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Efficient, comprehensive transitions from early phase (preclinical up to phase 1) to late phase  (phase 2 and beyond) are critical to the ultimate success of drug development programs. When  developers lose sight of their target product profile and fail to systematically review the molecule,  market and patient profile at each phase of development, they introduce risk into the program. The  program’s transition can become burdened by quality issues i.e., manufacturing at scale; further,  the project could undergo a major redirection or be totally abandoned before ever reaching  pivotal clinical trials. Key early planning strategies can help by minimizing many common pitfalls  encountered during this critical phase.

To produce a drug product with ideal biopharmaceutical properties, formulators must understand  the molecule’s characteristics and create optimal formulations by utilizing technologies and  processes that address the unique challenges presented by each API. But accelerating drug  development timelines can force innovators to opt for quick-to-clinic dosage form approaches  which may lead to suboptimal performance in patients.

An elegant solution is to implement a review of stability, pharmacokinetics (PK), and manufacturability  at key phases of development. A holistic assessment will enhance the drug developers’ appreciation  of the role the API/molecule dosage form plays in the successful outcome of a clinical trial.

Additionally, early identification followed by a proactive response to development challenges will  increase the probability of successful product development, launch and market success.

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In a recent webinar presented by Renejix—a leading global provider of advanced  drug delivery technologies, development and manufacturing solutions for drugs and biologics—  industry experts presented insights and techniques to help partners understand their molecules’  solubility and permeability challenges and create optimal dose forms.

By using methods of analyzing physicochemical and biopharmaceutical data to make early  drug development decisions, PK issues can be diagnosed and addressed. Using the Developability  Classification System (DCS) to predict the risks and challenges of creating an oral drug early in the  developmental stages could help with drug formulation design.

Although an optimal drug dosing  regimen is a prerequisite to the best possible care for every patient, a diversity of individual  factors—including current disease state, patient characteristics and the clinical outcome for the  patient—all need to be considered. During formulation development it is  essential to let the compound drive the formulation and not the other way around. Also, when  needed, partner with Contract Development and Manufacturing Organizations (CDMOs) that are  agile and bring together professionals from multiple disciplines with relevant prior experience in  finding solutions.

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These experts’ insights underscore the critical  need to build and engage a strong network of consultants and to leverage the expertise  of a CDMO if an innovator is to avoid common  pitfalls in early development.

Data-driven tools  employed by experts can help innovators  reach a comprehensive understanding of a  molecule and craft the optimal dosage form,  which can in turn lead to shorter development  timelines and optimal patient outcomes.


Renejix’s FormaDose® Design Solution was highlighted as a comprehensive  assessment to help guide the dose design process. The data driven approach considers API  physicochemical, biopharmaceutical, and PK properties, patient characteristics and physiologically  based PK (PBPK) modeling insights to generate recommendations that assist drug developers in  optimizing their outcomes and maximizing their drug development investment.

Key patient considerations may impact dose form selection; for example difficulties in drug administration can impact patient adherence. Addressing a drug bioavailability  issue could lead to a higher pill burden for the patient and even generate adverse events due to  patient variability. Moreover, a complex manufacturing process could lead to batch delays. Finally,  she cited examples of common oversights that can occur during the later phases of product  development.

As part of the FormaDose Design Solution assessment, a team of experts assess these and other  challenges then recommend a dose form best suited to progress the candidate to the next phase.  This methodology benefits both manufacturer and patient.

Formulation and the delivery technology must be aligned with both the patient and  the market in mind. Renejix has a multidisciplinary team of scientists with years of experience working with CDMOs in the pharmaceutical industry. Our  goal is to get to know your molecule and program, listen to your needs and provide solutions.  We remain open minded and agnostic to a solution until we have  collected the right data and executed the right analytical studies to set your molecule on its right  development path.

With a team of multi-talented experts at their  disposal, innovators have access to a wide  range of perspectives that help them better  understand their molecule. To complement  the formulation and manufacturing expertise,  PBPK modeling helps to reveal the “why”  behind a bioavailability challenge uncovered  during development.

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One of the most important points in a drug product’s development lifecycle is the lead nomination  step. A successful development program requires the medicinal chemist to use potency data to  narrow down the number of leads, but other factors must be considered. An OptiDose Design  assessment at this early stage can help formulators understand the challenges that may need to be  overcome.

Involving formulators in the drug candidate screening stage alongside medicinal chemists allows  for earlier determination of which salt form, formulation, dose form and drug delivery technologies  are appropriate for in vivo studies. Rather than selecting the most potent molecule to move  forward, renepharma considers preliminary drug metabolism and PK properties (i.e., PK data or in  vitro studies), DCS classification along with potency when recommending which molecule to  move forward to the next stage of development. This approach has proved a popular response to increasingly compressed drug manufacturing timelines, and it eases long, costly optimization work  later in development.

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In a case study of an oral small molecule designed for systemic uptake—a DCS 2a molecule, one that  is kinetic solubility challenged —the PK profile showed fair systemic exposure and fraction absorbed  along with a noticeably short half-life.

Based on the short half-life, we might need to have dosing up to three times per day. The question is,  could we get the dosing down to once per day if we were to develop a modified release dosage form? Critical to the analysis is the prediction of colonic absorption  as we extend the area of gut exposure through our modified release dosage form. Analysis of PK  profiles at a range of doses assists in that prediction through our modeling software. How the drug is  eliminated, and its half-life, also play critical roles in the analysis. The initial analysis of the available data  identified three areas that stood out:

The model showed that the drug was sensitive to particle size reduction. Next, the drug also  appeared to be absorbed in the lower intestine. Finally, drug release profiles could be modeled to  provide optimal release over 24 hours.

In addition to providing a path forward to once-a-day dosing, micronization was identified as a potential  approach for improving the fraction absorbed with the goal of reducing drug load. Micronization saves  time, money, lowers program risk and addresses the challenges of DCS 2a molecules.

Through FormaDose Design, a controlled-release approach was provided, with Renejix providing a  strategy to reduce drug load and maintain therapeutic levels for 24 hours.

This could be achieved through a combination of immediate-release and controlled-release multi-particulates, or possibly Minitabs.

The same approach also provided the opportunity for translating the molecule into a pediatric formulation.

Image showing Logo for RenejixRenejix is the leading global provider  of advanced delivery technologies,  development, and manufacturing  solutions for small molecule oral dosage forms.

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author avatar
Sridhar Gumudavelli
Sridhar Gumudavelli serves as the Vice President of Formulation R&D at Renejix Pharma Solutions, where he brings a wealth of knowledge and experience to the table. His leadership is instrumental in navigating the complex process of drug formulation, leveraging a variety of technologies to enhance drug absorption, bioavailability, and patient compliance.Sridhar’s expertise is not just limited to his hands-on experience; he is also an innovator with several patents filed under his name. These patents reflect his contributions to advancing drug delivery systems, showcasing his ability to tackle some of the most challenging problems in pharmaceutical sciences for the past 30+ years.

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