This document discusses in vitro dissolution testing methods. It defines dissolution as the process by which a solid substance solubilizes in a solvent, and dissolution rate as the amount of drug substance that goes into solution per unit time under standardized conditions. It then describes 7 common apparatus used for in vitro dissolution testing according to pharmacopeial standards, including the rotating basket, paddle, reciprocating cylinder, flow through cell, paddle over disk, rotating cylinder, and reciprocating disk methods. Each apparatus has distinct advantages and disadvantages for testing different drug products and dosage forms.
An in-vitro in-vivo correlation (IVIVC) has been defined by the U.S. Food and Drug Administration (FDA) as "a predictive mathematical model describing the relationship between an in-vitro property of a dosage form and an in-vivo response".
An in-vitro in-vivo correlation (IVIVC) has been defined by the U.S. Food and Drug Administration (FDA) as "a predictive mathematical model describing the relationship between an in-vitro property of a dosage form and an in-vivo response".
FORMULATION FACTORS EFFECTING BIOAVAILABILITY OF DRUGSN Anusha
Bioavailability means the rate and extent to which the active ingredient is absorbed from a drug product and becomes available at the site of action.
When the drug is given orally, only part of the administered dose appears in the plasma.
By plotting plasma concentrations of the drug versus time, one can measure the area under the curve (AUC).
This curve reflects the extent of absorption of the drug.
Physics of Tablet compression is very useful during study of the tablet. It contains the mechanism of tablet compression. It also contains the process of tablet compression.
1. Measurement of Bioavailability:
Direct and indirect methods may be used to assess drug bioavailability. The in-vivo bioavailability of a drug product is demonstrated by the rate and extent of drug absorption, as determined by comparison of measured parameters, e.g., concentration of the active drug ingredient in the blood, cumulative urinary excretion rates, or pharmacological effects.
For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
The design of the bioavailability study depends on the objectives of the study, the ability to analyze the drug (and metabolites) in biological fluids, the pharmacodynamics of the drug substance, the route of drug administration, and the nature of the drug product.
Pharmacokinetic and/or pharmacodynamic parameters as well as clinical observations and in-vitro studies may be used to determine drug bioavailability from a drug product.
1.1. Pharmacokinetic methods:
These are very widely used and based upon the assumption that the pharmacokinetic profile reflects the therapeutic effectiveness of a drug. Thus these are indirect methods. The two major pharmacokinetic methods are:
The major pharmacokinetic methods are:
Plasma / blood level time profile.
o Time for peak plasma (blood) concentration (t max)
o Peak plasma drug concentration (Cmax)
o Area under the plasma drug concentration–time curve (AUC)
Urinary excretion studies.
o Cumulative amount of drug excreted in the urine (Du)
o Rate of drug excretion in the urine (dDu/dt)
o Time for maximum urinary excretion (t)
C. Other biological fluids
1.2. Pharmacodynamic methods:
IT involves direct measurement of drug effect on a (patho) physiological process as a function of time. Disadvantages of it may be high variability, difficult to measure, limited choices, less reliable, more subjective, drug response influenced by several physiological & environmental factors.
They involve determination of bioavailability from:
Acute pharmacological response.
Therapeutic response.
1.3. In-vitro dissolution studies
Closed compartment apparatus
Open compartment apparatus
Dialysis systems.
1.4. Clinical observations
Well-controlled clinical trials
Rate limiting steps in drug absorption [autosaved]Nagaraju Ravouru
Rate limiting steps in drug absorption 1.Disintegration time
2.Dissolution and solubility
3.Physical and chemical nature of active drug substance
4.Nature of excipients
5.Method of granulation
6.Dissolution test conditions
7.Gastric emptying
Basic Approach to Dissolution Method Development – Challenges and Regulatory ...Dr. Harshal Pawar
This presentation explains the theoretical as well as practical aspects of dissolution. It provides a systematic and scientific path for development of dissolution method for a new pharmaceutical product.
