Isnare Free Articles
Authors Contents [Add OpenSearch]
Distribute your articles to more than 6,000+ sites and 40,000+ email group publisher subscribers for as low as $2 / article...
Index  Article Directory  Medicines and Remedies
Embed this Article  
Bruce Rehlaender, Ph.D.

Bruce Rehlaender, Ph.D. x 30 articles

Liked the article? Consider buying me a beer!

If there were a bar where all of the hip drug product formulators hung out at the end of a hard day of formulating, two things would be certain, the beers on tap would be from breweries like Avery, Greenflash, and Dogfish Head rather than Coors, Miller, and Anheuser Busch, and all of the jokes would be about discovery guys. We formulators would pick on the discovery guys in part because deep down inside we realize they are smarter than us and get more dates than we do and in part because they make our lives miserable, and they think that DMSO is a formulation. Just as likely in this bar is that no one would dare challenge out loud the sanctity of our bible, the FDA Inactive Ingredients Guide, for fear of being beaten up out back by a bunch of hooligan formulation zealots.

Just in case there are any discovery guys reading this, the Inactive Ingredients Guide ( is a list of (supposedly) all excipients used in marketed drug products listed by route of administration and level in the formulation. For a long time this was a pdf document that hadn’t been revised since 1996, but more recently, the Agency has maintained it as a searchable database that is presumably updated as new drug products are approved. We rely on it to know what has been safely done already so that we don’t come up with a formula that provides great solubility, stability, and bioavailability but does irreparable damage to the patient. And just as importantly, we rely on it so that when our boss or sponsor asks us if that excipient is precedented, we can point to the list and say “there it is; FDA said it’s okay.”

While the Inactive Ingredients Guide is certainly a useful reference, and we can be grateful to the Agency for providing it to us, there are a number of pitfalls with relying on it too heavily, and without trying to pick a fight, I want to point some of these out:

• First and foremost, the guide is only a list of excipients that have been used and not a list of excipients that are allowed in a particular type of dosage form. If an excipient is not on the list, it may mean that it is harmful, but it more likely means that no one has had the guts to venture off The List and use it. For example, anyone who has ever worked in inhalation can tell you, sometimes rather emphatically, that phosphate buffer cannot be used in nebulizer formulations, but I have yet to find anyone who can tell me why not. Even the pulmonary division at CDER may be unclear on this point, as I have seen phosphate buffered saline used as a nebulized placebo in some FDA-approved clinical trials.

• Just as importantly, the fact that an excipient is on the list for a particular route of administration does not necessarily mean that it is safe. Paclitaxel has been formulated with high levels of the PEGylated surfactants, Cremophor EL and Polysorbate 80, both of which are known to cause anaphylaxis in susceptible humans and in pretty much all dogs. The FDA accepted these formulations because they were the only thing that worked for a drug that isn’t used unless it is the only thing that works. It doesn’t mean you can go crazy with the Cremophor in an injectable formulation of ibuprofen.

• Even if a drug is on the list for a particular route of delivery, the details of administration never seem to match the target at hand. Looking up an excipient in the database is just the first step in assessing whether it is precedented. One need next dig out package inserts for the actual drug products it is used in and determine whether the level of the excipient and the site, rate, and duration of administration as well as the dosing frequency and period of dosing are sufficiently similar to the intended use at hand. Since the names of the drug products are not listed (or even hinted at) in the database, this is best done by searching the name of the excipient and the route of administration on a package insert-providing website such as or If you are doing anything more complicated than a bolus injection or an IR tablet, don’t count on finding an exact match to what you want to do.

• Since the list includes only approved products and since it takes so long to get a product approved, the fact that an excipient is not on the list does not mean that it has not undergone extensive clinical testing and been found to be safe. Only a few years ago many of our clients shied away from using hydroxypropyl-beta-cyclodextrin (HPBCD) even in Phase 1 formulations since the only two cyclodextrin-based formulations on the list used the sulfobutyl ether (Captisol®). The four HPBCD-containing products currently on the list would likely have been through most or all of their Phase 3 trials at the time.

• Contrary to what some may believe, the database is not complete. When performing the abovementioned searches on package insert websites I almost always come up with a few drug products that are not included on the FDA list.

• Another more trivial concern with using the database is that you really need to be sure that you know the correct name of whatever you are looking for. For example, if you do a search on ethanol, you will come up with a relatively short list of ethanolamides and ethanolamines but nothing that would taste good in your punchbowl. You need to search on alcohol if you want to know where the strong stuff is.

What are the disadvantages of using an excipient that is not precedented? From the regulatory perspective, the FDA is only interested in whether the overall drug product is safe and efficacious and well enough controlled to be consistent from batch to batch. They are not the ones telling us we can only use what is on their list. Nonetheless, besides pleasing your boss, there are some distinct advantages to sticking to what is tried and true:

• The prior use of an excipient in a similar formulation amounts to a clinical history, just as a drug that has been used before has a clinical history that it allows it to slide through on an ANDA or 505.b.2. Every drug product is its own entity and is judged on its own merits regardless of what excipients it contains, but having a precedent substantially reduces the risk of an unanticipated problem and makes for easier writing in the Pharmaceutical Development section of an NDA.

