Tanu is currently in her final year pursuing a Ph.D. in the Department of Pharmaceutics at the University of Connecticut, USA. Her academic journey began with a Bachelor's and Master's degree in Pharmacy from the University of Delhi, India. Her Ph.D. research focuses on assessing the influence of process parameters on the performance of dry powder inhalers. She employs both experimental and computational tools in her work, all with the overall objective of optimizing vacuum drum-filling parameters to enhance product performance. This project is the result of a collaborative partnership between the University of Connecticut and Experic in New Jersey. In addition to her primary research, Tanu is also involved in other exciting projects, including the development of a Computational Fluid Dynamics (CFD) model for inkjet-based 3D printing of pharmaceutical tablets and the creation of a Discrete Element Method (DEM) model for the continuous twin-screw wet granulation process."
Impact of Process Parameters on Dry Powder Inhaler Performance
Dry powder inhalers (DPI) are becoming increasingly popular due to growing interest in pulmonary drug delivery. The DPI performance is the net result of formulation properties and a series of processes carried out during the manufacturing process such as drug micronization, blending, and capsule filling. The DPI formulations are usually developed by considering formulation properties, but the impact of unit operations such as capsule filling is often the least explored. Therefore, this proposal has been designed with the goal to evaluate the impact of powder-filling conditions on DPI performance. The outcomes from this project will also be used to develop a machine learning Artificial Neural Network (ANN) model to predict the product performance. This project is a collaboration between Dr. Justin Lacombe’s group at Experic, USA, and the University of Connecticut, USA.
DPI formulation usually consists of micronized drug, coarse carrier, and additional components such as fine lactose. DPI manufacturing usually begins with API micronization to generate particles with an aerodynamic diameter of 1-5μm. However, this small size of API particles results in poor flow properties making the capsule filling a challenge. In this study, we will evaluate a formulation consisting of micronized Albuterol sulfate and a lactose carrier to study the impact of low-dose capsule filling conditions on DPI performance. The API will be micronized using an Air Jet mill and will be analyzed for amorphous content and surface energy. The formulation will be then blended using a high-shear mixer at different blending conditions (blending time and speed) and the blended formulation will be then filled in HPMC capsules using Harro Hofliger vacuum drum filler. The vacuum drum filler involves a rotating dosing drum below a hopper where the powder is continuously stirred, and powder is pulled into the drum bore by vacuum and dispensed into the capsule with positive pressure. The amount of powder dispensed is influenced by multiple factors such as vacuum pressure, drum bore size, dispense pressure, stirrer type, stirrer speed, and powder properties which consequently affect the product performance. After that, the filled capsules will be evaluated for their aerosol performance using NGI.
The ANN model will be developed using the experimental data where formulation properties (bulk density, tap density, and particle size distribution) and process parameters (vacuum, stirrer type, and stirrer speed) will be used as the input features to predict the filling performance (capsule fill weight and fill weight variability) and product performance (FPF and MMAD). The outcomes from this study will be useful in identifying and optimizing the critical process parameters during low-dose vacuum drum filling to achieve optimum product performance. The outcomes from this project will be published in renowned journals and will also be presented at various conferences such as DDL, AICHE, and AAPS.
I have always been drawn to the power of healthcare sciences to heal and improve human lives. This led me to pursue my career in a field which has the potential to revolutionize the way we treat diseases and make a real difference in the world by improving the quality of life for millions of people. I completed my bachelor’s degree in pharmacy from the Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), India, where I got an opportunity to get exposed to the pharmaceutical industry. As my course progressed, my fascination with pharmaceuticals, especially pharmaceutics, only grew stronger. During my coursework, I was granted the opportunity to intern in the drug delivery and pharmacological sciences department at the top medical college in India, All India Institute of Medical Sciences (AIIMS). At AIIMS, I worked with research scientists, professors, and doctors to learn about their work with ophthalmic formulations. I spent most of my time preparing ophthalmic formulations for use in surgeries and I got to see firsthand how these formulations could help to restore sight and improve quality of life. This work was incredibly impactful, as it helped to improve the lives of countless people and further grew my interest in pharmaceutical research. Therefore, I decided to continue my education in pharmacy by enrolling in a Master of Pharmacy program at the same university where I completed my bachelor’s degree. While pursuing my master’s degree, my passion narrowed down to exploring and designing ways to improve pharmaceutical drug product development, which motivated me to design my thesis in a similar domain. During this period, I also got the opportunity to work as a pharmaceutical sciences intern at Vyome Biosciences, where I worked with a team of esteemed research scientists to gain more exposure to the industry. Subsequently, I decided to dive deeper into my areas of interest and enrolled in a PhD program in the pharmaceutical department at the University of Connecticut. My initial research work was primarily focused on developing the computational models for pharmaceutical processes such as three-dimensional binder jet printing of pharmaceutical tablets and powder blending followed by experimental validation of the developed models. Shortly after that, I got an exciting opportunity to work with Dr. Justin Lacombe as a pharmaceutical development and engineering intern at Experic in New Jersey, where I learnt about the industrial aspects of formulation development and pharmaceutical manufacturing. Most of my work at Experic focused on the optimization of low dose powder filling process for Dry Powder Inhalers (DPI) and the manufacturing of inhalation formulations. I learned that research and innovation should go hand in hand with ease of manufacturing, packaging, and scalability, and because of that, I decided to design my doctoral thesis with an overall goal to bridge the gap between Dry Powder Inhaler manufacturing and final product performance. My doctoral thesis involves understanding the impact of process parameters such as formulation blending, and the DPI capsule filling on the final product performance with an overall goal to optimize the dry powder inhaler performance. Later, we will also develop a machine learning Artificial Neural Network (ANN) model to predict product performance. The DPI formulation development is mainly focused on material attributes to improve the product aerosol performance. However, the impact of process parameters on DPI performance is often less investigated.
The Drug Delivery to the Lung (DDL) career development grant will be instrumental in helping us achieve our project goals by providing the necessary funding for raw materials and equipment. With the help of this funding, we will be able to perform required performance analysis such as inverse gas chromatography, scanning electron microscopy (SEM), high-performance liquid chromatography (HPLC), and next generation impactor (NGI) analysis.
DDL grant will also play a vital role in funding my travel to various conferences such as DDL and American Association for Pharmaceutical Scientists Pharm Sci. (AAPS) where I will be able to present our work and provide an impetus to my professional growth in the inhalation sciences field. Being an international student, participating in conferences will be helpful in expanding my professional network and opening opportunities for research collaborations. The outcome of this project will serve as a vital source of information to understand the role of process parameters on DPI performance and consequently improve the manufacturing process.