To receive a master's degree
Polymer Engineering - Polymer Industries
May 1393
Abstract
With the progress of different sciences and knowledge, the boundaries of knowledge have reached each other and in some fields we are witnessing the fusion of different sciences. One of the important and very practical and extensive fields " Engineering of "drug release" systems It is a common border with many sciences such as: pharmacy, biology, histology, mathematical analysis, polymer engineering, biomaterial engineering and so on. has This field is one of the youngest topics in the world's sciences today, and today it has taken the major share of engineers' research. The purpose of designing these systems is to reduce repeated use, increase drug effect and reduce side effects.
In this thesis, the study and modeling of the drug release process from homopolymer (poly?-caprolactone), copolymer (polyDL lactide-co-glycolidacid) and a mixture of these two biodegradable polymers are discussed. The process considered for this permeation system is accompanied by a chemical reaction, which means that the drug is released through the chemical reaction that happened inside the polymer (including the destruction of the polymer, which is basically based on hydrolysis) and is released to the outside environment through permeation. Therefore, the model is based on polymer degradation, the polymer degradation equations are simplified by the moment equations, and finally the governing equations along with the initial and boundary conditions are numerically solved by the finite-implicit difference method. This model is able to predict the amount of drug release at a certain time and place. In order to determine the accuracy of the proposed model, the experimental results available in the articles for paclitaxel drug have been used. According to the results of the model and comparison with the experimental values, the high level of accuracy of the presented model is confirmed.
Key words: drug release, two-phase, biodegradable polymers, modeling, permeation, chemical reaction
Chapter one:
Introduction and generalities
Introduction
What comes to mind when hearing the name of the drug for the first time may be nothing more than pills, capsules or ampoules! While the world of medicine and the methods of transferring it to the body are not limited to these. Medicines usually enter the body in two digestive ways (entering through the mouth and being absorbed into the blood along the digestive tract) and non-digestive ways (injection, eye drops, etc.). The introduction of drugs from these methods entails problems and limitations, and for this reason, researchers were looking for ways that can solve the above problems to a large extent. Following these efforts, controlled drug release systems were proposed, which have many advantages. The most important of these advantages include the ability to maintain the concentration of the drug at a relatively constant level for a certain period of time, the ability to adjust the rate of drug release depending on the place of drug delivery, the possibility of delivering the drug to a specific organ or tissue, the ability to deliver several medicinal substances with one formulation, the possibility of drug delivery in nanometer dimensions, and so on. These systems have created a revolution in the treatment of many diseases and are progressing day by day [1]. 1-1. Controlled drug release systems (CDDS [1]) Controlled drug release systems (CDDS) are a new tool for releasing medicinal substances in the human body. They have found many applications in the field of pharmaceutical science and technology. These systems provide many benefits, including positive effects of drug kinetics, reducing the frequency of drug use, adjusting the level of fluctuations in the amount of drugs in the blood, reducing side effects, reducing the amount of accumulation and accumulation of drugs in the body, improving and modifying the bioavailability of some drugs, and finally increasing the efficiency of treatment compared to conventional drug delivery systems [2]. Among the disadvantages of these systems, we can point out the possibility of reducing the flexibility and correction of the dose, the risk of rapid or sudden drug release, defects in the manufacturing technology [3].
New drug delivery systems are divided into two main groups, which include:
1.. Controlled release systems [2]: In these systems, the speed of drug release from the pharmaceutical form is controlled in different ways and is released from the pharmaceutical form based on a predetermined mechanism within a certain time frame and at a certain speed.
2. Targeted drug delivery systems [3]: In these systems, the drug is transferred to tissues that are pharmacodynamically favorable by various methods and exerts its effect solely and exclusively in that area [1].
1-1-1. The difference between modern and traditional systems
In the drug delivery system and traditional pills, the amount of drug in the blood follows a profile similar to Figure 1-1 a), in such a way that the amount of the drug increases after each use and then decreases until the next use of the drug. The important point that was sought in the traditional drug delivery methods is to keep the amount of the drug in the blood between the state It was the maximum (which represents the toxic part) and the minimum state (below which the drug has no effect).
The goal of designing controlled drug delivery systems is long-term drug use. As it is clear from Figure 1-1b), in controlled drug delivery systems, the amount of drug in the blood remains constant for a long period between the desired state of maximum and minimum.
1-2. Mechanism of release
Description of the way drug molecules are transported or released and as the process or event that determines the rate of release. Table (1-1) shows the list of release mechanisms [4].
Example: Transfer through pores filled with water is the most important release method for drug in capsule form. Usually a biodrug, such as a protein or peptide, that is too hydrophilic to transport through the polymer phase, the most common method for transport through water-filled pores is permeation. That is, the random movement of derived molecules can be approximated by the chemical potential gradient, which can often be approximated by the concentration gradient. Another way is the transfer through pores filled with water, through heat transfer, which is derived by a force such as osmotic pressure [5]. Osmotic pressure may be caused by the penetration of water into an unswollen system, the transport of drug derived by this force is called osmotic pumping. Osmotic transport depends only on length, but the transferred penetration depends on both length and area.
The main methods of drug release include:
1. Permeation through pores filled with water 2. Penetration through polymer
3. Osmotic pressure 4. Erosion
The processes that control the release rate are called rate-controlled release mechanisms. The actual mechanisms of release are shown in figure (1-2). The osmotic pressure is caused by the penetration of the medium fluid. Processes promoting or inhibiting release
Drug solubility, drug-drug reactions, drug-polymer reactions, hydrolysis, pore structure, and pore closure are all dependent on pH, which in turn is dependent on the rate of hydrolysis (absorption of water causes hydrolysis).
Erosion as a rate-controlled release mechanism leads to A pore is formed, which increases the penetration rate. Disintegration is often the result of degradation and a decrease in Tg.
Hydrolysis causes erosion and pore formation, resulting in increased drug release. However, hydrolysis also causes a lower Tg and the possibility of rearrangement of polymer chains and pore closing, and thus the possibility of a decrease in drug release.
Table 1-2 processes that may increase or decrease the drug release rate are given.
Table 1-2: Processes that may increase or decrease the drug release rate [4].
1-4.