618
618
618
Dr. P. M. Armenante
New Jersey Institute of Technology
September 3, 2014
Principles of Pharmacokinetics and Drug Delivery
PhEn 618
Syllabus
Term: 2014 Fall Semester
NJIT Course Title: Principles of Pharmacokinetics and Drug Delivery
NJIT Course Number: PhEn 618, Section 101
Course Day and Time: Wednesday, 6:00 - 9:05 p.m.
Classroom: Kupfrian Hall, Room 204, NJIT
Course Instructor: Piero M. Armenante, Ph.D.
Distinguished Professor of Chemical Engineering
Director, Pharmaceutical Engineering Program
New Jersey Institute of Technology
Otto H. York Department of Chemical, Biological and Pharmaceutical
Engineering
Newark, NJ 07102-9895
Office: YCEES Building - Room 120
Telephone: (973) 596-3548; Mobile: (908) 347-8734 (preferred)
Fax: (973) 596-8436
E-Mail Address: piero.armenante@njit.edu
Instructors Office Hours:
Monday and Wednesday, 5:00-6:00 pm (meetings will likely take place in 150 Tiernan Hall CBPE
Departmental Office) or by appointment. Students are strongly encouraged to contact Prof.
Armenante via e-mail to arrange for a meeting. Please note that Prof. Armenante will not be available
for consultation when he is on business travel.
Teaching Assistant (TA): Ms. Lu Zhang, Ph.D. Candidate in Chemical Engineering; Office: YCEES 328.
Telephone: 973-596-8445; E-mail: lz74@njit.edu
TAs Office Hours: Monday and Tuesday, 4:00-5:00 pm, or by appointment. Meetings with
the TA will likely take place in the TA office in 322A Tiernan Hall.
Course Notes, Textbooks, and Other Reference Material:
Course Notes: Armenante, P. M., 2014, Pharmacokinetics and Drug Delivery Course Notes. The
Notes are duplications of the overheads used in class. The Notes are available on the internet and
can be accessed using the procedure described below.
Textbooks: The following books are recommended but not required as textbooks:
- Shargel, L., Wu-Pong, S. and Yu, A. B. C., Applied Biopharmaceutics and Pharmacokinetics, 6
th
Edition, McGraw-Hill, New York, 2012.
- Truskey, G. A., Yuan, F. and Katz, D. F., Transport Phenomena in Biological Systems, 2
nd
Edition,
Pearson Prentice Hall, Upper Saddle River, NJ, 2009.
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Additional reference books (not required) are:
- Welling, P. G., Pharmacokinetics: Processes, Mathematics, and Applications, American Chemical
Society, 1997.
- Allen, L. V., Popovich, N. G., and Ansel, H. C., Ansels Pharmaceutical Dosage Forms and Drug
Delivery Systems, 9
th
Edition, Lippincott Williams & Wilkins Publishers, 2010. [Remark: this is the
textbook used in PhEn 601].
- Lieberman, H. A., Rieger, M. M., and Banker, G. S. (eds.), Pharmaceutical Dosage Forms:
Dispersed Systems, Vol. 1, Marcel Dekker, 1996.
- Lieberman, H. A., Lachman, L., and Schwartz, J. B. (eds.), Pharmaceutical Dosage Forms: Tablets,
Vol. 1, Marcel Dekker, 1989.
- Avis, K. E., Lieberman, H. A., and Lachman, L. (eds.), Pharmaceutical Dosage Forms: Parenteral
Medications, Vol. 1, Marcel Dekker, 1991.
A list of reference books is attached.
Availability of Course Notes, Homework Assignments, Textbook, and References:
The Course Notes will be posted on the internet as PDF files (i.e., you will need Adobe Acrobat to
read and print them). The Course Notes can be downloaded from the NJIT website using Moodle.
