Down the Track: Different Speeds with Multiple APIs - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

Down the Track: Different Speeds with Multiple APIs
Formulators and manufacturers have many options for modifying release profiles in multiple-API products.


Pharmaceutical Technology
Volume 33, Issue 7, pp. 34-40


ILLUSTRATION BY S. STEWART. IMAGES: DAVID MADISON, MEDICALRF/GETTY IMAGES
Dosage forms that contain more than one active pharmaceutical ingredient (API) can improve patient compliance and facilitate the treatment of certain diseases. Strategies to control the release of APIs in tablets and inhalable drugs include modifying the formulation, implementing specific coating technologies, and using techniques in particle-engineering.

Hydrogels

The formulation stage offers many opportunities for scientists to impart controlled release to multidrug dosage forms. Hydrogels, extremely hydrated polymer gels that hold many times their weight in trapped water, are a drug-delivery mechanism that can be manipulated to change the release profiles of APIs (1).

Rather than using commercially available materials, which is the traditional method, a team of researchers at the Massachusetts Institute of Technology (MIT) created designer peptides from scratch that had both hydrophobic and hydrophilic parts. When exposed to water, the peptides' hydrophobic parts assemble into a hydrogel scaffold, explains Shuguang Zhang, associate director of MIT's Center for Biomedical Engineering. The scaffold, a nanofiber that contains nanopores, can house small- and large-molecule drugs and carry more than one API at a time.

By modifying the hydrogel scaffold's peptides, scientists could provide different release profiles for separate APIs. The scaffold could include peptides with physical hooks that are specific to particular receptors in the body. An API associated with a hook would be released earlier than an API housed in the scaffold's micropores, says Zhang.

The nanopores in the scaffold are components or "harbors" that protect biological drugs from water ingress, Zhang says. Because the scaffold is stable at high temperatures, it also protects proteins from becoming denatured. The team's recent research shows that protein drugs are still functional when they emerge from the hydrogel scaffold, which could be used to deliver erythropoietin by injection, says Zhang (2).

Scientists could modify the hydrogel scaffold to alter the release profile of the drugs it carries. Zhang's team engineered specific enzymes to cut a particular site on the peptide chain to degrade the scaffold quickly, which increased the release rate. If the scaffold remained intact longer, it would release drugs slowly. Scientists can engineer the scaffold to resist enzymatic degradation, but this technique is difficult, says Zhang. Another way to modify the release profile would be to change the thickness of the nanopore enclosures that house an API.

The hydrogel scaffold is safer for patients than other natural and synthetic materials. In contrast with animal-derived materials, MIT's hydrogel scaffold is entirely aseptic and has not provoked any immune response, Zhang says. The scaffold is easier for the body to process and reuse than synthetic polymeric materials, he adds. Innocuous polymers sometimes degrade into toxic monomers. In contrast, enzymes in the body break down the hydrogel scaffold's peptides into harmless amino acids. The team's isotope-labeling study found that the hydrogel scaffold breaks down at a rate of 10% every two weeks, an "almost perfect" rate for many drug-delivery applications, says Zhang. A conventional isotope takes two weeks to degrade by 10%.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
FDASIA was signed into law two years ago. Where has the most progress been made in implementation?
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
Reducing drug shortages
31%
Breakthrough designations
8%
Protecting the supply chain
42%
Expedited reviews of drug submissions
8%
More stakeholder involvement
12%
View Results
Jim Miller Outsourcing Outlook Jim Miller Health Systems Raise the Bar on Reimbursing New Drugs
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerThe Mainstreaming of Continuous Flow API Synthesis
Jill Wechsler Regulatory Watch Jill Wechsler Industry Seeks Clearer Standards for Track and Trace
Siegfried Schmitt Ask the Expert Siegfried SchmittData Integrity
Sandoz Wins Biosimilar Filing Race
NIH Translational Research Partnership Yields Promising Therapy
Clusters set to benefit from improved funding climate but IP rights are even more critical
Supplier Audit Program Marks Progress
FDA, Drug Companies Struggle with Compassionate Use Requests
Source: Pharmaceutical Technology,
Click here