2025 Summit on Innovations in Controlled Release, Bioavailability Enhanceme

The pharmaceutical industry is undergoing a profound transformation, shifting from traditional batch processes to continuous manufacturing. This evolution is partly propelled by advances in Process Analytical Technology (PAT) and the foundational principles of Quality by Design (QbD). Transitioning to a SMART factory mode of operation, however, requires technological innovation, significant professional development, and the maturity of regulatory and management systems. The issue of data integrity breaches (BAD-I), with its historical implications and current prevalence, serves as a critical backdrop for understanding how to balance technological progress with the necessary professional and systemic maturity. This balance is essential to ensure the successful guidance of pharmaceutical manufacturing through this revolutionary phase. In this presentation, we will introduce a SMART framework designed to provide a common-sense foundation for navigating the complexities of pharmaceutical manufacturing’s evolution. This framework will offer ways to ensure that data integrity, technological advancements, and professional maturity move in concert toward a more efficient and compliant future.

Amorphous solid dispersions (ASDs) are supersaturating formulations that enhance both the
apparent solubility, and the bioavailability of poorly water-soluble drugs following oral
administration. Upon dissolution, ASDs can generate nano-sized amorphous droplets of ∼100-
200 nm, when the concentration of the molecularly dissolved drug exceeds the amorphous
solubility, thereby maximizing the diffusive flux during the supersaturation window. In this
research, two poorly soluble drugs were prepared as ASDs with hydroxypropyl methylcellulose
acetyl succinate (HPMCAS), to characterize supersaturation and crystallization kinetics in
simulated and aspirated intestinal fluids. For each ASD, the onset of nucleation was found to be
highly medium dependent. Moreover, membrane flux was attributed to the resulting phase
behavior and remained high as long as supersaturation was maintained, whereas
desupersaturation, induced by drug crystallization, was coincident with a noticeable decrease in
flux. Importantly, it was shown that ASD dissolution in aspirated fluids led to the formation of
drug-rich nanodroplets, confirming same observations made in simulated fluids. These
observations provide insights into better understanding of the intraluminal supersaturation
potential of ASDs as well as the selection of appropriate dissolution media to improve
biopredictability for ASD formulations.

One of the many lessons that the SARS-CoV-2 pandemic has taught the world is the
vulnerability of supply chains. When factoring in wars, tit-for-tat tariffs, and safety recalls, an
actionable plan needs to be in place to swiftly adapt to rapidly changing supply demands. In
response, a call for more flexible manufacturing is desired to address such challenging
geographic, economical, and political climates. One aspect of flexible manufacturing is the
ability to quickly transfer product between manufacturing locations. When production of a
specific product cannot meet supply additional manufacturing lines, not previously utilized for
said product, could be implemented to meet the additional supply demand. One such instance
where this procedure would have been extremely useful during the recall and subsequential
lack of supply of baby formula in the United States, which resulted in the import of product
from foreign entities.
In the current practice of transferring between one manufacturing route, or site, to another,
the procedure is to perform multiple designed experiments and perform statistical analysis on
the results. While scientifically beneficial, practically this leads to significant waste in material
with little to no actionable items. This methodical approach is not suited to respond to a crisis.
Therefore, an approach is needed to focus on critical quality attributes of the existing drug
product and methods in which to reproduce the key attributes.
One step that is universal in making tablets is the compaction step. Whether it is roller
compaction, wet granulation, direct compaction, batch manufacturing, or continuous
manufacturing, a tablet press is utilized to bring punches together and compress the final blend
into a desired thickness, shape, and mass. Therefore, if the material entering the dies of the
press has the same properties (bulk packing, flow, etc.) similar tablet properties should be
obtained for both processes.
With this understanding, the research presented here is focused on how shearing of powder
that occurs in different manufacturing lines can be utilized to generate blend with similar
properties. Utilizing three different blenders and two different tablet press feed frames, an IR
shear sensitive formulation was blended in three different manufacturing routes, under
different shearing profiles, number of rotations, throughput, and RPM, to prove that the final
product can be manufactured on different lines.

• Significance of Multiparticulates
• Leveraging Multiparticulates for Customized Release
• Adare's Multiparticulates-based Technology - Diffucaps®
• Case Studies

Dr. Shahab Kashani Rahimi is the lead principal scientist in
the product development team at Ardena. Shahab has 7
years of experience in pharmaceutical oral solid and liquid
formulation and manufacturing process development, and his
work focuses on solubility/bioavailability enhancement
technologies including hot melt extrusion and spray drying,
development of immediate and modified release dosage
forms and novel complex drug delivery systems. His
experience spans all stages of product development, from
pre-clinical development and proof of concept to scale-up, clinical and registration
manufacturing. Shahab holds a PhD in polymer science and engineering and has
previously worked as a formulation principal scientist at Catalent Pharma Solutions and
BioDuro and as a postdoctoral research fellow at molecular pharmaceutics and drug
delivery department at University of Texas at Austin.

Lipid excipients offer tremendous in vivo performance benefits for oral drug delivery by improving solubility/bioavailability, enhancing absorption, and mitigating food effect. While lipids are typically employed in capsule formulations such as soft gels and liquid-filled hard capsules, there is growing interest in incorporating the benefits of lipid excipients into oral solid dosage forms, such as tablets.
 
In this presentation, we will provide an overview of how lipid excipients enhance bioavailability and discuss unique approaches to formulating oral solid dosage forms using well-known lipid chemistries.

Phil has been with digiM Solution since 2020 and is currently lead product specialist supporting microstructure characterization of oral solid dosage forms, with a strong focus on amorphous solid dispersions. Phil has a background in imaging ranging from diagnostic medical imaging in the field of dentistry to nanoscale imaging and microstructure characterization in the pharmaceutical industry. Phil is focused on the application of correlative image analysis to the optimization of pharmaceutical formulation, design, and performance assessment  Phil holds B.S. degrees in biomedical engineering from the University at Buffalo and biology from the University at Albany.