FORMULATION FACTORS EFFECTING BIOAVAILABILITY OF DRUGSN Anusha
Bioavailability means the rate and extent to which the active ingredient is absorbed from a drug product and becomes available at the site of action.
When the drug is given orally, only part of the administered dose appears in the plasma.
By plotting plasma concentrations of the drug versus time, one can measure the area under the curve (AUC).
This curve reflects the extent of absorption of the drug.
Physics of Tablet compression is very useful during study of the tablet. It contains the mechanism of tablet compression. It also contains the process of tablet compression.
1. Measurement of Bioavailability:
Direct and indirect methods may be used to assess drug bioavailability. The in-vivo bioavailability of a drug product is demonstrated by the rate and extent of drug absorption, as determined by comparison of measured parameters, e.g., concentration of the active drug ingredient in the blood, cumulative urinary excretion rates, or pharmacological effects.
For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
The design of the bioavailability study depends on the objectives of the study, the ability to analyze the drug (and metabolites) in biological fluids, the pharmacodynamics of the drug substance, the route of drug administration, and the nature of the drug product.
Pharmacokinetic and/or pharmacodynamic parameters as well as clinical observations and in-vitro studies may be used to determine drug bioavailability from a drug product.
1.1. Pharmacokinetic methods:
These are very widely used and based upon the assumption that the pharmacokinetic profile reflects the therapeutic effectiveness of a drug. Thus these are indirect methods. The two major pharmacokinetic methods are:
The major pharmacokinetic methods are:
Plasma / blood level time profile.
o Time for peak plasma (blood) concentration (t max)
o Peak plasma drug concentration (Cmax)
o Area under the plasma drug concentration–time curve (AUC)
Urinary excretion studies.
o Cumulative amount of drug excreted in the urine (Du)
o Rate of drug excretion in the urine (dDu/dt)
o Time for maximum urinary excretion (t)
C. Other biological fluids
1.2. Pharmacodynamic methods:
IT involves direct measurement of drug effect on a (patho) physiological process as a function of time. Disadvantages of it may be high variability, difficult to measure, limited choices, less reliable, more subjective, drug response influenced by several physiological & environmental factors.
They involve determination of bioavailability from:
Acute pharmacological response.
Therapeutic response.
1.3. In-vitro dissolution studies
Closed compartment apparatus
Open compartment apparatus
Dialysis systems.
1.4. Clinical observations
Well-controlled clinical trials
Rate limiting steps in drug absorption [autosaved]Nagaraju Ravouru
Rate limiting steps in drug absorption 1.Disintegration time
2.Dissolution and solubility
3.Physical and chemical nature of active drug substance
4.Nature of excipients
5.Method of granulation
6.Dissolution test conditions
7.Gastric emptying
Basic Approach to Dissolution Method Development – Challenges and Regulatory ...Dr. Harshal Pawar
This presentation explains the theoretical as well as practical aspects of dissolution. It provides a systematic and scientific path for development of dissolution method for a new pharmaceutical product.
Dissolution : Official and Non official methods, Alternative methods of dissolution testing and transport models, Drug release testing, Invitro drug release testing
Dissolution is a process in which a solid substance solubilizes in a given solvent.
Method for dissolution are-
1. Beaker methods
2. Open flow through compartment system
3.Dialysis concept
Here is all information about Invitro dissolution of drug by various Apparatus as per USP. It includes 7 Official and 3 Unofficial methods.in official method maintain condition in apparatus same as gastric fluid Example.Temperture, PH , Rpm( like Peristaltic movement ), Dissolution media.
Dissolution as one of the most important aspects of Pharmaceutical dosage form showing the correlation between the in-vitro & in-vivo availability. Importance of dissolution, comparison with Disintegration, Sampling point, acceptance criteria as per Pharmacopoeias.
