Effects of surfactant characteristics on drug availability from suppositories.
The addition of surfactants to suppository formulations is referred to in the scientific literature, but their effects on drug availability remain uncertain. Surfactants are reported to improve drug dispersion into hard fatty excipients, to increase the spreading of the melted suppository on the rectal mucosa leading to a greater contact surface, to reduce the viscosity of the molten mass and to reduce the pathway of drug particles to the interface. In the present study a systematic investigation based on tensiometric and rheological methods was carried out to evaluate the effects of nonionic surfactants with different HLBs (hydrophilic-lipophilic-balance) on drug availability and to clarify the possible mechanisms involved in the release process. The relationship between the melted suppositories and a membrane simulating the rectal barrier were investigated in the course of the in vitro release test by measuring their energy characteristics. At the same time, the potential influences of such interactions on drug release were investigated in suppositories formulated with different kinds and concentrations of surfactant additives. Drug availability was influenced not only by the interaction between the suppository and the rectal membrane but also by the interaction between surfactant, lipophilic excipient and suspended drug particles. Such interactions appear to greatly influence drug release from suppositories, which, in turn, is the main parameter determining drug availability.
Realdon
N
N
Department of Pharmaceutical Sciences, University of Padova, Italy. nicola.realdon@unipd.it
Dal Zotto
M
M
Morpurgo
M
M
Franceschinis
E
E
D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D005079:Excipients; D006601:Hexoses; D008567:Membranes, Artificial; D011136:Polysorbates; D012212:Rheology; D012995:Solubility; D013488:Suppositories / Q000737:chemistry*; D013500:Surface Tension; D013501:Surface-Active Agents / Q000737:chemistry*; D014783:Viscosity
D018712:Analgesics, Non-Narcotic; D005079:Excipients; D006601:Hexoses; D008567:Membranes, Artificial; D011136:Polysorbates; D013488:Suppositories; D013501:Surface-Active Agents; D000082:Acetaminophen; C014822:sorbitan monolaurate; C009298:sorbitan monostearate