THE PCCA BLOG

Choosing the Appropriate Oral Base Vehicle

Wed, 07 Dec 2022 12:00:00 GMT

by Stacey Lemus, BS, and Courtaney Davis, BBA, PCCA Senior Formulation Specialists

PCCA offers many oral base vehicle options for use in compounding. We break down the characteristics of several of these oral vehicles below to help guide you on choosing the most appropriate base for your compound.

Use caution when using certain vehicles in patients with special dietary restrictions such as diabetes or autism. When compounding for veterinary use, the pharmacist should assess each vehicle to ensure it is appropriate for the animal’s species. It is also important to check the pH of your compounded preparation to ensure adequate preservation in the chosen base.

PCCA SUSPENDIT® (PCCA #30-4825)

An all-in-one oral suspension base developed with superior anti-sedimentation technology.
Natural suspending agent with a patented synergistic polymer complex that offers a unique thixotropic flow— it thins as it’s shaken and thickens upon standing— which allows rapid redispersion of APIs with agitation and minimizes sedimentation.
All-natural sweetener derived from monk fruit.
Formulated without sugar, parabens, gluten, casein and dyes.
When wetting an active pharmaceutical ingredient (API) to make formulations using SuspendIt, most are wet with the vehicle base itself rather than using glycerin or propylene glycol.
Preserved with a combination of potassium sorbate and sodium benzoate, which is suitable for preparations with a pH below 6. In certain formulations where the pH may be higher, it would be suggested to refrigerate or additional testing may be required to validate the preservation.

Veterinary Use

SuspendIt contains sodium benzoate, a potential toxin to felines when chronically ingested, so limit use to two weeks. The pharmacist should assess each vehicle to ensure it is appropriate for the animal’s species.

PCCA-PLUS™ ORAL SUSPENDING VEHICLE (PCCA #30-3227)

Contains a suspending agent but no sweeteners.
Oral suspension base often used 1:1 with PCCA Sweet-SF™ Sugar Free Syrup Vehicle (PCCA #30-3228) or PCCA Syrup Vehicle™ (PCCA #30-3521).
Use glycerin or propylene glycol to wet APIs.
Preserved with potassium sorbate, methylparaben and propylparaben; effective over a wider pH range.

Veterinary Use

Appropriate for vet use, although the pharmacist should assess each vehicle to ensure it is appropriate for the animal’s species.

PCCA SWEET-SF SUGAR FREE SYRUP VEHICLE

Oral base vehicle used alone or 1:1 in combination with PCCA-Plus Oral Suspending Vehicle.
Contains no suspending agent. API must be soluble or mix 1:1 PCCA Sweet-SF with PCCA-Plus to suspend insoluble API.
Use sorbitol as sweetener and cherry as flavor.
Use glycerin or propylene glycol to wet API.
Preserved with potassium sorbate, methylparaben and propylparaben; effective over a wider pH range.

Veterinary Use

Appropriate for vet use, although the pharmacist should assess each vehicle to ensure it is appropriate for the animal’s species.

PCCA SYRUP VEHICLE

Contains approximately 56% sucrose, which is less than other syrup vehicles but still maintains a pleasant, sweet taste.
A good choice for medications that have a bitter and salty taste.
Use caution when using this vehicle in patients with special dietary restrictions such as diabetes or autism.
When wetting API to make formulations using Syrup Vehicle, most are wet with the vehicle base itself rather than using glycerin or propylene glycol.
Preserved with sodium benzoate, which when used alone requires a more acidic pH for preservative effectiveness (4.6 or below) unless combined with PCCA-Plus.

Veterinary Use

Appropriate for vet use, although the pharmacist should assess each vehicle to ensure it is appropriate for the animal’s species.

