Gastro retentive drug delivery system (GRDDS)Shweta Nehate
Oral route is the most acceptable route for drug administration. Apart from conventional dosage forms several other forms were developed in order to enhance the drug delivery for prolonged time period and for delivering drug to a particular target site. Gastro-retentive drug delivery system (GRDDS) has gainned immense popularity in the field of oral drug delivery recently. it is a widely employed approach to retain the dosage form in the stomach for an extended period of time and release the drug slowly that can address many challenges associated with conventional oral delivery, including poor bioavailability. different innovative approaches are being applied to fabricate GRDDS. Gastroretentive drug delivery is an approach to prolong gastric residence time, there by targeting site-specific drugs release in the upper gastrointestinal tract (GIT) for local or systemic effects. It is obtained by retaining dosage form into stomach and by releasing the in controlled manner.
Video Lecture is available at https://www.youtube.com/watch?v=DXu_CLgB4q0
Introduction, terminology/definitions and rationale, advantages, disadvantages, selection of drug candidates. Approaches to design-controlled release formulations based on diffusion, dissolution and ion exchange principles. Physicochemical and
biological properties of drugs relevant to controlled release formulations.
Mucoadhesive drug delivery system interact with the mucus layer covering the mucosal epithelial surface, & mucin molecules & increase the residence time of the dosage form at the site of the absorption.
Mucoadhesive drug delivery system is a part of controlled delivery system.
Since the early 1980,the concept of Mucoadhesion has gained considerable interest in pharmaceutical technology.
combine mucoadhesive with enzyme inhibitory & penetration enhancer properties & improve the patient complaince.
MDDS have been devloped for buccal ,nasal,rectal &vaginal routes for both systemic & local effects.
Hydrophilic high mol. wt. such as peptides that cannot be administered & poor absorption ,then MDDS is best choice.
Mucoadhesiveinner layers called mucosa inner epithelial cell lining is covered with viscoelasticfluid
Composed of water and mucin.
Thickness varies from 40 μm to 300 μm
General composition of mucus
Water…………………………………..95%
Glycoproteinsand lipids……………..0.5-5%
Mineral salts……………………………1%
Free proteins…………………………..0.5-1%
The mechanism responsible in the formation of mucoadhesive bond
Step 1 : Wetting and swelling of the polymer(contact stage)
Step 2 : Interpenetration between the polymer chains and the mucosal membrane
Step 3 : Formation of bonds between the entangled chains (both known as consolidation stage)
Electronic theory
Wetting theory
Adsorption theory
Diffusion theory
Fracture theory
Advantages over other controlled oral controlled release systems by virtue of prolongation of residence of drug in GIT.
Targeting & localization of the dosage form at a specific site
-Painless administration.
-Low enzymatic activity & avoid of first pass metabolism
If MDDS are adhere too tightlgy because it is undesirable to exert too much force to remove the formulation after use,otherwise the mucosa could be injured.
-Some patient suffers unpleasent feeling.
-Unfortunately ,the lack of standardized techniques often leads to unclear results.
-costly drug delivery system
Gastro retentive drug delivery system (GRDDS)Shweta Nehate
Oral route is the most acceptable route for drug administration. Apart from conventional dosage forms several other forms were developed in order to enhance the drug delivery for prolonged time period and for delivering drug to a particular target site. Gastro-retentive drug delivery system (GRDDS) has gainned immense popularity in the field of oral drug delivery recently. it is a widely employed approach to retain the dosage form in the stomach for an extended period of time and release the drug slowly that can address many challenges associated with conventional oral delivery, including poor bioavailability. different innovative approaches are being applied to fabricate GRDDS. Gastroretentive drug delivery is an approach to prolong gastric residence time, there by targeting site-specific drugs release in the upper gastrointestinal tract (GIT) for local or systemic effects. It is obtained by retaining dosage form into stomach and by releasing the in controlled manner.
Video Lecture is available at https://www.youtube.com/watch?v=DXu_CLgB4q0
Introduction, terminology/definitions and rationale, advantages, disadvantages, selection of drug candidates. Approaches to design-controlled release formulations based on diffusion, dissolution and ion exchange principles. Physicochemical and
biological properties of drugs relevant to controlled release formulations.
