Effect of drug solubility on in vitro availability rate from suppositorieswith polyethylene glycol excipients

Factors involved in the availability mechanism of different drugs from supp ositories with polyethylene glycol (PEG) excipients were studied using an i n vitro model of the rectal compartment with a porous membrane simulating t he rectal barrier. Different from lipophilic excipients, the drug is releas ed as a consequence of the progressive dissolution of PEG into the intrarec tal aqueous phase. Drug concentration in this small intrarectal phase produ ces the gradient against the large volume of the plasmatic phase. which reg ulates the diffusion rate through the barrier. As with lipophilic excipient s, drug solubility in water was found to be an important factor influencing suppository release rate. Nevertheless, PEG influenced in vitro drug avail ability considerably, by increasing both drug solubility and dissolution ra te. The osmotic effect of PEG in the intrarectal compartment influenced the increase in volume of the aqueous phase. The results, compared with those obtained from suppositories with a lipophilic excipient, show a higher diss olution rate from PEG excipient, but a higher diffusion rate across the bar rier did not always correspond. Drugs less soluble in water showed a greate r availability from PEG suppositories. On the contrary the more soluble dru gs were less available.