This document provides an overview of degradable polymeric carriers for controlled drug delivery. It discusses the factors that influence drug release from degradable polymer matrices, including environmental conditions, drug properties, and osmotically mediated mechanisms. It also describes the principles of polymer degradation and erosion, and different strategies to achieve near zero-order drug release profiles from degradable polymers. Commercial parenteral drug delivery products often use microparticles or preformed/in situ forming implants made of poly(lactic-co-glycolic acid) (PLGA) polymer. Drug release from these systems is complex and governed by the polymer's degradation and the drug's diffusion properties.
Biodegradable polymers based transdermal drug delivery systemDeepanjan Datta
Friends..me and my best buddy miss.pragya paramita pal prepared this presentation during the last semester of our graduation.I am just uploading this so that this can help you to prepare better presentations based on such topics.Thanks to my guide and my friend miss.pragya.Enjoy friends & best of luck..
Sustained drug delivery systems significantly improve therapeutic efficacy of drugs. Drug-release-retarding polymers are the key performers in sustained release drug delivery system for which various natural, semi-synthetic and synthetic polymeric materials have been investigated. Besides this several polymers are often utilized in the design of novel drug delivery systems such as those that target delivery of the drug to a specific region in the gastrointestinal tract or in response to external stimuli to release the drug.
Biodegradable polymers based transdermal drug delivery systemDeepanjan Datta
Friends..me and my best buddy miss.pragya paramita pal prepared this presentation during the last semester of our graduation.I am just uploading this so that this can help you to prepare better presentations based on such topics.Thanks to my guide and my friend miss.pragya.Enjoy friends & best of luck..
Sustained drug delivery systems significantly improve therapeutic efficacy of drugs. Drug-release-retarding polymers are the key performers in sustained release drug delivery system for which various natural, semi-synthetic and synthetic polymeric materials have been investigated. Besides this several polymers are often utilized in the design of novel drug delivery systems such as those that target delivery of the drug to a specific region in the gastrointestinal tract or in response to external stimuli to release the drug.
Methods of enhancing Dissolution and bioavailability of poorly soluble drugsRam Kanth
Greetings!
Good Day to all...
Topic: Methods of Enhancing Bioavailability
Several approaches discussed are
1. Micrnoization
2. Use of Surrfactants
3. Use of Salt forms
4. Alteration of pH of microenvironment
5. Use of metastable polymorphs
6. Solute-Solvent Complexation
7. Solvent Deposition
8. Selective Adsorption on Insoluble Carriers
9. Solid Solutions
10. Eutectic Mixtures
11. Solid Dispersions
12. Molecular Encapsulation with Cyclodextrins
Please do clarify for doubts if any....
Thank you all for watching this presentation.
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Vesicles are colloidal particles in which a concentric bilayer made-up of amphiphilic molecules surrounds an aqueous compartment Useful vehicle for drug delivery of both hydrophobic drugs and hydrophilic drugs, which are encapsulated in the interior aqueous compartment.
Biodegradable polymers based transdermal drug delivery systemDeepanjan Datta
Hello friends..I am back with new presentation which I am sure is going to help you all again.This presentation was prepared by me and my best buddy miss.pragya paramita pal during our graduation.A very thanks to my guide for guiding me.So go ahead FRIENDS & best of luck..........
Methods of enhancing Dissolution and bioavailability of poorly soluble drugsRam Kanth
Greetings!
Good Day to all...
Topic: Methods of Enhancing Bioavailability
Several approaches discussed are
1. Micrnoization
2. Use of Surrfactants
3. Use of Salt forms
4. Alteration of pH of microenvironment
5. Use of metastable polymorphs
6. Solute-Solvent Complexation
7. Solvent Deposition
8. Selective Adsorption on Insoluble Carriers
9. Solid Solutions
10. Eutectic Mixtures
11. Solid Dispersions
12. Molecular Encapsulation with Cyclodextrins
Please do clarify for doubts if any....