Similar to In vitro dissolution testing methods (20)
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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,
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5th edition of the Diagnostic and Statistical Manual of Mental Disorders
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disorder called alcohol use disorder (AUD), with mild, moderate,
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AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
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effects (tolerance, withdrawal). This chapter presents an overview
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comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
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Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
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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:
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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
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
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Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
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O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
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www.agostodourado.com
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
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1. In vitro Dissolution
Testing Methods
P.N.Mallikarjun
Associate Professor,
Vignan Institute of Pharmaceutical Technology
Duvvada,Visakhapatnam.A.P.
2. Definition-
Dissolution: is a process in which a solid
substance solubilizes in a given solvent i.e. mass
transfer from the solid surface to the liquid
phase.
Dissolution Rate: is the amount of drug substance
that goes in solution per unit time under
standardized conditions of liquid/solid interface,
temperature and solvent composition.
3. SOLUBILITY DISSOLUTION RATE
Absolute solubility is defined
as the maximum amount of
solute dissolved in a given
solvent under standard
conditions of temperature ,
pressure and pH.
Dissolution rate is defined
as the amount of solid
substance that goes into
solution per unit time
under standard
conditions of temperature,
pH, solvent composition
and constant solid surface
area.
It is a static process. It is a dynamic process.
4. It is a system to differentiate the drugs on the basis of their solubility
and permeability.
The drug substances are classified as:
Class I - High permeability, High solubility. Ex:- Metoprolol.
Class II - High permeability, Low solubility. Ex:- Ezetimibe.
Class III - Low permeability, High solubility. Ex:- Cimetidine.
Class IV-Low permeability,Low solubility.Ex:- Hydrochlorothiazide
5. Dissolution and drug release tests are in-vitro tests that measure the
rate and extent of dissolution or release of the drug substance from
a drug product, usually aq.medium under specified conditions.
It is an important QC procedure for the drug product and linked to
product performance in-vivo.
NEED FOR DISSOLUTION TESTING:
Evaluation of bioavailability.
Batch to batch drug release uniformity.
Development of more efficacious and therapeutically optical
dosage forms.
Ensures quality and stability of the product.
Product development, quality control, research and application.
7. 1. The initial step involves the breaking of a tablet into
granules (disintegration).
2. Some times, these granules further break to yield fine
particles (deaggregation)
3. The next step involves the releasing of the drug into solution
(dissolution)
4. Absorption.
Essential steps in Dissolution of a Tablet
8. FACTORS RELATING TO THE DISSOLUTION APPARATUS
Design of the container
Size of the container
Shape of the container
Nature of agitation
Speed of agitation
Performance precision of the apparatus
FACTORS RELATING TO THE DISSOLUTION FLUID
1.Volume
2.Temperature
3.Deaeration of dissolution medium
4. pH
5.Composition
9. IN VITRO DISSOLUTION METHODS
Various classification of Dissolution methods are there
Based on type of system
1.Basic methods
Based on sink condition
2.Sink and non sink methods
3.Official / Compendial methods and
4.Unofficial/Alternative methods
11. 2.NON SINK SINK
1) NATURAL CONVECTION
a) Klein solvmeter method
b)
c)
Nelson hanging pellet method
Levy static disk method
2) FORCED CONVECTION (NS)
a) Tumbling method
b) Levy or Beaker method
c) Rotating disk method
d) Particle size method
e) USP Rotating basket apparatus
f) USP Paddle apparatus
a) Wurster pollis adsorption
b)
c)
d)
Partition method
Dialysis method
Rotating disk apparatus
3) FORCED
CONVECTION(SINK)
4) CONTINOUS FLOW:
a) Pernarowski method
b) Langenbucher method
c) Baun and Walker
d) Tingstad and Reigelman
e) Modified column apparatus
f) Takenaka method
12. 3.COMPENDIAL/OFFICIAL METHODS
Compendial or Official tests are standardised methods
and specification testing for generic pharmaceutical
material and finished products.
