THE PCCA BLOG

USP Chapter 795-Related Changes to Formulations

Wed, 28 Jun 2023 11:00:00 GMT

by Melissa Merrell Rhoads, PharmD, PCCA Director of Formulations

The revised USP Chapter 795 will become official on November 1, 2023. This chapter describes the full guidelines for pharmaceutical compounding of nonsterile preparations (CNSPs). Specifically looking at the revisions related to the beyond-use date (BUD), we will be updating all PCCA formulas for compliance.

USP states the BUDs presented “are based on the ability of the CNSP to maintain chemical and physical stability and to suppress microbial growth.” The dosage forms are described as aqueous and nonaqueous based on water activity (a_wor Aw). An aqueous preparation is one that has an a_w ≥ 0.6 (e.g., emulsions, gels, creams, solutions, sprays or suspensions). Nonaqueous dosage forms have an a_w < 0.6 and are separated into two categories: “nonaqueous oral liquid” and “other nonaqueous dosage forms” (e.g., capsules, tablets, granules, powders, nonaqueous topicals, suppositories, and troches or lozenges).

Below are the revised BUDs and notes that will be added to all nonsterile formulas.

Non-preserved aqueous (PF) – 14 days refrigerated

Note: According to USP guidelines, “in the absence of a USP-NF Compounded Preparation Monograph or CNSP-Specific Stability Information,” the maximum BUD for a CNSP that is a non-preserved aqueous dosage form with a water activity (Aw) of >/= 0.6 is 14 days stored in a refrigerator, unless such storage affects the physical or chemical properties of the CNSP.

For more information, refer to current USP Chapter 795.

Preserved aqueous – 35 days

Note: According to USP guidelines, “in the absence of a USP-NF Compounded Preparation Monograph or CNSP-Specific Stability Information,” the maximum BUD for a CNSP that is a preserved aqueous dosage form with a water activity (Aw) of >/= 0.6 is 35 days.

For more information, refer to current USP Chapter 795.

Nonaqueous (anhydrous) oral liquid – 90 days

Note: According to USP guidelines, “in the absence of a USP-NF Compounded Preparation Monograph or CNSP-Specific Stability Information,” the maximum BUD for a CNSP that is a nonaqueous oral liquid dosage form with a water activity (Aw) of < 0.6 is 90 days.

For more information, refer to current USP Chapter 795.

Nonaqueous (anhydrous) excluding nonaqueous oral liquids – 180 days

Note: According to USP guidelines, “in the absence of a USP-NF Compounded Preparation Monograph or CNSP-Specific Stability Information,” the maximum BUD for a compounded CNSP that is a nonaqueous dosage form (excluding nonaqueous oral liquids) with a water activity (Aw) of < 0.6 is 180 days.

For more information, refer to current USP Chapter 795.

Additional notes are also being added to the formulas to bring awareness to some of the guidelines that the USP Chapter 795 now requires during the compounding process. The notes below are not all encompassing of the chapter requirements, so we recommend that you become familiar with the chapter and that you are in compliance with all requirements.

Component evaluation before use

Note: USP Chapter 795 states guidelines regarding “component evaluation before use.” “Compounding personnel must visually re-inspect all components to detect any container breakage, looseness of the cap or closure, or deviation from the expected appearance or texture of the contents that might have occurred during storage.”

Visual inspection

Note: USP Chapter 795 states guidelines regarding “visual inspection.” After the completion of compounding, the preparation must be visually inspected to determine whether the physical appearance is as expected. The inspection must also include visual inspection of container closure integrity.

Establishing and extending BUD

Note: USP Chapter 795 sets forth parameters to consider when establishing a BUD and states, “BUDs for CNSPs should be established conservatively to ensure that the preparation maintains its required characteristics to minimize the risk of contamination or degradation.” Stability testing may be performed by a FDA-registered laboratory using a stability-indicating assay to extend the BUD.  An antimicrobial effectiveness test (see USP Chapter 51) must also be performed by a FDA-registered laboratory when extending the BUD of an aqueous CNSP.

PCCA Members with clinical services may contact our Clinical Services Team for additional information on PCCA Formulas and other compounding concerns.

The complete version of this article originally appeared in PCCA’s members-only magazine, the Apothagram.

