No abstract

Vitamin C (ascorbic acid) is a naturally occurring, powerful anti-oxidant with the potential to deliver numerous benefits to the skin when applied topically. However, topical use of this compound is currently restricted by an instability in traditional formulations and the delivery and eventual fate of precursor compounds has been largely unexplored. Time of flight secondary ion mass spectrometry (ToF-SIMS) is an emerging technique in the field of skin research and offers detailed chemical analysis, with high mass and spatial resolution, as well as profiling capabilities that allow analysis as a function of sample depth. This work demonstrates the successful use of ToF-SIMS to obtain, in situ, accurate 3D permeation profiles of both ascorbic acid and a popular precursor, ascorbyl glucoside, from ex vivo porcine skin. The significant permeation enhancing effect of a supramolecular gel formulation, produced from an amphiphilic gemini imidazolium-based surfactant, was also demonstrated for both compounds. Using ToF-SIMS, it was also possible to detect and track the breakdown of ascorbyl glucoside into ascorbic acid, elucidating the ability of the hydrogel formulation to preserve this important conversion until the targeted epidermal layer has been reached. This work demonstrates the potential of ToF-SIMS to provide 3D permeation profiles collected in situ from ex vivo tissue samples, offering detailed analysis on compound localisation and degradation. This type of analysis has significant advantages in the area of skin permeation, but can also be readily translated to other tissue types.

No abstract

The oral route is the most common and practical means of drug administration, particularly from a patient’s perspective. However, the pharmacokinetic profile of oral drugs depends on the rate of drug absorption through the intestinal wall before entering the systemic circulation. However, the enteric epithelium represents one of the major limiting steps for drug absorption, due to the presence of efflux transporters on the intestinal membrane, mucous layer, enzymatic degradation, and the existence of tight junctions along the intestinal linings. These challenges are more noticeable for hydrophilic drugs, high molecular weight drugs, and drugs that are substrates of the efflux transporters. Another challenge faced by oral drug delivery is the presence of first-pass hepatic metabolism that can result in reduced drug bioavailability. Over the years, a wide range of compounds have been investigated for their permeation-enhancing effect in order to circumvent these challenges. There is also a growing interest in developing nanocarrier-based formulation strategies to enhance the drug absorption. Therefore, this review aims to provide an overview of the challenges faced by oral drug delivery and selected strategies to enhance the oral drug absorption, including the application of absorption enhancers and nanocarrier-based formulations based on in vitro, in vivo, and in situ studies.