- Follow up fun fact #2: This terminology may get you proverbially (or literally) smacked here in the US.
Anyways, for the remainder of this post, I’ll be using the terms Delayed or Extended. Those are the only 2 terms that the USP uses to describe a tablet or capsule with a mechanism of modified release.
No more getting lost in the diltiazem aisle because of the CC, CD, CR, DR, EC, ER, LA, SA, SR, TR, XL, XT, XR. Those are marketing terms, not pharmaceutical terms.
We won’t let you be confused by some marketing genius trying to put a clever (and profitable) spin on what amounts to either Delayed or Extended Release.
Especially since these letters can lead to some unfortunate issues.
Nonetheless, even if we’re boycotting the alphabet soup, the market will continue to use it. So you’ll need the ability to decipher which letters mean what kind of release system.
“But how? There are like 5 million denotations of release systems!”
The easy answer is to use your pharmacy database system to find AB-rated equivalents and trust that your coders did a good job. But that’s not really a satisfying answer for the NAPLEX, is it?
Alternatively, you can:
- Look at the FDA Orange Book for the equivalents, although that website is still terribly unintuitive
- Use Micromedex or some other drug information resource
- Use RxNav (if you’re comfortable with crazy interfaces…)
- Or if you want to dabble with creating your own tool, you can get the FDA Orange Book in separate files.
Alright, now that we have a better handle on that, let’s move on to the magic that makes these formulations possible.
Pharmaceutical Additives and Their Purpose
When you peruse the inactive ingredients in the package insert, you’ll find a word salad of ingredients (they’re the complex, “chemical-y” sounding names). Some of these same ingredients are also in cosmetics and other products, but you’ve probably glossed over them because we’re sorta “wired” to look at the active ingredient.
And who can pronounce 99% of them anyway?
But those inactive ingredients often have a purpose. They’re a lot less ‘inactive’ than you would think. Although a few of them are just fillers, many have a specific role in making the drug release in a certain way. This then goes on to impact the pharmacokinetics and possibly even pharmacodynamics of the drug
So let’s break them down by function with a few examples.
Sealing Coats
For tablets that have ingredients that might be affected by water (kind of like the aliens in Signs or the Wicked Witch of the West), a sealing coat is applied that is either shellac or polymer based.
For this, you’ll see either shellac or something like zein in the inactive ingredients.
Sweeteners
Mary Poppins knew her stuff with her patented spoonful remedy. And it’s not just plain glucose, it’s also our good friend sucrose.
Sugar syrups are used in coating tablets to mask or improve the flavor. Some powdering happens between coats with powdered sugar, starch, talc, acacia, or others to help dry between layers.
Some syrups also have some gelatin, acacia, or polyvinylpyrrolidone or other additives to enhance the coating. (Did someone yell caution with that alpha gal allergy and gelatin?)
In addition, sugar spheres are used for the core of micropellet formulations. One of the brand names for these sugar spheres is too great not to include here: Suglets! These balls are coated with the active ingredient and then coated multiple times with other substances before being packed into a capsule.
You might also see artificial sweeteners like aspartame, saccharin, or flavors like vanillin, grape, lime to improve the taste.
Colors
Artificial colors, like the ones found in our foods, are used to make tablets “stand out.”
There are a number of coloring agents out there, but a few are titanium dioxide, iron oxide, D&C, and FD&C colors.
Alloying Substances
These are agents that help with making the coating soluble or permeable to water. Polyethylene glycol (our good friend PEG) is a common example.
Plasticizers
No, these won’t help you in the Mean Girls universe.
These are for flexibility and elasticity of the coating (just like when we use plastic elsewhere in life). Diethyl phthalate, castor oil, or triacetin are some examples.
Surfactants
Not the stuff in your lungs. This is to help the film coating spread evenly.
So okay, maybe like the surfactant in your lungs. At least in terms of function.
You’ll see the term sorbitan in the name of some of these - better known as tween or span with a number after it.
Glossants
Nothing says “Take me!” like a shiny, beautiful coating. So get some wax and polish the tablet away, right? Our “go-tos” here are beeswax and shellac (you might remember shellac as an option for the Sealing Coat from above).
Solvents
There is nothing worse than a pile of wet tablets that won’t dry. The pharmaceutical way to fix this is to throw some volatile solvents into your coating that evaporate quickly. Acetone or alcohols are your BFFs here.
Film-Forming Agents
Depending on whether you want an enteric or non-enteric film coat, you’ll select different film-forming agents. For the enteric coatings, look for phthalate or shellac (yes, shellac again). In particular, you’ll run into Hydroxypropyl methylcellulose (aka hypromellose) phthalate, polyvinyl acetate (aka PVA) phthalate, diethyl phthalate, or cellulose acetate phthalate.
For non-enteric coatings, you might see methylcellulose, hydroxypropyl methylcellulose (again, hypromellose) without the phthalate, polyvinyl pyrrolidone, sodium carboxymethylcellulose, high molecular weight PEG, or ethyl cellulose pseudolatex.
These are just some examples of inactive ingredients used in pharmaceuticals. You can find many more on the interwebs, but here are some of our faves:
- “Inactive” Ingredients in Pharmaceutical Products: Update (Subject Review)
- Inactive Ingredients on Drugs.com