Mucoadhesive drug delivery system interact with the mucus layer covering the mucosal epithelial surface, & mucin molecules & increase the residence time of the dosage form at the site of the absorption.
Mucoadhesive drug delivery system is a part of controlled delivery system.
Since the early 1980,the concept of Mucoadhesion has gained considerable interest in pharmaceutical technology.
combine mucoadhesive with enzyme inhibitory & penetration enhancer properties & improve the patient complaince.
MDDS have been devloped for buccal ,nasal,rectal &vaginal routes for both systemic & local effects.
Hydrophilic high mol. wt. such as peptides that cannot be administered & poor absorption ,then MDDS is best choice.
Mucoadhesiveinner layers called mucosa inner epithelial cell lining is covered with viscoelasticfluid
Composed of water and mucin.
Thickness varies from 40 μm to 300 μm
General composition of mucus
Water…………………………………..95%
Glycoproteinsand lipids……………..0.5-5%
Mineral salts……………………………1%
Free proteins…………………………..0.5-1%
The mechanism responsible in the formation of mucoadhesive bond
Step 1 : Wetting and swelling of the polymer(contact stage)
Step 2 : Interpenetration between the polymer chains and the mucosal membrane
Step 3 : Formation of bonds between the entangled chains (both known as consolidation stage)
Electronic theory
Wetting theory
Adsorption theory
Diffusion theory
Fracture theory
Advantages over other controlled oral controlled release systems by virtue of prolongation of residence of drug in GIT.
Targeting & localization of the dosage form at a specific site
-Painless administration.
-Low enzymatic activity & avoid of first pass metabolism
If MDDS are adhere too tightlgy because it is undesirable to exert too much force to remove the formulation after use,otherwise the mucosa could be injured.
-Some patient suffers unpleasent feeling.
-Unfortunately ,the lack of standardized techniques often leads to unclear results.
-costly drug delivery system
Approaches Of Gastro-Retentive Drug Delivery System or GRDDSAkshayPatane
Approaches Of Gastro-Retentive Drug Delivery System
Includes:
Floating and Non-Floating drug delivery system with their subtypes
Like Non-effervescent system, Effervescent system, Raft forming system,
High Density system, Expandable system, Muco-adhesive system,
Super porous hydrogel system and Magnetic Systems, etc.
This presentation includes introduction, physiology of GIT, factors affecting GRDDS, Advantages and disadvantages, approaches to GRDDS and their mechanism, some of the marketed products using GRDDS mechanism.
Powerpoint presentation on controlled drug delivery system. Its introduction, terminologies, rationale, advantages, disadvantages, selection of drug, approaches for designing controlled release formulations and physicochemical and biological properties of drug
Mucoadhesive drug delivery system has gained interest among pharmaceutical scientists as a means of promoting dosage form residence time as well as improving intimacy of contact with various absorptive membranes of the bio- logical system
The device which is used in the intrauterine drug delivery system is known as an Intrauterine device (IUD) (2). IUDs or intrauterine devices are small artificial objects or devices inserted into the uterus to prevent the occurrence of pregnancy by disrupting the fertilization process as a result of sexual intercourse. They have gained popularity in recent times and are one of the most effective methods of birth control in terms of long-term contraception. It can be easily installed and is flexible. These devices are usually small in size and inserted through the cervix. IUDs reduce the need for abortion with unwanted pregnancies by preventing the effective movement of eggs and sperm. However, it cannot confirm the spread of STIs or STDs such as HIV, gonorrhoea, etc
Topics covered
Introduction
Advantages
Disadvantages
Development of intra uterine devices (IUDs)
Applications
References
Approaches Of Gastro-Retentive Drug Delivery System or GRDDSAkshayPatane
Approaches Of Gastro-Retentive Drug Delivery System
Includes:
Floating and Non-Floating drug delivery system with their subtypes
Like Non-effervescent system, Effervescent system, Raft forming system,
High Density system, Expandable system, Muco-adhesive system,
Super porous hydrogel system and Magnetic Systems, etc.
This presentation includes introduction, physiology of GIT, factors affecting GRDDS, Advantages and disadvantages, approaches to GRDDS and their mechanism, some of the marketed products using GRDDS mechanism.
