT POLYMERS AS DILUENTS, STP PHARMA SCIENCES, 7(5), 1997, pp. 348-353
The hard gelatin capsule has recently been shown to provide an alterna
tive dosage form for rectal drug administration. However, it is obviou
s that the pharmaceutical additives used in the capsule have a marked
effect on the biopharmaceutical characteristics of the product. The ai
m of this study was to investigate whether it is possible to develop p
rolonged-release hard gelatin capsules for rectal administration using
hydrophilic polymers, hydroxypropylmethyl cellulose and polycarbophil
as diluents in the capsule. An ibuprofen capsule containing only lact
ose as a diluent was used as the only diluent, adequate prolonged-rele
ase rectal capsules could be prepared with a low viscosity-grade (100
mPa) of hydroxypropylmethyl cellulose. As compared to the lactose-base
d capsule, the t(max) and increased and the C-max decreased, but there
was no change in the AUC value. With a higher viscosity-grade (4000 m
Pa) of hydroxypropylmethyl cellulose, the extent of bioadvailability b
egan to decline. Polycarbophil as the only diluent totally blocked the
absorption of the model drug. When the diluent consisted of 5% polyca
rbophil and 95% lactose, an appropriate prolonged-release ibuprofen ca
psule was once again obtained. Classic pharmacopoeial dissolution test
s poorly predicted the in vivo behaviour of the capsules in man. The p
resent study also confirmed that training in the administration techni
que and use of a glidant are of great importance for adequate dosing o
f hard gelatin capsules via the rectal route.