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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.

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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.

Lipophilic compounds constitute a majority of therapeutics in the pipeline of drug discovery. Despite possessing enhanced efficacy and permeability, some of these drugs suffer poor solubility necessitating the need of a suitable drug delivery system. Nanoemulsion is a drug delivery system that provides enhanced solubility for poorly soluble drugs in an attempt to improve the oral bioavailability. The purpose of this study is to develop a nanoemulsion system using ibuprofen as a model drug in order to investigate the potential of this colloidal system to enhance the absorption of poorly water-soluble drugs. Ibuprofen loaded-nanoemulsion with different drug concentrations (1.5, 3 and 6% w/w) were formulated from olive oil, sucrose ester L-1695 and glycerol using D-phase emulsification technique. A pseudoternary phase diagram was utilised to identify the optimal excipient composition to formulate the nanoemulsion system. In vitro diffusion chamber studies using rodent intestinal linings highlighted improved absorption profile when ibuprofen was delivered as nanoemulsion in comparison to microemulsions and drug-in-oil systems. This was further corroborated by in vivo studies using rat model that highlighted a two-fold increase in ibuprofen absorption when the drug was administered as a nanoemulsion relative to drug-in-oil system. On the other hand, when ibuprofen was administered as microemulsions, only a 1.5-fold increase in absorption was observed relative to drug-in-oil system. Thus, this study highlights the potential of using nanoemulsion as a drug delivery system to enhance the oral bioavailability of hydrophobic drugs.

Background: In this study, four nanoparticle formulations (F1 to F4) comprising varying ratios of alginate, Pluronic F-68 and calcium chloride with a constant amount of insulin and chitosan as a coating material were prepared using polyelectrolyte complexation and ionotropic gelation methods to protect insulin against enzymatic degradation. Methods: This study describes the formulation design, optimisation, characterisation and evaluation of insulin concentration via oral delivery in rats. A reversed-phase high-performance liquid chromatography (HPLC) method was developed and validated to quantify insulin concentration in rat plasma. The proposed method produced a linear response over the concentration range of 0.39 to 50 µg/ml. Results: In vitro release study showed that dissolution of insulin in simulated gastric juice of pH 1.2 was prevented by alginate core and chitosan coating but rapidly released in simulated intestinal fluid (pH 6.8). Additionally, Formulation 3 (F3) has a particle size of 340.40 ± 2.39 nm with narrow uniformity exhibiting encapsulation efficiency (EE) of 72.78 ± 1.25 % produced highest absorption profile of insulin with a bioavailability of 40.23 ±1.29% and reduced blood glucose after its oral administration in rats. Conclusion: In conclusion, insulin oral delivery system containing alginate and chitosan as a coating material has the ability to protect the insulin from enzymatic degradation thus enhance its absorption in the intestine. However, more work should be done for instance to involve human study to materialise this delivery system for human use.

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