Upcoming Seminars and Webinars,
Short Courses,
Local
Events In Your Area,
and Industry Trade Shows
Industry Events we'll be at this year:
Please feel free to contact us (link below) to arrange a free on-site consultation or meeting.
Date |
Event |
|
Monday, October 17, 2022 -
Wednesday October 19, 2022 |
AAPS PharmSci 360Boston Convention Center Boston MA Booth 255 |
Complimentary Cutting-Edge Lectures You'll Enjoy!
Please find below the available seminars for the upcoming months. You must register individually for each event. You may register more than one person for an event. We'll send you instructions for attending the web conference after registering. If you have questions please do not hesitate to contact Triclinic Labs.
Unless noted, the Seminars are FREE to attend.
The following seminars are available as webinars and can be given on site at your facility as well, as part of a visit to Triclinic Labs, or as an addition to an audit.
Upcoming Seminars:
Date & Time |
Seminar |
| TBD |
Direct Ranking of Relative Stability for Amorphous Solid Forms Using Total Diffraction AnalysisClick Here for Full Abstract Request More Info |
| TBD |
Improving Drug Substance Solubility and Bioavailability With Super Saturating Drug Delivery SystemsClick Here for Full Abstract Request More Info |
| TBD |
Intellectual Property from Solid Formsby Aeri Park, Ph.D. Click Here for Full Abstract Request More Info |
| TBD |
Development and Validation of GMP Methods for Solid Mixture Analysis. What does the FDA want?by Dave Bugay, Ph.D. Click Here for Full Abstract Request More Info |
| TBD |
Drug Product Analysis. Microscopic and Spectroscopic Techniques for Failure Analysis, Localization, and Improvement.by Tere Carvajal, Ph.D. Click Here for Full Abstract Request More Info |
Upcoming FREE Half Day Seminar Events:
Location and Date |
Syllabus, Registration, & Info |
|
South San Francisco, California
Marriott Oyster Point TDB |
Half Day Solid-State Seminars (3)Syllabus Link Request More Info |
| Boston, Massachusetts
Cambridge Marriott TBD |
Half Day Solid-State Seminars (3)Syllabus LinkRequest More Info |
|
Newark, New Jersey
Renaissance Newark TBD |
Half Day Solid-State Seminars (3)Syllabus Link Request More Info |
|
Basel, Switzerland
SwissHotel, Basel TBD |
Half Day Solid-State Seminars (3)Syllabus Link Request More Info |
|
London, UK
Renaissance London TBD |
Half Day Solid-State Seminars (3)Syllabus Link Request More Info |
Seminar Abstracts
General Solid-State Topics
Organic Solids
For scientists unfamiliar with the solid-state landscape of organic molecules, this presentation provides an overview. Subjects include organic crystals, polymorphism, non-crystalline (amorphous) structures, cocrystals, and the effect of chirality on solid form. Examples of the importance of solid form on properties and industrial, especially pharmaceutical, applications will be presented.
Contemporary Solid Form Screening and Selection
Part of pharmaceutical preformulation is solid form selection of the API. That includes salt or cocrystal screening as well as polymorph screening. While the existence of crystalline forms remains unpredictable, rational approaches to screening can be applied to increase the likelihood of hits. The use of two-phase reactions for salt and cocrystal screening will be discussed. In addition, some general considerations in deciding whether to screen and how to screen will be presented. Based on historical data with over 100 cocrystal screens on novel compounds and reproduced screens from the literature, the propensity for cocrystal development with a given API is ~75% in our hands. The key to a high propensity for cocrystallization is threefold: phase diagram-guided screening, an extensive guest list, and a wide variety of screening/sample generation techniques. This approach will be discussed.X-ray Diffraction from Organic Solids
This presentation is intended as a tutorial for scientists who are unfamiliar with x-ray diffraction analysis. An introduction to the origin of diffraction will be followed by discussions of single-crystal and powder diffraction experiments. Emphasis will be on utilization of diffraction data for solids characterization.Advanced Solid-State Topics
IIntellectual Property from Solid Forms
This presentation is intended as a tutorial for scientists who are unfamiliar with Intellectual Property aspects of solid forms (polymorphs, salts, cocrystals). Special attention will be placed on recent case law, claim construction strategies past and present, and insight into the US Patent & Trademark Office's recent views of solid-forms. Can one expect to obtain patents on new solid forms (polymorphs, salts, cocrystals, non-crystals)? If so, will the patents be listable in the FDA's Orange Book and, more importantly, will they survive a court challenge? Historical perspective and recent court decisions will be used to illustrate the complexity of such questions, as well as to provide some insight into current trends. Presented by Michelle O'Brien, EsqDealing with Poorly Soluble APIs
An increasing number of bioactive molecules arising from discovery research have poor water solubility, a property that can make development of drug products, particularly oral dosage forms, difficult. Brief descriptions of the relationship between solubility and dissolution rate, and of our current ability to predict solubility from structure, will be presented. Various approaches to improving solubility based on physical form include use of salts, polymorphs, cocrystals, non-crystalline materials, and molecular dispersions. Examples will be used to illustrate each approach.Solid Form Control in Crystallizations
