A solution for moisture-sensitive actives, focusing on Sitagliptin
Given that diabetes affects millions of individuals worldwide, it is critical to concentrate on medicine and treatment now more than ever. With 10 million Americans receiving prescriptions for Sitagliptin as a medication, it has proven to be both popular and beneficial for patients.
IMCD’s experts at the Pharmaceutical Technical Centre in Mumbai recently conducted a study to develop a solution for moisture-sensitive actives, focusing on Sitagliptin. The main aim was understanding Sitagliptin and other components to find an efficient, stable, and affordable solution.
We sat down with Prajal Pandhare, IMCD India’s Assistant Manager for Application Development, to discuss why Sitagliptin was chosen for the case study, the results, and the biggest challenges.
Why did you choose Sitagliptin for this study?
Prajal: Diabetes is a chronic global disease that can affect anybody at any age. One of the most used drugs in the treatment of type 2 diabetes is an orally taken Sitagliptin tablet. This is a blockbuster molecule with 3 billion $ sales in 2010 and its patent expires in 2022/2023. The active is quite difficult to work with since it’s moisture-sensitive and has poor flow & compactability, so a direct compression manufacturing process is almost impossible. We wanted to investigate and create a robust, stable formulation that is simultaneously cost-efficient.
What were your biggest challenges ?
Prajal: Our issues are the same as those of our customers – one being poor flowability, compactability, and the other being Sitagliptin’s moisture sensitivity. The high level of moisture sensitivity prevented us from using a MADG (moisture activated dry granulation) process. We opted for a special grade of anhydrous dicalcium phosphate that allowed us to test our formula in two different manufacturing processes. We evaluated the potential of using this grade of DCPA for moisture-sensitive APIs using both roller compaction and slugging methods. Additionally, we used a special coating grade using a PVA-PEG graft polymer that is favourable when working with moisture-sensitive drugs. This instant release coating is highly impermeable to water – making it ideal for moisture-sensitive active ingredients and significantly increasing formulation stability.
How can this help Sitagliptin manufacturers?
Prajal: We have developed a cost-effective formulation using the sustainable process of dry granulation. Our formula is equally robust for roller compaction and slugging methods. Additionally, our coating is ideal for any moisture-sensitive drug and better in many ways for a standard coating process. Our coating solution is fast and straightforward. You see, this highly flexible film former can be prepared at room temperature, and no plasticiser is required. Additionally, this polymer has low viscosity, which allows for the creation of spray suspensions with a solids content of 20-25%, resulting in exceptionally cost-efficient manufacturing processes. Furthermore, our three-month stability data showed excellent results and the dissolution profiles from our trials match those of the originator. Indirectly, we have shown formulation and process feasibility that can be beneficial for other moisture-sensitive APIs like Amlodipine Besylate, Sildenafil Citrate, Rosuvastatin, Varenicline Tartrate, Isosorbide Dinitrate, Efavirenz and Chlorzoxazone.
What are you particularly proud of as an outcome?
Prajal: At our Mumbai Pharmaceutical Technical Centre, we have created a robust formulation that is simultaneously efficient, stable, and affordable. With such persistent, chronic diseases like diabetes where people need everyday therapy, it's important to offer them quality medicines that can be affordable. I am happy that we can share and influence pharma manufacturers in offering them highly functional, yet affordable customer solutions.
For more information about our case study or any of IMCD's services, contact Prajal and the Mumbai PTC.
[email protected]
References:
1. https://clincalc.com/DrugStats/Drugs/Sitagliptin