Thank you all for watching this presentation.
Polymeric micelle formation , mechanism , Case study , applications , Factors affecting formation of Polymeric Micelle , Method of preparation , Types of polymers used in Polymeric micelle
Vesicles are colloidal particles in which a concentric bilayer made-up of amphiphilic molecules surrounds an aqueous compartment Useful vehicle for drug delivery of both hydrophobic drugs and hydrophilic drugs, which are encapsulated in the interior aqueous compartment.
Biodegradable polymers based transdermal drug delivery systemDeepanjan Datta
Hello friends..I am back with new presentation which I am sure is going to help you all again.This presentation was prepared by me and my best buddy miss.pragya paramita pal during our graduation.A very thanks to my guide for guiding me.So go ahead FRIENDS & best of luck..........
ABSTRACT
The parenteral administration route is the most effective and common form of delivery for active drug substances with poor bioavailability and the drugs with a narrow therapeutic index. Drug delivery technology that can reduce the total number of injection throughout the drug therapy period will be truly advantageous not only in terms of compliance, but also to improve the quality of the therapy and also may reduce the dosage frequency. Such reduction in frequency of drug dosing is achieved by the use of specific formulation technologies that guarantee the release of the active drug substance in a slow and predictable manner. The development of new injectable drug delivery system has received considerable attention over the past few years. A number of technological advances have been made in the area of parenteral drug delivery leading to the development of sophisticated systems that allow drug targeting and the sustained or controlled release of parenteral medicines.
Controlled Release Oral Drug Delivery System
Controlled drug delivery is one which delivers the drug at a predetermined rate, for locally or systemically, for a specified period of time.
Polymers with their use in pharmaceutics. Approaches in designing of control drug release delivery system. Classification of polymers according to their use in pharmacy field with their use in various use in dosage form development.
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CLASSIFICATION AND CHARACTERISTICS OF POLYMERS
MECHANISM OF DRUG RELEASE FROM POLYMER
BIO DEGRADATION OF POLYMERS
SYNTHESIS OF POLYMERS
POLYMERS USED IN FORMULATION OF DIFFERENT DRUG DELIVERY SYSTEM.
APPLICATION OF POLYMERS
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People: The contributors and community that have supported Albumentations.
Metrics: The success indicators such as downloads, daily active users, GitHub stars, and financial contributions.
Challenges: The hurdles in monetizing open-source projects and measuring user engagement.
Development Practices: Best practices for creating, maintaining, and scaling open-source libraries, including code hygiene, CI/CD, and fast iteration.
Community Building: Strategies for making adoption easy, iterating quickly, and fostering a vibrant, engaged community.
Marketing: Both online and offline marketing tactics, focusing on real, impactful interactions and collaborations.
Mental Health: Maintaining balance and not feeling pressured by user demands.
Key insights include the importance of automation, making the adoption process seamless, and leveraging offline interactions for marketing. The presentation also emphasizes the need for continuous small improvements and building a friendly, inclusive community that contributes to the project's growth.
Vladimir Iglovikov brings his extensive experience as a Kaggle Grandmaster, ex-Staff ML Engineer at Lyft, sharing valuable lessons and practical advice for anyone looking to enhance the adoption of their open-source projects.
Explore more about Albumentations and join the community at:
GitHub: https://github.com/albumentations-team/albumentations
Website: https://albumentations.ai/
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In this work, we equipped AFL, a popular fuzzer, with DIAR and examined two critical Linux libraries -- Libxml's xmllint, a tool for parsing xml documents, and Binutil's readelf, an essential debugging and security analysis command-line tool used to display detailed information about ELF (Executable and Linkable Format). Our preliminary results show that AFL+DIAR does not only discover new paths more quickly but also achieves higher coverage overall. This work thus showcases how starting with lean and optimized seeds can lead to faster, more comprehensive fuzzing campaigns -- and DIAR helps you find such seeds.
