INFLUENCE OF AMOUNT OF HARD FAT IN SUPPOSITORIES ON THE IN-VITRO RELEASE RATE AND BIOAVAILABILITY OF PARACETAMOL .2. A COMPARISON BETWEEN 3COMPOSITIONS AND A RECTAL SOLUTION
K. Gjellan et C. Graffner, INFLUENCE OF AMOUNT OF HARD FAT IN SUPPOSITORIES ON THE IN-VITRO RELEASE RATE AND BIOAVAILABILITY OF PARACETAMOL .2. A COMPARISON BETWEEN 3COMPOSITIONS AND A RECTAL SOLUTION, International journal of pharmaceutics, 104(3), 1994, pp. 215-226
The flow-through cell has been used to investigate whether it is possi
ble to discover any relationship between the in vitro dissolution rate
of paracetamol from suppositories and the plasma concentrations reach
ed after administration to eight healthy volunteers. A rectal solution
was used as a reference. Three suppository compositions were varied w
ith regard to amount of drug substance in relation to total suppositor
y weight and size. The in vivo study was designed to explore the use o
f statistical moment analysis and convolution/deconvolution in the ass
ociation of in vivo data and in vitro dissolution results. An increase
in both rate and extent of bioavailability was observed when decreasi
ng the fraction and increasing the size, but it was not explained to w
hat degree each of these factors contributed. The flow-through method
using a 22.6 mm cell, primarily developed for oral dosage forms, was f
ound to produce dissolution profiles which associated well with the pl
asma concentration profiles obtained both when a statistical moment an
alysis and the convolution method was applied. The most optimal flow r
ate studied was 28 ml/min which reflected the in vivo situation better
than a lower or a higher flow rate.