Redesigning and manufacturing oral dosage forms for optimal drug therapies

Our Mission

It is well-known that for an optimal drug therapy the drug concentration in blood should be within a narrow, optimal range. With the present oral solid dosage forms (the tablets and capsules), however, the optimal range often cannot be attained.

We are a clinical-stage pharmaceutical company founded to optimize the design of oral solid dosage forms.
We develop gastroretentive dosage forms that expand in the stomach, reside there for a day, release drug at a constant rate, and ensure a steady drug concentration in blood within the optimal range.
We aim to show that our dosage forms enable to achieve a faster therapeutic response and reduced side effects of a myriad of drug therapies.
Furthermore, we are developing a new 3D-printing process to manufacture our dosage forms. We intend to demonstrate that our dosage forms can be manufactured rapidly and economically at any scale.

Fluoroscopic image of the abdomen of a dog after administering an Enzian dosage form. The dosage form is retained in the stomach, and delivers drug into the stomach (and into the blood) at a constant rate over time. This enables a constant drug concentration in blood, and an optimal drug therapy. Image adapted from A.H. Blaesi et al., Int. J. Pharm. 613 (2022) 120792.

Technical Opportunity

As shown schematically in Fig. 1, at present the oral tablets and capsules are lightly compacted or loose mixtures of drug and excipient particles.

While such dosage forms have served to treat disease for decades, for numerous applications they are not optimal.

Fig. 1. Schematic of a state-of-the-art particle-filled capsule and its microstructure. Schematic adapted from A.H. Blaesi and N. Saka, Int. J. Pharm. (2024) 124360.

Drugs moderately soluble in gastric but insoluble in intestinal fluid

For example, many kinds of drug are moderately soluble in the acidic gastric fluid, but are essentially insoluble in the pH-neutral intestinal fluid.

As shown in Fig. 2, upon ingesting a particulate dosage form containing such a drug, the dosage form fragments into its constituent particles in the stomach, and the drug particles dissolve partially.

The dissolved drug molecules and the un-dissolved drug particles then gradually flow into the intestine. In the intestine the drug molecules are absorbed by the blood stream. The drug particles, however, will not dissolve any further, and will be excreted through the feces.

Thus, drug absorption stops as soon as the drug has been swept out of the stomach.

Fig. 2. Schematic of the gastrointestinal passage of a state-of-the-art particulate dosage form. Schematic adapted from A.H. Blaesi and N. Saka, Int. J. Pharm. (2024) 124362.

The drug concentration in blood rises while drug is absorbed, but when absorption stops it falls.

Thus, because the gastric residence time of the drug particles and molecules, t_r ~ 3 hrs, is much shorter than the convenient dosing interval, t_d ~ 12-24 hrs, upon repeated dosing the drug concentration in blood rises and falls, Fig. 3.

This is therapeutically not optimal: the maximum drug concentration is high, promoting acute side effects, and the minimum and average are low, compromising the efficacy of the therapy.

Fig. 3. Schematic of the drug concentration in blood after administering multiple particulate dosage forms. c_d,b: drug concentration in blood; t_d: dosing interval; t_r: gastric residence time; t: time. Schematic adapted from A.H. Blaesi and N. Saka, Int. J. Pharm. (2024) 124360.

Enzian’s Technology

To mitigate the present limitations, the microstructure of Enzian dosage forms comprises a cross-ply structure of drug-bearing fibers, Fig. 4.

Fig. 4. Schematic of a fibrous dosage form, and the top and sectional views of its microstructure. Schematic adapted from A.H. Blaesi et al., Int. J. Pharm. 642 (2023) 122378.

Upon ingestion, gastric fluid percolates the open inter-fiber spaces, the water diffuses into the fibers, and the dosage form expands, Fig. 5. The expanded dosage form does not pass into the intestine due to its size. It resides in the stomach for about 24 hours, and delivers drug into the gastric fluid and the blood at a constant rate over time.

Fig. 5. Schematic of the gastrointestinal passage of a gastroretentive fibrous dosage form. Schematic adapted from A.H. Blaesi and N. Saka, Int. J. Pharm. (2024) 124362.

Drugs moderately soluble in gastric but insoluble in intestinal fluid

Thus, even drugs moderately soluble in gastric but insoluble in intestinal fluid are absorbed during the entire dosing interval, and the drug concentration in blood is constant and within the optimal range, Fig. 6.

