Drug Names and Their Pharmaceutical Salts - Clearing Up the Confusion
You’ve given the pharmacist a prescription for your new diabetes medication called metformin hydrochloride, but when you receive your bottle and look it up on the internet, all you see is “metformin”, not “metformin hydrochloride.” Why is this? Is it the same drug your doctor ordered? What is “hydrochloride”?
Why do some drugs exist in salt forms?
Over 50% of all drug molecules used in medicine exist as salts, most frequently as the hydrochloride, sodium, or sulfate salts. Drugs are often formed as a weak acid or base, but this drug form is not always optimal for dissolution or absorption into your body. Without absorption, a drug cannot have a therapeutic effect, so some forms require a salt. Many medications need to be water-soluble, too. Therefore, drugs are often chemically made into their salt forms to enhance how the drug dissolves, boost its absorption into your bloodstream, and increase its effectiveness.
The choice of a salt in the lab is determined primarily by how acid or basic the chemical is (the pH), the safety of the ionized form, the intended use of the drug, how the drug is given (for example, by mouth, injection, or on the skin), and the type of dosage form (such as tablet, capsule, or liquid).
Other advantages of drug salt formation include development of controlled-release dosage forms, improved stability to extend shelf life, targeted drug delivery in the gastrointestinal tract (stomach or intestine), improved taste, improved drug effectiveness, reduced pain on injection, ease of processing, and extended patent life.
The Top 15 Most Common Drug Salts
- hydrochloride (15.5%)
- sodium (9%)
- sulfate (4%)
- acetate (2.5%)
- phosphate or diphosphate (1.9%)
- chloride (1.8%)
- potassium (1.6%)
- maleate (1.4%)
- calcium (1.3%)
- citrate (1.2%)
- mesylate (1%)
- nitrate (0.9%)
- tartrate (0.8%)
- aluminum (0.7%)
- gluconate (0.7%)
Note: as a percentage of salt form as a function of all medicinal compounds
Can I switch around between different drug salts?
Most drug salts are not automatically substitutable without an okay from your doctor or pharmacist. If you plan on using a drug that exists in a different salt form from the one your doctor originally prescribed, be sure to get your healthcare provider’s approval before you make a substitution. There may be important differences in absorption, dosing, or uses.
According to FDA, drug products are considered pharmaceutical alternatives (not pharmaceutical equivalents) if they contain the same therapeutic moiety (active ingredient), but are different salts. An example of this would be tetracycline hydrochloride, 250 mg capsules vs. tetracycline phosphate complex, 250 mg capsules.
Most drug salts do not lend a therapeutic action to a drug other than enhancing how well it dissolves, is absorbed, or its formulation characteristics. However, a few drug salts may have an added therapeutic effect. In fact, as noted by the United States Pharmacopeia (USP) Salt Policy, if the drug salt is considered an active ingredient, the drug product monograph will only be called by its active ingredient drug name, without the salt at the end of the name, to help prevent confusion.
Why are drugs called by both their “parent drug name” and “salt” name?
An example is the best way to explain this question. The nonprescription (over-the-counter or OTC) version of prescription omeprazole (Prilosec) is omeprazole magnesium (Prilosec OTC). Prilosec OTC is the magnesium salt of omeprazole in a delayed-release capsule form.
Whether omeprazole has a salt or not really results in little difference is how well it works, although, according the FDA, they are not bioequivalent or interchangeable. In fact, they have different uses based on the clinical studies completed.
- Prescription Prilosec is indicated for multiple acid-related conditions, like ulcer treatment or erosive esophagitis, while Prilosec OTC is only indicated for “heartburn” in adults.
- Your doctor may suggest you use Prilosec OTC for other “off-label” conditions, especially if your insurance does not cover the prescription drug due to the availability of the OTC product.
- Erosive esophagitis is a condition that should not be treated without first consulting a doctor. Heartburn can be treated short-term with OTC medications.
- In addition, Prilosec OTC is to be used once a day (every 24 hours), but only for 14 days straight, and then repeated not more often than every 4 months unless directed otherwise by your doctor.
