Learning Facilitator

R. Gary Hollenbeck, Ph.D.
Associate Dean and
Associate Professor of Pharmaceutical Sciences
Room 656, Pharmacy Hall
Phone: (410)-706-7670
e-mail: ghollenb@rx.umaryland.edu

Principles of Pharmaceutical Science
Course Map

Modules

12. Evaluation of the Pharmaceutical Care Plan
11. Evaluation of Drug Delivery Systems
10. Evaluation of Drugs
9. Drug Metabolism
8. Pharmacokinetics
7. Pharmaceutics
6. Pharmacology
5. Drug Design, Structure, and Optimization
4. Fundamental Mathematical Concepts
3. Fundamentals of Biotechnology
2. Fundamentals of Molecular Biology
1. Contemporary Pharmaceutical Sciences

Presented below are sample questions from previous midterm and final exams. Please note that the specific topics included on your exam may differ.
(Click here for an answer key for Dr. Hollenbeck's questions.)

PHNT 512: Principles of Pharmaceutical Sciences

Sample Midterm Examination Name _____________________________
Instructions: This examination is an open book, open notes, in-class examination. While these information resources are available, each individual student must complete the examination independently. Answers to questions must be presented on this examination packet, in the space provided.

________________________________________________________________

1. Principles of Kinetics and Diffusion - Hollenbeck

Consider a situation where a drug was being administered intravenously to achieve a steady state plasma concentration using an implanted infusion pump (pump #1) set at a rate that delivers 0.10 mg/min. Because of an acute episode, a higher level of the drug in plasma was desired, and an additional external infusion line (pump #2) was established that pumped the same drug in at a constant rate of 0.25 mg/min for 120 minutes.

Drug is eliminated by an apparent first order process with an elimination rate constant of 0.2 min^-1. This situation is depicted in the model above.

A.) Assuming that the patient’s volume of distribution to be 5000 mL, what would you expect the steady state concentration to be when drug is delivered by the implanted pump?

(3)

B.) On the graph below, sketch what would happen when the second line was established. Indicate the initial steady state concentration (answer from part A) and show the change that would take place when the second pump was started and then stopped after 120 minutes.

(3)

C.) The process of passive drug absorption across a membrane can be quantitatively described by the following relationship:

Absorption rate = P A (C_D - C_R)

(4)

The ability of a drug to be absorbed generally depends on a balance between its solubility in water and its solubility in oil. How are these terms represented in the relationship above?

6. Fundamentals of Solubility and Stability - Hollenbeck

Cefotaxime Sodium is the salt of a strong base (sodium hydroxide) and a weak acid (cefotaxime), whose solubility and stability in aqueous solution are both influenced by pH. Depicted below is a graphical representation of data from a study of the effect of pH on the chemical stability of Cefotaxime Sodium (m.w. = 477). The degradation process is an apparent 1st order process. Note that k_obs has units of hr-1. The stability was studied in aqueous buffer systems with pH values of 2, 3, 4, 5, 6, 7, and 8, at 25 oC.

The desired initial concentration of an injectable solution of Cefotaxime Sodium is 1 g in 50 mL, and the pH of such a solution is 5.5. Consider designing a formulation that is to be buffered from pH = 5.5 to a more physiologically compatible pH = 7.4.

Would there be any danger of a precipitate forming if the solution were buffered to the higher pH of 7.4?

(5)

Would the drug be stable enough at pH = 7.4 to be marketed as a solution? If not, would it be stable enough to be marketed as a solid formulation to be reconstituted as a solution for injection? (Note: As seen from the graph above, the rate constant for Cefotaxime Sodium at pH = 7.4 is approximately 3.16 x 10-4 hr-1. To support your answer, estimate the half-life at pH = 7.4.)

3. Controlled Release Oral Drug Delivery Systems - Dr. Hollenbeck

Consider the following mechanistic classification for controlled-release drug delivery systems was presented:

I. Reservoir system

a. Barrier erosion
b. Non-porous membrane
c. Porous membrane

II. Matrix System

a. Non-erodible, Non-porous system
b. Non-erodible, Porous system
c. Erodible System

III. Ion-exchange System

IV. Osmotic System

For each of the following products: (1) classify the system using the outline provided above; (2) discuss, relate, or explain the observation(s) in terms of the expectations for this class of controlled release drug delivery systems.

Product	Description	Classification	Observations	Comment of the Claim(s)
Example
Inderal LA	"Long acting propranolol consists of small spheroids contained in a gelatin capsule. Each spheroid contains propranolol and a microcrystalline cellulose mixture; this is shaped into a pellet and coated with a semipermeable membrane. The membrane is composed of ethylcellulose (water insoluble), hydroxy-propylcelluose (water soluble), and plasticizer."	I.c. - Reservior System Porous Membrane	"Compared to conventional propranolol, time to peak concentration is increased, and systemic bioavailability is reduced 30-50%."	Consistent with a sustained release product that has a drug that undergoes first-pass metabolism.
			"No dose dumping has been observed."	Important observation since dose-dumping is a concern with a reservoir system. Consistent with expected behavior since dose dumping is less likely with a bead-based product.

Product	Description	Classification	Observations	Comment of the Claim(s)
A.) Procardia XL (6)	The Nifedipine gastrointestinal therapeutic system (GITS) consists of a semipermeable membrane that surrounds a bilayer core. The core is composed of an active drug layer and a pharmacologically inert and osmotically active layer. With absorption of water throughout the GI tract there is a continuous dispensing of nifedipine through a laser-drilled hole over a 24 hour period.		"... GITS is unaffected by GI pH or motility and produces zero order drug release"
A.) Procardia XL (6)			"Because the surrounding shell is so hard, patients are advised to swallow the tablet without chewing."
B.) Isoptin SR (6)	Sustained release verapamil tablets consist of verapamil homogeneously distributed in a matrix of the natural polysaccharide sodium alginate, which swells when it comes into contact with GI fluid. Verapamil then diffuses through a gel-like matrix.		"Pharmacokinetic studies comparing the maximum concentration of one 240 mg tablet of Isoptin SR vs two half 240-mg tablets (e.g., tablet broken in half) show a non-significantly higher (plasma) concentration with two half tablets, without any difference in area under the curve or time to maximum concentration."
Product	Description	Classification	Observations	Comment of the Claim(s)
C.) Verelan (8)	The spheroidal oral drug absorption system (SODAS) consists of multiple particles stored in a hard gelatin capsule. Some of the 1 mm spherical particles release drug immediately, while some are surrounded by rate-controlling polymers.		"Dissolution and release of verapamil from SODAS are independent of pH"
			"For elderly patients that have difficulty swallowing, a dose may be administered by distributing the entire contents of a capsule in juice or food, such as yogurt or applesauce."
			"A 140 mg dose may be administered by distributing 1/2 the contents of a 240 mg capsule in juice or food, such as yogurt or applesauce. The remaining 1/2 can be used for the next dose.

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Learning Facilitator

Principles of Pharmaceutical Science Course Map

Modules

3. Controlled Release Oral Drug Delivery Systems - Dr. Hollenbeck

Principles of Pharmaceutical Science
Course Map