PCCA FIXED OIL SUSPENSION VEHICLE™ (PCCA #30-4316)

Anhydrous vehicle for APIs that are known to be unstable in water or if the aqueous stability is unknown.
Anhydrous, contains no water, which allows for extended beyond-use dating of the formulation depending on the API used.
When appropriate, oil bases can help coat a drug particle in suspension, thus making a bad-tasting drug more palatable.
Contains suspending agent but no sweeteners, giving you the flexibility to add your own sweetener for customization.
When wetting API to make formulations using Fixed Oil Suspension Vehicle, most are wet with the vehicle base itself rather than using glycerin or propylene glycol.
pH not applicable since anhydrous.

Veterinary Use

Certain species, such as avian (birds), are prone to aspiration when using oil vehicles. Make sure to consult with the pet owner and ensure a proper handling relationship with the animal to avoid issues. This vehicle is not appropriate for use in equine (horses) and certain species of rodents and reptiles. The pharmacist should assess each vehicle to ensure it is appropriate for the animal’s species.

PCCA BITTER DRUG POWDER™ USE 26 MG/ML (PCCA #30-3447)

Contains a suspending agent and a blend of sweeteners.
Helps mask the undesirable taste of medications as well as suspend the actives that may not be soluble in the preparation.
For use in aqueous formulations only and when no other suspending agent is used.
The recommended use is 26 mg/mL.
See PCCA Formula #5795, Bitter Drug Powder Oral Suspension.
Contains sodium benzoate.

Veterinary Use

Not suggested for vet use. May use Dry Powersweet (PCCA # 30-4948) 0.1-1%, acesulfame potassium 0.1-0.5% or steviol glycosides 95% 0.1-0.5% instead.

PH AND PRESERVATIVES

It is important to check the pH of your compounded preparation to ensure adequate preservation. Since some formulas have a higher pH, refrigeration may be required (per USP guidelines for preservative-free preparations) due to potential lack of preservative action of the base in a higher pH environment. Parabens may be added to the preparation to ensure preservative action.

FLAVORING

Every API has a specific taste characteristic such as bitter, sour, sweet or salty, so it is important to have a variety of flavors in stock to enhance the taste of compounded oral formulations.

ADDITIONAL INFORMATION

See our PCCA Blog post, How to Start Building Your Flavoring Inventory , for general information on flavoring, emulsifiers and sweeteners for oral bases.
For detailed information on flavoring, refer to our PCCA Flavor Guide on the Members-Only Website > Formulas > Flavor Guide or at Members-Only Website > Resources > Formula Tools > Flavor Guide
Access FormulaPlus™ extended beyond-use date studies using PCCA oral bases in the FormulaPlus Master Formula List (PCCA Document #98004).
For additional information on PCCA Bases, refer to Exclusive PCCA Bases (PCCA Document #99650).

PCCA members with Clinical Services access who have questions about compounding our formulas may contact our Clinical Services team at 800.331.2498.

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

Compounding with FlackTek DAC 1200-500

Wed, 30 Nov 2022 12:00:00 GMT

by Courtaney Davis, PCCA Sr. Formulations Specialist

The FlackTek DAC 1200-500 model is the newest addition to our ever-growing toolbox in the practice of compounding. It uses a dual/asymmetric centrifuge to mix a variety of compounding dosage forms, such as creams, gels, powders, suspensions, suppositories and troches. The technology is bladeless – which greatly reduces or eliminates the amount of air bubble entrapment typically incorporated into preparations when using more traditional methods of mixing. This results in quiet and efficient mixing, saving your pharmacy time and money!

The first question most people ask is how much can I mix in the FlackTek DAC 1200-500? To answer this question, we first must discuss two important factors – volume requirements within the mixing jar and total system weight.

First, you must determine the proper jar size for mixing the formulation. Mixing quality depends on proper volume inside the mixing jar. For optimal mixing, we recommend a fill volume of 1/3 - 1/2 of the jar capacity. Of course, there may be some exceptions. For example, when working with Progesterone powder formulations, you can push the upper limit to approximately 80% fill. The powders will compact during mixing to approximately 60% capacity, but mixing quality is not adversely affected.

