29 May 2022
en
With the rapid development of biopharmaceutical technology, the field of small molecule drug discovery continues to achieve significant breakthroughs. In this context, pharmaceutical formulations play a pivotal role in enhancing drug performance, improving research and development efficiency, and increasing the success rate of clinical studies.
This article will focus on introducing a widely used technology in formulation development - Amorphous Solid Dispersion, and delve into the unique advantages offered by Crystal Pharmaceutical in providing formulation development and manufacturing services for small molecule drug discovery companies.
Amorphous solid dispersion is a formulation technology based on the core principle of mixing drug molecules with suitable polymer carriers to uniformly disperse drug molecules within the polymer matrix, thereby forming an amorphous solid solution or suspension. The application of ASD technology in drug formulation development can significantly enhance drug solubility and bioavailability, thereby optimizing drug pharmacokinetic (PK) performance. The following outlines the key advantages of ASD technology in drug formulation development:
Enhanced Drug Solubility: ASD technology, by dispersing drug molecules within a polymer matrix to form an amorphous solid, significantly improves drug solubility. Amorphous solids have higher free energy, leading to improved solubility compared to crystalline drugs. Additionally, polymer carriers can form hydrogen bonds with drug molecules, further increasing drug solubility.
Sustained Supersaturation: ASD technology allows drugs to maintain supersaturation in solution, enhancing their dissolution rate in the gastrointestinal tract. Sustained supersaturation is beneficial for increasing drug bioavailability, as supersaturated drugs are more readily absorbed in the gastrointestinal tract.
Improved Drug Bioavailability: ASD technology enhances drug bioavailability by improving drug solubility and reducing drug crystalline transformation in the body. Oral drug bioavailability is influenced by solubility and permeability. ASD technology can increase drug solubility, maintain supersaturation, and aid in dissolution and permeability in the gastrointestinal tract, thereby enhancing bioavailability.
Optimal Oral Administration: ASD technology improves drug release performance, making drugs more readily absorbable in the gastrointestinal tract, which is favorable for oral administration. ASD formulations can enhance drug dissolution and release performance in the gastrointestinal tract, leading to improved drug absorption. Furthermore, compared to conventional formulations, ASD technology helps reduce the food effect of drugs, minimizing interactions with food and ensuring consistent efficacy when taken on an empty stomach or with meals.
Shortened Development Timelines: ASD technology increases the success rate of drug formulation development, avoiding bridging experiments in late-stage clinical trials, thus shortening the development timeline. This technology is highly flexible, allowing the selection of different polymer carriers and preparation processes based on drug characteristics and bioavailability requirements. Additionally, ASD technology enables early-stage performance optimization in drug development, contributing to reduced development timelines and costs.
Crystal Pharmaceutical' CDMO division is dedicated to providing high-quality formulation development and manufacturing services to innovative pharmaceutical clients worldwide. As a formulation CDMO, Crystal Pharmaceutical is committed to tailoring the best formulation formulas and processes for each innovative drug molecule based on its unique characteristics. With extensive experience in amorphous solid dispersion (ASD) formulation development and production, Crystal Pharmaceutical has established an internationally leading platform for ASD formulation development and manufacturing, serving global small molecule innovative pharmaceutical companies.
Our key strengths in ASD technology include:
Rich Experience in Novel Drug Formulation Technologies: The team at Crystal Pharmaceutical' CDMO division has years of experience in ASD formulation development and is well-versed in ASD formulation development strategies for different types of drugs, providing clients with professional technical support.
Advanced Formulation Development Processes and World-Class Equipment: Crystal Pharmaceutical employs advanced formulation development processes such as spray drying and hot melt extrusion, and invests in high-end formulation equipment. We have the Buchi-290 spray drying equipment for small-scale development, the GEA PSD-1 spray drying equipment for clinical samples and early-stage commercial production. For hot melt extrusion (HME), we utilize the Thermo Fisher Rheometer for rheological studies and early formulation screening, and Leistritz 12 mm and 18 mm HME equipment for small-scale, pilot, and early-stage commercial production to ensure stable performance and excellent bioavailability of formulations.
Compliant Quality Management System: Crystal Pharmaceutical has established a comprehensive compliant quality management system to ensure that formulation development and production processes strictly adhere to the GMP standards of China, the US, and Europe, delivering high-quality products to global innovative pharmaceutical clients.
"Crystal Form + Formulation" One-Stop Customized Service: Crystal Pharmaceutical offers end-to-end, one-stop customized services, including crystal form research, pre-clinical formulation research, ASD screening, formulation development and production, and clinical supply, helping clients shorten development timelines and reduce development costs.
