title: The "bubble point" for validation of drug release or simulated absorption tests for ointments.
abstract: The aim of the present study was to design a test to ascertain the behaviour and reliability of a membrane used in drug release and simulated absorption tests in order to arrive at useful indications for simulating topical as well as gastro-intestinal absorption. The membrane can be used in two different conditions: a) as a simple porous membrane placed between the ointment and an accepting liquid phase, generally water phase; b) as a membrane soaked in a lipophilic liquid phase to simulate the horny layer between the ointment and accepting water phase. In this study the "bubble point test" was used to test the integrity of the soaking film as well as the membrane, during and after drug release and simulated absorption tests with different types of ointment. In the case of a drug release test from an ointment, the bubble point test may determine the test conditions, that is the ointment applied to either a dry or hydrated membrane. Only the use of a previously hydrated membrane can guarantee constant conditions in the in vitro model. Use of a dry membrane may lead to infiltration of liquid components of the ointment base, thus altering the contact conditions between the two phases of the cutaneous compartment model (lipogel and W/O creams). The use of a hydrated membrane may also lead to interactions between the two phases of the compartment, with osmotic exchanges between the acceptor phase and ointment sample (hydrogel, PEG gel, O/W creams). The hydrated membrane is therefore reliable only for comparison between lipophilic base ointments. In a simulated absorption test, determination of the bubble point makes it possible to ascertain the physical integrity of the lipoid liquid film immobilized by capillary action in the inner microporous structure of the membrane during the test. This condition is essential to maintain a balance between the parameters regulating the diffusion process between the different compartments of the system. The use of a lipoid-soaked membrane makes it possible to avoid interactions between the ointment sample and an aqueous acceptor phase, such as hydrosoluble bases. Since the diffusion across a lipoid film immobilised within a porous membrane depends on the drug release rate from the ointment base, the test allows a contextual evaluation of the release kinetics as well as an indication of the drug absorption possibilities through an in vitro model of the cutaneous compartment.
authors.affiliation: Department of Pharmaceutical Sciences, University of Padova, via F. Marzolo 5, I-35131 Padova, Italy. nicola.realdon@unipd.it
authors.forename: N
authors.initials: N
authors.lastname: Realdon
authors.forename: A
authors.initials: A
authors.lastname: Tagliaboschi
authors.forename: F
authors.initials: F
authors.lastname: Perin
authors.forename: E
authors.initials: E
authors.lastname: Ragazzi
mesh_terms: D000465:Algorithms; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000737:chemistry; D019540:Area Under Curve; D001566:Benzocaine / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D005079:Excipients; D005374:Filtration; D007700:Kinetics; D008567:Membranes, Artificial; D008956:Models, Chemical; D009823:Ointment Bases; D009824:Ointments / Q000592:standards*; D016062:Porosity; D012869:Skin Absorption
chemical_list: D000779:Anesthetics, Local; D005079:Excipients; D008567:Membranes, Artificial; D009823:Ointment Bases; D009824:Ointments; D001566:Benzocaine