They are utilised as basic requirements needed for
most regulatory submission around the world
13. I.P U.S.P B.P E.P
TYPE 1 Paddle
apparatus
Basket
apparatus
Basket
apparatus
Basket
apparatus
TYPE 2 Basket
apparatus
Paddle
apparatus
Paddle
apparatus
Paddle
apparatus
TYPE 3 Reciprocating
cylinder
Flow through
cell
Flow through
cell
TYPE 4 Flow through
cell
TYPE 5 Paddleover
disk
TYPE 6 Rotating
cylinder
TYPE 7 Reciprocating
disk
14. USP.APPARATUS DESCRIPTION ROT.SPEED DOSAGE FORM
TYPE 1 Basket apparatus 50-120 rpm IDR,DR,ER
TYPE 2 Paddle apparatus 25-50 rpm IDR,DR,ER
TYPE 3 Reciprocating
cylinder
6-35 rpm IDR,ER
TYPE 4 Flow through cell N/A ER,Poorlysoluble
API
TYPE 5 Paddle over disk 25-50 rpm TRANSDERMAL
TYPE 6 Rotating cylinder N/A TRANSDERMAL
TYPE 7 Reciprocating
holder
30 rpm ER
16. METHOD(Rotating basket):
Place the stated volume of the dissolution medium(±1 %) in the
vessel and equilibrate dissolution medium to 37±0.5°C.
Place 1 tablet or capsule in the apparatus ,taking care to exclude air
bubbles from the surface of the dosage form unit and immediately
operate the apparatus at the rate specified(100rpm).
Withdraw a specimen from a zone midway between the surface of the
dissolution medium and the top of the rotating basket,not less than
1cm from the vessel wall at each times stated.
Replace the aliquots withdrawn for analysis with equal volumes of
fresh dissolution medium at 37°C.
Keep the vessel covered for the duration of the test and verify the
temperature of the mixture under test at suitable times.
Perform the analysis as directed in individual monograph and repeat
the test with additional dosage form units.
18. Advantages
Full pH change during the test
Can be easily automated
which is important for routine
investigations.
Disadvantages
Basket screen is clogged with
gummy particles.
Hydrodynamic „dead zone“
under the basket
Degassing is particularly
important
Mesh gets corroded by HCl solution.
19. APPARATUS-2 (ROTATING PADDLE)
DESIGN:
Vessel: -Same as basket apparatus
Shaft: -The blade passes through the shaft so that the bottom of the
blade fuses with bottom of the shaft.
Stirring elements: -Made of tefflon
For laboratory purpose
-Stainless steel 316
Water-bath: -Maintains at 37±0.5°C
Sinkers : -Platinum wire used to prevent
tablet/capsule from floating
20. METHOD
It consists of a special coated paddle formed from a blade and a
shaft that minimizes turbulence due to stirring.
The coated material is inert.
The paddle is attached vertically to a variable -speed motor that
rotates at a controlled speed.
The tablet or capsule is placed into a round-bottom dissolution
flask and the apparatus is housed in a constant temperature water
bath maintained at 37°C.
Most common operating speeds are 50rpm for solid oral dosage
forms and 25 rpm for suspensions.
A sinker ,such as few turns of platinum wire may be used to
prevent a capsule or tablet from floating
Used for film coated tablets that stick to the vessel walls or to
help to position tablet/capsule under the paddle.
21. Advantages
Easy to use
Robust
pH change possible
Can be easily automated which is important for
routine investigations
Disadvantages
pH/media change is often difficult
Hydrodynamics are complex, they vary with site of the dosage
form in the vessel (sticking,floating) and therefore may
significantly affect drug dissolution
Sinkers for floating dosage forms
25. APPARATUS-3(RECIPROCATING CYLINDER)
DESIGN:
Vessel: -Set of cylindrical flat bottom glass vessels
-Set of reciprocating cylinders
-stainless steel fittings(SS316) and
screens made of nonsorbing or
non-reactive materials.
Agitation type: -Reciprocating
-5-35 rpm
Volume of dissolution medium:-200-250ml
Water bath:- Maintain at 37±0.5°C
USE: Tablets, beads, controlled and
extended release formulations
26. METHOD(Reciprocating cylinder):
Place the stated volume of dissolution medium in each vessel of the
apparatus, assemble the apparatus, equilibrate the dissolution
medium to 37±0.5 and remove the thermometer
Place one dosage form unit in each of the cylinders taking care to
exclude the air bubbles from the surface of each dosage unit and
immediately operate the apparatus as specified in the monograph.