PCCA carries an assortment of jar sizes, from 60 mL to 1200 mL jars, to get you started. Most jars (except the two largest jars) require a separate holder. The table below outlines the various jars and holders stocked by PCCA; however, additional sizes can be ordered directly from FlackTek if desired.

The next factor to consider when mixing is total system weight, which refers to the combined weight of the: JAR + HOLDER (if required) + FORMULATION. Functional operation relies on proper total system weight, which is between 300 Gm – 600 Gm. As an example, let’s assume you want to mix a 100 Gm batch of Estriol/Estradiol [50%/50%] 1 mg/Gm Topical Gel (VersaBase® Anhydrous HRT). Since the density of this formula is close to 1, you would want to choose the SC250 (mL) jar. This would result in a fill volume of approximately 40%. Next, let’s look at total system weight: SC250 JAR + SC250 HOLDER = 450 Gm, + FORMULATION weight of 100 Gm = 550 Gm COMBINED WEIGHT. Now you have met the two requirements to start mixing!

When utilizing our largest jar (MAX XL – SC 1200 mL), we typically mix no more than 480-490 mL’s (or Gm’s) for most liquid or cream formulations due to the weight of the SC 1200 JAR, which is approximately 110 Gm (to not exceed the 600 Gm combined weight limit). For mixing 500 mL (or Gm) formulas in the MAX XL cup (assuming volume is within the proper range in the jar), a FlackTek representative can work with you to adjust the setting to allow for the additional 10 Gm weight. Please note that pushing the weight limitations on this machine any further than this can result in balance issues, which over time can reduce the life of the machine.

For powder mixing, the maximum amount that can be mixed successfully greatly differs from one API/excipient to the next due to the density of the powder and the volume it occupies in the jar. To put this into perspective, approximately 320 Gm’s of Lactose Monohydrate will occupy 50% of the SC1200 mL jar, compared to only 90 Gm’s of Progesterone USP Special Micronized or 209 Gm’s of Microcrystalline Cellulose NF.

PCCA has tested over 40 formulations in the FlackTek DAC 1200-500 using a variety of PCCA Bases. All formulas in the database have been validated through chemical potency testing of multiple points within the formula to ensure potency and uniformity. It is important to note that any deviation from the listed procedure, container or batch size would require re-validation of that process to ensure potency/uniformity is met.

The FlackTek DAC 1200-500 is known for its world-class quality. It is hand built in the United States to the highest standards, producing an exceptionally robust machine that stands up to frequent and heavy use. In addition, FlackTek customer service is unmatched in their industry. If you are looking to optimize efficiency by reducing cleanup and mixing time of many popular formulas, look no further than the FlackTek DAC 1200-500.

What PCCA Formulas Mean for Compounders

Wed, 04 Sep 2019 14:44:00 GMT

By PCCA

From research and development to testing and updating, our 9,000+ formulas are far more than a list of ingredients and procedures. We have developed a robust system to ensure that we create and maintain formulas that provide PCCA members with what they need to compound high-quality, pharmaceutically elegant customized medications for their patients — all while complying with the latest standards in pharmacy compounding. But what does that look like? What’s in a PCCA formula? Let’s take a look at the work our Formulation Development team puts into every formula and what that ultimately means for PCCA members and their pharmacies.

Developing a PCCA Formula
There are many ways it can begin. A compounder receives a prescription from a physician and would like assistance with the formulation. Or there is a shortage of a commercial product in the industry that compounders can help with. Or our clinical compounding pharmacists notice a trend or a significant patient need. Or we develop a new base, and our Research and Development, Clinical Services, and Formulation Development departments work together to determine new formulas for it based on research and clinical need. Regardless of where it started, every potential formula is entered as a request in our formula management system, the custom-built software that hosts our formula database, in which we’ve invested over $500,000. Then our Formulation Development team gets to work.