- These are slides of the talk given at IEEE International Conference on Software Testing Verification and Validation Workshop, ICSTW 2022.
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- A fully editable and extendable library for grid component modelling;
- Visualization tools to display your network;
- Grid simulation tools, such as power flows, security analyses (with or without remedial actions) and sensitivity analyses;
The framework is mostly written in Java, with a Python binding so that Python developers can access PowSyBl functionalities as well.
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Threats to mobile devices are more prevalent and increasing in scope and complexity. Users of mobile devices desire to take full advantage of the features
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2. Contents
• Abstract
• Introduction
• Factors influencing drug release from
degradable polymer matrices
• Principles of polymer degradation and erosion
• Drug release characteristics of degradable
polymeric carriers
• Strategies to control drug release rates from
degradable polymers toward zero order profiles
• Conclusion
2
4. Introduction
• Microencapsulation concepts developed in the 1980s
and 1990s of the last century led to injectable particulate
depot formulations, e.g., for leuprolide acetate (Lupron®
Depot, Enantone®, Trenantone®) and goserelin acetate
(Zoladex®)
• These matrices typically consist of degradable polymers,
which slowly degrade under physiological conditions and
thus avoid accumulation of exhausted drug carriers in
the body or the need of a second surgery for ex-
plantation.
• Degradability is often a strong benefit in terms of
patients’ convenience, marketing, and hospitalization
costs.
4
5. • The term degradation (or biodegradation if
driven by contributions of living cells)
usually refers to a breakdown of polymers
at the molecular level, i.e., chain cleavage
that leads to degradation products that are
safely eliminated by the body.
5
Cont’d
6. • In contrast, the term erosion refers to the
process of polymer mass loss, which
includes not only degradation but several
other processes, such as water uptake
leading to microscopic or macroscopic
changes of the structural integrity of the
drug carrier and eventual removal of
degraded or nondegraded material to the
surrounding medium
6
Cont’d
7. • In principle, drug release from hydrophobic
polymers can be controlled by diffusion and/or
degradation of the matrix, typically by
spontaneous hydrolysis.
• The uptake of distinct quantities of water into the
matrix is required to enable drug diffusion and
hydrolytic cleavage of polymer chains.
7
Cont’d
8. • If the extent of water uptake is rather low, in this
case, the type of erosion mechanism may largely
depend on the involved rates of two mechanisms,
water uptake and hydrolytic degradation, and which
of them is dominating over the other.
• In this chapter, temporal controlled injectable and
implantable delivery systems are reviewed, which
involve degradation and erosion of the polymer
matrix.
8
Cont’d
9. Factors Influencing Drug Release from
Degradable Polymer Matrices
• Factors controlling drug release behavior can be
classified into two major groups, i.e.,
• (1) physical processes and
chemical/physicochemical molecular properties
associated with the involved materials and
• (2) the environmental conditions as well as
properties related to the engineered shape of
the drug carrier.
9
10. 10
Fig. 8.1 Scheme of major factors that may
influence drug release rates from drug
carriers based on degradable polymers
11. • Other important parameters or processes that
contribute to the release profile are
• Indication and Required Release Rates Define
Preferred Carrier Type
• Effect of Environmental Conditions on Release
• Impact of Drug Properties
• Contributions of Osmotically Mediated Mechanisms
11
Cont’d
12. Indication and Required Release Rates
Define Preferred Carrier Type
• The desired release rates, duration of release and
total dose,
• The route of administration (e.g., sc, im, ip, or site of
surgical placement),
• Type of drug carrier (e.g., particles or implants),
• Specific shapes or dimensions of the carrier (e.g.,
particle size distribution or shape of implants such
as polymeric stents).
