Assessment of Finite and Infinite Dose In Vitro Experiments in Transdermal Drug Delivery

Abstract

Penetration, usually with finite dosing, provides data about the total active amount in the skin and permeation, being the most used methodology, usually with infinite dosing, leads to data about pharmacokinetic parameters. The main objective of this work is to assess if results from permeation, most of them at finite dose, may be equivalent to those from penetration usually at infinite dose. The transdermal behavior of four drugs with different physicochemical properties (diclofenac sodium, ibuprofen, lidocaine, and caffeine) was studied using penetration/finite and kinetic permeation/infinite dose systems using vertical Franz diffusion cells to determine the relationships between permeation and penetration profiles. Good correlation of these two in vitro assays is difficult to find; the influence of their dosage and the proportion of different ionized/unionized compounds due to the pH of the skin layers was demonstrated. Finite and infinite dose regimens have different applications in transdermal delivery. Each approach presents its own advantages and challenges. Pharmaceutical industries are not always clear about the method and the dose to use to determine transdermal drug delivery. Being aware that this study presents results for four actives with different physicochemical properties, it can be concluded that the permeation/infinite results could not be always extrapolated to those of penetration/finite. Differences in hydrophilicity and ionization of drugs can significantly influence the lack of equivalence between the two methodologies. Further investigations in this field are still needed to study the correlation of the two methodologies and the main properties of the drugs that should be taken into account.

Formulation Development for Transdermal Delivery of Raloxifene, a Chemoprophylactic Agent against Breast Cancer

“…Thus, applying these gels as a typical semi-solid formulation (finite dose) may not be a practical strategy to achieve the desired therapeutic concentration. On the other hand, the infinite dose showed significantly higher delivery, which can be due to the occlusive effect observed in the case of the large volumes applied [ 39 ]. Infinite dosing is generally recommended for pharmacokinetics evaluation, whereas finite dosing is important to determine drug distribution in the skin [ 39 ].…”

“…On the other hand, the infinite dose showed significantly higher delivery, which can be due to the occlusive effect observed in the case of the large volumes applied [ 39 ]. Infinite dosing is generally recommended for pharmacokinetics evaluation, whereas finite dosing is important to determine drug distribution in the skin [ 39 ]. This study indicates that an infinite dose of these gels can be used for sustained systemic delivery of RLX over 7 days.…”

Preparation, Characterization and Permeation Study of Topical Gel Loaded with Transfersomes Containing Asiatic Acid

“…When it is necessary to know the real amount of drug absorbed into the different layers of the skin, the finite doses are required. However, to compare the penetration of various formulations through the skin, infinite dosage is chosen to evaluate the amount of drug permeated in the receptor fluid [ 67 , 68 , 69 , 70 ]. Therefore, in the present study, 1 g of tested gels as an infinite dose regimen was used for the in vitro permeation study to ensure that detectable amounts of drug in the receptor fluid will be obtained.…”

Non-invasive evaluation of transdermal drug delivery using 3-D transient triplet differential (TTD) photoacoustic imaging

“…Typically, the efficiency of TDD systems is evaluated using the Franz diffusion cell, which measures the diffusion of drugs across the skin to a receptor fluid reservoir [11] , [12] . However, it can only quantitatively describe drug permeation rate and the drug distribution in skin can’t be represented.…”