Why do drug excipients matter?

When you take medication, you assume that if the active ingredient is the same, the effect will be too. Same molecule, same amount, same result.

End of debate. Or so we think.

Because the reality is that two medications with the same active ingredient don't always behave the same way in the body. And no, it's not the placebo effect, nor paranoia, nor nostalgia for the brand-name box.

As we discussed in another article, generic medications can differ significantly from brand-name drugs: in the speed at which they take effect, their duration of action, their allergens, digestive tolerance, and the occurrence of side effects. And the explanation lies not in the key molecule, but in its silent entourage.

The excipients.

These are substances that rarely feature in the conversation, but they determine how a tablet dissolves, when the drug is released, how much is absorbed, and how the body responds. They are not filler. They are not neutral. And, of course, they are not irrelevant.

Thinking that a drug is only its active ingredient is like believing that a car is only the engine. Technically appealing. Clinically naive.

In this article we're going to put excipients under the microscope and explain, with science and without anesthesia, why they can make the difference between two drugs that "in theory" are the same... but in practice they are not always.

What are excipients and what is their function in a medicine?

Excipients are all those substances that accompany the active ingredient in the formulation of a medicine and that, although they do not have a direct therapeutic effect, are essential for that effect to occur safely, effectively and in a controlled manner.

Without excipients, most modern medicines could not exist.

The excipients are not there "to fill up". Each one fulfills one or more very specific functions.

Structural excipients: give shape to medicines

They allow a drug to be a tablet, a capsule, a syrup, a cream, or an injection. Without excipients, many active ingredients would simply be powders impossible to administer.

This includes substances such as:

• Lactose, microcrystalline cellulose or calcium phosphates, used as diluents.
• Starches or cellulose derivatives, which act as binders.

Real example:

A 1g paracetamol tablet may contain only a small fraction of the active ingredient; the rest are structural excipients that allow the tablet not to break, to be scored, and to maintain the correct dose.

Excipients that control drug release

They determine when, where, and how quickly the active ingredient is released into the body. This explains why there are immediate-release, delayed-release, and prolonged-release tablets.

They include:

• Disintegrants, which cause the tablet to break down upon contact with digestive fluids.
• Enteric coatings, which prevent the drug from being released in the stomach.
• Extended-release matrices, which deliver the active ingredient over several hours.

Real example:

Omeprazole requires an enteric coating because stomach acid destroys it. If that coating changes, the medication may lose effectiveness even if the active ingredient is identical.

Another classic case is prolonged-release analgesics or antidepressants, where the "smooth and continuous" effect depends almost entirely on the excipient, not the molecule.

Stability and preservation excipients

Some active ingredients are chemically unstable. Excipients protect them from oxygen, moisture, light, and the passage of time, ensuring that the medication continues to work effectively from the first dose to the last.

To prevent this, the following are used:

• Antioxidants
• Preservatives
• pH regulators
• Chelating agents

Real example:
Pediatric syrups often contain preservatives to prevent bacterial growth after opening. Changing this preservative can alter the medication's shelf life… or its tolerability in sensitive children.

Excipients that facilitate administration

Flavorings, sweeteners, coatings, or colorings make a medication easier to swallow, taste better, or be more easily identifiable. This is especially important in pediatrics and for chronic treatments.

They do not directly affect the therapeutic effect, but they do affect treatment adherence, which is key in real-world medicine.

Here we find:

• Sweeteners and flavorings
• Dyes
• Lubricants to facilitate swallowing and manufacturing

Real example:
A children's antibiotic that tastes bad is much more likely to not be completed properly. The active ingredient may be perfect, but without a suitable excipient, the treatment will fail.

Excipients with relevant biological impact

Some excipients act as physical or chemical buffers, preventing the active ingredient from damaging the gastric mucosa, skin, or subcutaneous tissue.

Although excipients do not have a direct pharmacological action, they do have biological activity. They can interact with the body, cause intolerances or allergies, or modify the response to treatment.

Although they are not active ingredients, some excipients do have biological effects:

• Lactose, a problem for those with intolerances
• Sorbitol, with a laxative effect
• Gluten
• Certain colorants and preservatives

Real example:
Two “equivalent” tablets can cause diarrhea, digestive discomfort or poor tolerance in a sensitive person simply due to a difference in the excipient, not in the drug.

Therefore, from a scientific and clinical perspective, a medication is not defined solely by its active ingredient, but by its entire formulation. And this is where excipients cease to be secondary players and become a fundamental part of the treatment.

This does not mean that generics are worse or less effective, but rather that pharmaceutical equivalence does not always imply an identical clinical experience in all patients.

The concept of bioequivalence

When discussing generic medications, one word always comes up as a guarantee of peace of mind: bioequivalence. It sounds definitive, almost absolute. But it's important to understand what it means… and what it doesn't mean.

From a regulatory standpoint, two medications are bioequivalent when, administered under the same conditions, they produce similar concentrations of the active ingredient in the blood, within statistically acceptable limits. In other words, the body receives the active molecule in a comparable manner.

