Have you ever pondered why most pharmaceutical drugs have no taste? Or, if you do not swallow the tablet in a timely manner, an unpleasant taste forms in your mouth?
Pharmaceutical drugs have had plenty of problems. One notable conflict is the aversion toward the taste of the tablets. The pharmaceutical industry has tried to develop mechanisms to alleviate this problem such as increasing the speed of the tablets to dissolve, using liquids and syrups, the usage of patches and gums, and lastly dissolving the tablets in liquid. Most of these methods ended in failure and disapproval from customers. Professor Rajesh N. Davé (of the New Jersey Institute of Technology Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering) and two of his former graduate students, Daniel To and Maxx Capece, presented a solution with their 2015 patent “Solventless Mixing Process for Coating Pharmaceutical Ingredients.” This patent thoroughly explains the different techniques in coating a taste-masking tablet. The thought process for this patent is that children and adults refuse to take medicine and remedies due to the taste. It will be easier for patients to swallow or chew tablets when there isn’t any taste.
What ingredient does the unpleasant taste come from and what is the process of coating?
The undesirable taste of the tablet comes from an active pharmaceutical ingredient (API). To mask the taste, the mixing must occur in water soluble materials or swellable coating materials and water insoluble polymer particles. The six methods of coating are:
- Coating with fine wax particles using fluid energy milling
- Dry-coating core particles with distribution
- Mechanical dry coating of wax onto copper powder
- Coating process when ascorbic acid particles are pulverized and coated with wax
- Dry coating using polymer powders
- Dry coating solid dosage
What are some realizations of the Patent US9107851B2?
This invention is the use of mechanical dry process. The first step in the taste-masking process is mixing the API fine particles first with the soluble coating materials, then with water insoluble polymer particles. After the mixing and the coating is formed, the tablet must go through a mechanical stress of high temperature in which it develops a film. After that film is complete, the API is masked for approximately one minute before the coating dissolves in its entirety. The tablet size must be between 30μm and 2mm. The amount of coating depends on the size of the pill; larger tablets will need more soluble and insoluble materials than a smaller pill would.
A water swellable version contains characteristics in which the material absorbs the water and swells. The materials in the tablet include croscarmellose, crospovidone, and sodium starch glycolate. The median size must be in the range of 0.5μm to 20μm. The water soluble material must have a solubility of at the very least 50 mg/mL at 20 degrees Celsius with a neutral pH. Some examples of soluble materials are lactose, poly-ethylene oxide, and hydrophilic polymers. For the water- insoluble polymer, the median size for the particle size can range from 1μm to 20μm. For the material to deform in this polymer, the temperature must be elevated, it has to go under a great deal of mechanical stress, or a combination of both. Castor wax, polypropylene, and polyamide wax are insoluble materials.
What is the mixing process?
The mixing process is applied with mechanical stress for about 1 minute to 4 hours. The amount of mixing time depends on the coating process used and the machine in use for the mixing. One method of mixing can be carried out by high energy vibrations with an acceleration of 9.81 m/s^2. The intensity number must not be lower than 10 or exceed 100 and the API size cannot exceed 100μm. The particles in the soluble and polymer must collide at high velocity, causing the coating surface to deform the API, which will lead to continuous coating. Another mixing process is executed by acoustic mixing at a high-intensity, low frequency acoustic energy being transferred to a mixing chamber.
What is the last processing method?
The insoluble polymer must be distributed over the API via vibrating, impacting, and tumbling in a mill. The mixing must be at high energy but not too excessive for the polymers to break the host particle. The average size of the particles is no less than 95% of the original particle size. A reduction of the expected size can be a sign that the process was not conducted correctly and that the coating is not thoroughly spread. A well-coated tablet will feature the desired dissolution characteristics along with the API being restricted for at least 30 minutes.
The presence of media particles enhances the formations of the continuous polymer coating, which could possibly better mask the taste. The API size to the media particles size ratio has to be between 3:1 to 10:1.
How long does it take for the coating to dissolve entirely and the unpleasant taste to be revealed?
The dissolution tests have shown that after 1 minute of the tablet in one’s mouth, about 95% of the API ingredient is concealed, and there is still no taste. The drug coating is less than 0.01% of taste-release. For most methods of coating, a little less than 0.5% of the API element is released after 2 minutes of the tablet in one’s mouth. After 30 minutes with the tablet in mouth, 90% of the API element is released, the same as if the tablet had not been coated. If the methods stated above are not thoroughly conducted such as running out of coating or inadequate taste-masking, the water soluble coating will dissolve quickly which will lead to the API being revealed before expected. Another factor in which the API will be released before expected is when the particles for the water soluble and insoluble polymers are not close enough to react.
In 2016, the inventors of this patent were awarded a Thomas Alva Edison Patent Award from the Research & Development Council of New Jersey.[i] The patent was licensed to a global health care company, which is attempting to bring this technology to market.
By Hakilah Hudson, Glenn Monroe, John Saviano
[i] Tracey Regan. “NJIT Engineers Win an Edison Patent Award for Technology that Masks the Taste of Bitter Drugs,” Innovations at NJIT. Nov. 4, 2016, http://www6.njit.edu/features/innovations/dave-edison-awards2.php