This mitigates acute side effects and maximizes the efficacy of the therapy.

The concept is particularly useful for optimizing a myriad of cancer therapies.

Fig. 6. Schematic of the drug concentration in blood after administering multiple Enzian dosage forms. c_d,b: drug concentration in blood; t_d: dosing interval; t_r: gastric residence time; t: time. Schematic adapted from A.H. Blaesi and N. Saka, Int. J. Pharm. (2024) 124360.

Technology validation

Particulate and fibrous dosage forms: Microstructures

Fig. 7 is a scanning electron micrograph of the mixture of drug and excipient particles obtained from a marketed pharmaceutical capsule containing 200 mg of a cancer drug. The “radius” of the particles is about 18 μm.

Fig. 7. Scanning electron micrograph of loose particles of drug and excipient obtained from a marketed pharmaceutical capsule. Image adapted from A.H. Blaesi and N. Saka, Int. J. Pharm. (2024) 124361.

Figs. 8a and 8b, respectively, are the top and sectional views of the microstructure of a fibrous dosage form with the same drug. The fiber radius and the inter-fiber spacing are precisely controlled.

Fig. 8. Scanning electron micrographs of (a) top view and (b) sectional view of the microstructure of a fibrous dosage form. Image adapted from data presented in A.H. Blaesi et al., Int. J. Pharm. 642 (2023) 122378.

Particulate and fibrous dosage forms: Gastric residence times

Fig. 9 presents fluoroscopic images of the abdomen of a dog at various times after administering a particle-filled capsule. Initially, the capsule was unimpaired in the stomach. But already after 2 minutes it fragmented. By 6 minutes, the capsule was essentially disintegrated, and after 90 minutes the stomach was mostly empty.

Fig. 9. Fluoroscopic images of the abdomen of a dog at various times after administering a particle-filled capsule. Image adapted from A.H. Blaesi et al., Int. J. Pharm. (2024) 124363.

Fig. 10 presents fluoroscopic images of the abdomen of a dog at various times after administering an Enzian dosage form. The dosage form expanded due to water absorption, and formed an expanded semi-solid that resided in the stomach for prolonged time. By 22 hours the semi-solid was fragmented. The fragments dissolved rapidly; by 28 hours they were essentially invisible.

Fig. 10. Fluoroscopic images of the abdomen of a dog at various times after administering an Enzian dosage form. Image adapted from A.H. Blaesi et al., Int. J. Pharm. (2024) 124363.

Drug moderately soluble in gastric but insoluble in intestinal fluid: Drug concentration in blood

Fig. 11 presents data of the concentration of a select cancer drug in the blood of a dog.

If the drug is administered by a particulate dosage form, the drug concentration in blood rises and falls. The width of the peak at half-height is small (3.6 hrs).

By contrast, if the drug is administered with an Enzian dosage form the drug concentration in blood approaches a steady-state value. The peak-width at half-height is much greater (12 hrs).

Thus, upon repeated dosing the Enzian dosage form enables a steady drug concentration in blood for enhancing the efficacy and reducing side effects of the drug therapy.

Fig. 11. Drug concentration in blood after administering a particulate and a fibrous dosage form to a dog. Image adapted from data published in A.H. Blaesi et al., Int. J. Pharm. (2024) 124363.

Scientific Publications

Enzian’s technology is based on in-depth theoretical and experimental scientific investigations. It is published in high-quality, peer-reviewed scientific journals. A list of selected scientific publications by year of acceptance is shown below.

2024

Aron H. Blaesi, Henning Richter, Nannaji Saka, Enhancing the bioavailability of sparingly soluble drugs by expandable, solid-solution fibrous dosage forms, International Journal of Pharmaceutics, 2024, under review.