Powerpoint presentation on controlled drug delivery system. Its introduction, terminologies, rationale, advantages, disadvantages, selection of drug, approaches for designing controlled release formulations and physicochemical and biological properties of drug
Mucoadhesive drug delivery system has gained interest among pharmaceutical scientists as a means of promoting dosage form residence time as well as improving intimacy of contact with various absorptive membranes of the bio- logical system
The device which is used in the intrauterine drug delivery system is known as an Intrauterine device (IUD) (2). IUDs or intrauterine devices are small artificial objects or devices inserted into the uterus to prevent the occurrence of pregnancy by disrupting the fertilization process as a result of sexual intercourse. They have gained popularity in recent times and are one of the most effective methods of birth control in terms of long-term contraception. It can be easily installed and is flexible. These devices are usually small in size and inserted through the cervix. IUDs reduce the need for abortion with unwanted pregnancies by preventing the effective movement of eggs and sperm. However, it cannot confirm the spread of STIs or STDs such as HIV, gonorrhoea, etc
Topics covered
Introduction
Advantages
Disadvantages
Development of intra uterine devices (IUDs)
Applications
References
Fundamental concept of modified drug releaseAbhinayJha3
Different Terminologies used in a modified release
1. Sustained release
2. Delayed release
3. Prolonged release
4. Extended-release
5. Controlled release
6. Site-specific targeting and receptor targeting
SELECTION OF DRUG CANDIDATE FOR ORAL SUSTAINED RELEASE SYSTEMS, BIOPHARMACEUTICAL CLASSIFICATION SYSTEM.
Fundamental concept of modified drug releaseAbhinayJha3
BIOPHARMACEUTICAL CLASSIFICATION SYSTEM
Different Terminologies used in a modified release
1. Sustained release
2. Delayed release
3. Prolonged release
4. Extended-release
5. Controlled release
6. Site-specific targeting and receptor targeting
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
1. CONTROLLED
RELEASE DRUG
DELIVERY SYSTEM
Prepared By :
Ms. Bansari B. Patel
Mpharm sem-1
Department of pharmaceutics
Bhagwan Mahavir College of Pharmacy ,Surat.
Gujarat technological university
Guided By :
Mr. Vinod D. Ramani
Associate Professor
Department of Pharmaceutics
Bhagwan Mahavir College of Pharmacy
3. WHAT IS CRDDS?
Controlled drug delivery system refers to system that provides some
control to either temporal or spatial or both nature of the drug release.
Temporal :- refers to controlling the rate of specific time of drug delivery
to targeted tissue .
Spatial :- refers to targeting a drug to a specific organ or tissue.
Ideal condition for DDS :-
i. It should deliver drug at a rate that is required by the body over a
period of treatment.
ii. It should deliver drug solely to the site of action.
4. Hence , CRDDS attempts to :-
i. sustain drug action at a predetermined rate by maintaining effective
drug level in body and thereby minimizing undesirable side effects of
drug.
ii. Localize drug action by spatial placement of controlled release
system in diseased tissue or organ.
Generally , very few systems fulfil the above principles .
In most cases , the release system creates constant conc. of drug
within body over extended period of time.
Ideally , it is desirable to place drug at site of target , be it a tissue
,organ or receptor, leaving rest of the body drug free , but it would be
quiet difficult if the target is covered by some barriers.
WHAT IS CRDDS?
5. As shown , conventional
tablet or capsule provides
single burst of drug . As long
as amount of drug is above
MEC , pharmacological
response is observed,. But as
it rises above MSC , toxicity or
side effects may occur.
Whereas , in CR , drug is
released at a constant rate.
Hence it will not rise above
MSC and thereby minimizing
toxicity or side effects.
SR also decreases side effect
but the rate of release varies
over period of time.
6. ADVANTAGES OF CRDDS
CR formulation release drug at a required rate for prolonged time
,thereby decreasing frequency of drug administration and also side
effects.
• E.g. : Nifedipine in conventional formulation causes hypotension
in patients.CR Nifedipine product avoids high initial blood conc
which causes sudden hypotension .
As frequency of dosing decreases , patient compliance improves.
Maximum utilization of drug enabling reduction in total amount of
drug dose administered.
