How Scientists Trick Insoluble Drugs Into Healing Our Bodies
The key to effective medication isn't just what you take, but how it gets where it needs to go inside your body.
Imagine pouring a tablespoon of sand into a glass of water and expecting it to completely disappear. This is the fundamental challenge pharmaceutical scientists face with nearly 70% of new drug compounds discovered today—they simply don't dissolve well in water 3 .
Without dissolution, these promising medications pass through our bodies without being absorbed, rendering them therapeutically useless. This article explores the brilliant scientific strategies that transform these reluctant compounds into effective treatments, focusing on the groundbreaking work of Dr. Jim Jingjun Huang and his company, Ascendia Pharmaceuticals, in designing advanced drug delivery systems.
of new drug compounds have poor solubility
When you swallow a pill, it embarks on an intricate journey through your digestive system before its healing components can enter your bloodstream and reach their intended destination. For this to happen, the drug must first dissolve in the fluids of your gastrointestinal tract.
A drug's ability to dissolve and become available for your body to use is what scientists call bioavailability 3 6 .
The proportion of a drug that enters the circulation when introduced into the body and so is able to have an active effect.
The pharmaceutical industry classifies drugs using the Biopharmaceutical Classification System (BCS), which categorizes them based on their solubility and permeability:
| BCS Class | Solubility | Permeability | Example Drugs |
|---|---|---|---|
| Class I | High | High | Mefoquine hydrochloride |
| Class II | Low | High | Ibuprofen, Nifedipine |
| Class III | High | Low | Amoxicillin |
| Class IV | Low | Low | Acetazolamide 6 |
Class II and IV drugs, which have poor solubility, represent the most significant formulation challenge. Surprisingly, 40% of marketed products and 70-90% of drug candidates in development fall into these poorly soluble categories 3 6 . This bioavailability barrier has forced scientists to devise clever ways to outsmart nature and make the insoluble soluble.
Researchers have developed an array of innovative techniques to enhance drug solubility. Dr. Jim Huang's company, Ascendia Pharmaceuticals, has introduced several proprietary technologies that address this exact challenge 2 5 :
Production of nano-sized drug particles to increase surface area for dissolution
Increased dissolution rate through size reductionCreating oil-in-water nano-emulsions
Improved solubility of lipophilic compoundsEncapsulating molecules in lipid nanoparticles
Delivery of both small and large moleculesForming amorphous solid dispersions
Bypassing crystalline lattice energy that inhibits dissolution 2These technologies represent the cutting edge of a field that employs both physical methods (like reducing particle size to nanoscale) and chemical approaches (such as altering the drug's crystalline form) to overcome solubility challenges 6 .
To understand how these technologies work in practice, let's examine a detailed experiment involving piperine—the bioactive compound that gives black pepper its pungency and a challenging poorly water-soluble drug candidate.
In a 2015 study published in Drug Delivery, researchers sought to enhance piperine's bioavailability using a Self-Emulsifying Drug Delivery System (SEDDS) 1 . This approach falls under the emulsion-based technologies similar to Ascendia's EmulSol® method.
The research team developed an optimized formulation containing:
The specific ratio of 3:5.5:1.5 (w/w) allowed piperine concentration to reach 2.5% in the final formulation—a significant improvement over its natural solubility limits.
Researchers determined optimal component ratios through solubility tests and ternary phase diagrams.
The team compared dissolution rates between the SEDDS formulation and conventional piperine capsules in simulated biological fluids.
Scientists administered both formulations to laboratory rats and measured piperine concentration in blood plasma over time.
Using an in situ single-pass intestinal perfusion technique, researchers directly evaluated how well piperine was absorbed through intestinal walls 1 .
The findings demonstrated a dramatic improvement in piperine's performance:
| In Vitro Dissolution Comparison | ||
|---|---|---|
| Formulation Type | Dissolution Rate | Relative Improvement |
| Conventional Capsule | Baseline | 1x |
| SEDDS Formulation | Significantly Higher | Markedly Improved 1 |
Even more impressive were the results from the animal studies:
| In Vivo Bioavailability Enhancement in Rats | ||
|---|---|---|
| Parameter | SEDDS vs. Conventional Capsule | Fold Increase |
| Cmax1 (First Peak Concentration) | Significantly Higher | 3.8x |
| Cmax2 (Second Peak Concentration) | Significantly Higher | 7.2x |
| AUC (Total Exposure) | Substantially Greater | 5.2x 1 |
The relative bioavailability of the SEDDS formulation reached 625.74% compared to the conventional capsule—more than six times greater absorption 1 .
The intestinal permeability study confirmed these findings, with the SEDDS formulation showing significantly higher effective permeability and absorption rate values compared to simple piperine solutions 1 .
This experiment demonstrates conclusively that advanced delivery systems can transform barely absorbable compounds into highly bioavailable medications.
Dr. Jim Huang founded Ascendia Pharmaceuticals in 2012 specifically to address the critical drug delivery gap for poorly soluble compounds 2 . With over 15 years of experience in pharmaceutical R&D at companies like Pfizer and Roche, Huang recognized that traditional formulation approaches often failed for modern drug candidates 4 .
His research interests have centered on improving solubility and dissolution through nano-emulsion, nanoparticle, and amorphous solid dispersion technologies—the very foundations of Ascendia's proprietary platforms 4 .
The company's growth reflects the pressing industry need for these solutions. From humble beginnings in an 800-square-foot lab, Ascendia has expanded to a 60,000-square-foot facility in North Brunswick, New Jersey, and has earned placement on the Inc. 5000 list for four consecutive years thanks to 280% three-year revenue growth 2 .
Founder & CEO, Ascendia Pharmaceuticals
As drug discovery continues to yield increasingly complex molecules, delivery challenges will grow accordingly. The future lies in combining solubility enhancement with targeted delivery—ensuring medications not only dissolve properly but reach specific tissues, cells, or even subcellular compartments with precision.
Nanotechnology-based approaches have already shown remarkable success, with lipid nanoparticles playing a crucial role in the effective COVID-19 mRNA vaccines from Pfizer/BioNTech and Moderna 6 . These same principles are now being adapted to improve conventional small-molecule drugs.
Ongoing research explores increasingly sophisticated materials—including dendrimers, micelles, metal-organic frameworks, and nanogels—as potential carriers for poorly soluble drugs 6 . Each offers unique advantages for specific therapeutic challenges.
Future drug delivery systems will not only enhance solubility but also incorporate targeting mechanisms to deliver medications precisely to diseased cells while minimizing side effects on healthy tissues.
The science of making insoluble drugs soluble represents one of pharmaceutical research's most critical frontiers. Through ingenious approaches like those developed by Dr. Huang and his team, previously abandoned drug candidates are getting a second chance at saving lives.
The next time you take a pill that works effectively, remember that its journey from manufacturing to medicine involved far more than mixing ingredients.
It required overcoming nature's resistance through clever formulation—making the impossible possible, one nanometer at a time.
As Dr. Huang's team at Ascendia aptly demonstrates, sometimes the biggest medical breakthroughs come not from discovering new compounds, but from learning how to deliver them properly.