2023

Aron H. Blaesi, Nannaji Saka, Gastroretentive fibrous dosage forms for prolonged delivery of sparingly soluble tyrosine kinase inhibitors. Part 1: Dosage form design, and theoretical models of expansion, mechanical strength, and in vitro drug release, International Journal of Pharmaceutics, 2024, 124360. https://doi.org/10.1016/j.ijpharm.2024.124360

Aron H. Blaesi, Nannaji Saka, Gastroretentive fibrous dosage forms for prolonged delivery of sparingly soluble tyrosine kinase inhibitors. Part 2: Experimental validation of the models of expansion, mechanical strength, and in vitro drug release, International Journal of Pharmaceutics, 2024, 124361. https://doi.org/10.1016/j.ijpharm.2024.124361

Aron H. Blaesi, Nannaji Saka, Gastroretentive fibrous dosage forms for prolonged delivery of sparingly soluble tyrosine kinase inhibitors. Part 3: Theoretical models of drug concentration in blood, International Journal of Pharmaceutics, 2024, 124362. https://doi.org/10.1016/j.ijpharm.2024.124362

Aron H. Blaesi, Henning Richter, Nannaji Saka, Gastroretentive fibrous dosage forms for prolonged delivery of sparingly soluble tyrosine kinase inhibitors. Part 4: Experimental validation of the models of drug concentration in blood, International Journal of Pharmaceutics, 2024, 124363. https://doi.org/10.1016/j.ijpharm.2024.124363

2022

Aron H. Blaesi, Thomas Echtermann, Henning Richter, Nannaji Saka, The effect of a strengthening, semi-permeable fiber coating on the expansion, mechanical properties, and residence time of gastroretentive fibrous dosage forms, International Journal of Pharmaceutics 642, 2023, 122378. https://doi.org/10.1016/j.ijpharm.2022.122378

2021

Aron H. Blaesi, Dolf Kümmerlen, Henning Richter, and Nannaji Saka, Mechanical strength and gastric residence time of expandable fibrous dosage forms, International Journal of Pharmaceutics 613, 2022, 120792. https://doi.org/10.1016/j.ijpharm.2021.120792

Aron H. Blaesi, Nannaji Saka, Expandable, dual-excipient fibrous dosage forms for prolonged delivery of sparingly-soluble drugs, International Journal of Pharmaceutics and Biopharmaceutics, 615, 2022, 120396. https://doi.org/10.1016/j.ijpharm.2021.120396

2020

Aron H. Blaesi, Nannaji Saka, The role of excipient molecular weight in drug release by fibrous dosage forms with close packing and high drug loading, International Journal of Pharmaceutics, 606, 2021, 120009. https://doi.org/10.1016/j.ijpharm.2020.120009

2019

Aron H. Blaesi, Nannaji Saka, Expandable fibrous dosage forms for prolonged drug delivery, Materials Science and Engineering C, 120, 2021, 110144. https://doi.org/10.1016/j.msec.2019.110144

Aron H. Blaesi, Nannaji Saka, Solid-solution fibrous dosage forms for immediate delivery of sparingly soluble drugs: Part 2. 3D-micropatterned solid dosage forms, Materials Science and Engineering C, 129, 2021, 110211. https://doi.org/10.1016/j.msec.2019.110211

Aron H. Blaesi, Nannaji Saka, Solid-solution fibrous dosage forms for immediate delivery of sparingly soluble drugs: Part 1. Single fibers, Materials Science and Engineering C, 109, 2020, 109918. https://doi.org/10.1016/j.msec.2019.109918

2018

Aron H. Blaesi, Nannaji Saka, Fibrous dosage forms by wet 3D-micro-patterning: Process design, manufacture, and drug release rate, European Journal of Pharmaceutics and Biopharmaceutics, 130, 2018, 345-358. https://doi.org/10.1016/j.ejpb.2018.06.015

2017

Aron H. Blaesi, Nannaji Saka, 3D-micro-patterned fibrous dosage forms for immediate drug release, Materials Science and Engineering C, 84, 2018, 218-229. https://doi.org/10.1016/j.msec.2017.07.003

Aron H. Blaesi, Nannaji Saka, Continuous manufacture of polymeric cellular dosage forms, Chemical Engineering Journal, 320, 2017, 549-560. https://doi.org/10.1016/j.cej.2017.02.057

Aron H. Blaesi, Nannaji Saka, Microstructural effects in drug release by solid and cellular polymeric dosage forms: A comparative study, Materials Science and Engineering C, 80, 2017, 715-727. https://doi.org/10.1016/j.msec.2017.05.080

2016

Aron H. Blaesi, Nannaji Saka, Determination of the mechanical properties of solid and cellular polymeric dosage forms by diametral compression, International Journal of Pharmaceutics, 509, 2016, 444-453. https://doi.org/10.1016/j.ijpharm.2016.05.020

Aron H. Blaesi, Nannaji Saka, On the exfoliating polymeric cellular dosage forms for immediate drug release, European Journal of Pharmaceutics and Biopharmaceutics, 103, 2016, 210-218. https://doi.org/10.1016/j.ejpb.2016.03.032

2015

Aron H. Blaesi, Nannaji Saka, Melt-processed polymeric cellular dosage forms for immediate drug release, Journal of Controlled Release, 220, 2015, 397-405. https://doi.org/10.1016/j.jconrel.2015.10.046

Patents

Enzian’s technology is patented by more than 20 Patent applications and issued Patents. A list of selected United States Patents by year of issue is shown below.