Robust Confidentiality System: We fully respect and protect our clients' intellectual property and confidential information.
With its wealth of technical expertise, advanced formulation development equipment and processes, and a comprehensive service system, Crystal Pharmaceutical provides comprehensive support in the field of ASD formulation development, helping clients successfully develop drugs with outstanding performance.
There are several successful application cases of ASD technology. Here are some representative examples:
Case One: Enhanced Bioavailability of Anti-Cancer Drug
In this case, researchers significantly improved the solubility of a poorly soluble anti-cancer drug using ASD technology. By selecting an appropriate polymer carrier, the drug was dispersed within the polymer matrix to form an amorphous solid dispersion formulation. The results showed a five-fold increase in drug solubility in water, leading to a three-fold increase in bioavailability. Clinical trials confirmed the significant efficacy of the drug in patients, opening up new possibilities in cancer treatment.
Case Two: Innovative Stability Enhancement for Cardiovascular Drug
In this case, researchers used ASD technology to improve the dissolution performance and stability of a cardiovascular drug with poor stability. This transformation resulted in an orally administered formulation with excellent efficacy, enhancing the patient's medication experience.
Case Three: Transition from Injectable to Oral Administration for Diabetes Treatment
To address patient reluctance to long-term injectable diabetes treatment, a research team used ASD technology to convert an injectable diabetes drug into an oral form. By improving the drug's solubility and absorption in the gastrointestinal tract, compliance issues among patients were reduced, providing a more convenient option for diabetes treatment.
Case Four: Enhanced Blood-Brain Barrier Penetration for Neurodegenerative Disease Drug
In this case, a drug designed to treat neurodegenerative diseases originally had inadequate blood-brain barrier penetration, limiting its effectiveness in patients. Using ASD technology, researchers dispersed the drug with specific polymers to create an amorphous solid dispersion formulation. This optimization improved the drug's solubility and absorption in the body, increasing its ability to penetrate the blood-brain barrier. Preliminary clinical trials showed potential improvements in drug efficacy, but further research and validation are needed to confirm its actual effectiveness in patients.
Case Five: Improved Bioavailability of PROTAC Drug
In this case, researchers faced a PROTAC (Proteolysis Targeting Chimeras) drug with potential therapeutic benefits but low solubility, leading to suboptimal bioavailability. By applying ASD technology and selecting suitable polymer carriers, researchers dispersed the PROTAC drug with the polymer to create an amorphous solid dispersion formulation. This optimization significantly improved the drug's solubility in water, enhancing its absorption and bioavailability in the human body. Clinical trials demonstrated a substantial improvement in the drug's efficacy in patients, providing a more effective option for targeted therapy.
These examples illustrate the versatility and effectiveness of ASD technology in enhancing the solubility, stability, and bioavailability of various drugs, ultimately improving their therapeutic potential and patient outcomes.
As scientific and technological advancements continue to unfold, amorphous solid dispersion (ASD) technology is expected to play an increasingly vital role in future drug formulation development. Here are some anticipated trends for the future:
Development of Novel Polymers: With a deeper understanding of the mechanisms behind ASD technology, scientists will continue to research and develop new polymers to enhance drug compatibility, stability, solubility, and bioavailability. These novel polymers will expand the applicability of ASD technology in drug formulation development.
Innovative Formulation Processes: Pharmaceutical companies will explore more advanced and efficient formulation processes in the future to improve the production efficiency and product quality of ASD formulations. These innovative formulation processes will help reduce drug development costs and shorten development timelines.
Personalized Drug Formulations: With the advancement of precision medicine and personalized drug treatments, ASD technology is expected to be applied in the development of personalized drug formulations to meet the needs of individual patients. This will contribute to higher patient satisfaction and improved drug efficacy.
Collaboration and Supply Chain Integration: With the widespread adoption and application of ASD technology, pharmaceutical companies, raw material suppliers, and formulation development service providers will strengthen collaboration to collectively advance the development and application of ASD technology. Through supply chain integration, resource sharing and complementary strengths will be realized, bringing greater benefits to drug development.
In summary, the significance of amorphous solid dispersion (ASD) technology in the field of drug formulation development is becoming increasingly evident, and it is poised to become a critical tool in future innovative drug research and development. Crystal Pharmaceutical remains committed to innovation, striving to provide clients with outstanding and efficient ASD formulation development and manufacturing services to drive progress in drug development and contribute to the ongoing improvement of clinical therapies.
