Particle Engineering Steps Into the Spotlight as Drug Makers Chase Hard-to-Formulate Molecules

Some of the most promising drug molecules discovered in modern laboratories never reach patients, and the reason is rarely a failure of biology. It is a failure of physics. A compound may bind its target with exquisite precision in a test tube, yet dissolve so poorly in water that the human body absorbs almost none of it. Others crumble under humidity, switch crystal forms on the shelf, or refuse to survive the journey through manufacturing equipment without degrading. The discipline that confronts these problems head-on, particle engineering combined with formulation science, is now being given a dedicated platform, with the Journal of Pharmaceutical Investigation announcing a special issue devoted to translational advances in pharmaceutical dosage form development, scheduled for publication in January 2027.

The special issue, tentatively titled Translational Advances in Pharmaceutical Dosage Form Development Based on Particle Engineering and Formulation Science, is being assembled by a trio of guest editors drawn from leading South Korean research institutions: Sung-Joo Hwang of Yonsei University, Min-Soo Kim of Pusan National University, and Heejun Park of Duksung Women’s University. Researchers have until June 30, 2026 to submit their work, and the scope of the call reflects how dramatically the field has broadened. The editors are soliciting contributions that span particle engineering approaches for enhancing solubility, stability, and bioavailability; advanced formulation strategies for oral, injectable, inhalable, transdermal, and other dosage forms; solid-state characterization and control; translational formulation science and the scale-up of drug products; emerging manufacturing technologies; and applications of Quality by Design and Process Analytical Technology in formulation and manufacturing.

To understand why this collection matters, it helps to grasp the scale of the solubility problem. Estimates across the pharmaceutical industry consistently suggest that a large proportion of newly discovered chemical entities, and in some analyses as many as seventy to ninety percent of candidates in development pipelines, fall into the poorly water-soluble category. These are molecules built to slip through cell membranes and hit intracellular targets, which means they are often hydrophobic by design. When a pill containing such a compound is swallowed, the active ingredient may pass through the gastrointestinal tract largely undissolved, never entering the bloodstream in therapeutic quantities. Particle engineering attacks the problem at its physical root, typically by dramatically increasing the surface area available for dissolution.

The best-known example is nanonization, in which drug crystals are milled or precipitated down to particle sizes in the range of a few hundred nanometers. Because dissolution rate scales with surface area, and surface area explodes as particles shrink, nanocrystal suspensions can achieve absorption profiles that coarse micronized powders never could. Several nanocrystal-based products have already reached the market, validating the approach commercially as well as scientifically. But size reduction is only one lever. Amorphous solid dispersion, in which a drug is molecularly dispersed in a polymeric carrier and locked in a higher-energy, non-crystalline state, offers apparent solubility gains that can exceed those of crystalline nanosuspensions, at the cost of a persistent risk: the amorphous material may recrystallize during storage, wiping out the solubility advantage and potentially altering the dose the patient actually receives.

That risk is where solid-state characterization and control, another theme of the special issue, becomes indispensable. Polymorphism, the ability of a single molecule to pack into multiple distinct crystal lattices, is a notorious source of formulation failure. Different polymorphs of the same compound can differ in solubility, melting point, mechanical behavior, and stability, and a thermodynamically stable form may slowly convert a more soluble metastable form into itself during months of storage. Regulators worldwide now require developers to identify, characterize, and control the solid form of their active ingredients, because a silent phase transition can change both efficacy and safety. Techniques such as powder X-ray diffraction, differential scanning calorimetry, dynamic vapor sorption, and solid-state nuclear magnetic resonance form the analytical backbone of this work, and increasingly they are paired with computational prediction to screen candidate forms before a single gram of material is synthesized.