Students can either access Moodle directly (http://njit2.mrooms.net/) and follow the instructions
there, or go through Highlander Pipeline as follows:
1. Go to http://my.njit.edu and login using your UCID.
2. Click on the My Courses tab
3. Click on the link towards the bottom of the screen for NJIT Moodle Rooms: Click here to
access your course in Moodle
4. You will automatically be logged into NJITs new Moodle server.
5. Locate your course and click on the link with the course title.
6. If at any time you are experiencing problems and are unable to log in please let the
helpdesk know at 973-596-2900.
The homework is also posted weekly through Moodle
The Shargel et al. book, and Allen et al. book are available in the NJIT bookstore (973-596-3200;
www.njit.edu, then click on Bookstore under Quick Links) or from the publishers
Additional material (reading material, etc.) will be distributed in class. For additional information,
please contact Prof. Armenante
Most additional references (not required as textbooks) as well as the textbooks are available in
most university libraries, including the NJIT library
Course Prerequisites:
PhEn/PhB Students: PhEn 601; and successful completion of the bridge program (PhEn 500, PhEn
501 and PhEn 502) if required in the students admission conditions, as well as any other
undergraduate-level courses, if any. However, students who have taken PhEn 500 and PhEn 501
and are currently enrolled in PhEn 502 could take PhEn 618 provided that they did well in those
courses (A or B+) or have permission from Prof. Armenante. PhEn/PhB students who do not have
these prerequisites will have to drop the course. [Remark: PhEn/PhB students who are not required
to take the bridge course, do not need to take bridge courses, of course]
Non-PhEn/PhB Students: PhEn 601 (recommended but not required). Students with appropriate
engineering backgrounds (e.g., ChE, BME) do not need to have taken the bridge courses to take this
course. Students with non-engineering background should have the appropriate math background
(differential equations) and be familiar with the basic engineering concepts (e.g., mass balances)
required for this course. Therefore, they should talk to Prof. Armenante to make sure that they are
adequately prepared for this course before taking it.
Course Objectives: This course is one of the common core courses for the Pharmaceutical Engineering
and Biopharmaceutical Engineering MS Degree Programs. The main objectives of this course are to:
present the different pharmacokinetic principles affecting drug adsorption, distribution, metabolism
and excretion; quantitatively study and apply mathematical models used to describe these
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phenomena, and; provide the students with basic concepts of drug delivery, pharmacokinetics and
pharmacodynamics.
Course Description: The course covers the basic principles of pharmacokinetics, including absorption,
transport distribution, metabolism, and excretion of drugs and metabolites in the human body, drug
transport, parenteral and enteral routes of drug administration, and factors affecting drug absorption,
distribution, and metabolism. Mathematical pharmacokinetic models and drug delivery processes are
also presented and quantitatively studied. The course also covers basic aspects of drug delivery of
different drug delivery systems and dosage forms.
Course Outline by Topic Areas: Introduction; pharmacokinetics and its role in drug discovery; drug
development and process development; drug absorption, distribution, metabolism, and excretion;
routes of drug administration, drug absorption by different routes of administration; enteral and
parenteral routes; drug transport in biological systems, transport across cell membrane: osmosis,
passive diffusion, ion channels facilitated transport, active transport; transport across endothelial cell
layers and epithelial cells layers; drug distribution; transcapillary exchange of drugs; perfusion-limited
and permeability-limited distribution; binding of drugs to proteins; physiological barriers; renal
excretion; renal clearance; drug metabolism; mathematical approach to pharmacokinetic modeling;
one-compartment open models and data analysis; multiple-dose pharmacokinetics; two-compartment
open models; physiological pharmacokinetic models; nonlinear pharmacokinetics; pharmacokinetic-
pharmacodynamic modeling.
