Smart pills and drug delivery devices enabling next generation oral dosage forms

Oral dosage forms are the preferred solution for systemic treatment and prevention of disease conditions. However, traditional dosage forms face challenges regarding treatment adherence and delivery of biologics. Oral therapies that require frequent administrations face difficulties with patient compliance. In addition, only a few peptide- and protein-based drugs have been commercialized for oral administration so far, presenting a bioavailability that is generally low. Therefore, research and development on novel formulation strategies for oral drug delivery has bloomed massively in the last decade to overcome these challenges. On the one hand, approaches based on lumen-release of drugs such as 3D-printed capsules and prolonged gastric residence dosage forms have been explored to offer personalized medicine to the patient and reduce frequent dosing of small drug compounds that are currently in the market as powdered tablet or capsules. On the other hand, strategies based on mucus interfacing such as gastrointestinal patches, or even epithelium injections have been investigated in order to enhance the permeability of biologic macromolecules, which are mostly commercialized in the form of subcutaneous injections. Despite the fact that these methods are at an early development stage, promising results have been revealed in terms of personalized medicine and improved bioavailability. In this review, we offer a critical overview of novel ingestible millimeter-sized devices and technologies for oral drug delivery that are currently used in the clinic as well as those that could emerge on the market in a not too distant future.