• Depending on these application-dictated
requirements, a specific drug carrier may be
selected that fits the indication of interest
12
13. Effect of Environmental Conditions on
Release
• The drug release rates from a specific carrier are
largely affected by,
• environmental or physiological conditions,
• drug physicochemical properties,
• matrix ultrastructure and shape,
• osmotically driven mechanisms,
• biodegradation and erosion pathways of the
polymeric matrix.
13
14. Impact of Drug Properties
• Low solubility drugs are typically characterized by
lower diffusion rates due to a lower concentration
gradient of the drug from the inside to the outside
the matrix.
• Large substances such as proteins do often not
show release by diffusion through a dense,
nonporous polymer matrix.
• Noncovalent binding between drug and polymer
may reduce release rates or cause incomplete
release until complete erosion of the polymer.
• Molecular weights and hydrodynamic radii.
14
15. Contributions of Osmotically Mediated
Mechanisms
• In the polymer matrix, osmotic pressure builds
up by encapsulated highly water-soluble
compounds, resulting in water influx.
• Such water penetration through the polymer
phase and/or pore network can result in rupture
of pore walls for rapid release out of the polymer
and/or release by osmotic convective mass
transfer.
15
16. • Moreover, polymer properties have a very
important impact on drug release rates from
degradable matrices. This includes several
aspects, e.g.
• polymer hydrophilicity/hydrophobicity,
• drug–polymer interactions,
• polymer mesh width,
• drug diffusibility, polymer morphology and physical
state,
• polymer degradation and erosion behavior.
16
Cont’d
17. Principles of Polymer Degradation and
Erosion
• Principles of Polymer Degradation:
• The degradation i.e. the molecular breakdown of
polymers is governed by
• chemical composition,
• architecture and morphology,
• environmental conditions and device properties.
• e.g. , in hydrolytically degrading (co)polymers, the
uptake of water into the matrix is an essential
precondition for chain cleavage and is affected by
the matrix hydrophilicity as a function
17
18. • Three concepts of polymer degradation with
relevance for controlled drug release can be
differentiated
• First, linear polymers as most often used for
controlled drug release matrices can degrade into
mono- or oligomers by random or selective scission
of bonds in the polymer main chain.
• All commercialized drug loaded implants and
microparticle products based on polyesters or
polyanhydrides follow this pathway.
18
Cont’d
19. • Second, linear polymers may contain side chains
that, after cleavage, convert into hydrophilic or
charged groups attached to the polymer backbone,
which enable aqueous solubility of the polymer.
Besides other pathways.
• This mechanism is discussed as the major pathway
in polyalkyl-cyanoacrylate degradation.
• Third, polymer networks may disintegrate into water-
soluble linear polymer chains by selective
degradation of netpoints.
• Polyacrylate-based networks crosslinked with
hydrolytically cleavable copolyester segments are
examples for hydrophobic matrices. 19
Cont’d
20. • Principles of Erosion Triggering Mass Loss:
• Polymer erosion, i.e., the release of degraded or
nondegraded polymeric material, resulting in mass
loss of the sample.
• Degradation induced by exposure to different factors
including, e.g., heat, light, or oxidative stress.
• copolymers synthesized from dilactides and
diglycolide (PLGA) is the example of controlled
release matrices.
20
21. • For polymer erosion that relies on aqueous
hydrolysis, four different steps can be differentiated,
i.e.,
• (1) wetting of the polymer surface including a
possible internal porous structure,
• (2) water uptake with a material-specific rate into the
polymer bulk,
• (3) degradation of the polymer following a
characteristic pathway with a material- and possibly
geometry dependent rate, and
• (4) if possible, diffusion controlled removal of
degradation products.
21
Cont’d
22. • For instance, incorporation of acidic substances into
the matrix acting as catalysts can increase the
degradation rate, thus changing degradation pattern
and drug release to a surface erosion controlled
mechanism for certain polymers.
