Drug Formulation Techniques and Strategies Based on Micronization
Tuesday, May 7 2013
8:00 am – 10:00 am
Location: MassBio, 300 Technology Square, 8th Floor, Cambridge, MA
Significant percentages of active pharmaceutical ingredients identified through modern discovery screening programs are poorly soluble in water, particularly in therapeutic areas such as cancer and CNS. These molecules are often difficult to formulate using conventional approaches and are associated with innumerable formulation-related performance issues, e.g. poor bioavailability, lack of dose proportionality, slow onset of action and other attributes leading to poor patient compliance. In addition, for parenteral products, these molecules are generally administered with co-solvents and thus have many undesirable side effects.
The essence of micronizing poorly water-soluble compounds rests primarily within the increased surface area that results when a drug is fractured into smaller particles. As predicted by the Noyes–Whitney model of dissolution wherein the surface area of the drug is directly proportional to its rate of dissolution, drug particles in the micro- and nanometer size range will dissolve more rapidly than a conventional formulation. In addition to affecting the rate of dissolution, there has been consideration of a potential enhancement in solubility when the particle size of a drug is in the micro- and nanometer size range.
There are a number of methodologies available for producing micro- and nanometer sized drug particles including industrially available technologies and more modern techniques on a pathway to become widely adopted options. Join us for a discussion of the latest trends in the field, including a snapshot of the services and activities offered by local companies.
- Carl Beckett, General Manager, Covaris Process Technologies
- Dr. Trevor P. Castor, President and CEO, Aphios Corporation
- Dr. Konstantin Tsinman, Director, Science and Research, Pion Inc.
Nanoparticle formation using Advanced Focused Acoustics
Mr. Carl Beckett, General Manager, Covaris Process Technologies
In this presentation we will discuss the use of Focused Acoustics for the processing of key nanoparticle delivery systems, including liposomes, emulsions, and nanosuspensions. Key limitations of current methods will be addressed, including temperature and solvent sensitive API’s, scalability, and sterile, continuous flow manufacturing capabilities. Example data is provided to show that the method or process by which a Formulation is formed, has a direct impact on the effectiveness of the Formulation. Both small molecule and biological Formulations will be discussed.
SuperFluids Nanotechnology Drug Delivery Platforms
Dr. Trevor P. Castor, President and CEO, Aphios Corporation
Aphios’ enabling nanotechnology platforms – CFN, PNS and PNP utilize SuperFluids [SFS]. CFN manufactures phospholipid nanosomes that encapsulate and/or co-encapsulate hydrophilic and hydrophobic drugs for intravenous and topical delivery. PNS encapsulates proteins and hydrophobics in biodegradable polymer nanospheres for oral and subcutaneous delivery. PNP is used for disaggregating proteins, enzymes and inorganics into nanoparticles for pulmonary delivery. These drug delivery platforms do not utilize organic solvents which denature target molecules or leave residual toxics in nanoparticles. Additionally, they are environment-friendly, can be operated in a semi-continuous mode and are scalable. Examples will be provided including oral delivery of PNS nanoencapsulated insulin.
Real Time Dissolution Monitoring of Nanosuspensions and Micronized Formulations
Dr. Konstantin Tsinman, Director, Science and Research, Pion Inc.
The miniaturized in situ fiber optic UV-based measurements will be introduced as a tool of choice for monitoring the concentration of pure and formulated API in the solutions. The dissolution curves from the untreated and micronized powders will be compared and analyzed to estimate the effective particle size evident from the concentration-time profiles.
A novel method to assess the concentration of free (dissolved) drug in the presence of its nanoparticles without a need for solid separation will be described and its application will be demonstrated.
Mr. Carl Beckett is General Manager of Covaris Process Technologies, where he leads all aspects of the development of Focused Acoustic equipment for use in pharmaceutical processing, including novel drug delivery systems and biological manufacturing. Prior to Covaris, Mr Beckett held positions as General Manager of IDEX Medical, a contract medical device manufacturer, and was with Hewlett-Packard for 10 years in various R&D, Manufacturing, and Product Management roles. Mr. Beckett is inventor or co-inventor on 9 patents with others pending, and holds a Masters of Science Degree from the Massachusetts Institute of Technology.
Dr. Trevor P. Castor is President and CEO, Aphios Corporation. He has over 30 years of diversified business experience ranging from management, marketing and finance to technology and business development. He graduated from the University of California, Berkeley with a PhD in Mechanical Engineering and MS in Chemical Engineering. He graduated summa cum laude with a BS from the University of Toronto and studied Business at St. Mary's College, NY, and Harvard Extension, MA. He is the author of 39 U.S. and international patents. Dr. Castor has collaborated with several multinational companies including Baxter, Bayer, BMS, Lilly, Novartis and Pfizer.
Dr. Konstantin Tsinman, Director of Science and Research at Pion Inc., joined Pion in 1998 as principal developer of the very first commercial Parallel Artificial Membrane Permeability Assay (PAMPA) instrument and subsequently the high-throughput methods for measuring solubility. He was involved in joint research with scientists from Hoffmann La-Roche that resulted in three joint publications and a patent regarding high throughput pre-formulation screening. Dr. Tsinman has been participating in numerous studies expanding the scope of applications for Pion’s in situ UV fiber-optic instruments. He has co-authored more than 25 articles in primary scientific journals and holds several patents. He received his PhD in Physics in 1994 from the Institute for Metal Physics, Kiev, Ukraine.