In vitro methods for the evaluation of drug availability from suppositories: comparison between biological and artificial membranes.
Drug availability from suppositories is currently evaluated in vitro by means of a model consisting of a dialysis tube (porous membrane) or isolated biological membrane (animal rectum). We propose a new alternative in vitro method to determine drug availability from suppositories consisting of an artificial membrane soaked with n-octanol, coupled with a filter paper sheet soaked with phosphate buffer. This method provides for an integrated hydro-lipophilic simulation of the biological membrane, including the mucus layer adhering to the rectal mucosa. By simply using the porous membrane, the amount of drug released varied directly according to its solubility for formulations with lipophilic excipients. For formulations with hydrophilic excipients, drugs with low/intermediate solubility in water showed increased availability in comparison to lipophilic excipients. The in vitro rat rectum model provided overall results that were similar to those obtained with the porous membrane method, although the percentage values of AUC were lower. The new model of in vitro simulated absorption produced a degree of drug availability that was lower in comparison to both previous methods. However, the simulated model appeared to give a pattern of drug availability closer to that of the model of in vitro rat rectum. The new in vitro artificial model thus appears to be useful in suppositories preformulation studies, allowing for an estimate of drug availability and the choice of the most adequate excipient.
Realdon
N
N
Department of Pharmaceutical Sciences, University of Padova, Italy. nicola.realdon@unipd.it
Ragazzi
Eug
E
Morpurgo
M
M
Ragazzi
Enr
E
D000465:Algorithms; D000628:Aminophylline / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004058:Diffusion; D005079:Excipients; D008297:Male; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism*; D014677:Pharmaceutical Vehicles; D011092:Polyethylene Glycols; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013488:Suppositories / Q000737:chemistry; D014280:Triglycerides
D005079:Excipients; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D014677:Pharmaceutical Vehicles; D013488:Suppositories; D014280:Triglycerides; C009683:witepsol; D000628:Aminophylline; D011092:Polyethylene Glycols