• The fact that an excipient has been used for the same route of delivery in an approved product means that there is a Drug Master File on it as well as a supply that is appropriate for the use. A little carnauba wax might be just the thing to brighten up your injectable formulation, but you might be hard pressed to find an endotoxin-tested grade.

The main reason we formulators have such a hard time getting dates is that we are inherently boring people. While the discovery guys are creating spanking new molecules for novel targets, we are stuck in our dingy labs searching the shelves for those same old bottles of HPMC or PEG or lactose. We tend to blame our conservative ways, directly or indirectly, on the FDA, but it is really not they who are holding us back. In most cases it makes sense to stick to what we know, but I wonder how often safer or otherwise better formulations have been overlooked simply because they were not sufficiently similar to what had been done before.

As some final advice for my fellow formulators:

1. Never forget that all those sexy discovery, pre-clin, and clinical people are useless without us.

2. As to the title of this piece, I would certainly not advise you to try bacon fat as an excipient, especially if you are trying to reformulate Lipitor, but if there were a demonstrated safety or efficacy advantage and you had a well-controlled supply, there is no legal reason you could not throw in a bit.

3. If you are thinking about a novel excipient, be bold and stand your ground. Don’t let anyone tell you that you can’t use it just because it is not on some list. Go ahead and throw in a sodium rather than a potassium salt or a sulfate rather than a chloride. Be the first on your block to put whatever crazy new thing Gattefosse comes up with into an injectable. Use phosphate in a nebulizer or black pepper extract in a nasal spray. Whatever you put in, I promise I will find a way to use it too. Once you get it on The List.

Find more articles like this one by searching for "PharmaDirections Formulation Development Blog".

Rate this article:
Bruce Rehlaender, Ph.D., Principal, Formulation Development, PharmaDirections, a pharmaceutical consulting and project management company specializing in preclinical development, formulation development and regulatory affairs. We direct development for virtual biotechs.
Important NoticeDISCLAIMER: All information, content, and data in this article are sole opinions and/or findings of the individual user or organization that registered and submitted this article at without any fee. The article is strictly for educational or entertainment purposes only and should not be used in any way, implemented or applied without consultation from a professional. We at do not, in anyway, contribute or include our own findings, facts and opinions in any articles presented in this site. Publishing this article does not constitute's support or sponsorship for this article. is an article publishing service. Please read our Terms of Service for more information.

Most Recent Articles

Renovate Your Lawn Beautifully With Lawn Care and Maintenance Services

An Article by LAZICH LEO in Gardening

10 months ago

An unkempt and ugly lawn is not only an eyesore, it also creates a negative impact on your property. If you have let go of lawn care so much so that it is over run with weeds or shows bare patches, a lawn renovation is in order. Repairing your lawn may be a good idea if the about 25% of your lawn is in bad shape...

Custom Hanging Signs Sydney - Affordable Way of Promoting Your Business

An Article by Mike Layman in Marketing

10 months ago

Hanging Signs are not just an amazing and highly cost effective way of advertising your products and services; they are easier to setup in comparison to other advertisement signs Ė just hang them from a pair of hooks or whatever and you're done. Needless to add, this also makes them more economical than other outdoor or indoor advertisement material...

Armor Your Laptop in Style With Printable Laptop Sleeves

An Article by Rohit B in Finances

10 months ago

To help you with both of your purposes, let us discuss about such a service which will help you out here to create your own laptop sleeve. So as I told you in the above paragraph, which I would have started my personal service or something to help you out of this situation. But let me inform you what you must be thinking is just something hypothetical, but thatís not true...

Start School in Time by Using Automatic School Bell

An Article by Vivency Global in Education

10 months ago

School is first place where children learn discipline, good manners and punctuality. The automatic school bell solutions are really important and makes away from manual errors. Humans may ring the bell at in appropriate time but the machine cannot. The most of the school are digitalized with interactive boards, automatic bells, CCTV and many...

Applying For No Credit Check Mortgage Loan? Ė Expert Tips to Follow

An Article by Roy Robbins in Finances

10 months ago

Interestingly, the option of no credit check mortgage loan has been made available by some lenders. So, one does not need to undergo tedious process of credit assessment. However getting quick approval for an affordable mortgage no credit check loan is not easy. Some stringent approval criteria may apply...

70-345 Microsoft Exchange Server 2016 Study Books

An Article by Chung Crissler in Internet

10 months ago

Examunion offers you a comprehensive look at the best prospects available in 70-345 exam questions throughout the Industry. Not only will you be given theoretical, but also given 70-345 Microsoft Exchange Server 2016 study books which will give you even more practice than before. Try our Designing and Deploying Microsoft Exchange Server 2016 70-345 exam test today and succeed in your Designing and Deploying Microsoft Exchange Server 2016 70-345 exam...

