Advanced Physical Pharmacy (PHS 931)

 

Instructor:         M. Savva                                                                                                    Spring 2008

Office:              HS 610                        

Telephone         488-1471

 

Course description

This course investigates the application of physical chemical principles to problems in the pharmaceutical sciences.  Physical and theoretical foundations are discussed and applied and problem solving is emphasized.  The prerequisites for this course are general and organic chemistry some calculus.  To pass this course, students must be able to solve problems.  Therefore, problems will be assigned for homework.  While problems will not be collected, students will be responsible for their content on exams.

 

Grading

Grades will be based on one Midterm exam (40 %) and a cumulative final exam (60 %).  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, an oral make-up exam will be given at a time to be determined by the instructor.  Failure to make up the exam in a timely manner will result in grade of Incomplete or F.

 

Text

A. Martin, et al, Physical Pharmacy, 4th Edition, Lea & Febiger, 1993, or 5th edition, Lippincott Williams & Wilkins, Baltimore, MD 2006.

 

Objectives

1.     Understand the concept of primary units (mass, length, time, electric charge, temperature) and use unit analysis to express all relevant physical quantities in terms of these units.

2.     Understand basic thermodynamics of equilibrium constants, chemical potential and heats of reaction, phase change, etc.

3.     Calculate properties for non-electroytic and electrolytic solutions.

4.     Apply methods of complex equilibria to calculate pH’s and prepare buffers.

5.     Understand basic chemical kinetic mechanisms and interpret experimental data

6.     Understand saturable kinetics and apply the model to enzyme kinetics, protein binding, etc.

7.     Calculate steady state diffusion profiles and interpret experimental data to determine diffusion and permeability coefficients.  Design diffusion experiments.

8.     Understand and apply the Noyes-Whitney and Hixson-Crowell dissolution models.

9.     Understand properties of interfaces and adsorption processes. 

10. Be familiar with colloids and coarse dispersions and their preparation (if time permits).

 

Course Outline

 

Topics marked with an “*” represent prerequisite material.  Students are responsible for knowing these topics, even though they may not be covered in class lectures (instructor’s option). 

 

Chapter I:  Introduction and basic material*

A.    Math review

·        Some important derivatives and integrals

·        Natural logs and exponents, common logs and powers of 10 (and conversions)

·        Linear regression and semi-log plots

·        Significant figures and plot representation

B.    Physical units and unit analysis

·        Weights, moles, equivalent weights, etc.

·        Density, specific gravity, molar volume (and conversions)

·        Concentration (molarity, molality, mole fractions, normality)

·        Pressure

·        Energy and heat

 

Homework: 1-1,1-4, 1-5, 1-7, 1-8, 1-10, 1-13, 1-17, 1-18, 1-20, 1-21

 

CHAPTER II: 

A.   Binding forces between molecules

·        Repulsive and attractive forces

·        Van der Waals forces

·        Hydrogen bonds

      States of matter

A.    The gaseous state

·        Ideal gas

·        MW determination

·        Real gases

·        Hydrogen bonds

 

CHAPTER III:

               Thermodynamics

A.    Basic thermo review

·        First, Second and Third Laws

A.    Thermochemistry

·        Heats of reaction and formation

·        Heats of melting, vaporization and sublimation

·        Differential and Integral Heats of solution and hydration

·        Heats of reaction from bond dissociation energies

·       

Homework: 2-1-2-5, 2-7-2-10, 3-1-3-3, 3-5, 3-6, 3-9-3-11.

 

CHAPTER III:

               Free Energy functions and applications

·        Pressure and temperature coefficients of free energy

·        Criteria of equilibrium

CHAPTER II:

               Phase equilibria and the phase rule

·        The phase rule

·        Two-component systems containing solid and liquid phases; Eutectic mixtures

·        Solid dispersions

·        Phase equilibria in three-component systems

·        Rules relating to triangular diagrams

CHAPTER III:

·        Open systems

·        Chemical potential

·        Equilibrium in a heterogenous system

CHAPTER II

·        Vapor pressure of liquids

·        Boiling point

·        Melting point and heat of fusion

·        Melting point and intermolecular forces

CHAPTER III:

·        The Clapeyron equation

·        The Clausius-Clapeyron equation

·        Activities: activity coefficients

·        Standard free energy and the equilibrium constant

·        The van’t Hoff equation

 

Homework: 2-11-2-14, 2-17, 2-18, 2-10, 2-21, 2-22, 2-25, 3-12, 3-15, 3-17, 3-19-3-27.

 

CHAPTER V:

      Solutions of Non electrolytes

A.   Properties of solutions

·        Concentration expressions

·        Equivalent weight

·        Ideal solutions

·        Escaping tendency

·        Ideal solutions and Raoult’s law

·        Aerosols and Raoult’s law

·        Real solutions

·        Henry’s law

·        Distillation of binary mixtures

B.  Colligative properties

·        Lowering of the vapor pressure

·        Determination of the vapor pressure of solutions (isopiestic method)

·        Elevation of the boiling point

·        Freezing point depression

·        Determination of freezing point lowering

·        Osmotic pressure

·        Measurement of osmotic pressure

·        Van’t Hoff and Morse equations

·        Connection of osmotic pressure and vapor pressure lowering

·        MW determination

 

Homework: 5-1, 5-2, 5-9-5-12, 5-14, 5-15, 5-20, 5-22, 5-23, 5-24, 5-30.

