University of Wisconsin–Madison

Developing Oral Drug Formulations

Practical Strategies for Preclinical and Phase 1

an array of test tubes filled with liquids for developing oral drug formulationsThis course focuses on developing oral drug formulations for Preclinical and phase I.  Preclinical drug development is strenuous. Drug development teams must test early stage candidates for viability. They have to show quick progress within tight timelines.

Evaluating a drug candidate for viability involves a wide number of tasks such as

  • devising formulation approaches
  • enabling PK and toxicological studies
  • addressing solubility and bioavailability issues
  • developing solubization strategies
  • optimizing formulation
  • analyzing experimental data

These tasks must be completed quickly and efficiently with as few experiments as possible. This course provides a practical guide for selecting and evaluating oral dosage forms. You will learn how to conduct drug development tasks quickly and efficiently.

This course is part of the Applied Drug Development Certificate. It fulfills one of three required courses. You may take this course as is or as part of the certificate. Students interested in mastering drug development should complete the certificate program.

Developed & Conducted by the Division of Pharmacy Professional Development, School of Pharmacy, University of Wisconsin-Madison.

Registration Information

Register

Refund Policy

Course date:Feb 1, 2019 - Feb 1, 2022
Location:
Course fee:

$1300/$1050 two or more registrants from the same company
$650 Academic/$350 Graduate Student

Course Objectives

Goals and Objectives

This course covers practical aspects of dosage form development for preclinical and phase 1 formulations.  The formulation approaches include solubilization and disperse phase systems (suspensions, emulsions, microemulsions, liposomes and micelles) for preclinical as well as powders for reconstitution, capsules and tablets for phase 1. 

The course is a practical guide in that its focus is on major considerations in selecting and evaluating oral dosage forms for preclinical and phase 1 studies by examining the excipients used, their typical level ranges and various preparation/processing procedures on small laboratory and pilot scales.  The challenges in developing oral dosage forms at this early stage will be examined in detail, including the major problems encountered and the common strategies that are used to overcome them. 

In addition to its focus as a formulation guide, the course content includes key points in stability evaluation, such as excipient compatibility approaches and the ICH guidelines.  The major physical tests used to assess formulations are an integral part of the course material and are covered in terms of their application to problem solving and in setting the product specification.

Upon completion of the course, the attendees should be able to describe:

  • Solubilization approaches used for poorly soluble compounds
  • Preclinical animal species considerations for testing formulations
  • Strategies and major issues to consider in oral dosage form development for phase 1, including lab and pilot scale processing factors, excipient compatibility for capsules and tablets, common problems encountered and problem solving approaches
  • Bioenhanced formulation strategies for phase 1 capsules and tablets, including particle size reduction techniques, solid dispersions and liquid-filled capsules
  • Stability assessment of solid oral dosage forms for phase 1, including common problems encountered and problem solving approaches

Who Should Attend

Scientists and technical managers who work in early drug development and who are responsible for preclinical and/or phase 1 clinical formulations.  Attendees should include BS, MS and PhD graduates with less than 5 years of experience in the formulation discipline. 

Additional scientists and managers who would benefit from the course include those working in analytical, preformulation, various biological sciences (toxicologists, pharmacokineticists, pharmacologists), and other groups interested in gaining a better understanding of principles and practices in early formulation development. 

Other individuals who would be well-suited to attend this short course are those who have previously completed the other core Applied Drug Development short courses.

Course Outline

Module 1

Introduction and overview of course

Module 2

Preclinical Formulation

pH adjustment, cosolvents, complexation and oil/lipid-based formulations; small scale processing considerations; dosing small volumes; filling and dosing small capsules; comparing solution and suspension results

Module 3

Preclinical Formulation Problem Set

Given a compound with certain properties, provide a formulation strategy, including details of excipients used, their levels and dosing limitations for the animal species

Module 4

Drug Substance Considerations

Salt forms; role of drug substance crystal form and particle size in capsule and tablet formulations

Module 5

Dosage Form Selection for Phase 1 and Placebo Considerations

Drug-in-bottle approach, reconstitution (solutions and suspensions), advantages and disadvantages, when and when not to use; time, resource and drug substance requirement comparison with capsules and tablets; excipient compatibility and stability considerations; matching; controls for stability

Module 6

Excipient Compatibility

Traditional and statistical design approaches vs. the miniformulation strategy

Module 7

Excipient Compatibility Problem Set

Given a compound with certain properties, design an excipient compatibility study; a dataset will be provided and groups will review results to determine next steps and select the optimum ingredients for a formulation

Module 8

Physical Property Tests

Physical characterization of powders and granules: size, morphology, density, porosity, flowability, water content
Physical characterization of tablets: hardness/tensile strength, friability, water content, disintegration, dissolution

Module 9

Tablet Formulation Development

Advantages and when to use tablets; excipients used, functionality and levels; tablet compaction process, manual vs. automated; direct compression, wet granulation, dry granulation, film coating; processing formulations at lab and pilot scales; ICH guideline; stability protocols for tablets (e.g., decrease in dissolution)

Module 10

Capsule Formulation Development

Advantages and when to use capsules; excipients used, functionality and levels; capsule filling process, manual vs. automated; gelatin and nongelatin capsules, gelatin specific issues; processing formulations at lab and pilot scales; ICH guideline; stability protocols for capsules (e.g., decrease in dissolution)

Module 11

Capsule/Tablet Problem Set

Given a drug with certain properties, anticipate potential problems and devise a formulation strategy, including excipients and processing details

Module 12

Milling and Solid Dispersions to Enhance Oral Bioavailability

Assessing dissolution rate limited oral bioavailability; milling, micronization and wet milling at lab and pilot scales; key methods for physicochemical characterization of processed drug substance and small particles
When to and not to consider solid dispersions; eutectics and amorphous solid dispersions; excipients used; methods of manufacture at lab and pilot scales; importance of physicochemical characterization; physical and chemical stability

Module 13

Solid Dispersion Formulation Problem Set

Given a compound with certain properties, devise a formulation strategy, including excipient choices, levels considered and stability assessment

Module 14

Liquid Filled Capsule Formulations to Enhance Oral Bioavailability

Assessing solubility limited absorption; when to and not to consider liquid filled capsules; excipients used and their functionality; excipient levels and capsule shell compatibility; liquid fill process considerations for hard shell capsules (e.g., temperature and banding); soft gel capsule filling process

Module 15

Liquid Filled Capsule Formulation Problem Set

Given a compound with certain properties, devise a formulation strategy, including excipient choices, levels considered and stability assessment

Instructors

Edmund (Ed) Elder, Jr., RPh, PhD
Director, Zeeh Pharmaceutical Experiment Station
School of Pharmacy, University of Wisconsin–Madison
Madison, WI

Mark Sacchetti, PhD
Scientific Director, Zeeh Pharmaceutical Experiment Station
School of Pharmacy, University of Wisconsin–Madison
Madison, WI

Program Coordinator

Eric Buxton, PhD

Division of Pharmacy Professional Development
777 Highland Avenue
Madison, WI 53705
(608) 262-2431 FAX
(608) 265-2259
eric.buxton@wisc.edu

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