Course Learning Outcomes: Upon successful completion of this course, students will be able to:
Identify and compare the different types of administration routes used in drug delivery
Recognize and describe the different physiological mechanisms responsible for drug adsorption,
distribution, metabolic and elimination
Quantitatively predict key parameters and transfer rates of importance in the description of
physiological processes
Categorize, analyze, and contrast different types of pharmacokinetics models
Interpret and analyze pharmacokinetic data to determine the underlining compartment model best
describing the observed drug distribution behavior among compartments over time
Regress pharmacokinetic data to determine the compartment model kinetic parameters
Assemble compartment models best suited for a specific drug based on its adsorption, distribution,
metabolic and elimination characteristics
Determine the most effective drug delivery method to achieve the desired pharmacokinetic effect
based on a quantitative analysis of the underlying pharmacokinetic model
Course Requirements:
Examinations: Two exams, i.e., a midterm exam and a final exam
Homework: Assigned by the instructor at the end of each class
Quizzes: Possibly, several very short quizzes on homework just completed
Projects: One, or possibly two, short projects will be assigned after the midterm exam (see
below for details)
Grading Policy*:
Midterm exam* ................................ 38%
Final exam* ....................................... 38%
Homework and quizzes ..................... 12%
Projects ............................................. 12%
Total ................................................ 100%
(*) Students performing very poorly on the exams will fail the course irrespective of their performance
in the homework and projects, as specified below.
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Course Final Grade: a tentative guideline for the assignment of final grades is the following:
Cumulative Points Overall Grade
85-90 to 100% A
70-75 to 85-90% B/B+
60 to 70-75% C/C+
50 to 60% D
0 to 50% F
The grade of D is not assigned to students taking graduate courses. Students averaging a cumulative
point score corresponding to a D in the above table could receive either a C or an F, depending on
their overall performance.
Please remember that this is only a guideline designed to help the students understand how they are
performing in the course. Dr. Armenante will feel free to change the grading scale (both ways) when
assigning the final grades.
Important Remark: Each exam (midterm and final) will be graded on a point scale from 0 to 100
(100 points in an exam=38% of the final grade; see above). However, failing to achieve a
combined average of at least 55/100 in the two exams will imply failing the course (F grade)
irrespective of the points obtained through the homework and the projects. In other words,
students who perform extremely poorly in the exams will not be able to use the homework and
the projects to pass the course. If this minimum requirement is satisfied, the final grade will be
assigned based on the grading policy outlined above.
Exams:
a calendar of exams is included in the Course Outline given below;
all exams are typically 3 hours long unless otherwise stated;
all exams are typically open-book and open-note. However, changes could be made and will be
announced by the instructor prior to the exams;
the final exam will be on all material covered throughout the course (although the main emphasis
of the exam will be on the material covered after the midterm exam);
make-up exams will only be given to students who cannot attend the regular exam time, and only
under documented and extraordinary circumstances. In any case, no student will be allowed to
take a make-up exam unless he/she has the prior consent of the instructor. If a student will simply
not come to an exam, the exam grade will automatically be zero.
Because of confidentiality issues, the Office of the Dean of Students now handles all issues related
to medical conditions (including justification for postponing exams)
Homework: it will be assigned at the end of each class period, collected the following week at the
beginning of the class period, and returned the week after that. No late homework will be accepted.
The homework problems will be posted on the internet and can be retrieved by the students as
described previously for the Course Notes. If appropriate (typically for quantitative problems)
homework solutions will be posted on the internet (as described for the Course Notes) after the
homework has been collected.
Important Remark: Previous experience has clearly shown that those students who do not
work on the assigned problems (or at least seriously try to solve them) typically perform very
poorly on the exams.
Homework Grading: The homework will be graded using a simplified grading scale, i.e., 0 (no or
minimal effort); 5 (intermediate effort); 10 (significant effort).
Quizzes: Very short quizzes focused on selected homework assignments could possibly be given
immediately after a particular homework assignment is completed and collected. Typically, a quiz will
consist of a problem similar to one of the problems in the homework assignment that was just
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completed. Quizzes could be used to determine whether the student will earn the points associated
with that assignment or not.