Similar Names. Different Products - SuspendIt® & SuspendIt® Anhydrous

Wed, 05 Apr 2023 11:00:00 GMT

by Matt Martin, PharmD, BCSCP, PCCA Director of Clinical Services

Although SuspendIt® and SuspendIt® Anhydrous share similar names and some characteristics, the two oral suspending vehicles are very different. Each product offers distinct benefits to compounders and patients. Most notably, SuspendIt is an aqueous (containing water) base and SuspendIt Anhydrous is a nonaqueous (anhydrous) base.

Water Activity

In the revisions to USP 795, effective November 1, 2023, a distinction is made between aqueous and nonaqueous preparations based on their water activity (a_w).

Water activity is not a measure of water content, but rather the water in a substance that is unbound and freely available to participate in reactions such as hydrolysis that may cause drug degradation or in the proliferation of microbes, causing microbial growth or contamination. A water activity equal to or greater than 0.6 defines a preparation as aqueous, while a water activity below 0.6 defines a nonaqueous preparation. Compounders are not expected to test for water activity, but rather to consider the dosage form they are making against a lengthy table in the revisions to 795.

Aqueous preparations are offered shorter BUDs compared to nonaqueous preparations unless the appropriate data exists to support longer BUDs. PCCA has created a number of formulations with this stability data and designates these as FormulaPlus^TM formulations.

SuspendIt

SuspendIt (PCCA #30-4825) is our “all in one” aqueous (a_w > 0.6) oral suspension vehicle. SuspendIt contains a unique synergistic polymer complex, which allows rapid redispersion of APIs with agitation and minimizes sedimentation. It is made with an all-natural sweetener derived from monk fruit, making SuspendIt an ideal choice for patients requiring formulations without sugar, casein, gluten or any condition that requires an oral suspension formula. SuspendIt is compatible with all feeding tubes.

SuspendIt is a preserved aqueous oral suspension vehicle that uses sodium benzoate as the preservative. The revisions to USP 795 offers BUDs of up to 35 days for an aqueous preserved preparation. Please note that in felines, sodium benzoate can be a potential toxin when chronically administered and use should be limited to two weeks.

PCCA has created many formulations for SuspendIt including FormulaPlus^TMformulations supported by a stability indicating assay and USP 51 antimicrobial effectiveness testing.

SuspendIt Anhydrous

SuspendIt Anhydrous (PCCA #30-5176) is our patent-pending anhydrous oral suspension vehicle. As an anhydrous vehicle, its water activity is less than 0.6, which meets the definition of nonaqueous in the revisions to USP 795. The revised 795 provides up to a 90-day BUD for nonaqueous oral preparations.

We combined surfactants within our anhydrous vehicle to make SuspendIt Anhydrous water miscible. The self-emulsifying properties of SuspendIt Anhydrous may also improve the solubility, dispersibility and possibly enhance bioavailability of APIs with poor water-solubility.

SuspendIt Anhydrous is compatible with hydrophilic or lipophilic drugs. Naturally sweetened with monk fruit, it offers improved palatability and mixes easily with water, juice or breast milk. Its ability to mix with fluids may make patient compliance to medication adherence easier.

SuspendIt Anhydrous is also compatible with polyurethane nasogastric (feeding) tubes. It is preservative free and free of many allergens.

For veterinary compounding, please note that in animals with pancreatitis, the use of any anhydrous vehicle that contains a high concentration of oils is not recommended. Caution must also be exercised in certain species, such as birds or herbivorous animals.

Access to SuspendIt (aqueous) and SuspendIt Anhydrous provides opportunities for compounders to serve the needs of their patients as is appropriate between aqueous and nonaqueous preparations and BUDs that work for prescribers, patients and compounding pharmacists.

We are happy discuss these innovative bases with you and the value of PCCA Membership. Members with clinical services can call our Clinical Services team at 800.331.2498 to discuss use of these and other PCCA bases, or any additional compounding concerns.

At-a-Glance Reference

SuspendIt	SuspendIt Anhydrous
Part #30-4825	Part #30-5176
Aqueous – water activity > 0.6	Nonaqueous (anhydrous) – water activity
USP default BUD: 35 days	USP default BUD: 90 days