Solubility and Complex Equilibria (PHS 991)

 

Instructor:      Michalakis Savva, Ph.D.                                                                 Fall 2005

Contact Information: Office:             HS 610                                   

Telephone:     488-1471

e-mail:             msavva@liu.edu

Website:         myweb.brooklyn.liu.edu/msavva/

 

Course description

This is a core course in the Ph.D. program. It investigates solution’s theory and emphasizes solubility and solubilization of drug molecules. The approach to this study is based on theoretical and physical foundations, and leads to the application of the theory to systems of pharmaceutical importance. The prerequisites for this course are Physical Chemistry I (PHS 701) and Calculus I and II (MAT 40 and MAT 100, respectively). Physical Chemistry II (PHS 702) and Differential Equations I (MAT 610) are not required but they are highly recommended.

 

Grading

Grades will be based on three quizzes (5% each), one Midterm exam (35 %) and a cumulative final exam (50 %).  The grading scale will be determined at the end of the course.  No grades will be dropped. If an exam is missed for any reason, the lowest numerical grade from the other exams (Quizzes, Midterm and Final) will be entered for the missed exam grade at the end of the semester. If both midterm and final exam are missed, zero will be entered for both exams. It the final exam is missed, a grade of incomplete will be submitted to the registrar and a make up will be given at a time and day determined by the instructor. The material for the exams will be extracted from the assigned text books, from lectures and other handouts/scientific articles.

 

Required Texts

Samuel H. Yalkowsky, Solubility and Solubilization in Aqueous Media, Oxford University Press, 1999.

Book can be purchased from PolySurfaces Bookstore at www.polysurfacesbookstore.com tel. 603 5430038

A. Martin, et al, Physical Pharmacy, 4th Edition, Lea & Febiger, 1993.

 

Other Useful Texts

Physical Chemistry

 

Objective

Upon completing this course, students should be able to:

          Describe and calculate the properties of solutions.

          Understand factors that govern solubility, in general, and aqueous solubility in particular.

          Describe and determine the properties of solute, critical in evaluating the solubility and solubilization of it in aqueous media.

          Apply the various techniques available for altering the solubility and dissolution rate of organic compounds in aqueous media.

 

 

 

 

Course Outline

 

Chapter 0:      Fluids

            0.1. Fluid Classification

            0.2. Properties of Fluids

                        0.2.1. Density

                        0.2.2. Pressure

            0.3. Fluids at rest

            0.3.1. Applications of Pascal’s Principle

            0.4. Archimedes’ Principle

                        0.4.1. Apparent Weight in a Fluid

            0.5 Ideal Fluids in Motion

                        0.5.1 Streamlines and Velocity of Fluids

            0.6. The Equation of Continuity

            0.7. Bernoulli’s Equation

            0.8. Practice Problems

 

Chapter 1:  Mixing and Properties of Mixing

1.1. Thermodynamics of Mixing

1.2. Description of Mixtures

1.3. Colligative Properties

1.4. Other Properties of Mixtures

 

CHAPTER 2: Characterization of Solutions 

            2.1. Ideal Solutions

            2.2. Athermal Nonideal Solutions

            2.3. Regular Solutions

            2.4. Solvated Solutions

            2.5. Self-Associated Solutions

            2.6. Solvated, Self-associated solutions

            2.7. Aqueous Solutions

 

CHAPTER 3: Solubility and Partial Miscibility

            3.1. Partial Miscibility of Liquids

            3.2. Critical Solution Temperatures

            3.3. Solubility and Activity Coefficient of Liquid Solutes

            3.4. Solubility of Crystalline Solutes

            3.5. Dependence of Solubility on Gas Properties

            3.6. Alteration of Aqueous Solubility

            3.7 Temperature and Solution Composition

            3.8 Partition Phenomena

 

CHAPTER 4: Physical Modification of the Solute

            4.1. Apparent Solubility and Dissolution Rate

            4.2. Particle Size and Crystal Quality

            4.3. Amorphic Solid Modification

            4.4. Crystal Form Modification

            4.5. Crystal Hydrate Formation

            4.6. Complex Systems

            4.7. Factors Affecting Reversion

              

CHAPTER 5: Solubilization by pH Control

            5.1. Buffers

            5.2. Dependence of Solubility on pH

            5.3. Dependence of pKa on Solute Structure

            5.4. Temperature and Solution Composition

            5.5. Pharmaceutical Aspects of pH Solubilization

 

CHAPTER 6: Solubilization by Cosolvents

            6.1. Properties of Pure Cosolvents

            6.2. Solubilization by Cosolvents

            6.3. Dependence of Solubilization on Cosolvents

            6.4. Dependence of Solubilization on Solute Structure

            6.5. Temperature and Solution Composition

            6.6. Pharmaceutical Aspects of Solubilization by Cosolvents

 

CHAPTER 7: Solubilization by Surfactants (Briefly)

            7.1. Solubilization by Micellar Surfactants

            7.2. Pharmaceutical Aspects of Solubilization by Surfactants

 

CHAPTER 8: Solubilization by Complexation

            8.1. Complex Stoichiometry

            8.2. Chemical Classification of Complexes

            8.3. Solubilization by Inclusion Complexation

            8.4. Solubilization by Stacking Complexation

            8.5. Temperature and Solution Composition

            8.6. Pharmaceutical Aspects of Solubilization by Complexing Agents

 

CHAPTER 9: Effect of Cosolutes on Solubility

            9.1. Liquid Solutes

            9.2. Solid Solutes and Liquid Cosolutes

            9.3. Solid Solutes and Solid Cosolutes

 

Lecture, Quiz, Midterm and Final Exam Schedule

September

October

November

December

7

5

2

7

14

12 (Quiz 2)

16

14 (Final Exam)

21 (Quiz 1)

19

23 (Quiz 3)

 

28

26 (Midterm Exam)

30