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

Abstract

Factors involved in the availability mechanism of different drugs from suppositories with polyethylene glycol (PEG) excipients were studied using an in vitro model of the rectal compartment with a porous membrane simulating the rectal barrier. Different from lipophilic excipients, the drug is released as a consequence of the progressive dissolution of PEG into the intrarectal aqueous phase. Drug concentration in this small intrarectal phase produces the gradient against the large volume of the plasmatic phase, which regulates the diffusion rate through the barrier. As with lipophilic excipients, drug solubility in water was found to be an important factor influencing suppository release rate. Nevertheless, PEG influenced in vitro drug availability considerably, by increasing both drug solubility and dissolution rate. 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 dissolution rate from PEG excipient, but a higher diffusion rate across the barrier did not always correspond. Drugs less soluble in water showed a greater availability from PEG suppositories. On the contrary the more soluble drugs were less available.