The guest editors’ emphasis on translational science and scale-up signals a second, equally important dimension of the field. A formulation that performs beautifully in a laboratory beaker can fail catastrophically when scaled to industrial production. Wet milling dynamics change with vessel geometry; spray drying droplet evaporation behaves differently at high throughput; hot-melt extrusion screw configurations must be redesigned for continuous industrial lines. Ensuring that the product manufactured in ton lots is identical to the one validated in clinical trials is one of the hardest problems in pharmaceutical engineering, and it is precisely the boundary the special issue aims to interrogate. Translational formulation science, as the editors frame it, is the bridge between discovery-stage proof of concept and the reproducible, compliant, economically viable manufacture of real drug products.

Framing that bridge are two regulatory and engineering philosophies that have reshaped the industry over the past two decades: Quality by Design, known as QbD, and Process Analytical Technology, or PAT. Quality by Design inverts the traditional approach to manufacturing control. Instead of testing finished batches and rejecting failures, developers systematically identify the parameters that genuinely affect product quality, called critical material attributes and critical process parameters, then build a design space within which those parameters can vary without compromising the product. Process Analytical Technology supplies the eyes: inline and at-line sensors, including near-infrared spectroscopy, Raman spectroscopy, and laser diffraction, that monitor critical attributes in real time as the process runs. Together they enable continuous manufacturing, a paradigm in which powder flows uninterruptedly from blending through granulation, drying, compression, and coating, replacing the batch-based stop-and-start model that has dominated pharmaceutical production for a century.

The scope of dosage forms covered in the call also reflects how delivery science has fragmented into specialized sub-disciplines, each with its own physics. Inhaled formulations demand aerodynamic particle sizes tightly clustered around one to five micrometers, small enough to reach the deep lung yet large enough to avoid exhalation, and they must remain stable in dry powder blisters or propellant-driven metered-dose inhalers. Injectable formulations face the strictest sterility and tolerability constraints, with particle size limits for intravenous products and osmolality and pH windows for tolerability. Transdermal systems must push molecules through the skin’s lipid barrier, motivating chemical enhancers, microneedle arrays, and adhesive matrix engineering. Oral advanced delivery systems, from gastroretentive tablets to lipid-based self-emulsifying systems, each solve a different slice of the absorption problem. A single special issue that gathers work across all of these routes is a statement about convergence: the same particle-level principles govern them all.

The timing is significant for a field under pressure. The industry’s pipeline is increasingly populated by poorly soluble small molecules, complex biologics, and emerging modalities such as peptide and oligonucleotide therapeutics, all of which strain conventional formulation toolkits. At the same time, regulators are pushing manufacturers toward continuous processes and real-time release testing, while supply chain vulnerabilities exposed in recent years have intensified interest in domestic, flexible, and automated production. Advances in machine learning are beginning to touch formulation development itself, with models trained on historical datasets predicting excipient compatibility, crystal form stability, and process outcomes before experiments begin. The papers the guest editors hope to attract will sit at the intersection of these currents, documenting not just laboratory innovations but their journey toward commercial reality.

For researchers in pharmaceutics, chemical engineering, and materials science, the June 30, 2026 deadline marks an opportunity to contribute to a snapshot of where dosage form science stands as it enters a decade of rapid change. For the broader scientific readership, the special issue promises a concentrated look at the unglamorous but decisive engineering that determines whether a brilliant molecule becomes a medicine. The gap between a potent compound and a shelf-stable, manufacturable, absorbable drug product is wide, and it is crossed by particle engineers and formulation scientists one crystal, one polymer, one process parameter at a time. The Journal of Pharmaceutical Investigation’s January 2027 issue will chronicle the newest crossings of that bridge.

Subject of Research: A special issue of the Journal of Pharmaceutical Investigation on translational advances in pharmaceutical dosage form development based on particle engineering and formulation science.

Article Title: Special Issue: Translational Advances in Pharmaceutical Dosage Form Development Based on Particle Engineering and Formulation Science

Article References: Special Issue: Translational Advances in Pharmaceutical Dosage Form Development Based on Particle Engineering and Formulation Science. (n.d.). Original publication

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Keywords: particle engineering, formulation science, drug delivery, bioavailability, solubility enhancement, solid-state characterization, Quality by Design, process analytical technology, pharmaceutical manufacturing, dosage form development, scale-up, Journal of Pharmaceutical Investigation