Candidate Selection

This program has been developed and will be presented in cooperation with the Lenor Zeeh Pharmaceutical Experiment Station in the School of Pharmacy at the University of Wisconsin-Madison.

More information about the Pharmaceutical Experimental Station

Registration

Your registration options are as follows:

	Register Online. Login in using your user account. If you don't have a user account creating one is free & easy.
	Download the registration form, complete & mail to: Drug Development Extension Services in Pharmacy UW School of Pharmacy 777 Highland Avenue Madison, WI 53705
	By phone at 608.262.3130 or toll-free at 877-947-4255 using a credit card for payment.
	Download the registration form, complete & fax to 608.262.2431 using a credit card for payment.

Short Course Program General Information

Limited Enrollment

Enrollment is limited to 30 registrants.

Course Location

Courses are presented at the Pyle Center on the University of Wisconsin-Madison Campus. Summer time in Madison and the beauty of the on-campus location provide a relaxing atmosphere for learning. Evenings can be used to explore the University and the city. For more information about Madison, WI see www.visitmadison.com.

Accommodations

On-campus housing is available to short course registrants. Housing information will be sent to individuals when they receive their registration confirmation. Other hotels are also conveniently located around the campus. The approximate cost per night range from about $80-130.

Registration Fee

Tuition for the program will be $1,995.00. Cancellations after June 4 are non-refundable. Cancellations prior to June 4 are subject to a $75 administration fee. In the event that an accepted applicant cannot attend, a substitute may be sent by the same company. Early bird discounts ($1,995 - $300 = $1,695) are offered to individuals registering prior to June 4, 2010.

Laptops required

A proportion of the course will be workshops using Excel utilities developed by the faculty. Participents will be required to bring a laptop computer with Excel installed. Program files will be provide on memory sticks distributed during the course.

Goals & Objectives

This course covers practical aspects of pharmaceutical development at the early stage of drug discovery leading to candidate selection. The learner will become familiar with strategies and techniques pertaining to preformulation experiments conducted during lead optimization and selection. Specifically, the course is devoted to (1) those critical physicochemical properties of candidate molecules that are evaluated in order to assess their “developability” and (2) the formulation approaches used in discovery support to enable animal efficacy, PK and toxicological studies. Each day of the course focuses on one or more major topics: solubility, partition coefficients, solubilization, formulating poorly soluble compounds, oral bioavailability concepts, salt and crystal form searching and characterization, and chemical stability evaluation for solution and solid state. These key aspects of early pharmaceutical development will be integrated into a framework for candidate selection. This course is divided into morning sessions that are didactic in nature, covering background and experimental design aspects for each of the topics, illustrated by literature examples. The afternoon sessions are “case driven” in which attendees will learn how to analyze and interpret preformulation data through case examples. All data will be provided in spreadsheet format and analyzed at a computer in an instructor-led manner. Upon completion of the program, the learner will be able to:

Conduct solubility experiments with an ability to analyze pH-solubility data for pKa, intrinsic solubility and salt solubility product constants
Understand the basis for calculated solubility approaches and calculate solubility and pH-solubility profiles using a predominant method based on the “general solubility equation”
Design partition coefficient experiments to analyze pH-distribution data for partition coefficients inclusive of ion-pairing
Understand the basis for calculated partition coefficient approaches with an illustration of one such computer program (ACD/logP)
Apply major solubilization strategies for parenteral delivery, and for enhancing oral bioavailability of poorly soluble drugs for early preclinical evaluation, inclusive of practical limitations in pH, levels of organic solvents, oils, cyclodextrins and surfactants that can be dosed to animals and humans
Analyze solubilization data for key parameters such as solubilization power than enable optimization of formulations with minimal experimental data
Understand oral bioavailability concepts in the context of the biopharmaceutics classification system (BCS) and distinctions between dissolution rate, solubility and permeability limited absorption
Assess the relevance of solid state form and characteristics on prediction and measurement of physicochemical properties.
Apply solid state analysis techniques and crystallization concepts to salt and crystal form screening and selection.
Analyze solution and solid state stability data for candidate selection using principles of chemical kinetics
Design pH-rate and solid state stability protocols and perform appropriate experiments for early developability assessment and candidate selection
Analyze pH-rate and other stability data for catalytic constants and estimation of retest period and shelf life
Integrate all of the preformulation data into a composite profile to assess the developability of a candidate drug, identifying low and high risk features in the decision process

View last years evaluation results.

