Ascendia Pharmaceutical Solutions Puts Customers First During Formulation Development & Manufacturing

The rise in novel drugs to battle infectious and chronic diseases is a main driver of the global formulation de­velopment and manufacture outsourcing market. Higher R&D expenses, desire to shorten time spent on these activities, lack of internal resources, and more complex formulations are leading many drug development companies to look beyond and identify appropriate contract development and manufacturing organizations (CDMOs) with expertise and state-of-the-art manufacturing capabilities.

Ascendia Pharmaceutical Solutions is a "one-stop-shop" for pharma companies seeking comprehensive CDMO services. Our four core platform technologies improve solubility and bioavailability of many modalities, helping Make the Impossible Possible. All four proprietary nanotech­nologies - Lipidsol®, Nanosol®, Emulsol®, and Amorsol®, can be applied to enable small and large molecules, including bio­logics.

Beyond the technology platforms is Ascendia Pharmaceutical Solutions' continuous manufac­turing capability for lipid nanoparticle/liposome fab­rication. We offer scale ups from milliliters to hundreds of liters to meet the need of early- to late-stage drug development.

Among the manufacturing capabilities based in our North Brunswick, New Jersey are a microfluidic chip mixer, Tangential Flow Filtration (TFF), ster­ile filtration, and filling of single-use vial, cartridge or prefilled syringe under aseptic conditions. We offer rapid turnaround of lipid nanoparticle (LNP) development and manufac­turing that bears the hallmarks of continu­ous manufacturing for sustained-release injectable (parenteral, intramuscular, and subcutaneous) drug formulations. Our 60,000 square foot facility has Class 10,000 (ISO 7) and Class 100 (ISO 5) cleanrooms for cGMP manufacture of sterile products, and Class 100,000 (ISO 8) manufacturing suites for manufacturing of lipid nanoparticles and liposomes.

Customer-first Approach

Utilizing our B.E.S.T. (Brilliant Technology, Excellent Service, Superior Quality, and Trust) solutions philosophy, Ascendia Pharmaceutical Solutions' scientists are integral Chemistry, Manufacturing, and Controls (CMC) team members for our clients' drug develop­ment projects. This means we proactively take appropriate strategies to implement new technologies for innovative molecules, especially those with poor solubility and bioavailability.

Drugs being discov­ered that are poorly soluble and challenging during development due to their brick dust structures and high melting/logP. To overcome those hurdles, Ascendia Pharmaceutical Solutions conducts first-hand API screening by utilizing different excipients, solubilizers, and polymers approved in drug products, and have been listed in the FDA's in­active ingredient database (IID) database. -. The result is enhanced molecule's formulation and in vivo performance!

Challenges also stem from drug insta­bility due to API degradation or lack of compatibility with excipients in oral and parenteral formulations. Ascendia Pharmaceutical Solutions fol­lows decision trees based on the dosage forms and nature of the drugs to select the most appropriate solubilizer and/or polymers in the formulations.

Step one in the process is to identify prototype formula­tions that enhance bioavailability in animal models by assessing the pharmacokinetic (PK) data. Based on these results, our formulation scientists further optimize the process and formulations, which leads to the next step of drug development in human clinical trials.

Ascendia Pharmaceutical Solutions' expertise in LNPs, liposomes, and sur­factant-based nanoemulsions and mi­croemulsions and polymeric nanoparticles derived from PLGA, are critical in design and assessment of innovative formulations in pre-clinical studies. This leads to further early-phase evaluation to manufacturing of late clinical-phase drug products.

Identifying Most Viable Enhancement Pathway

Our expertise is particularly important in determining the most effective pathways in today's drug development. Drug manufacturers looking for appropriate technologies to bring new chemical entities (NCEs) to clinic faster are adapting novel excipients or technologies to expedite the development. Such strategies, aligned with formulation technologies, do pose some risks, but have led to the advancement of drug candidates across all modalities for oncology, anti-in­flammatory, antiviral, CNS, and rare dis­eases. In addition to novel excipients, there is considerable interest in co-processed excipients comprised of polymers and solubilizers to address the poor solubility of new drug candidates.

Poor solubility stems from higher melt­ing and logP, meaning the molecules bear­ing high melting are highly crystalline or have the higher partition coefficient in the or­ganic phase. These attributes are creating a bottleneck in drug development, as more than 80% new molecules coming out of discov­ery possess high melting and logP, yielding poor solubility.

Fortunately, the pharma industry is adopting new technologies and excip­ients to expedite drug development. Con­ventional approaches like micronization, pH modification, salt and/or complex with cyclodextrin, have limited scope for medium- to high-dose drugs. Therefore, the new molecules belonging to BCS Class IIb (solubility limited) and Class IV require non-conventional approaches. Examples include amor­phous dispersions or lipid-based emulsify­ing systems (SEDDS/SNEDDS) to achieve higher solubility and bioavailability.

Lipophilic molecules with logP <2-4> are most suited for lipid-based liquid dis­persions, while those possessing high melt­ing logP (>4) are ideal candidates for amorphous dispersions. For example, spray drying and hot-melt extrusion are commonly used for preparation of amorphous solid disper­sions (ASDs). For NCEs with a high melting point, NanoSol for nano-sized API particle engineering has been used to tackle solubility challenges.

BCS Class II/IV are the most challenging molecules so they require non-conven­tional approaches to identify the right ex­cipients and formulation technologies. Ascendia Pharmaceutical Solutions' enabling technologies, in­cluding AmorSol for amorphous solid dispersions and EmulSol for SEDDS/SNEDDS, can help expedite the development and save time and cost. Our approach includes early molecule screening to find maximum solu­bility and compatibility of APIs in the appro­priate excipients (polymers/solubilizers).

We achieve this by dissolving API and excipients in varied concentration in polar solvents and casting the aliquot on a glass plate for drying in air or heating in oven at low temperature. The resulting film is ex­amined under light microscopy for any im­miscibility/crystallinity or homogenous mixing.

This procedure allows shorter screen time of a number of molecules for AmorSol. For EmulSol, the APIs are screened against a range of compatible and FDA-approved solvents, co-solvents, and solubilizers to identify the maximum solubility, which is taken as the benchmark to design the best SEDDS/SNEDDS formu­lations for an API.

Not one size fits all, so each API is screened individually to identify the appropriate compatible excipients. This approach leads to a Fast, Flexible, and First Time Right drug development process that helps customers overcome challenges with poor solubility and bioavailability, and to meet tight timelines and adhere to budget allocations.

To learn more, contact us today.