2024

US 12,059,503 B2 titled “Method for the manufacture of solid dosage forms”.

2023

US 11,865,216 B2 titled “Expandable structured dosage form for immediate drug delivery”.

2022

US 11,478,427 B2 titled “Dosage form comprising structural framework of two-dimensional elements”.

US 11,285,116 B2 titled “Method for the manufacture of fibrous dosage forms”.

2021

US 11,129,798 B2 titled “Fibrous dosage form”.

2020

US 10,751,292 B2 titled “Method and apparatus for the manufacture of fibrous dosage forms”.

About Enzian

Enzian Pharmaceutics has emerged from the doctoral thesis of Dr. Aron H. Blaesi at the Massachusetts Institute of Technology (MIT). It was founded by Dr. Blaesi counseled by Dr. Nannaji Saka, also an MIT alumnus.

To achieve its mission, Enzian has a pharmaceutical laboratory in Zurich, Switzerland, for producing its dosage forms and testing them in vitro. Additionally, Enzian collaborates with University research laboratories and University hospitals (most notably at the University of Zurich, MIT, and Harvard Medical School) to validate the dosage forms in vitro, and in vivo in animals and in humans.

A short history of Enzian can be found here.

Technopark Zurich where Enzian has its laboratories.

Investment opportunities

Enzian is a fast-growing company on track to transform the design and manufacture of oral solid dosage forms.

We are currently seeking series A/B investors to conduct clinical trials, scale up manufacturing processes, and bring the gastroretentive dosage form to market.

For investment opportunities, please contact info@enzianpharma.com.

Enzian’s Leadership

Aron H. Blaesi, Ph.D.

Dr. Blaesi is the founder and CEO of Enzian. He obtained his Bachelors and Masters degrees in Mechanical Engineering from ETH Zurich in 2007 and 2009, respectively, and a Ph.D. in Mechanical Engineering from the Massachusetts Institute of Technology (MIT) in 2014. After his Ph.D., while working on developing Enzian, Dr. Blaesi spent two years as a post-doctoral fellow in the laboratory of the late Dr. Warren M. Zapol at the Massachusetts General Hospital, Harvard Medical School. Since 2016 Dr. Blaesi has been working full-time on Enzian. He developed Enzian from scratch to the clinical-stage company it is now. He is the first inventor of fibrous dosage forms and more than twenty other patents and patent applications forming Enzian’s core technology. His work is widely published; he first-authored more than twenty peer-reviewed scientific publications. Lists of selected publications can be found on ResearchGate and Google Scholar.

Nannaji Saka, Sc.D.

Dr. Saka is the lead advisor to Enzian. He was graduated with a bachelor’s degree in Mechanical Engineering (in first class with honors) from Andhra University (India), with a master’s degree in Metallurgical Engineering from the Indian Institute of Technology/Kanpur (India), and with a doctoral degree in Materials Science and Engineering from MIT (Cambridge, MA). After graduating with a doctoral degree, Dr. Saka joined the Department of Mechanical Engineering at MIT as a post-doctoral fellow and was later promoted as a principal research scientist. Over the decades, he has published more than 100 technical papers, is an inventor on more than 20 patents, organized conferences, taught graduate and undergraduate courses, served as an advisor to scores of graduate and undergraduate students in their research, and advised several companies. A list of selected publications can be found on ResearchGate.

Contact Addresses

Switzerland
Enzian Pharmaceutics Blaesi AG
Technopark Zurich
Technoparkstrasse 1
CH-8005 Zurich
Email: info@enzianpharma.com

and

Enzian Pharmaceutics Blaesi AG
CH-7078 Lenzerheide

United States
Enzian Pharmaceutics, Inc.
955 Massachusetts Avenue, #126
Cambridge, MA 02139
Email: info@enzianpharma.com