Special Offer for Academic Institutions

Extension Services in Pharmacy at the University of Wisconsin School of Pharmacy has instituted a new policy for industrial professional development programs to encourage greater participation by faculty, graduate students and post doctoral students at academic institutions. Programs will be offered at a significantly reduced price, based on space availability. For information about any specific course please contact Dr. James E. De Muth by email.

Who Should Attend

Scientists and technical managers working in preformulation at the drug discovery interface responsible for lead optimization and candidate selection. Attendees should include MS/PhD graduates new to the discipline and BS level scientists with significant experience in preformulation. Additional disciplines that would benefit from attendance include pharmaceutics/formulations scientists and managers interested in gaining better understanding of pre-formulation issues and discovery scientists desiring to increase their understanding of physical/chemical characterization principles. Individuals who have previously completed the CMC track of Applied Drug Development 1: Pre-Clinical and Drug Development Design Strategies would likely be well suited to attend this short course.

Planning Committee

Edmund (Ed) Elder, Jr., R.Ph., Ph.D., University of Wisconsin-Madison
Nivedita (Nita) Pandit, Ph.D., Drake University
Mark Sacchetti, Ph.D., University of Wisconsin-Madison
Lian Yu, Ph.D., University of Wisconsin-Madison
James E. De Muth, Ph.D., University of Wisconsin-Madison

2009 Contents

Monday, June 22

8:30am

Welcome

James E. De Muth, Ph.D.
Professor, School of Pharmacy, University of Wisconsin-Madison

8:40am

Introduction and Acid-Base Dissociation
The relevance of dissociation equilibria for drug acids, bases, ampholytes and zwitterions; definition of pKa; distinction between and relevance of thermodynamic and apparent pKa; application of Debye-Hückel and Davies equations; importance of ionic strength control; fractional species concentrations; pKa of some major functional groups and heterocycles; pKa databases and software

9:40am

Introduction to Solubility
Introduction to basic concepts; solubility of ionizable molecules; pH-solubility profile for weak acids, bases and ampholytes/zwitterions

10:00am

Break

10:20am

Solubility
Solubility of salts; common ion effect; experimental aspects of solubility experiments; importance of controlling pH, ionic strength and temperature; role of purity, particle size and powder processing; curve fitting the pH-solubility profile for pKa, intrinsic solubility and salt solubility products; exploiting pH-solubility profiles; solubility in biologically relevant media; solubility and BCS; solubility in topical and MDI formulations; calculating solubility using some common algorithms

12:00

Lunch

1:00pm

Analysis of the pH-solubility profile of a weak acid and its salts
Calculate the solubility of a weak acid using the general solubility equation; calculate the pH-solubility profile of the weak acid; data for the pH-solubility profile of a weak acid and several salts thereof will be provided in Excel; data will be analyzed by nonlinear regression to extract pKa, intrinsic solubility and salt solubility product constants

2:10pm

Partition Coefficients
Introduction to basic concepts; pH-partition hypothesis; ion-pairing; distribution coefficient and its dependence on pH and ionic strength; experimental aspects; data analysis; curve fitting pH-distribution coefficient data; labile compounds; problematic ultralow solubility compounds; calculating partition coefficients using some common algorithms

3:10

Break

3:30pm

Analysis of the pH-distribution Coefficient of a Weak Base
Data for the pH-distribution coefficient will be provided in Excel for a weak base; data will be analyzed by nonlinear regression to extract partition coefficients for the neutral and ionic species