Crystallization method development is often carried out using the traditional process development approach of sequentially altering process conditions to optimize the desired product characteristics. In crystallization, that can lead to an out-of-control process that appears, in the short term, to be under control. Most often such a situation results from lack of nucleation control. A brief review of crystallization basics will be followed by a discussion of the fundamental information necessary to provide solid form control.Cocrystals: Recent Advances in Discovery and Utilization
Cocrystals have become an accepted solid dosage form option and the majority of pharmaceutical research laboratories have begun to experiment with cocrystals to some degree. While a cocrystal may present a route to physical property improvement for an API, the development of that cocrystal into a product may present some unanticipated challenges. The experimental methods for cocrystal dissolution are often more focused on powder dissolution profiles under non-sink conditions rather than intrinsic dissolution experiments.Other experimental considerations, including the choice of the appropriate dissolution media, will be discussed. The use of carefully designed powder dissolution experiments using cocrystal formulations containing appropriate excipients can significantly increase the potential for a successful pharmacokinetic study. The formulation of cocrystals that are intended to increase the bioavailability of an API can be difficult if cocrystal dissolution is quickly followed by uncontrolled crystallization of the API. A more soluble cocrystal will often result in a supersaturating system in which the API will precipitate at equilibrium conditions. Understanding and controlling the key parameters of such a system is necessary in order to translate the increased solubility potential of a cocrystal into a promising powder dissolution profile and, in turn, into a significant increase in plasma concentrations compared to the free form of the API.
The FDA issued draft guidance on the topic of the regulatory classification of cocrystals in December of 2011. The FDA proposed that cocrystals be regulated as drug product intermediates rather than drug substances. The implications of this regulatory approach will be discussed in the context of the public comments on this draft guidance that were submitted by the March 1, 2012 deadline at regulations.gov for Docket ID FDA-2011-D-0800. A review of the comments will be presented as they relate to the requirements for identifying a substance as a cocrystal, the different regulatory approaches for cocrystals, salts, and polymorphs, the effect on Orange Book therapeutic equivalence codes and ANDA/generic drug applications, as well as implications for manufacturing of cocrystals and impact on global regulatory harmonization.
The Salt-Cocrystal Continuum
The question "it a salt or is it a cocrystal?" will be addressed. For organic salts, the question hinges on the extent of proton transfer in the solid state. For a crystalline solid containing an acid and base having a small delta pKa, the crystalline environment is the primary determinant of hydrogen bond geometry. The argument will be made that it is the physical properties of a solid, not whether it can be classified as a salt or cocrystal, that are important for determining the viability of that solid for commercial use.Amorphous Material Characterization using Total Diffraction Analysis
When comparing powder patterns from amorphous and crystalline materials, it initially appears that there is very little information content in the amorphous powder pattern due to the lack of clearly visible diffraction peaks and the presence of just a few broad halos. Indeed, from the perspective of the Bragg model of diffraction (peak based), the information content is very limited. However, from a Total Diffraction perspective, every point in the measured powder pattern contains some information related to the 'structure' of an amorphous material. The 'structure' typically observed in amorphous materials relates to localized inter-molecular coordination. The Pair wise Distribution Function (PDF) approach has been used extensively in the past to extract information on local coordination numbers and correlation lengths from X-ray powder patterns collected on disordered solids and liquids. Although the PDF transform can be useful analytical technique, when dealing with organic molecules the PDF trace is complicated by the overlap between inter- and intra- molecular order.
A simpler direct analytical method is to use the well-known Paracrystalline Scattering Function (PSF) to model the measured powder pattern. The PSF approach assumes that the preferred inter-molecular stacking of neighboring organic molecules is the one that gives the shortest mean packing distance, leading to short partially ordered stacks of molecules. The intra-molecular order is taken of using a calculated molecular form factor. The PSF is a Total Diffraction Transform, in that every data point is calculated and not just peak positions and intensities. The information returned using the PSF is similar to that obtained from the PDF. That is the number and values of the preferred stacking distances and their respective correlation lengths.
Perhaps the most complete use of the Total Diffraction concept is to calculate the X-ray scattering from molecular models of the amorphous state. Using the Debye diffraction transform, the complete powder pattern is calculated from a localized molecular model. The molecular packing is modified, often using energetic constraints. Until the measured powder pattern can be completely described by the calculated powder pattern. The resulting molecular configuration is verified as being a realistic structure through packing energy calculations and comparison to know crystalline structures. Very often, the result of initial PDF and PSF calculations can be used to help design good starting models.