7. Decreased side effect
• Eg:-CR product of paroxetine delays release of paroxetine until tablet
has passed through stomach . As a result , side effect like nausea is less
as compared to immediate release.
Increase in safety margin of high potency drug due to better control of
plasma level.
Decrease in health care cost with CR products due to :-
i. Short term therapy
ii. Decrease in frequency of dosing
iii. Improved therapy
ADVANTAGES OF CRDDS
8. DISADVANTAGES OF CRDDS
Higher cost of formulation .
Poor in -vivo in-vitro co-relation.
Failure of controlled release mechanism may result in release of a large
toxic dose.
Reduced potential for drug adjustment of drug normally administered in
varying strengths.
Retrieval of drug is difficult in case of toxicity , poisoning or
hypersensitivity reaction.
9. FACTORS AFFECTING CRDDS
Factors affecting CRDDS
Physiochemical Pharmacokinetic Pharmacodynamic
properties properties properties
a. Molecular Size a. Absorption rate a. Drug dose
b. Aqueous solubility b. Elimination half life b. Therapeutic range
c. Partition co-efficient c. Metabolism rate c. Therapeutic Index
d. Dissociation constant d. Dosage form index d. Plasma conc
e. Ionization at physiological response
pH relationship
f. Stability in GI milieu
g. Route of administration
10. I. Physio Chemical Proprerties:-
a. Molecular size and weight of drug :-
Lower the molecular weight or size , faster and complete the absorption
For drugs absorbed by pore mechanism , the molecular size threshold is
150 Daltons for spherical compound and 400 Daltons for linear
compound.
But 95% of drugs are absorbed by passive diffusion. Diffusivity , i.e. , the
ability of a drug to diffuse to a membrane is inversely proportional to
molecular size. So larger the molecular size , lower will be the diffusivity
and hence the absorption. It can be expressed as :
logD = -Sv logV + Kv
= -Sm logM +Km
Where , D=diffusivity , V = molecular volume
M= molecular weight or mass
Sv , Sm , Kv , Km =constant
11. b. Aqueous Solubility :-
Drug must be in solution form before they can be absorbed. Hence
compounds having lower aqueous solubility suffers oral bioavailability
problems. Eg : Warfarin , Digoxin , Griesofulvin
Aqueous solubility plays an important role in selecting mechanism for
CR.
Eg : For slightly soluble drug , diffusion systems are poor choice as the
driving force in such system is conc in aqueous solution. On other hand ,
such drug can be effectively incorporated in matrix system.
In selecting polymer coatings for CR system , dissolution rate of drug
must be considered.
Aqueous solubility limits the loading efficiency of drug in carriers such
as liposome .Most water soluble drug tends to leak from such carriers
12. c. Partition co-efficient / Lipophilicity of drug :-
Partition co efficient influence not only the permeation of drug through
biological membrane but also diffusion across the rate controlling
membrane or matrix .
Drugs with extremely high partition co-efficient readily penetrate the
membranes but are unable to proceed further. Such drugs have
increased tendency to cross even the more selective barriers like BBB.
Whereas drugs having high aqueous solubility cannot penetrate
through the membranes.
Hence a balance in partition co-efficient is necessary to give an
optimum flux for permeation through the biological and rate controlling
membranes.
13. d. Drug dissociation and ionization at physiological pH :-
For optimum absorption , drug should be unionized at the site .
Acidic drugs remains unionized in acidic pH (3.0 -7.5) and basic drug
remains unionized in basic pH (7.0-11.0).
Drugs existing mostly in ionized form are poor candidates for CRDDS.
Eg : Hexamethonium.
14. e. Protein Binding :-
It is well known that many drugs bind to plasma protein with the
influence on duration of action.
Drug-protein binding serve as a depot for drug producing a
prolonged release profile, especially it is high degree of drug binding
occurs.
Extensive binding to plasma proteins will be evidenced by a long half
life of elimination for drugs and such drugs generally most require a
sustained release dosage form. However drugs that exhibit high
degree of binding to plasma proteins also might bind to biopolymers
in GI tract which could have influence on sustained drug delivery. The
presence of hydrophobic moiety on drug molecule also increases the
binding potential.