This is the genesis of a PCCA formula, one that will, if everything goes as planned, join the others in our database — over 9,000 of them representing almost 40 years of development and centuries of combined pharmacy, chemistry and laboratory experience across multiple teams involved.

Once someone submits a request in our formula management system, the Formulation Development team reviews it and takes many factors into consideration:

Patient safety
Clinical need
Existing patents
Existing commercial products
Regulatory status
Chemical stability, compatibility, solubility, melting point, pH and other relevant properties
Route of administration
Whether we have all needed ingredients
Related studies and other literature references

While researching each formula request, they may look at the United States Pharmacopeia and National Formulary, The Merck Index, Martindale, Trissel’s Stability of Compounded Formulations, the Handbook of Pharmaceutical Excipients and other references. This initial research period involves Melissa Merrell Rhoads, PharmD, PCCA Director of Formulation Development, as well as our scientists, pharmacists and formulation specialists.

If the request is feasible based on the many considerations they take into account, one of our formulation scientists, pharmacists or specialists reviews all of the information again, and then they compound it in the lab, carefully documenting the procedures, calculations and any relevant findings, such as the preparation’s appearance, pH and the time it took to prepare. This typically includes three to four lab trials and about three hours of lab time per formula, though simple formulas could require only one half-hour compounding trial, and complex ones could take over eight hours of lab time across several trials. Regardless, they record their notes in our formula management system, which contains all of the information from the initial request and research to the final formula.

Once they complete the preparation, the Formulation Development team observes it for an amount of time determined by the default beyond-use date (BUD) allowed by USP. For example, they will observe a preserved aqueous topical formulation for 35 days. The maximum allowable default BUD for this type of preparation indicated in the current USP General Chapter <795> is 30 days, and it’s 35 days in the new version of the chapter that becomes official on December 1, 2019. Depending on the type of preparation, the team monitors for changes in physical characteristics, such as precipitation, discoloration, redistribution upon agitation, separation, crystallization, hardening, pH and others. If they do not observe any changes, they assign the appropriate BUD, and the formula then proceeds to the final review process.

During final review, the Formulation Development team triple-checks the formula. That is, every aspect has to be approved without any changes by three separate team members, including Melissa. The team reviews the original formulation research; regulatory status; clinical need and use; all lab-trial notes, calculations and procedures; and any other accompanying information. The team also reviews the BUD listed in the formula again to ensure that it complies with the applicable USP standard. If the team needs to make any changes during the final review, the triple-check process begins again. Once three of our Formulation Development team members approve the formula and all supporting information, then it is submitted for publication in PCCA’s formula management system. When it is published, it is available on the PCCA Members-Only Website.

Stability and Preservative Testing
Our Formulation Development team also submits our most popular formulas for stability testing to extend their BUDs beyond the standard ones determined by USP. This is what we call our FormulaPlus™ program. FormulaPlus formulas are studied using a stability-indicating assay method over the course of a period of time at refrigerated and room temperature. The assay also undergoes method development and validation, a costly process ensuring that it works appropriately to indicate the stability over time of the preparation within the study conditions.

Due to the recent changes in USP General Chapter <795>, we are also subjecting all of our FormulaPlus formulas to USP <51> antimicrobial effectiveness testing. Also known as preservative efficacy testing, this validates the preservative system in a formulation. Most of our FormulaPlus formulas have already been tested according to USP <51> standards and passed, and all of them will be tested by December 1, 2019, when the new Chapter <795> goes into effect.

When our formulas have passed all of this testing, they are indicated in our formula database with the “BUD Study” designation in the title and accompanied by the FormulaPlus symbol: . We also add the report of the stability-indicating assay results to the Members-Only Website so that compounders can keep a copy of it for their records if they use the corresponding formula. A link to the report is available in each FormulaPlus formula. We currently have over 140 such formulas with extended BUDs, and we study more every year.