Projects: Every student will complete one, or possibly two, small projects, which will be assigned after
the midterm exam and collected on the day of the final exam. The first project will consist of critically
reviewing (critiquing) 2 papers published in scientific journals (as if the papers had been submitted for
publication to the student). The papers will have to be related to each other and to be within the
scope of the course. The students will be asked to write a short review of the papers. The student will
have to justify whatever conclusions he/she may reach. The second project (if assigned) will consist of
a small case study assigned by the instructor. The problem will be open-ended to allow each student
to come up with his/her own analysis of the problem and solution.
Class Attendance: As for all graduate courses at NJIT, attendance is not mandatory, but strongly
recommended. Experience shows that students who do not regularly attend class typically perform
poorly in the course. In addition, examples are worked out during the lectures. These examples are
not in the Course Notes. Students are responsible for all material covered in class.
Time Commitment: Students are expected to allocate some three to six hours per week to study and
work on the assignments for this course.
Students with Disabilities: NJIT adheres to Section 504 of the Rehabilitation Act (ADA) of 1990.
Appropriate accommodations are provided at no cost to the student. Additional questions should be
directed to Dr. Phyllis Bolling, Center for Counseling and Psychological Services (C-CAPS), Campbell
Hall, (entry level), Room 205, (973) 596-3420. For further information, visit the Student Disability
Services website.
Code of Conduct and Academic Integrity: The NJIT University Code on Academic Integrity, found at
http://www.njit.edu/academics/integrity.php, will be followed. The Code is being upheld on all issues
related to the course. Students are expected to be familiar with the code and conduct themselves
accordingly.
Important Dates According to NJIT Calendar (Fall 2014):
Sep 01 Monday Labor Day
Sep 02 Tuesday First Day of Classes
Sep 06 Saturday Saturday Classes Begin
Sep 08 Monday Last Day to Add/Drop a Class
Sep 08 Monday Last Day for 100% Refund, Full or Partial Withdrawal
Sep 09 Tuesday W Grades Posted for Course Withdrawals
Sep 15 Monday Last Day for 90% Refund, Full or Partial Withdrawal - no refund for
partial withdrawal after this date
Sep 29 Monday Last Day for 50% Refund, Full Withdrawal
Oct 20 Monday Last day for 25% Refund, Full Withdrawal
Nov 03 Monday Last Day to Withdraw
Nov 25 Tuesday Thursday Classes Meet
Nov 26 Wednesday Friday Classes Meet
Nov 27 Thursday Thanksgiving Recess Begins
Nov 30 Sunday Thanksgiving Recess Ends
Dec 10 Wednesday Last Day of Classes
Dec 11 Thursday Reading Day 1
Dec 12 Friday Reading Day 2
Dec 15 Monday Final Exams Begin
Dec 20 Saturday Final Exams End
Additional important dates are available on the web at the following site:
http://www.njit.edu/registrar/calendars/index.php.
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Course Outline (Fall 2014)
Week Date Topic
1 September 3 Introduction; pharmacokinetics and its role in drug discovery;
drug development and process development; drug
absorption, distribution, metabolism, and excretion; routes
of drug administration
2 September 10 Routes of administration; enteral and parenteral routes
3 September 17 Drug transport in biological systems - Transport across cell
membranes: osmosis, passive diffusion
4 September 24 Drug transport in biological systems (continued) - Transport
across cell membranes: ion channels facilitated transport,
active transport
5 October 1 Drug transport in biological systems (continued) - Transport
across endothelial cell layers and epithelial cells layers
6 October 8 Drug distribution; transcapillary exchange of drugs;
perfusion-limited and permeability-limited distribution;
binding of drugs to proteins; physiological barriers
7 October 15 Renal excretion; renal clearance. Drug metabolism
8 October 22 Midterm exam
9 October 29 Review of midterm exam
Mathematical approach to pharmacokinetic modeling
10 November 5 One-compartment open models and data analysis
(continued)
11 November 12 One-compartment open models and data analysis
(continued)
Multiple-dose pharmacokinetics
12 November 19 Multiple-dose pharmacokinetics (continued)
November 26 No class (Wednesday classes follow Friday schedule)
13 December 3 Two-compartment open models; physiological
pharmacokinetic models; nonlinear pharmacokinetics
14 December 10 Pharmacokinetic-pharmacodynamic modeling
15 December 17 Final exam
Important: It is conceivable that some changes in the above outline will take place, depending on the
overall performance of the class and the time actually required to cover the most important subjects of
the course.