• However, occasionally observed higher degradation
rates in vivo are repeatedly assigned to enzymatic
catalysis, but may also be based on other factors,
e.g. inflammatory cell/tissue responses or
plasticization of the polymer by molecules present in
vivo.
22
Cont’d
23. Drug Effects on Polymer Degradation
• The incorporation of any substances including drugs
into a polymer matrix may change the polymers
degradation behavior.
• This is very obvious in the case of embedded highly
soluble drugs or additives of similar properties, which
may change the osmotic pressure in the matrix and
increase water uptake.
• E.g., an increased catalytic degradation of PLGA
implants was observed depending on the loading with
a water-soluble N-acetyl cysteine, which enhanced
water uptake.
23
24. • For basic drugs, e.g., thioridazine, an
amine catalyzed hydrolysis of the polymer
matrix during the particle preparation and
a faster release were observed,
• This could be reduced by performing the
o/w emulsification at lower temperatures
or erasing the drug’s basicity by the
formation of salts.
24
Cont’d
25. Drug Release Characteristics of Degradable
Polymeric Carriers
• Polymers in Commercial Parenteral Drug
Delivery Products:
• The employed carrier strategies include
microparticles, preformed implants, and in situ
forming implants.
• Importantly, in all but one of the so far
commercialized products, PLA/PLGA is used
as matrix polymer.
25
27. Microparticles
• The largest number of degradable parenteral
controlled release products are based on
microparticles as drug carriers.
• Beneficial aspects of microparticles as drug depots
compared to preformed implants include their
injectability through needles of smaller diameters as
well as the advantages of all multiple unit dosage
forms, i.e., a possibly better average reproducibility
of their properties.
27
32. Preformed Implants
• Preformed implants in the classical rod-like
shape with the single functionality to act as drug
depot, processing of drug loaded degradable
polymers into advanced shapes has opened
new fields of application that combine drug
release and a supporting function.
• Particularly the stent technology for the
treatment of coronary artery diseases is
demanding such degradable material concepts
32
37. In Situ Forming Drug Depots
• In situ implants are formed in the tissue after
injection, mostly due to polymer precipitation
from organic solutions.
• In situ forming gels, i.e., solvent rich matrices
consisting of hydrophilic or amphiphilic
molecules, may employ various mechanisms of
intermolecular binding,
• (1) thermosensitive materials gelling upon
decrease in temperature include materials like
block copolymers
37
38. 38
• (2) thermosensitive materials, which gel upon
increase in temperature, gelation occurs, e.g.
due to the formation of block copolymer micelles
• (3) covalent crosslinking of network precursors,
e.g. by enzymatic reactions
• (4) ionic crosslinking, e.g. of charged polymers
• (5) pH changes, e.g. for charged polymers such
as chitosan
Cont’d
40. Strategies to Control Drug Release Rates
from Degradable Polymers Toward Zero
Order Profiles
• Relevance of In Vitro Zero Order Release and
Common Limitations:
• Research on controlled release formulations aims to
provide delivery systems that show zero order drug
release i.e., constant release rates over time.
• for degradable matrix polymers, e.g. plasticization,
potential catalytic activities of enzymes, or possible
alterations in local environment due to cellular
immune response, may have to be included for in
vitro zero order release.
40
41. • Approaches to overcome undesired high initial
release include,
• improve miscibility of the drug and the polymer,
• to reduce diffusion to interfaces by advanced
carrier processing techniques.
• In addition to the drug/polymer properties on the
molecular level, processing-derived properties of
the carrier such as the surface area and the
porosity will impact the release kinetics.
41
Cont’d
42. Conclusion
• Degradable, polymer-based drug carriers remain a
scientifically and commercially important strategy to
control the release of bioactive molecules over time
periods ranging from several days to several
months.
• Drug release from these carriers is governed by a
complex interplay of parameters including drug
properties, polymer degradation/erosion
characteristics, and osmotically driven mechanisms,
as well as environmental conditions and processing-
derived device properties
42