PCCA members can view all of our formulas with extended BUDs in the FormulaPlus master list.

Recently, our Formulation Development team has also begun to develop and submit bracketed formulas for FormulaPlus testing. These allow compounders to use a single formula to create a number of compounds with extended BUDs as long as the active ingredient in each compound is within the range of strengths listed in the formula. We currently have over 35 bracketed formulas with extended BUDs in our formula database, and we will continue to develop more in the future.

Revising and Updating PCCA Formulas
As any experienced compounder knows, it’s necessary to change formulas from time to time. This is why our Formulation Development team also meticulously maintains our formula database, ensuring that all of the individual formulas are up to date and that PCCA members have access to the latest information about them.

Under certain circumstances, such as when we need to change a chemical supplier, we may need to make adjustments to existing formulas that contain that chemical. Furthermore, if an ingredient in a formula is no longer available and we do not have a viable replacement for it, our Formulation Development team will retire the formula from the database. The team also monitors lot-specific formulas, and when the lot of the chemical listed in the formula expires, they retire the formula from the database as well.

At the top of a PCCA formula, one of the first things the compounder will notice is the version number. Currently, PCCA Formula #12956 (a bracketed FormulaPlus formula with estriol and estradiol in VersaBase® Cream) is in version six, for example. The version number may represent changes to the procedures or ingredients, or it may indicate additional notes or literature citations being added. Regardless, whenever Formulation Development makes a change to a PCCA formula, the formula’s version is automatically updated in the formula management system. This is why we encourage our members to check our database when using a PCCA formula to ensure that they are always using the latest version.

Sometimes, Formulation Development will also remove formulas due to regulatory changes. When the FDA made its initial ruling for the 503A Bulk Drug Substances list in early 2019, in which it indicated that tranilast was not going to be included on the list, our Formulation Development team identified all of our tranilast formulas for human use. When the FDA’s final ruling went into effect on March 21, 2019, the team had already removed all of those formulas from our database to ensure that we were not providing formulas that no longer complied with regulations.

Also on The PCCA Blog: FDA Guidance Explained: Compounding with Bulk Drug Substances.

Similarly, the new and updated USP General Chapters <795>, <797> and <800> affect formulations, and we are updating formulas to comply with these changes. For example, the new Chapter <795> changes how default BUDs are assigned and which types of compounds receive which BUDs, so Formulation Development will update the BUDs for every PCCA formula that these changes affect by December 1, 2019, when the chapter becomes official. Formulation Development is also updating all PCCA formulas that contain ingredients included on the National Institute for Occupational Safety and Health’s list hazardous drugs (known commonly as the NIOSH list). The updated formulas indicate that they contain hazardous drugs, which will help compounders with USP <800> compliance.

All of this formula and database maintenance ensures that PCCA members have access to formulas that comply with the latest standards in the pharmacy compounding industry. It’s also a testament to the dedication and diligence of our Formulation Development department. In 2018 alone, they developed 431 new formulas — including 22 new FormulaPlus studied formulas — and updated over 8,000 existing formulas.

What PCCA Formulas Mean for PCCA Members
What all of this means for PCCA members is saved time, money and stress as well as reduced risk for their pharmacies and patients. Every PCCA formula they use has been researched, compounded, observed, reviewed, approved and (when necessary) updated by a team of experienced formulation scientists, pharmacists and specialists, representing hours of work as well as lab space and materials. When it comes to FormulaPlus formulas, we’ve taken care of stability and preservative efficacy testing, saving members thousands of dollars per formula, and potentially tens of thousands of dollars for complex formulations. For bracketed formulas, the cost savings double.

So what’s in a PCCA formula? A lot. And we want to make sure everything that goes into it is scientifically sound and of high quality to save our members time and money, to reduce risk for their pharmacies, and to promote safety and efficacy for their patients.

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