Is “tramadol” the same drug as “tramadol hydrochloride”?
Often, generic drug names will be used by healthcare providers and the general public without the salt ending, just out of convenience. So for example, while the narcotic-like painkiller tramadol and tramadol hydrochloride may sound like two different drugs, they are actually the same drug. The official name is tramadol hydrochloride, but commonly it is often just shortened to “tramadol”. That may be how your doctor writes it on the prescription and how it reads on your pharmacy label. However, oral tramadol only exists in its salt form “tramadol hydrochloride”, even though people don’t always refer to that name.
When you check for a drug interaction, you may run into the same problem. While the official name of the drug may include a salt name, the text written for the drug interaction may not include the salt name because the drug is more commonly referred to without it’s salt name, as is the case with oral tramadol.
Remember that only about 50% of drugs are linked with salts; the others are called by the “parent” name because they exist as a free acid or base and do not require a salt formulation to be active in the body. If you are unsure about the true name of your drug, be sure to check with your pharmacist or look at the manufacturer’s package insert provided with your prescription.
Does a salt form add any therapeutic effect to the drug?
It depends. Usually, the salt form of a drug does not lend therapeutic qualities to the active ingredient. It’s primary purpose is to enhance pharmaceutical characteristics like dissolution, absorption, and onset of action. Different salt forms may not be bioequivalent, meaning that the therapeutic effect in the body is not expected to be the same.
On the other hand, some drugs may have qualities where the salt does lend a therapeutic effect, and for this reason it is important to check with your pharmacist and physician to make sure that different salt forms can be interchanged. Your pharmacist can check The Orange Book, which will define if the drugs are “AB” rated, meaning they are bioequivalent.
Drug names can be confusing for healthcare providers and patients alike. If you have questions about a particular drug or its salt form, be sure to ask your pharmacist, who can provide detailed information to both you and your doctor, if needed.
Can a drug salt be patented?
Yes, drug salts can be patented when combined as part of a proprietary drug product by a pharmaceutical manufacturer. A new salt form may alter how a drug can be given or it’s dosage form.
- For example, diclofenac sodium salt was originally marketed orally as the brand Voltaren.
- However, other salts like diclofenac epolamine (Flector Patch) - a diclofenac salt with good skin penetration - was developed and patented, too.
- Another salt form is diclofenac potassium (Cambia), an oral powder for solution of diclofenac, which is also is also patented.
- Once patents expire, generic manufacturers can market these salt forms even though they were previously patented. That's when the price will drop, too.
Omeprazole was originally developed in a capsule dosage form, but was later formulated into a tablet after it was combined with a magnesium salt. A new patent timeline would be issued with the new molecular entity. The unauthorized use of a proprietary salt form is restricted by patent law, and often results in legal battles between drug manufacturers. It's also one way that a drug company may try to extend the patent life on an active ingredient in a medication.
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- Bansal AK. Kumar L. Amin A. Salt Selection in Drug Development. Pharmaceutical Technology. 2008:3. March 2008. Accessed April 9, 2021.
- Verbeeck RK. Kanfer I. Walker RB. Generic substitution: the use of medicinal products containing different salts and implications for safety and efficacy. European Jounral of Pharmaceutical Sciences. June 2006. Accessed April 9, 2021.
- Brittain HG. Strategy for the Prediction and Selection of Drug Substance Salt Forms. Pharmaceutical Technology. Accessed April 9, 2021 at https://www.pharmtech.com/view/strategy-prediction-and-selection-drug-substance-salt-forms
- Salt Selection in Drug Development. PharmTech.com. Accessed April 9, 2021 at https://www.pharmtech.com/view/salt-selection-drug-development
- Monograph Naming Policy for Salt Drug Substances in Drug Products and Compounded Preparations1 (the USP Salt Policy). U.S. Food and Drug Administration (FDA). Accessed April 9, 2021 at https://www.fda.gov/media/85022/download
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.