4:10pm

Open Discussion

4:30pm

Adjournment

6:00pm

Reception: Hilton Monona Terrace

Sponsored by:

Invitrogen

7:00pm

Dinner at the University Club

Tuesday, June 23

8:30am

Solubilization Part 1
Introduction; pH-adjustment, pH-dilution and precipitation; cosolvents, log-linear relation for cosolvent solubilization; combined pH-adjustment and cosolvents; cosolvent dilution and precipitation; common surfactants used often with cosolvents; in vitro assessment of hemolysis; complexation with cyclodextrins, common binding models; combined pH-adjustment and complexation; dilution of complexed solutes; static serial dilution procedure

10:00am

Break

10:20am

Solubilization Part 2 and Enhancing Oral Bioavailability
Oils and lipids; some common materials and formulations used; solubilization summary and strategy; nonsolubilization approaches – particle size reduction and amorphous solids; flow chart for solubilization strategy

11:20am

Concepts in Oral Bioavailability
GI tract pH and transit times; modes of transport; Lipinski’s “rule of five”; permeability including pH dependence for ionizable molecules; human intestinal permeability and maximum absorbable dose; Caco2 permeability and relation to human dose absorbed; artificial membrane permeability (PAMPA); dissolution rate vs. solubility vs. permeability limited absorption

12:00

Lunch

1:00pm

Solubilization of a Weak Base using pH and Cosolvents
Data for the solubility of a weak base will be provided in Excel as a function of pH and cosolvent; data will be analyzed by nonlinear regression to extract solubilization power for interpolation and formulation development

2:00pm

Solubilization of a Compound for Parenteral Delivery
A weak base drug has a target solubility required for IV delivery; a set of physicochemical data will be provided; solubility will be calculated at the lowest pH practical in saline and D5W; solubility will be calculated in a cosolvent mixture and in a cyclodextrin vehicle; solubility in some oils will be considered; based on solubility results and estimations from calculations, a decision will be reached on the best formulation to use to advance the compound

3:00pm

Break

3:15pm

Solubilization of a Compound for Oral Delivery
Solubility and oral bioavailability data for multiple formulations will be given for a poorly soluble candidate; an analysis of dose, solubility and practical limitations for capsules will be done to assess viability of a solution dosage form in comparison to an alternative amorphous solid dispersion; a decision will be made regarding the best formulation to advance

4:00pm

Open Discussion Pertaining to Solubility and Solubilization

4:30pm

Adjournment
Evening Free to Explore Madison

Wednesday, June 24

8:30am

Solid State Stability for Early Preformulation Assessment
Practical considerations; accelerated conditions inclusive of light; use of accelerated data to estimate long term stability of drug candidates; statistical evaluation of data

9:00am

Chemical Kinetics & Solution Stability Part 1
Introduction; review of key rate equations used for solution and solid state stability studies in early development; temperature dependence of reaction rates; transition state diagrams for catalysis and medium effects; hydrolysis reactions; pH-rate profiles for nonionizable and ionizable drugs; theoretical basis for shapes of pH-rate profiles

10:00am

Break

10:20am

Solution Stability Part 2
Buffer catalysis and determining which species reacts; role of ionic strength and organic cosolvents; temperature dependence of pH-rate profiles; experimental aspects inclusive of sample preparation, buffer preparation for pH control at elevated temperature, ionic strength control, stopping reactions, data analysis for rate constant determination, extrapolation for shelf life estimation, potential oxidation and photolysis complications

11:30am

Oxidation and Antioxidants
Definition of oxidation reactions; the chain reaction mechanism; catalysis by metals; oxidation in solution; classes of antioxidants; antioxidant water/oil solubility, levels and synergism; case example of antioxidants used in an oil-based formulation