 

CHAPTER VI:

               Solutions of Electrolytes

A.   Properties of solutions of electrolytes   

·        Electrolysis

·        Transference numbers

·        Electrical units

·        Faraday’s laws

·        Electrolytic conductance

·        Measuring the conductance of solutions

·        Equivalent conductance

·        Equivalent conductance of strong and weak electrolytes

·        Colligative properties of electrolytic solutions and concentrated solutions of nonelectrolytes

B.  Arrhenius theory of electrolytic dissociation

·        Degree of dissociation

C.   Theory of strong electrolytes

·        Activity and activity coefficients

·        Activity of the solvent

·        Reference State and Standard State

·        Ionic strength

·        The Debye-Huckel Theory

·        Extension of the Debye-Huckel approximation to higher concentrations

D.  Coefficient for expressing colligative properties

·        The L-value

·        Osmotic coefficient

·        Osmolarity

 

Homework: 6-1-6-6, 6-8, 6-10-6-18, 6-22, 6-24, 6-26, 6-27.

 

CHAPTER VII:

               Ionic equilibria

A.   Acid-Base equilibria

·        Ionization of weak acids

·        Ionization of weak bases

·        Ionization of water

·        Relationship between Ka and Kb

·        Ionization of polyprotic electrolytes

B.   Sorensen’s pH scale

B.     Species concentration as a function of pH

C.     Calculation of pH

·        Proton balance equations

·        Solutions of strong acids and bases

·        Conjugate acid-base pairs

·        Solutions containing only a weak acid

·        Solutions containing only a weak base

E.   Acidity Constants

·        Effect of ionic strength on acidity constants

·        Free energy of ionization and the effect of temperature upon ionic equilibria

 

Homework: 7-1-7-5, 7-7, 7-12, 7-16, 7-18, 7-227-24, 7-29.

 

CHAPTER VIII:

               Buffered and isotonic solutions

A.     The buffer equation

·        Common ion effect and the buffer equation for a weak acid and its salt

·        The buffer equation for a weak acid and its salt

·        Activity coefficients and the buffer equation

·        Factors affecting the pH of buffer solutions

B.    Buffer capacity

·        Approximate calculation of buffer capacity

·        More exact equation of buffer capacity

·        The influence of concentration on buffer capacity

·        Neutralization curves and buffer capacity

C.   In vivo biological buffer systems

·        Carbonic acid/carbonate system

·        Preparation of pharmaceutical buffers

·        Influence of buffer capacity and pH on tissue irritation

·        Stability vs optimum therapeutic response

D.  Buffer isotonic solutions

·        Measurement of tonicity

·        Calculating tonicity using Liso values

E.   Methods of adjusting tonicity using Liso values

·        Cryoscopic method

·        Sodium chloride equivalent method

·        White-Vincent method

 

Homework: 8-1-8-3, 8-5, 8-6, 8-8-8-10, 8-16, 8-18-8-19, 8-21-8-23.

 

CHAPTER X:

               Solubility and distribution

D.   Definition and expressions

E.    Physical properties of solvents and solutes and effects on solubility

F.    Liquid-liquid systems, solubility and miscibility

G.   Partitioning between immiscible solvents and partition coefficients

H.   Non-electrolyte solutions

·        Ideal solutions

·        Real solutions

I.      Slightly soluble electrolyte solutions and the solubility product

J.     Acids/bases

·        Effects of pH on solubility

·        The pHp

K.   Partitioning effects

·        Definition of partition coefficient and expressions

·        Acids/bases, the apparent partition coefficient (APC) vs. the true partition coefficient (TPC)

 

Homework: 10-1, 10-5, 10-9, 10-12-10-16, 10-31-10-43, 10-47-10-49.

 

 

CHAPTER XII:

               Kinetics

A.   Rates and Orders of Reactions

·        Specific rate constant

·        Units of basic rate constants

·        Zero-order reactions

·        Suspensions-apparent zero-order kinetics

·        1st-order reactions

·        2nd order reactions

·        the steady-state approximation

B.    Influence of temperature and other factors on reaction rates

·        Effect of temperature

·        Effect of solvent

·        Influence of ionic strength

·        Influence of dielectric constant

C.   Decomposition and stabilization of medicinal agents

·        Influence of oxygen. Oxidation

·        Influence of light. Photodegration

D.  Accelerated stability analysis

·        Arrhenius equation

 

Homework: 12-1-12-5, 12-9-12-10, 12-14.

 

CHAPTER XIII:

               Diffusion and Dissolution

A.   Steady-State diffusion

·        Fick’s 1st law

·        Fick’s 2nd law

B.   Dissolution

·        Noyes-Whitney model

·        Hixson-Crowell model

·        Temperature effects

·        Effects of solubility, solid properties and stirring rate

·        Limitations of the model in real systems

C.   Drug Release

·        Polymer matrices

·        Porosity and tortuosity

·        Lipid based drug delivery systems

·        Multiplayer diffusion

 

Homework: 13-2, 13-3, 13-5, 13-25.

 

 

CHAPTER XIV:

               Interfacial Phenomena (if time permits)

 

 

-        Lecture/Exam Schedule

-        Lecture Notes/Homework Introductory Chapters

-        Introductory notes Partition Phenomena

-        Very Introductory Notes Complex Equilibria