15. f. Drug stability :-
Drugs unstable in GI environment cannot be administered as oral CR
formulation . E.g. Nitroglycerine . For such drugs a different route of
administration should be used.
Drugs unstable at gastric pH can be designed as sustained release in
intestine with limited or no delivery in stomach . Eg , Propantheline.
On the other hand , drug unstable in intestine can be designed as
gastroretentive dosage form . Eg, Probanthine .
16. g. Route of administration :-
Different route of administration are selected based on various physical
parameters of drugs . Various commonly used routes for CRDDS are :-
i. Oral route :-
The drug whose administration is pH dependent , destabilized by gastric
fluid or enzymes , undergoes extensive presystemic metabolism
(nitroglycerine) , has an absorption window and / or absorbed actively
(riboflavin) are poor candidates for this route .
For a drug to be successful as oral controlled release formulation , it
should be absorbed through the entire length of GIT.
The main limitation of this route is the transit time . The duration of
action can be extended for 12 to 24 hrs.
This route is suitable for drug given in dose as high as 1000mg .
17. ii. Intramuscular / subcutaneous route :-
This route is suitable when duration of action is to be prolonged for 24
hrs to 12 months.
Only a small dose of drug , about 2ml or 2 grams can be administered
by this route.
Factors affecting drug release and selection are solubility of drug in
surrounding tissues , molecular weight ,partition co efficient and pKa of
drug and contact surface between the drug and surrounding tissues .
iii. Transdermal route :-
This route is used for drugs showing extensive first pass metabolism
upon oral administration or drugs with low dose such as nitroglycerine.
Factors affecting are partition co-efficient , contact area , skin condition
skin permeability rate ,etc.
18. II. Pharmacokinetic characteristics of drug :
a. Absorption rate :-
For a drug to be administered as controlled release formulation ,
absorption must be efficient .
Rate of release Kr > rate of absorption Ka.
A drug with slow absorption rate is poor candidate as continuous
release of such drug results in pool of unabsorbed drug . E.g. , Iron ,
decamethonium.
b. Elimination half life :
Ideally , rate of absorption = rate of elimination
Smaller the t½, larger the amount of drug to be incorporated in
controlled release dosage form .
Drugs with t½ 2 to 4 hrs are suitable for such system . E.g. Propranolol.
19. c. Rate of metabolism :-
A drug which is extensively metabolized is a suitable candidate for such system
unless the metabolism is too rapid.
A drug capable of inducing or inhibiting metabolism is poor candidate since
state levels would be difficult to maintain.
d. Dosage form index :-
DI =Css max/ Css min
where , DI=dosage form index , Css max = maximum conc of drug at time t,
Css min = minimum conc of drug at time t.
The drug release rate should be monitored so that a steady plasma conc is
by reducing DI ratio , while maintaining the drug level within the therapeutic
window.
Ideally the rate of drug release from the formulation should be greater then rate
absorption.
Ideally it should be close to one.
20. III. Pharmacodynamic characteristics of drug :
a. Drug Dose : -
In general a single dose of 1.0 gm is considered for a conventional
dosage form this also holds for controlled release dosage forms.
In case, the dose already high, then formulating the same into
controlled release will further increase the overall dosage size &
reduced patient compliance.
For drugs with an elimination half-life of less than 2 hours as well as
those administered in large doses, a controlled release dosage form
need to carry a prohibitively large quantity of drug.
b. Therapeutic Range :-
The ideal drug for CRDDS should have therapeutic range wide enough
such that variation in release rate do not result in concentration
the level.
21. c. Therapeutic index :-
In general the larger the volume of therapeutic index safer the drug.
Drug with very small values of therapeutic index usually are poor
candidates for CRDDS due to pharmacological limitation of control over
release rate .e.g.- induced digoxin, Phenobarbital, phenytoin.
Here , TI = Therapeutic index , TD50 =median toxic drugs ,
ED50=median effective dose
d. Plasma Concentration Response (PK/PD) Relationship :-
Drugs such as Reserpine whose pharmacological activity is independent
of its concentration are poor candidates for controlled release system.