12:00pm

Lunch

1:00pm

Analysis of a pH-rate Experiment
Data provided in Excel for a complete pH-rate experiment; data will be analyzed for overall rate constants, specific catalysis rate constants and buffer catalysis all at elevated temperatures; extrapolation conducted for shelf life estimation with and without buffer catalysis to determine an maximally stable formulation

2:30pm

Break

2:45pm

Case Example of Buffer Selection and Cosolvent Evaluation
Data will be provided for the stability of a drug in multiple buffers and cosolvents; data will be analyzed for rate constants and shelf life; a decision will be reached on the best buffer and cosolvent to use for further formulation development

3:30pm

Analysis of a Solid State Stability Study
Results provided in Excel; data will be plotted and analyzed for degradation rates for 1 month and more extensive 3 month data sets (the latter involving statistics); will need to decide if the drug candidate exhibits acceptable stability for progression and if not can steps be taken to improve stability

4:15pm

Adjournment - Optional Tour of School of Pharmacy or Pharmaceutical Station Labs and Illustration of ACD Software

6:00pm

Evening Free to Explore Madison

Thursday, June 25

8:30am

Relevance of Solid Forms
Introduction; crystalline and amorphous solids; polymorphs, hydrates/solvates, cocrystals and salts and their distinct properties; pharmaceutically acceptable counterions and frequency of use in marketed salts

10:00am

Break

10:20am

Characterization of Solid Forms
Key physical properties relevant to drug development; identification of crystal forms by x-ray diffraction, spectroscopic and thermal analysis techniques; characterization of micromeritic properties by microscopy, particle size, surface area, true and bulk densities; moisture sorption techniques

11:10am

Screening and Selection of Solid Forms
Crystallization techniques; high throughput screening; key selection criteria inclusive of relative physical stability, moisture sorption, solubility, bioavailability and stability; decision flow charts for salt and crystal form selection

12:00pm

Lunch

1:00pm

Case Example of a Salt and Crystal Form Selection
Give data for multiple salts and decide on best form; give data on multiple crystal forms of selected salt and decide on best crystal form

2:00pm

Identification and Relative Physical Stability of Polymorphs
Data will be provided for a polymorphic pair; solubility data will be analyzed to determine relative physical stability and if the pair is monotropic or enantiotropic

3:00pm

Break

3:20pm

Case Example of a Mini In Situ Salt Screen
Data will be provided for a small scale in situ salt screen; the data will be analyzed for the salt solubility products and salt solubilities; based on the results a formulation for toxicology will be decided

4:00pm

Open Discussion

4:30pm

Adjournment

6:00pm

Reception: University Club

2009 Instructors

Mark Sacchetti, Ph.D.
Scientific Director, Zeeh Pharmaceutical Experiment Station
School of Pharmacy, University of Wisconsin-Madison

Edmund (Ed) Elder, Jr., R.Ph., Ph.D.
Director, Zeeh Pharmaceutical Experiment Station
School of Pharmacy, University of Wisconsin-Madison

Nivedita (Nita) Pandit, Ph.D.
Professor, Pharmaceutical Sciences
College of Pharmacy and Health Sciences
Drake University, Des Moines, IA

Lian Yu, Ph.D.
Associate Professor, Pharmaceutical Sciences
School of Pharmacy, University of Wisconsin-Madison

For More Information

James E. De Muth, Ph.D., Course Coordinator
Extension Services in Pharmacy
777 Highland Avenue
Madison, WI 53705
(608) 262-3130
FAX (608) 262-2431
Send Email

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Principles and Experimental Strategies in Physicochemical Characterization, Solubilization and Solid Form Screening for Candidate Selection (Applied Drug Development Core Course)
June 21-25, 2010
Pyle Center
702 Langdon Street
Madison, WI

This program has been developed and will be presented in cooperation with the Lenor Zeeh Pharmaceutical Experiment Station in the School of Pharmacy at the University of Wisconsin-Madison.

More information about the Pharmaceutical Experimental Station

Menu

Registration