Dr. Firouz Asgarzadeh, Director Technical Services, Pharma Polymers & Services, North America, Evonik Corporation
Dr. Firouz Asgarzadeh, Director Technical Services, Pharma Polymers & Services, North America Evonik CorporationWhat solutions does Evonik provide for formulating poorly soluble active ingredients?
Evonik has been manufacturing the EUDRAGIT® line of polymers for over 50 years for the traditional use in the preparation of functional coatings. Beyond that, over the past decade, EUDRAGIT® polymers have been used increasingly in the formulation development of poorly soluble drugs in combination with Hot Melt Extrusion and Spray Drying techniques. In addition, Evonik has developed a systematic approach called “MemFis” (Melt Extrusion Modeling and Formulation Information System) to facilitate the selection of appropriate polymer matrices for stable solid solution formation based upon structure-property relationships between the polymer and the active pharmaceutical ingredients. We have coupled this time saving tool with an extensive searchable database of over two thousand melt extrusion experiments that can be used to estimate optimal processing conditions.
How does Evonik confront challenges associated with time and resource exhaustive development programs for poorly soluble compounds?
As described above, Evonik’s highly efficient MemFis tool allows for the rational selection of formulation ingredients for solid solution formations leading to a significant reduction in the number of experiments and hence shorter formulation development times. Evonik has installed Hot Melt Extrusion (HME) and Spray Drying capabilities throughout its global technical services laboratories network to closely assist customers with formulation development activities. We support formulation development with our broad product know how and deep process understanding resulting in a reduced time to market.
What advantages does hot melt extrusion offer to the pharmaceutical industry?
Ideally to become bioavailable, a drug should be soluble in gastrointestinal fluids and then also be permeable through the cell membranes in the intestine. Currently, over 70% of the new drugs in development are categorized as “highly permeable but poorly soluble” (BCS class II). Hot Melt Extrusion (HME) techniques transform poorly soluble crystalline drugs into an amorphous, metastable higher state of energy structure that is more easily solubilized leading to enhanced bioavailability. Alternatives to the HME process are Spray Drying Dispersions (SDD), as well as co-precipitation and self (micro)emulsifying drug delivery systems [S(M)EDDS] technologies that are also used to enhance the solubility of poorly soluble drugs. Contrary to SDD and co-precipitation, HME is a solvent and water free process which is often preferred when practical. The S(M)EDDS materials are usually made through a soft gelatin technology that requires the use of lipids to solubilize crystalline API powders. Although a viable technique, a drawback might be the retention of process water in the shell structure that requires long drying times. Additionally it should be noted that S(M)EDDS, Spray Drying and co-precipitation processes are more difficult to implement and install internally by pharmaceutical companies and projects are typically outsourced to specialized CROs and CMOs. Relatively speaking, Hot Melt Extrusion has proven to be more versatile, easier to acquire and install by small as well as large pharmaceutical companies as evidenced by the number of extruders installed at research and production facilities over the last decade as compared to the alternative technologies. Another significant inherent advantages of HME results from the fact that it is a continuous process which leads to the possibility of better in-process controls and higher manufacturing efficiencies. In many instances, solid solution formulations are developed on a small scale utilizing other techniques in the early development stages, when minimal amounts of API are available, and then the manufacturing process is transferred to HME at the later stages of development when more API becomes available.
What educational services does Evonik provide to hot melt extrusion customers?
For several years Evonik has organized many scientific symposiums and workshops around the globe focusing on solubility enhancement and HME techniques. The number of offerings and the attractiveness to the participants has been continuously increasing. Our customers are also invited and encouraged to visit our support laboratories to be trained first hand by Evonik staff. Furthermore, Evonik has been very active with online support and education through our easy to use e-Lab website. We also sponsor a variety of webinars to educate users of melt extrusion technologies and other important topics. The popular EUDRAGIT® Application Guidelines book provides useful general information supported with real examples to enhance working with HME. Evonik continues to support the advancement of this technology through ongoing university affiliations as well as timely publications on new developments.
Can you provide a breakdown of Evonik’s pharmaceutical melt extrusion equipment and offerings?
Evonik has installed several pharmaceutical twin screw extruders at its global technical services sites to support customer formulation and process development projects since the late 1990’s. R&D scale melt extrusion capabilities are available in our technical service laboratories in the US, India, China and Germany. Spray-drying capabilities are available at sites in the US, Japan, Germany and India. Additionally, GMP melt extrusion capabilities are available in our German and US facilities for phase I and II clinical supplies (APIs OEL >1 μg/m3). Evonik is also investing in a new multi-million dollar project in 2013 to install high potency API (OEL < 0.03 μg/m3) melt extrusion and spray drying capabilities at its Birmingham, AL site.
What’s in store for Evonik’s portfolio of products and services over the next year?
Evonik is making substantial investments in solubility enhancement services in our German and US labs specifically for the handling and the melt extrusion of high potency APIs (HPAPIs) from pre-formulation through phase II clinical supply manufacturing. Evonik has also launched a new Modular Drug Delivery technology (MDD) that enhances the passive uptake of BCS III and IV drugs. This technology can be further combined with HME or SDD techniques for synergistic benefits. We also have novel drug delivery technologies in the pipeline to further promote the active uptake of drugs that will be launched in 2013. Evonik is also working on the development and marketing of several new easy to use products, in-line with the recent launches of: 1) PlasACRYL® T20 and HTP20 for EUDRAGIT® L30 D-55 and EUDRAGIT® FS 30 D, respectively reducing the coating preparation steps for our customers and 2) EUDRAGIT® E PO ReadyMix which offers custom color matching services and an easy to use compound for best in class taste masking / moisture protection applications.
Evonik Industries, a global leader in specialty chemicals, provides API custom manufacturing services, intermediates, amino acids and drug delivery technologies for the pharmaceutical industry. Drug delivery technologies include development services, functional excipients and GMP manufacturing for oral and parenteral formulations. Evonik has solutions for BCS Class III/IV compounds and expertise in bioavailability enhancement techniques for oral applications. A broad platform of drug delivery technologies for extended-release parenterals are available to pharmaceutical clients. These options include injectable microparticles, nanoparticles, implants, coatings, liposomes, liquid polymers, films, and meshes for systemic and local delivery of small molecules, peptides, proteins, antibodies, and nucleic acids. Partnered programs range from proof-of-concept studies to product development and optimization, process scale up, clinical trial manufacturing, and commercial manufacturing of drug delivery formulations and biomaterials. Evonik offers its EUDRAGIT® polymers for modified release oral delivery and a wide range of RESOMER® and LAKESHORE BIOMATERIALSTM PLG polymers for parenteral drug delivery and medical device applications.