Transcript Poster Presentation - University of Oklahoma

Microcapsule-Based Drug
Leann M.
**
Johnson ,
Mark Trosper
**
McClendon ,
*
Delivery
and Miguel J. Bagajewicz
School of Chemical, Biological, and Materials
University of Oklahoma-Chemical Engineering
(*) This work was done as part of the capstone Chemical Engineering class at the University of Oklahoma
(**) Capstone Undergraduate students
Oral versus Extended Release Drug Delivery
Abstract
Significant advances in drug delivery technology have been made over
the past two decades. One of the most important of these advances is
the development of long acting drug injections. These long acting drug
injections allow for a drug to be continually released for time periods
exceeding one month. This biotechnology has the potential to
revolutionize pharmaceuticals. Many drugs such as Haloperidol (a
psychosomatic drug) and Naltrexone (an opioid antagonist drug) have
recently been made available as long acting injections in the form of
microspheres. Prescribing these long acting medications is no easy task.
Doctors will need tools and methods to aid them in achieving optimal
blood plasma drug concentrations (BPDC) in their patients. We have
created one such tool. This prescription program analyzes a patient’s
drug metabolism and microsphere drug release rate to calculate the
correct dosage of microspheres to be injected. An economic analysis
was also performed to assess the profitability of producing microsphere
injections, specifically for alcoholism, in the pharmaceutical market.
The typical drug concentrations in the blood when an oral medication is taken daily (left) and a
single extended release injection (right). The target drug concentration is notated by the dashed line.
Microsphere Production
Economic Analysis
A schematic of microsphere production1.
This process has three major steps. First,
there is emulsification (stirring) of a
solution containing polymer, drug, and a
small amount of stabilizer. For PLGA
polymers, ethyl acetate is used as a
solvent and poly (vinyl alcohol) is a
stabilizer. Next, the solvent is extracted
from the “continuous phase” and
allowed to evaporate. This leaves the
polymer-rich phase droplets that begin to
harden. Finally, the harden microspheres
are then filtered, washed and lyophilised
(freeze dried). This leaves only the
desired polymer with encapsulated drug
throughout.
Method
-
Microspheres
100 μm
The demand model used to calculate quantity demanded at each price2 (top). A chart
of net present value (NVP) versus time in years for the $50 and $75 price of the
monthly microsphere injection (middle). The net present value for the microsphere
production process over a ten year period. Nine different prices were compared
ranging from $25 per month to $250 per month (bottom).
Results
(Left) Microspheres are used as
extended release delivery
system. This is and image of
PLGA microspheres taken with
a simple light microscope.
These microspheres are loaded
with a drug which will be
release when the microspheres
are injected into a patient.
(Right) Light micrograph of
intramuscular microspheres
after 3 months of follow-up3
m = muscular tissue
cbv = capillary blood vessel.
The arrow points to an
endothelial cell in the capillary’s
wall. Scale bar = 100
micrometers.
Conclusions
Drug
Step 1: Patient is injected with the desired drug intravenously.
Step 2: The Blood Concentration of that drug is measured for a period of 1 to 24 hours.
Step 3: The doctor obtains the patients metabolic rate by the blood concentration levels.
Step 4: The doctor inputs all information into our program and receives a calculated prescription.
Step 5: The patient is injected with the extended release prescription.
(Top Left) A chart of concentration of drug in the body versus drug clearance. The rate of clearance is described as a
function of drug concentration in the blood. The parameters D and delta are specific to each patient and must be
measured (Step 3 of Method).(Top Right) Nine different microsphere types were used in the prescription program.
These release profiles were used to calculate the optimal mass of each individual type of microsphere to achieve the
target drug concentration in the body. (Bottom) A chart of drug concentration in the blood versus time in days. The
pink line represents the target concentration that can be specified by a doctor, and the blue line is the actual drug
concentration circulating in the blood. The Prescription program chooses the mass of each of the nine types of
microspheres that will produce the target drug concentration.
We have created a computer simulation that models the drug concentration in a
person’s blood stream. With this program a doctor can specify a target blood drug
concentration. The computer simulation will then calculate the correct dosage of
microspheres that will achieve this target blood drug concentration. We predict that
this method of prescribing microspheres will become essential for future
medications because of the many drugs that will soon be administered in
microsphere form.
References and Acknowledgements
Yahya Lazrak
Rufei Lu
Warren Yates
Samaneh Noor-Mohammadi
1. Microspheres for Controlled Release Drug Delivery. Neelesh K. Varde and Daniel W. Pack, 2004 in Expert
Opinion in Biological Theory, 4(1): 35-51.
2. On the Role of Microeconomics, Multiscale Planning and Finances in Product Design, M. Bagajewicz.
3. Development of new injectable bulking agents: Biocompatibility of radiopaque polymeric microspheres
studied in a mouse model, Pieter J. Emans, Ketie Saralidze, Menno L. W. Knetsch, Marion J. J. Gijbels, Roel
Kuijer, Leo H. Koole, 2005 in Wiley InterScience 73A: 430-436.