Oral Formulation Strategies for Poorly Soluble and Permeability-Limited Drugs

Oral drug delivery remains the preferred route of administration because it is convenient, patient-friendly, scalable, and generally cost-effective. However, many small-molecule drug candidates show poor aqueous solubility, limited intestinal permeability, chemical or physical instability, food effects, or variable gastrointestinal absorption. These properties can prevent adequate and reproducible systemic exposure and complicate product development. Advances in materials science, gastrointestinal biopharmaceutics, analytical methods, and pharmaceutical manufacturing now allow formulation scientists to address these barriers through approaches such as amorphous solid dispersions, cocrystals, lipid-based systems, particle engineering, and permeability-enhancing strategies. Translating these approaches into robust oral products requires a clear understanding of drug-excipient interactions, gastrointestinal conditions, in vitro performance, in vivo relevance, manufacturability, stability, and scale-up.This Research Topic aims to connect the design of enabling formulations for poorly soluble and permeability-limited small molecules with their biopharmaceutical evaluation and translation into scalable oral drug products. It will examine how formulation strategies can improve dissolution, maintain supersaturation, enhance intestinal absorption, reduce variability, protect unstable compounds, and support clinically relevant exposure. The collection will bring together research spanning formulation selection, physicochemical characterization, gastrointestinal performance, pharmacokinetics, modelling, and manufacturing. Particular emphasis will be placed on studies that explain why a formulation works and link material or process attributes to oral product performance. By integrating academic and industrial perspectives, the Topic seeks to identify practical and mechanistically informed approaches for selecting, optimizing, and scaling oral formulations for challenging small-molecule drugs.We welcome articles addressing small-molecule oral formulations that address poor solubility, limited permeability, variable absorption, or stability challenges. Submissions should connect formulation design with oral absorption, pharmacokinetics, stability, manufacturability, or clinical performance. Macromolecule delivery, general polymeric nanocarrier design, and non-oral platforms are outside scope unless they address a specific oral absorption or product-development question.Subthemes include, but are not limited to:- Amorphous solid dispersions and supersaturation management- Cocrystals, salts, cyclodextrin complexes, and particle engineering- Lipid-based and self-emulsifying drug-delivery systems- Precipitation inhibitors, permeability enhancers, and enabling excipients- Strategies for drugs with combined solubility and permeability limitations- Gastrointestinal biopharmaceutics, including food effects- Biorelevant dissolution, permeation, and absorption testing- In vitro–in vivo relationships, preclinical pharmacokinetics, and physiologically based pharmacokinetic modelling Topic editors: DINESH NYAVANANDI, Madhur Kulkarni Source: https://www.frontiersin.org/research-topics/83923/oral-formulation-strategies-for-poorly-soluble-and-permeability-limited-drugs