22. FACTORS AFFECTING CRDDS
SR NO PROPERTIES DESIRED FEATURES
A Biopharmaceutics Properties
1Molecular Size Less than 600 Daltons
2Aqueous solubility More than 0.1 mg / ml
3Partition Co-efficient 1 to 2
4Dissociation constant pKa Acidic drugs, pKa >2.5 , and Basic Drugs , pka<11.0
5Ionisation at Physiological pH Not more than 95%
6Stability in GI milieu Stable at both Gastric and intestinal pH
7Absorption mechanism Passive but not through a window
B Pharmacokinetic Properties
1Absorption Rate High
2Elimination Half-Life 2-6 hrs
3Metabolism Rate Not Too High
4Dosage Form Index (DI) 1
C Pharmacodynamic Properties
1Drug Dose Maximum 1 gm
2Therapeutic Index (TI) Wide
3Therapeutic Range Wide
4PK/PD relationship Good
23. APPROACHES FOR CRDDS
Chemical approach
Biological approach
Pharmaceutical approach
25. PHARMACEUTICAL APPROACH
A. Dissolution controlled Release:
Matrix dissolution control
Encapsulation or Reservoir dissolution control
B. Diffusion Controlled Release:
Reservoir devices
Matrix devices
C. Dissolution-Diffusion Controlled (Combination)
26. DISSOLUTION CONTROLLED RELEASE:
Controlled release oral products employing dissolution as the rate-
limiting step are in principle the simplest to prepare.
1. Encapsulation or reservoir dissolution control:
These methods generally involve coating individual particles or
of drug with a slowly dissolving material.
The coated particles can be compressed directly into tablets as in
Spacetabs or placed in capsules as in the Spansule Products.
27. Since the time required for dissolution of the coat is a function of its
thickness and aqueous solubility, one can obtain repeat or sustained
action by employing a narrow or a wide spectrum of coated particles of
varying thicknesses respectively.
There are several ways for coating. A common method is to coat the
seeds with the drug , followed by a coat of slow dissolving materials
such as carbohydrate sugar, cellulose, polyethylene glycol, polymeric
material and wax.
Marketed:- Progestasert_ IUD, Occusert_ system, Transderm-Nitro_
system, Norplant_ subdermal implant
28. II. Matrix or Monolithic system:-
An alternative approach is to compress the drug with a slowly dissolving
carrier of some sort into a tablet form.
Here, the rate of drug availability is controlled by the rate of
penetration of the dissolution fluid into the matrix.
The carrier used are bees wax, carnauba wax, castor oil ,etc.
29. Controlled dissolution by:
1.Altering porosity of tablet.
2.Decreasing its wettability.
3.Dissolving at slower rate.
The drug release is determined by dissolution rate of the polymer.
• Examples:
1. Dimetane extencaps,
2. Dimetapp extentabs.
30. DIFFUSION CONTROLLED RELEASE:
This system is hollow containing an inner core of drug.
The water insoluble polymeric material surrounds drug reservoir.
The drug partitions into the membrane and exchanges with the
surrounding fluid by diffusion.
There are basically two types of diffusion controlled systems which
been developed over the past two decades, reservoir devices and
devices.
32. Reservoir systems are hollow devices in which an inner core of the drug
is surrounded by a polymer membrane.
In this device, the drug core is encapsulated in a water-insoluble
polymeric membrane.
The mesh (i.e., the space between macromolecular chains) of these
polymers , through which drug penetrates or diffuses after partitioning,
is of MOLECULAR LEVEL.
The rate of drug release is dependent on the rate of drug diffusion but
not on the rate of dissolution.
In short, mass transport phenomena at molecular level occurs.
Examples: Nico-400, Nitro-Bid.
33. The drug release rate is dependent on the type of polymer. High
molecular weight compounds are difficult to deliver through the device.
Delivery systems designed on this principle can be administered by
different routes: intrauterine such as Progestasert , implants such as
Norplant, transdermal such as Transderm-Nitro, and ocular such as
Occusert.
34. II. Matrix Device :
A matrix or monolithic device consists of an inert polymeric matrix in
which a drug is uniformly distributed.
Drugs can be dissolved in the matrix or the drugs can be present as a
dispersion.
35. Matrix may be HOMOGENEOUS or POROUS with water filled pores.
The rate of drug release is dependent on the rate of drug diffusion but
not on the rate of solid dissolution.