During the upward and downward stroke, the reciprocating cylinder
moves through a total distance of 9.9 to 10.1cm.
Within the time interval specified raise the cylinders and withdraw a
portion of the solution under test from a zone midway between the
surface of the dissolution medium and bottom of each vessel.
27. Advantages
Easy to change the pH
pH-profiles
Hydrodynamics can be
directly influenced by
varying the dip rate
Disadvantages
Small volume (max. 250 ml)
Little experience
Limited data
28.
29. APPARATUS-4 (FLOW THROUGH CELL)
DESIGN:
Reservoir : -For dissolution medium
Pump : -Forces dissolution medium through cell
-Holding a sample
-Flow rate 10-100ml/min or 240-960ml/h
-Laminar flow is maintained
-Peristaltic/centrifugal pumps are not recommended
Water bath:- Maintain at 37±0.5°C
USE:
Low solubility drugs ,micro particulates ,implants, suppositories
controlled release formulations
30. METHOD(Flow through cell):
The flow through cell is transparent & inert mountedvertically
with filters.
Standard cell diameters are 12 & 22.6 mm.
The bottom cone usually filled with glass beads of 1 mm
diameter.
Tablet holder used for positioning special dosage form e.g. inlay
tablets.
Place the glass beads into the cell as specified in the monograph.
Place one dosage unit on top of the beads or on a wire carrier.
Assemble the filter head and fix the parts together by means of a
suitable clamping device.
Introduce by the pump of the dissolution medium warmed to
37±0.5 through the bottom of the cell to obtain the flow rate
specified and measured with an accuracy of 5%.
Collect the eluate by fractions at each of the times stated.
31. d.
Advantages
easy to change media pH
pH-profile possible
Sink conditions maintaine
different modes
a) open system
b) closed system
Disadvantages
Deaeration necessary
high volumes of media
labor intensive
32. Cell types:
Tablets 22.6 mm Powders / Granules ImplantsTablets 12 mm
Suppositories /
Soft
gelatincapsules
35. APPARATUS-5(PADDLE-OVER-DISK)
DESIGN:
Vessel
Shaft
Stirring elements- rotating speed 25-50 rpm
Sample holder:-disk assembly that hold a product in such a way
that release surface is parallel with paddle
-Paddle is directly attached over disk assembly
-Samples are drawn between surface off the medium
and top of the paddle blade
Volume:900ml
Temperature:32°C
36. USE: Transdermal patches, ointments, floaters , emulsions.
Modification: Disk design and volume
Advantages:
Easy to handle
Sink conditions are maintained.
Membrane effect is minimum.
i.e. drug is placed on a disc at the bottom.
Disadvantages:
Disk assembly restricts the patch size
Borosilicate glass
17 mesh is standard(others available)
Accommodates patches up to 90mm.
37. This method is used for testing the release of drugs from
transdermal products.
The apparatus consists of a sample holder or disc assembly that
holds the product.
The entire preparation is placed in a dissolution flask filledwith
specified medium maintained at 32ºC.
The paddle is placed directly over the disc assembly.
The disk assembly holds the system flat and is positioned such that
release surface is placed parallel with the bottom of the paddle
blade. Vessel is covered to minimize evaporation during test.
Samples are drawn midway between the surface of dissolution
medium and the top of the paddle blade at specified times.
38. APPARATUS-6( CYLINDER)
DESIGN:
Vessel:- In place of basket, cylinder is used.
Shaft :-Stainless steel 316
Sample :- Mounted to cuprophan (inner porous cellulosic material)
an entire system adheres to cylinder.
- Dosage unit is placed in cylinder and release from side out.
Water-bath: maintained at 32±0.5°C
USE:
Transdermal patches cannot be cut into small size.
