The Role of Pharmaceutical Formulation Development
Unlike other drug development activities, which are checkbox activities to meet FDA requirements, a good formulation solves a problem: “I’ve got this new molecule with fantastic in vitro activity, but how do I dose it? Will it be stable? Can I measure this? Is this suitable for the given therapeutic indication? Will it get to the target cell/binding site? Will it resist degradation long enough to get there?” While there may be many problems to solve, the solutions can be life-changing, literally!
I’m a synthetic/medicinal chemist by training so the bits of formulation services I’ve done throughout my career have been either modestly successful or heavily guided. For the most part, the typical organic chemist formulation strategy – dissolve it in DMSO. That actually works. Sometimes. However, there are so many subtle considerations. Many years ago, I was formulating an eye drop and I was reminded that osmolality needed to be considered to prevent pain during application. Color, odor… these attributes are important not only for the end game of commercial marketing but also for blinded, placebo-controlled clinical trials. Not to mention the use of only approved inactive ingredients! My guides helped me subvert the tendency to simply “blast it into the cell any which way.” Formulation is an art as well as a science.
Pharma Formulation Considerations
More recently, selling formulation services, I have learned to ask the right questions, not only of the prospective customer but also my team. “Do you have experience with this route of administration? Do you have experience with this molecular class? Do you have the capacity to work within our desired time frame? Will you work collaboratively with us? These kinds of questions need to be presented upfront to both customers and my colleagues, and this will hopefully establish a successful relationship where both groups are aligned on everything from metrics of success to who owns the intellectual property. Choosing a formulator can be an exercise in Visio charting.
In my 20+ year biopharmaceuticals career the formulator has always been either the hero or the villain. The hero when she comes up with an efficacious and manufacture-able dosage form. The villain when she asks the synthetic chemist (aka me, for many years) for 100 g of API. The hero when PK/PD shows sustained, high levels of API in circulation. The villain when an additional toxicology study is prescribed. The hero when clinical product shows up on time. The villain when a hiccup in the manufacturing process results in a costly delay. Whichever the case, a drug’s dosage form and formulation is at the heart of its development program. It sets the pace for cost of goods, clinical trial design, pharmacoeconomics and commercial sales projections.
Dosage Forms and Delivery Systems
Therefore, whether you’re conducting the project in-house or by contracting a formulation services partner, it is of key importance during product development to make sound formulation decisions and allocate adequate resources for a suitable dosage form. The process starts by securing a thorough understanding of the candidate API’s properties; the therapeutic indication will have a huge impact on acceptable dosage form and route of administration, and, in fact, the goals of the development project are important. What is the API? Its properties? Is the disease acute or chronic? Deadly or merely annoying? Is the intent of the project to deliver a commercially viable drug product or simply show proof of concept to investors? The process ends with a clinical supply. The interim is busy with days, weeks, even months of experimentation paired with laborious analytical
In this four-part blog post series, I will talk about these various elements of the process informatively and, hopefully with some much-needed humor for those of us working through such projects day to day. Part 2 will muse about API and physicochemical considerations, part 3 will consider scaling from lab bench to production suite, and part 4 will consider the multitude of analytical tasks that surround a formulation effort.
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