Technical Articles
07 Oct 2023
ASD Column | How to Select Polymers in Hot-melt Extrusion Process?
07 Oct 2023
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The swift advancements in pharmaceutical technology are consistently leading to significant breakthroughs in the realm of small molecule development. In this scenario, pharmaceutical formulations are playing a pivotal role in enhancing drug performance, fostering research and development efficiency, and elevating the success rate of clinical studies.
This article will center on a frequently employed technology in formulation development—Amorphous Solid Dispersion (ASD). It will explore the distinctive advantages offered by Crystal Formulation Services (referred to as “CFS”, a CDMO division of Crystal Pharmatech) in the development and manufacturing of ASD, catering to the needs of pharmaceutical companies.
ASD, a formulation technology, operates on the fundamental principle of blending drug molecules with suitable polymer-carriers. This process ensures the uniform dispersion of drug molecules within the polymer matrix, resulting in the formation of an amorphous solid solution or suspension. The following delineates the primary benefits of applying ASD technology in drug formulation development:
Improve drug solubility: ASD significantly improves drug solubility by dispersing drug molecules in the polymer matrix to form an amorphous solid. The elevated free energy of amorphous solid results in superior solubility compared to crystalline form. Additionally, polymer-carriers have the capacity to establish hydrogen bonds with drug molecules, further enhancing drug solubility.
Maintain supersaturation: ASD preserves drug supersaturation within a solution, consequently enhancing the dissolution rate of the drug in the gastrointestinal tract. Sustaining supersaturation proves advantageous in enhancing drug bioavailability, as drugs in a supersaturated state are more readily absorbed in the gastrointestinal tract.
Enhance drug bioavailability: Oral drug bioavailability is influenced by solubility and permeability. ASD plays a role in improving solubility and maintaining supersaturation, facilitating drug dissolution in the gastrointestinal tract and enhancing permeability. Consequently, this contributes to an overall increase in drug bioavailability.
Optimize of oral administration: ASD improves the dissolution rate and release performance of drugs, facilitating easier absorption in the gastrointestinal tract, making it favorable for oral administration. Additionally, in comparison to conventional formulations, ASD mitigates the food effect, minimizing interactions between drugs and meals and ensuring stable efficacy under both fasting and fed conditions.
Shorten development cycle: ASD increases the likelihood of success in drug formulation development by eliminating bridging experiments in the later clinical stages, thereby shortening the overall development cycle. Its high flexibility is evident through a broad range of available polymer carriers and preparation processes, adaptable to specific drug characteristics and bioavailability requirements. Furthermore, ASD allows for performance optimization in the early stages of drug development, leading to a reduction in both development cycles and costs.
CFS specializes in delivering top-notch formulation development and manufacturing services for innovative drug companies worldwide. Operating as a formulation CDMO, CFS is committed to tailoring the optimal formulation formula and process for each innovative drug molecule, taking into account its molecular characteristics. With a wealth of experience in formulation development and manufacturing of ASD, CFS has established a global leading platform for ASD technology.
CFS's main advantages in ASD technology are summarized below:
Extensive expertise in innovative drugs formulation development: CFS team is well-versed in ASD formulation development strategies for various types of drugs, enabling them to offer expert technical support to clients.
State-of-art formulation equipment: CFS is furnished with cutting-edge equipment, including spray drying and hot melt extrusion (HME). For spray drying, CFS utilizes the Buchi-290 for lab-scale development and GEA PSD-1 for manufacturing clinical samples and early commercial batches. In terms of HME equipment, CFS employs the Thermo Fisher Rheometer for rheological studies and early formulation screening, along with the Leistritz 12 mm and 18 mm HME equipment for lab-scale, pilot-scale, and early commercial manufacturing. This comprehensive setup ensures the robust performance and optimal bioavailability of formulations.
Compliance with quality management systems: CFS has implemented an all-encompassing and compliant quality management system, ensuring that the formulation development and manufacturing strictly adhere to the Good Manufacturing Practice (GMP) standards of China, the United States and Europe. This commitment ensures the delivery of high-quality products for global innovative drug companies.
"Crystal+ Formulation" one-stop customized service: Crystal Pharmatech offers a comprehensive one-stop customized service encompassing solid-state research, pre-clinical formulation research, ASD screening, formulation development and manufacturing, and clinical samples supply. This approach assists clients in streamlining the development cycle and minimizing development costs.
Rigorous confidentiality system: CFS places utmost importance on respecting and safeguarding the intellectual property and confidential information of its clients.
Leveraging its extensive technical expertise, cutting-edge equipment, and comprehensive service systems, CFS is well-positioned to offer professional ASD technology, supporting clients in successfully development of high-performing innovative drugs.
With the continuous progress of science and technology, the role of ASD technology in drug formulation development is anticipated to grow significantly. The following outlines potential future development trends:
Development of novel polymers: Through a profound comprehension of ASD mechanisms, scientists will persist in innovating polymers to augment drug compatibility, stability, solubility, and bioavailability. These advancement in polymer development are poised to broaden the application scope of ASD technology in drug formulation development.
Innovation in formulation processes: Pharmaceutical companies will continue to explore more advanced and efficient formulation processes to improve the manufacturing efficiency and product quality of ASD formulations. Innovations in these formulation processes are anticipated to contribute to the reduction of drug development costs and shorten development cycles.
Personalized drug formulations: With the development of precision medicine and personalized drug therapy, the application of ASD technology is anticipated in the development of personalized drug formulations tailored to meet the unique needs of individual patients. This will contribute to increasing patient treatment satisfaction and drug efficacy.
Collaboration and industry chain integration: As ASD technology becomes more widespread, collaboration among pharmaceutical companies, raw material suppliers, formulation development service providers, and others will be intensified. This collective effort aims to advance the development application of ASD technology. Industry chain integration will facilitate resource sharing and leverage complementary advantages, ultimately delivering greater benefits for drug development.
In conclusion, the importance of ASD technology in drug formulation development is progressively prominent, positioning it as a key tool for future innovative drug research and development. CFS is dedicated to delivering outstanding and efficient ASD formulation development and manufacturing services to support drug development and enhance clinical efficacy for its clients.
