Biopharmaceutics & Pharmacokinetics

Chapters 9 to 12

Factors Affecting Drug Product Performance

Most of these have their effect on dissolution rate since that is the first step to absorption.

Many of the concepts in these chapters were discussed in Pharmaceutics I & II. If you understand the nature of the various dosage forms it will help with the discussion of the material in this weeks work. Go back to your notes to add to the completeness of the discussion in each chapter.

Chapter 9 Physicochemical Factors:

Particle Size – Remember the Noyes Whitney Equation and the factors that affect dissolution.

dc/dt = k A (Cs – Ct)

A is the area of the solid exposed to the solvent. As you decrease particle size you increase A and therefore make the rate of dissolution (dc/dt) increase

What do these terms mean

Salting out

Clathrate

Solid in Solid Solutions

The next thing we can change is Cs or the solubility of the drug itself. If we can change the nature of the compound we can change its solubility and therefore change its rate of dissolution. BE SURE TO KNOW THE DIFFERENCE BETWEEN SOLUBILITY & RATE OF DISSOLUTION>

Crystal Energy State – Another way of affecting the rate of dissolution is to change the energy pattern.

Why are freeze dried products so easy to get to go into solution?? Free Energy (G)

What about the medium for dissolution??

See figure 9-6 on page 85

What else can we do - Surfactants? Co Solvents?

Chapter 10 The GI Tract

Now is the time to remember the things you learned in A&P about the GI Tract.

The Stomach has three types of glands.

What are they called and what do they do?

Tables 10 1,2,3 lay out some key elements of the anatomy and physiology of the GI tract.

Which structure affects absorption positively??

Which activities can change the rate of absorption?

Page 103 table 10-6 is a good summary.

Chapter 11 The Circulatory system

Once a drug gets absorbed it still has to take a journey throughout the body. The bodies super highway is the circulatory system. If a drug is highly soluble in the blood it get to travel alone. (Private car) The highway is crowed however and if the drug is poorly soluble it is better to take the Bus. The drug will bind to the circulating proteins like albumin and alpha glycoprotein.

Factors that affect the operation of the circulation can affect how soon a drug will take effect and how well it will work.

What is Homeostasis?

What is the microcirculation?

It is also important to have a good estimate of the amount of fluid available to dissolve the drug.

This information changes with age and desease. See table 11-2 on page 115

Chapter 12 Binding of drugs.

Drugs can bind to the circulating protein or to sites in the tissue. They can also accumulate in tissues such as adipose tissue or bone.

What happens to the level if drugs bind to tissue or blood protein?

What effect does it have on duration of affect of the drug?

What are possible drug interactions that might occur?

Equation 12.2 on page 122 looks like what other relationship we have already discussed?

What conditions can change the amount of binding site available for the drug?

See table 12-5 on page 130

Where else can drugs go in the blood supply?

What would be the effect of living in Denver versus Baltimore on drug storage in the RBC??