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Reference Books
The United States Pharmacopoeia & The National Formulary. The Official Compendia of Standards,
USP 36NF 31, Pharmacopeial Convention Inc., 2013.
Amiji, M. M. and Sandmann, B. J., Applied Physical Pharmacy, McGraw-Hill, New York, 2003.
Allen, L. V., Popovich, N. G., and Ansel, H. C., Ansels Pharmaceutical Dosage Forms and Drug
Delivery Systems, 9
th
Edition, Lippincott Williams & Wilkins Publishers, 2010.
Banker, G. S. and Rhodes, C. T., Modern Pharmaceutics, 3
rd
Edition, Marcel Dekker, New York,
1995.
Boroujerdi, M. Pharmacokinetics: Principles and Applications, McGraw-Hill, New York, 2002.
Chien, Y. W., Novel Drug Delivery Systems, 2
nd
Edition, Marcel Dekker, New York, 1991.
Gennaro, A. R. (editor), Remington: The Science and Practice of Pharmacy, 20
th
Edition,
Philadelphia College of Pharmacy and Science, 2000.
Lieberman, H. A., Rieger, M. M., and Banker, G. S., Pharmaceutical Dosage Forms: Dispersed
Systems, Vol. 1 (1996); Vol. 2 (1996), Vol. 3, (1998), Marcel Dekker, New York.
Lieberman, H. A., Lachman, L., and Schwartz, J. B., (eds.), Pharmaceutical Dosage Forms: Tablets,
Vol. 1 (1989); Vol. 2 (1990), Vol. 3 (1990), Marcel Dekker, New York.
Avis, K. E., Lieberman, H. A., and Lachman, L., (eds.), Pharmaceutical Dosage Forms: Parenteral
Medications, Vol. 1 (1991); Vol. 2 (1992), Vol. 3 (1993), Marcel Dekker, New York.
Mitra, A. K., Kwatra, D., Vadlapudi, A. D., Drug Delivery, Jones & Bartlett Learning, 2014.
Martin, A. N., Bustamante, P. and Chun, A. H. C., Physical Pharmacy: Physical Chemical Principles in
the Pharmaceutical Sciences, Lippincott Williams & Wilkins Publishers, Philadelphia, 1993.
Notari, R. E., Biopharmaceutics and Clinical Pharmacokinetics: An Introduction, Marcel Dekker,
New York, 1986.
Shargel, L., Wu-Pong, S. and Yu, A. B. C., Applied Biopharmaceutics and Pharmacokinetics, 6
th
Edition, McGraw-Hill, New York, 2012.
Tyle, P. (ed.) Drug Delivery Devices: Fundamentals and Applications, Marcel Dekker, New York,
1988.
Truskey, G. A., Yuan, F. and Katz, D. F., Transport Phenomena in Biological Systems, 2
nd
Edition,
Pearson Prentice Hall, Upper Saddle River, NJ, 2009.
Welling, P. G., Pharmacokinetics: Processes, Mathematics, and Applications, American Chemical
Society, 1997.
Welling, P. G. and Tse, F. L. I. (eds.), Pharmacokinetics: Regulatory-Industrial-Academic
Perspectives; 2
nd
Edition, Marcel Dekker, New York, 1995.