A matrix (or monolith) device is easy to formulate and gives a higher
initial release rate than a reservoir device and can be made to release at
a nearly constant rate.
High molecule weight compounds are delivered through the matrix
devices.
Matrix devices are favored over other design for their simplicity, low
manufacturing costs, and lack of accidental dose dumping, which may
occur with reservoir systems when the rate controlling membrane
ruptures.
Marketed:- Nitro-Dur_ system , Compudose_ implant
36. o Types of Matrix :
Rigid Matrix Diffusion
Materials used are insoluble plastics such as PVP & fatty acids.
Swellable Matrix Diffusion
Also called as Glassy hydrogels . Popular for sustaining the release of
highly water soluble drugs.
Materials used are hydrophilic gums.
Examples :
Natural- Guar gum, Tragacanth.
Semisynthetic -HPMC, CMC, Xanthum gum.
Synthetic -Polyacrilamides.
Examples: Glucotrol XL, Procardia XL
37. Dissolution-Diffusion Controlled (Combination):
The main feature of this system is that the drug is enclosed with a
partially soluble membrane. In this system, the drugs were
homogenously dispersed in a matrix.
Dissolution of part of the membrane allows for diffusion of the
contained drug through pores in the polymer coat.
The drug release from this type of matrix follows zero order kinetics.
38. CHEMICAL APPROACHES :
a. pH- activated DDS
b. Ion- activated DDS
c. Hydrolysis- activated DDS
39. pH- activated drug delivery system :
This type of chemically activated system permits targeting the delivery
of drug only in the region with selected pH range.
40. It is fabricated by coating the drug-containing core with a pH – sensitive
polymer combination.
The pH range of fluids in various segments of the gastrointestinal tract
may provide environmental stimuli for responsive drug release.
Altering the pH of the solution will cause swelling or deswelling of the
polymer. Thus, drug release from devices made from these polymers will
display release rates that are pH sensitive
Polyacidic polymers will be unswollen at low pH, because the acidic
groups will be unionized. With increasing pH, Polyacidic polymers will
swell. The opposite holds for polybasic polymers, because the ionization
of the basic groups will increase with decreasing pH.
The most commonly used pH-sensitive polymers are derivatives of
acrylic acid and cellulose.
41. In the stomach, coating membrane resists the action of gastric fluid
(pH<3) & the drug molecule thus protected from acid degradation.
After gastric emptying the DDS travels to the small intestine & intestinal
fluid (pH>7.5) activates the erosion of the intestinal fluid soluble
polymer from the coating membrane.
This leaves a micro porous membrane constructed from the intestinal
fluid insoluble polymer, which controls the release of drug from the core
tablet.
The drug solute is thus delivered at a controlled manner in the intestine
by a combination of drug dissolution & pore-channel diffusion.
42. Ion- activated drug delivery system:
An ionic or a charged drug can be delivered by this method & this system are
prepared by first complexing an ionic drug with an ion-exchange resin
containing a suitable counter ion.
Resins are water-insoluble materials containing anionic or cationic groups in
repeating positions on the resin chain.
The granules of drug-resin complex are first treated with an impregnating
agent & then coated with a water-insoluble but water-permeable polymeric
membrane.
This membrane serves as a rate-controlling barrier to modulate the influx of
ions as well as the release of drug from the system.
Resin- Drug+ + X+ Resin- ....X+ + Drug+ ՜
Resin- Drug+ + X+ Resin- ....X+ + Drug+
In an electrolyte medium, such as gastric fluid ions diffuse into the system
react with drug resin complex & trigger the release of ionic drug.
43. Since the GI fluid regularly maintains a relatively constant level of ions,
theoretically the delivery of drug from this ion activated oral drug
delivery system can be maintained at a relatively constant rate.
R-SO3 H+ + H2N-A ↔ R-SO3 – H3N-A
R-N+ H3OH- + HOOC-B ↔ R-N+ H3 –OOC-B+H2O
H2N-A → basic drug , R-SO3H+ → cation exchanger resin , HOOC-B → acidic drug
R-NH3 + OH- → anion exchanger resins.
44. Hydrolysis- activated drug delivery system
This type of system depends on the hydrolysis process to activate the
release of drug.