Microsoft MCSE 70-339 Practice Exam SharePoint Server 2016 70-339 Questions Material

An Article by Chung Crissler in Education

10 months ago

Maybe on other web sites or books, you can also see the related training materials. But as long as you compare Examunion product with theirs, you will find that our product has a broader coverage of the certification exam's outline. You can free download part of Microsoft MCSE 70-339 exam books from Examunion website as a try to detect the quality of our products...

Gain Weight and Build Muscle

An Article by Arati Shah in Wellness, Fitness and Diet

10 months ago

Several individuals do not succeed in their passion to maintain a healthy diet due to the lack of knowledge of eating healthy at work. When at work, many find it difficult to stay committed to a diet plan due to several unavoidable reasons such as colleagues might request to eat with them, availability of lots of delicious food at workplace, etc...

XenApp and XenDesktop 7.6 LTSR 1Y0-202 Questions

An Article by Kruis Barry in Education

10 months ago

1Y0-202 is a challenging exam, with our XenApp and XenDesktop 7. 6 LTSR 1Y0-202 questions; you can feel safe with our question and answers that will help you in obtaining your successful completion of your 1Y0-202 exam. All of our practice exams including the 1Y0-202 exam will prepare you for success...

VSphere 6.5 Foundations Exam 2V0-602 Dumps

An Article by Kruis Barry in Education

10 months ago

Passcert vSphere 6. 5 Foundations 2V0-602 dumps 2V0-602 help you to save a lot of time and effort. You 2V0-602 also use the extra time and effort to earn more money. Passcert provide you the product with high quality and reliability. You 2V0-602 free download online part of Passcert providing vSphere 6...

Citrix Certification 1Y0-202 Exam Answers Passtcert

An Article by Nigel Reyez in Computers and Technology

10 months ago

Passtcert is a website which can help you save time and energy to rapidly and efficiently master the Citrix certification 1Y0-202 exam related knowledge. If you are interested in Passtcert, you can first free download part of Passtcert Citrix Certification 1Y0-202 exam answers on the Internet as a try...

Benefits to Your Wedding Provided by Limo Service in Pittsburgh, PA

An Article by Iris K. Allen in Marriage

10 months ago

Using professional transportation on your wedding day may seem like a given and a basic booking to make, but considering the effect that it can have, youíd serve your wedding day well to be selective with your booking. Find a worthwhile company and secure every wedding transportation need with a suitable Pittsburgh Limousine...

Mark the Family Wedding With a Denver Bus Rental

An Article by Lucille W. Hill in Travel

10 months ago

The obligatory family wedding comes with challenges, but it also offers opportunities. A Coach Bus Denver will make it possible for your extended family to reconnect, save some cash, and all attend the family wedding as part of a group. Take Note of Transportation NecessitiesComprehensive research into all elements of transportation should come before you make reservation from any of the Charter Bus Companies Denver...

Killtest 2017 Microsoft MCSA 70-764 Test Questions Microsoft 70-764 Practice Test

An Article by Delia Green in Education

10 months ago

70-764 Administering a SQL Database Infrastructure is among the many most respected exams so you can get good work opportunities. We can complete devoid of much frantic use the particular help regarding Microsoft MCSA 70-764 Test Questions Microsoft 70-764 Practice Test that are exclusively made for people who will need advice...

2V0-602 VSphere 6.5 Foundations VMware VCP6.5-DCV 2V0-602 Exam Test Prep

An Article by Morris Porreca in Education

10 months ago

About VMware 2V0-602 exam, you can find these questions from different web sites or books, but the key is logical and connected. Our questions and answers will not only allow you effortlessly through the exam first time, but also can save your valuable time. Examgood can provide professional and high quality products...

MLA Style Citation:
Ph.D., Rehlaender, Bruce "Pharmaceutical Formulation Development Series: Why Canít I Use Bacon Fat In My Drug Product Formulation?." Pharmaceutical Formulation Development Series: Why Canít I Use Bacon Fat In My Drug Product Formulation?. 08 Apr. 2013 24 Jun. 2018 <>.
APA Style Citation:
Ph.D., Rehlaender, Bruce (2013, April 08). Pharmaceutical Formulation Development Series: Why Canít I Use Bacon Fat In My Drug Product Formulation?. Retrieved June 24, 2018, from
Chicago Style Citation:
Ph.D., Rehlaender, Bruce "Pharmaceutical Formulation Development Series: Why Canít I Use Bacon Fat In My Drug Product Formulation?." Pharmaceutical Formulation Development Series: Why Canít I Use Bacon Fat In My Drug Product Formulation?
Copy and paste the code below to embed this article:
<a class="embedly-card" href="">Pharmaceutical Formulation Development Series: Why Canít I Use Bacon Fat In My Drug Product Formulation?</a> <script>!function(a){var b="embedly-platform",c="script";if(!a.getElementById(b)){ var d=a.createElement(c);,d.src=("https:"===document.location.protocol?"https":"http")+"://"; var e=document.getElementsByTagName(c)[0];e.parentNode.insertBefore(d,e)}}(document);</script>