That's very good news. But it doesn't mean that both medications are identical in every way.

Bioequivalence is not absolute identity

Bioequivalence studies focus on key pharmacokinetic parameters, such as:

• How much of the active ingredient reaches the blood
• How fast does it do it?
• How long does it last?

These values must fall within a range accepted by regulatory agencies. However, that range is not an exact point, but rather an interval. And within that interval, excipients play a crucial role.

Here's the important distinction: Bioequivalence guarantees efficacy and safety at the population level, but it does not ensure an identical clinical experience in all patients.

The silent role of excipients in bioequivalence

Two drugs can be bioequivalent and still differ in:

• The speed at which the effect begins
• Digestive tolerance
• The appearance of mild discomfort
• The subjective feeling of "I'm doing better" or "I feel worse"

Why?

Because studies focus on the active ingredient, while excipients can modify dissolution, absorption, or tolerance without breaking the legal criteria for bioequivalence.

It's not a trap set by the system. It's a natural consequence of how pharmacology works in real, not ideal, organisms.

So, do generics work?

Yes. Generic medications work, are safe, and effective. They meet the same regulatory standards as brand-name medications in terms of active ingredient.

But assuming that bioequivalent means identical in all contexts and for all people is an oversimplification of a complex biological system.

And it is precisely here that excipients once again take center stage: not as enemies of the drug, but as variables that explain why, sometimes, two seemingly identical drugs are not experienced in exactly the same way in the body.

Tablet instead of pill

If you've made it this far, you may have noticed something curious: the term "pill" hasn't been used throughout this entire article. This isn't an oversight or a stylistic quirk. It's a conscious decision.

In everyday language, "pill" is used to refer to almost any solid medication taken orally. But from a pharmaceutical perspective, it is an imprecise and, strictly speaking, incorrect term.

The correct term is compressed.

A tablet is a solid pharmaceutical dosage form obtained by compressing a powder containing the active ingredient and excipients. This definition is not a minor technical detail: it describes exactly how the drug is manufactured and why the excipients are so important for its structure, dissolution, and absorption.

Talking about tablets allows us to correctly differentiate between:

• Tablets
• Capsules
• Tablets
• Envelopes
• Syrups
• Solutions or suspensions

Each of these pharmaceutical forms has a distinct formulation, a different behavior in the body, and a specific role for the excipients.

The term "pill," on the other hand, defines none of that. It doesn't indicate how the medication is manufactured, how the active ingredient is released, or what role the excipients play. It's a convenient word for everyday conversation, but scientifically empty.

Therefore, in an article that aims to rigorously explain how a drug works internally, using the correct terminology matters. Just as we don't call every organ in the body an "apparatus" or anything that moves "energy," in pharmacology, words also carry weight.

Frequently asked questions about excipients and medications

Can the excipients cause side effects?
Yes. Although they have no therapeutic effect, some excipients can cause digestive discomfort, allergic reactions, or intolerances in sensitive individuals. Lactose, sorbitol, certain colorings, or preservatives are common examples.

Are the excipients the same in generic and brand-name medications?
Not necessarily. The active ingredient must be the same, but the excipients may vary. This difference does not imply less efficacy, but it can influence patient tolerance or experience.

Does a generic drug work worse than a brand-name drug?
No. Generic drugs are effective and safe. They meet the bioequivalence criteria required by regulatory agencies. However, the fact that they work the same does not mean that they will always have the same effect on every patient.

Does bioequivalence guarantee that two medicines are identical?
No. It guarantees that the active ingredient is absorbed comparably within acceptable limits. It does not imply absolute identity in the formulation or in the individual response.

Can I notice differences when changing medications even if they have the same active ingredient?
Yes. Some people notice changes in the speed of onset, digestive tolerance, or overall sensation of the treatment. This may be due to differences in excipients and individual biological variability.

Who is most sensitive to excipients?
People with food intolerances, digestive disorders, children, the elderly, and patients taking multiple medications at once are more likely to notice these differences.

Should I always ask for the same medication at the pharmacy?
If a medication works well for you and you tolerate it well, staying on the same formulation may be reasonable. If persistent discomfort arises after a change, it's advisable to discuss it with a healthcare professional.

Is changing medication dangerous?
No, as long as it's done with clinical judgment. The change should be based on real and persistent symptoms, not on general mistrust or unverified information.

Where can I find the excipients of a medicine?
The package leaflet and the official technical data sheet detail all the excipients present in the formulation.

Why isn't excipients discussed more?
Because they are not the focus of marketing or popular conversation. However, from a clinical and pharmacological point of view, they are an essential part of the medication.

Do the excipients always appear in the package leaflet?
Yes. All excipients in a medicine must be declared in the package leaflet and the official summary of product characteristics. Regulations require that those that may cause intolerances, allergies, or significant adverse effects, such as lactose, gluten, certain sugars, colorings, or preservatives, be included.

However, the fact that they are listed does not mean that the function of each one is explained in detail. Therefore, although the package insert is the correct source to consult, interpreting their actual impact usually requires pharmacological context or the help of a healthcare professional.