The driving force behind the Total Diffraction Methods for amorphous materials is the ability to derive models of the local molecular order than can be related to the key physical properties such as stability.
Amorphous Materials and Stability Prediction
With amorphous pharmaceutical materials showing relaxation, re-crystallization and chemical instability, the local molecular structure within an amorphous form is of paramount importance. In part I of the 'Amorphous Materials' webinar, the nature of structure (local molecular order) in the amorphous state will be discussed along with how different structures might result from different production pathways and how structure and configuration entropy are related. The behavior of water and amorphous ice will be used a illustrative examples.
A number of different X-ray diffraction methods will also be introduced that allow insight into and characterization of the type of local molecular order that exists in real pharmaceutical amorphous materials. This will include some simple direct methods that can be employed in any solid state lab the more extensive indirect molecular modeling and total diffraction approaches used at Triclinic labs.
Solid-State Analytical Techniques
Characterization of Organic Solids
An overview of analytical techniques used to characterize solids will be presented. Techniques include spectroscopy (infrared, Raman, NMR), thermal (differential scanning calorimetry, thermogravimetry, hot-stage microscopy), x-ray diffraction, microscopy, moisture sorption, and particle sizing.Development and Validation of Methods for Solid Mixture Analysis
Both qualitative and quantitative methods for analysis of solid mixtures will be discussed. Various techniques can be used, including x-ray diffraction, vibrational spectroscopy, NMR spectroscopy, differential scanning calorimetry, and moisture sorption. However, solid mixtures pose unique validation issues that are not currently addressed in ICH guidelines. Those issues, and approaches for dealing with them, will be presented.
Mapping and Imaging
Spectroscopic mapping and imaging are relatively new techniques that are useful for a variety of tasks. They are particularly valuable for analysis of finished products containing multiple components. For example, drug products such as tablets, caplets, microspheres, etc. can be analyzed with little or no sample preparation. Applications for such analyses include detection of minute amounts of a specific component of interest (such as a potentially patent-infringing solid form), determination of the spatial locations of components, identification of component interactions leading to changed product performance, and verification of content uniformity. Examples will be presented.
Counterfeit Detection
The problem of counterfeit drugs is immense. Aside from the cost, lives have been lost because of dependence on what turned out to be counterfeit medicines. According to the US FDA web site, The World Health Organization (WHO) estimates that counterfeit drugs range from less than 1% in developed countries to over 30% in some developing countries. Analytical techniques and methodologies that allow detection of counterfeit drug products will be discussed.
Cryo-SEM and Its Application in Hydrated Pharmaceutical Sample Analysis
An image can easily clarify questions about sample properties. Scanning Electron Microscopy is an important tool for documenting the fine structure of many different types of dry products. However, what if the sample is hydrated and too small for light microscopic observation? How does a dry sample change when hydrated? Does it swell? Can you observe the stability, or lack thereof, of the formulation? This is where cryoSEM becomes a valuable tool. This webinar will present information on this technique and how it can be used on hydrated pharmaceutical samples, along with other examples from the world of hydrated samples.
Frequenty Asked Questions about our seminars:
Are the Seminars Free?
Yes, we're happy to provide one or two seminars for your institution and colleagues at no cost. Additionally, if you would like either extended, in-depth seminars or an entire course on given topics, we are happy to construct a customized multi or single day "short-course" for your internal continuing education at our standard consulting rates for a fee. During the "short-course", actual internal projects can be discussed as well as how to apply the topics at hand.Many of our clients find that after the seminars they would like to have confidential discussions on how to apply the techniques and methods described during the seminar. Our experts are available for fixed fee consultations as well.
Can the seminars be tailored for my group?
Yes. We're happy to tailor the presentations toward specific areas of interest or under CDA discuss specific issues you may be encountering. Please contact us at least two weeks prior to your seminar to discuss specifics.Can Triclinic Labs conduct the experiments and techniques discussed during the seminars?
Yes. We employ not only industry-recognized experts in the topics we lecture on but also are able to conduct the experiments discussed. For solid-state discovery and development we offer polymorph and cocrystal screening and selection, salt screening, and method development for the control of solid-forms. Additionally our laboratories are recognized as leaders in the field of routine analytical testing or development of methods for release testing, intellectual property matters, and imaging and mapping of drug substance and drug product.Is there a copy of the Seminars I can distribute?
When you schedule a seminar on-site or in-house we will send you a meeting template and abstract that you can customize and distribute. We'll also provide a copy of the slides if you wish.