By Matt Martin, PharmD, PCCA Clinical Services Manager

Omeprazole belongs to a class of drugs that reduce stomach acid production. These compounds accomplish this by inhibiting an enzyme system of the cells in the stomach lining. The enzyme system acts as the acid (proton) pump in the stomach, which is why omeprazole and similar drugs are often called gastric acid pump inhibitors or proton pump inhibitors.¹

Compounded formulations of omeprazole are commonly prescribed as oral aqueous suspensions. These suspensions require a basic pH to prevent chemical degradation. According to Trissel’s Stability of Compounded Formulations, “Omeprazole exhibits maximum stability at pH 11 and rapidly decomposes below pH 7.8. Increasing temperature accelerates decomposition.”² Temperature and pH are therefore important considerations when compounding with omeprazole. However, compounders can still encounter challenges with these suspensions.

The Curious Case of the Purple Preparations
Recently, PCCA’s Clinical Services department talked to pharmacies in different parts of the country who had an issue with their omeprazole suspensions. The pharmacies independently reported that their formulations had begun to turn purple or that they had noticed purple specs in the preparations within days of compounding it. The pharmacies stated that they were following a PCCA formula that has been tested with a stability-indicating assay as part of our FormulaPlus™ program. The pharmacies reported that their documentation from compounding the formulations showed that the preparations had a pH of approximately 8.5. Further, the preparations with the purple specs or purple discoloration still maintained a pH of approximately 8.5.

Possible Causes
This discoloration issue most likely indicates degradation of the active ingredient. Trissel’s Stability of Compounded Formulations points out that “as omeprazole decomposes, discoloration appears. A pale yellow discoloration does not necessarily mean unacceptable decomposition. However, suspensions with greater discoloration including dark yellow, orange, purple, brown, or black, should be discarded”² (emphasis added). Even though this was most likely what was going on, we compounders need to not just identify such issues, but also investigate possible causes to prevent them in the future. There are a few potential reasons contributing to the degradation.

1. The Manufacturer
The rate of degradation of the chemical itself can be related to how it was produced or handled by the manufacturer. All of the pharmacies indicated that they had used USP-grade omeprazole from suppliers other than PCCA. Active pharmaceutical ingredients (APIs) for human compounding are required to come from an FDA-registered manufacturer by federal law. However, PCCA only purchases APIs from FDA-registered manufacturers that have also been recently inspected for following current good manufacturing practices (CGMPs), and we consider over 40 other qualifications as well that ultimately ensure the highest quality products. This is a big part of our commitment to going beyond what is required, which we call The PCCA Standard™.

2. The Supplier
Degradation of the chemical may also be related to the processes used by the wholesaler itself. Omeprazole USP has the following packaging and storage specification in its monograph: Preserve in tight containers, and store in a cold place, protected from moisture.³ Chemical suppliers need a comprehensive quality system to ensure that pharmacies receive the right chemicals and that they have not been degraded or contaminated from the time they arrive, through the process of being packaged into containers, stored and finally shipped to arrive at the pharmacy. To ensure that this happens, PCCA employs over 20 checks, tests and verifications throughout this process, including testing the API for identity upon arrival and after repackaging the chemical.

3. The Pharmacy
One of the pharmacies indicated that they had received the omeprazole approximately 10 months ago and used it often based on the prescriptions received for this formulation. It is also possible that the pharmacy had exposed the chemical to moisture through usage, leading to more rapid degradation.

4. The Excipients
One pharmacy also noted that their excipients came from a variety of suppliers. USP Chapter <1059> discusses the importance of excipients: “The effects of excipient properties on the critical quality attributes (CQAs) of a drug product are unique for each formulation and process and may depend on properties of excipients that are not evaluated in USP or NF monographs.”⁴ It is therefore possible that the excipients they used may have also played a role in the degradation of the active ingredient.

This is why it’s important to follow a PCCA FormulaPlus formula exactly and use the PCCA ingredients listed. It has been tested in the PCCA lab using only PCCA chemicals (including APIs and excipients) and proprietary bases, except when noted. We cannot know how chemicals from other suppliers are produced, handled or repackaged, and we haven’t tested them. We can only test our own chemicals in our formulations. So any variations to these formulations, including substitution with a non-PCCA chemical or non-PCCA base, may affect physical integrity, solubility or organoleptic properties, or it may result in potency or content uniformity issues. Substitutions also cause the formula’s assigned beyond-use date (BUD) to be invalid, in which case it reverts to the default BUD indicated in USP Chapter <795> for nonsterile preparations.

As so many compounders know, “quality” in pharmacy compounding isn’t just a word; it’s knowledge and commitment, and it’s systems that we need to have in place from the chemical manufacturer through the supply chain all the way to the final preparation. We at PCCA know all of you want to provide the best possible compounded medications to your patients. That’s why the pharmacies we talked to about their omeprazole suspensions called us in the first place. And that’s why we want to be a resource for them and for you. 

If you’re interested in gaining access to our Clinical Services experts, learn more about PCCA membership. 

Matt Martin, PharmD, is the Clinical Services Manager at PCCA. He joined the PCCA Clinical Services department in September 2014. Matt graduated from Morehead State University with a BS in Chemistry in 2002, and received his PharmD from the University of Kentucky College of Pharmacy in 2006. Prior to joining the PCCA team, Matt worked in pharmacy compounding for more than eight years, and has experience with both sterile and nonsterile preparations.

References

1. AstraZeneca Pharmaceuticals. (2012). Prilosec (omeprazole) label [PDF file]. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019810s096lbl.pdf
2. Trissel, L. A. (2012). Trissel’s stability of compounded formulations (5th ed.). Washington, D.C.: American Pharmacists Association.
3. United States Pharmacopeial Convention. (2019). Omeprazole. In United States pharmacopeia and national formulary (USP 42nd ed. & NF 37th ed.). Rockville, MD: United States Pharmacopeial Convention, Inc.
4. United States Pharmacopeial Convention. (2019). General chapter <1059> excipient performance. In United States pharmacopeia and national formulary (USP 42nd ed. & NF 37th ed.). Rockville, MD: United States Pharmacopeial Convention, Inc.