In the realm of pharmaceutical innovation, a persistent challenge threatens to impede the transition of many novel drugs from the laboratory bench to patient bedsides—a challenge known as the solubility crisis. Approximately 90% of active pharmaceutical ingredients currently under development exhibit poor water solubility, significantly limiting their bioavailability when administered orally, the most widely preferred route of drug delivery. This stark limitation stems from the intrinsic crystalline nature of many drug molecules, which assures stability but hampers dissolution in the aqueous environment of the gastrointestinal tract. To address this bottleneck, a pioneering team of researchers at Tokyo University of Science, led by Professor Takehisa Hanawa, has unveiled a transformative, environmentally conscious method designed to enhance drug solubility through an innovative gas-phase adsorption technique.
This cutting-edge approach tackles the solubility dilemma by substantially modifying the structural state of the drug. Traditionally, drugs are administered in their crystalline form, where molecules are tightly packed in a fixed lattice that resists dissolution. Scientists have long known that disrupting this order to render drugs amorphous—characterized by a disordered molecular arrangement—can dramatically increase dissolution rates. The conventional process to achieve this involves the evaporation/condensation (EV) method, where drugs are first dissolved in potent organic solvents and subsequently adsorbed onto mesoporous silica (MPS), porous materials that help maintain the amorphous form by preventing recrystallization. However, the reliance on toxic organic solvents poses significant safety, environmental, and regulatory challenges, driving the scientific community to seek a greener alternative.
Professor Hanawa and his team have pioneered a novel sealed heating (SH) technique that eliminates the need for organic solvents altogether by exploiting a drug’s sublimation properties—the capacity to transition directly from solid to vapor without passing through a liquid phase. In this method, a powder mixture of the mesoporous silica carrier and the drug is enclosed within a vacuum-sealed container and gently heated. This environment permits the drug to sublime, allowing its vapor-phase molecules to intricately diffuse and adsorb onto the internal cavities of the MPS. This physical adsorption immobilizes the drug molecules in an amorphous state, substantially enhancing their potential to dissolve rapidly upon ingestion.
To validate the efficacy of the SH method, the researchers selected ibuprofen, a widely used anti-inflammatory drug known for its sublimation characteristics, as a model compound. Through an array of sophisticated analytical techniques, including powder X-ray diffraction (PXRD), nitrogen adsorption-desorption isotherms, and molecular interaction analytics, they meticulously compared SH-processed formulations against those prepared by conventional simple mixing and the EV method. Remarkably, PXRD data revealed that SH-treated samples achieved a complete loss of characteristic drug crystallinity, indicative of amorphous dispersion, paralleling the results of the EV method. This outcome demonstrates the SH method’s capability to replicate the solubility-enhancing effect of traditional techniques without their associated chemical hazards.
An equally critical aspect investigated was the influence of mesoporous silica’s pore volume on drug adsorption efficiency. Larger pore volumes facilitated better distribution and accommodation of ibuprofen’s vapor-phase molecules, thus optimizing the amorphization process. These findings highlight the significance of selecting appropriately engineered carrier materials to maximize the benefits of SH technology. Importantly, subsequent dissolution tests underscored the practical implications of this approach: SH formulations released ibuprofen at a rate 2.7 times faster than crystalline drug samples within the initial ten minutes, signifying substantially improved bioavailability prospects for orally administered medications.
The team also conducted rigorous chemical stability assessments to ensure that the sealed heating process did not induce any degradation or chemical transformation of the drug molecules. Analytical results confirmed that ibuprofen remained chemically intact following SH treatment, and no adverse interactions with the mesoporous silica carrier were detected. This chemical integrity is paramount for drug safety and efficacy, enhancing the practical appeal of the SH method for pharmaceutical manufacturing.
Beyond its scientific merits, the SH method offers compelling environmental and operational advantages. Its complete avoidance of organic solvents mitigates potential health risks for manufacturing personnel, decreases environmental contamination, and simplifies regulatory compliance. Professor Hanawa eloquently emphasizes, “The fact that pharmaceuticals can be loaded onto mesoporous silica directly via the gas phase makes the SH method an environmentally friendly and safe drug loading technique that does not require the use of organic solvents.” This innovative technique portends not only a new era in drug formulation but also a responsible, sustainable path forward for pharmaceutical industries.
Moreover, the implications of the sealed heating method extend beyond single-drug formulations. Due to the physical nature of adsorption rather than chemical bonding, the process holds promise for creating complex combination therapies by sequentially or simultaneously loading multiple pharmaceutical agents onto the same mesoporous silica carrier. Such versatility could revolutionize the design of multi-drug regimens, enhancing therapeutic outcomes and patient compliance. Professor Hanawa anticipates that this aspect could facilitate advances in treatment strategies for multifaceted medical conditions.
The spectrum of drugs amenable to SH processing is currently defined by the requirement that candidates must possess sublimation properties. Nevertheless, this criterion includes several significant pharmaceutical compounds beyond ibuprofen, such as para-hydroxybenzoic acids, mefenamic acid, etenzamide, flufenamic acid, and aspirin. Consequently, this method has the potential to impact a wide range of widely used medications, injecting new vitality into the improvement of their pharmacokinetic profiles and clinical performance.
Additionally, this technique carries promising implications for industries handling porous materials beyond pharmaceuticals, including companies engaged in the production of mesoporous silica. Incorporating the SH method into manufacturing workflows could catalyze development efficiencies, material utilization, and product performance enhancements across diverse sectors involved in drug formulation and delivery systems.
While not universally applicable to every drug candidate due to the sublimation prerequisite, the sealed heating method initiates a paradigm shift in pharmaceutical science. By marrying fundamental physical chemistry principles with practical formulation strategies, this solvent-free, gas-phase drug loading technique advances the quest for safer, more effective, and environmentally responsible medicines. As this research propels from experimental validation toward industrial adoption, it may well fulfill its promise as a cornerstone technology addressing one of the most pressing pharmaceutical challenges of the 21st century.
As pharmaceutical innovation relentlessly pursues the development of life-saving treatments, the solubility crisis represents a formidable adversary, thwarting the therapeutic potential of countless compounds. The application of vapor-phase adsorption embodied in the sealed heating method offers a beacon of hope, fostering not only enhanced drug solubility and bioavailability but also exemplifying sustainable and scalable pharmaceutical manufacturing. This breakthrough embodies the fusion of scientific ingenuity and environmental stewardship, charting a promising course for future medicines and reaffirming the commitment to delivering health solutions that are both effective and conscientious.
Subject of Research: Not applicable
Article Title: New method for adsorbing the pharmaceuticals on mesoporous silica: Adsorption behavior of ibuprofen on mesoporous silica via the sealed and heating method
News Publication Date: 1-Feb-2026
References: DOI: 10.1016/j.xphs.2025.104140
Image Credits: Professor Takehisa Hanawa from Tokyo University of Science, Japan
Keywords: Pharmaceuticals, Drug delivery, Drug development, Chemistry, Materials science, Health and medicine, Environmental issues, Manufacturing, Research and development