Drug reservoir is either encapsulated in microcapsules or
homogeneously dispersed in microspheres or nano particles for
injection.
It can also be fabricated as an implantable device. All these systems
prepared from bioerodible or biodegradable polymers (polyanhydride,
polyorthoesters).
45. It is activated by hydrolysis-induced degradation of polymer chain & is controlled by
rate of polymer degradation.
E.g. LHRH – releasing biodegradable subdermal implant, which is designed to deliver
goserline, a synthetic LHRH analog for once a month treatment of prostate carcinoma.
47. Enzyme - activated drug delivery system
This type of biochemical system depends on the enzymatic process to
activate the release of drug.
Drug reservoir is either physically entrapped in microspheres or
chemically bound to polymer chains from biopolymers (albumins or
polypeptides).
The release of drug is activated by enzymatic hydrolysis of biopolymers
(albumins or polypeptides) by specific enzyme in target tissue.
Another approach in enzyme activated DDS is use of pH change . They
include :
i. GLUCOSE-RESPONSIVE INSULIN RELEASE DEVICES
ii. UREA-RESPONSIVE DELIVERY SYSTEM
48. i. GLUCOSE-RESPONSIVE INSULIN RELEASE DEVICES
In case of Diabetes mellitus there is rhythmic increase in the levels of
glucose in the body, requiring injection of the insulin at proper time.
Several systems have been developed which are able to respond to
changes in glucose concentration.
One such system includes pH sensitive hydrogel containing glucose
oxidase, immobilized in the hydrogel encapsulating saturated insulin
solution.
When glucose concentration in the blood increases, glucose oxidase
converts glucose into gluconic acid which changes the pH of the system.
This pH change induces swelling of the polymer which results in insulin
release. Insulin by virtue of its action reduces blood glucose level and
consequently gluconic acid level also gets decreased.
49. ii. UREA-RESPONSIVE DELIVERY SYSTEM :
Heller and Trescony firstly reported the alteration in local pH by
immobilization of enzymes that lead to change in polymer erosion
rate.
The proposed system is based on the conversion of urea to
and NH4OH by the action of urease.
As this reaction causes a pH increase, a polymer that is subjected
increased erosion at high pH is required.
A partially esterified copolymer of methyl vinyl ether and maleic
anhydride was developed that displays pH dependent drug
This polymer dissolves by ionization of the carboxylic acid group.
50. This pH sensitive polymer containing dispersed drug is surrounded
by a hydrogel, containing urease, immobilized by crosslinking of
urease and bovine serum albumin with glutaraldehyde.
Diffusion of urea into hydrogel and its subsequent interaction with
urease lead to increase in pH which causes erosion of polymer with
concomitant drug release.
51. ANTIBODY INTERACTIONS ACTIVATED DDS :
This approach has been proposed for antibody mediated release of
contraceptive agent.
The β- subunit of human chorionic gonadotropin (HCG) is grafted to the
surface of the polymer, which is then exposed to antibodies to β-HCG.
After implantation, this delivery system remains quiescent until
triggered by the first biochemical indication of pregnancy, i.e
appearance of HCG in the circulatory system.
The HCG competes for the polymer bound antibodies to HCG and
initiates release of the contraceptive drug.
This approach to contraception serves to minimize the frequency of
drug administration and the side effects associated with contraceptive
drugs.
52. REFERENCES:
1. Y.W.CHIEN;NOVEL DRUG DELIVERY SYSTEM ;FUNDAMENTALS
DEVELOPMENT CONCEPTS AND BIOMEDICAL ASSESMENTS.SECOND
EDITION,
2. ENCYCLOPEDIA OF PHARMACEUTICAL TECHNOLOGY;VOLUME 2
3. CONTROLLED DRUG DELIVERY: FUNDAMENTALS AND APPLICATIONS,
Second Edition, Revised and Expanded, Joseph R. Robinson and Vincent H. L.
Lee
4. DESIGN OF CONTROLLEDRELEASE DRUG DELIVERY SYSTEMS
Steve I. Shen, Bhaskara R. Jasti, and Xiaoling Li
5. Controlled Release Drug Delivery Systems Debjit Bhowmik, Harish Gopinath,
B. Pragati Kumar , S. Duraivel , K. P. Sampath Kumar