Solid dosage forms, pH profile , small volumes
39. METHOD( cylinder):
Use the assembly from apparatus 1 except to replace the basket and
shaft with a stainless steel cylinder stirring element.
The temperature is maintained at 32±0.5°C.
The dosage unit is placed on the cylinder with side out .
The dosage unit is placed to the exterior of the cylinder such that
long axis of the system fits around the circumference of the cylinder
and removes trapped air bubbles.
Place the cylinder in the apparatus and immediately rotate at the rate
specified in the individual monograph.
Samples are drawn midway between the surface of the dissolution
medium and the top of the rotating cylinder for analysis.
40. cylinder:
Advantages: -Equipment (apparatus 1)available with the
manufacturers can be used with modification as apparatus 6.
Disadvantages:-Large volume of medium is required.
-Drug gets diluted & causes difficulties in analysis
-Difficult to clean the cylinder.
41. APPARATUS-7(RECIPROCATING-DISK)
DESIGN:
Vessel:-Flat bottomed cylindrical vessel
-Volume of dissolution medium
Shaft :
Sample : -Placed on disk shaped holders
Agitation :-Reciprocation
-Reciprocating frequency 30
cycle/minute
Water-bath:-Maintain at 32±0.5°C
USE:
Transdermal patches
shaft
disk
dissolution medium
constant temp
water bath
42. METHOD(Reciprocating disk):
The assembly consists of a set of volumetrically calibrated solution
containers made of glass or suitable inert material, a motor , a drive
assembly used to reciprocate the system vertically.
The samples are placed on the disk shaped holders using cuprophan
supports
The test is carried out at 32°C.
The reciprocating frequency is 30cycles/min.
Advantages:-Convenient method for selecting the volume of the
medium.
-sink conditions can be maintained.
-more sensitivity
Disadvantages: -Investment is high because the design is totally
different from standard equipment already available in industry.
43.
44.
45. 4.ALTERNATIVE METHODS
1.ROTATING/STATIC DISK METHOD
Developed by late Eino Nelson and described by Levy and Sahli.
In this method ,the drug is compressed in a non-disintegrating disc
without excipients.
The disc is mounted in a holder so that only one face of the disc is
exposed to the dissolution medium.
The holder and disc are immersed in medium and held in a fixed
position as in static disc method and rotated at a given speed in
rotating disc method.
Samples are collected at predetermined times.
Surface area of the drug through which dissolution
occurs is kept constant –intrinsic dissolution rate.
46. 2.BEAKER METHOD:
Reported by Levy and Hayes(1960).
Dissolution medium, 250ml of 0.1N HCl at 37°C placed
in a 400ml beaker.
Agitation by three blade polyethylene stirrer,5cm diameterand
rotates at 60 rpm.
Stirrer immersed to a depth of 2.7 cm in medium and in the center.
Tablets are placed in a beaker and test was carried out.
Samples are removed and assayed for the content.
3.FLASK STIRRER METHOD
Developed by Poole(1969).It includes RBF and a stirring element
similar to that of beaker method.
RBF used to avoid the formation of moulds of particles in different
positions on the flat bottom of a beaker.
47. 4.PERISTALSIS METHOD:
To stimulate hydrodynamic condition of GIT tract in an in-vitro
dissolution device.
It consists of rigid plastic cylindrical tubing fitted with septumand
rubber stopper at both ends.
Dissolution chamber consists of a space between septum and lower
stopper.
Dissolution medium is pumped with peristaltic action through the
dosage form.
5.ROTATING BOTTLE METHOD:
It consists of rotating rack to hold sample drug products in bottles
and they are capped tightly & rotated in 37°C temperaturebath.
Sample are decanted through a 40 mesh screen and residue are
assayed.
48. 6.DIALYSIS METHOD:
Cell consist of 32mm inflated membrane.
Plugged at the lower end by tight fitting cylindrical perspex box.
Upper end of the tube held by thin perspex ring inserted into the
tube and secured by an elastic band.
The cell suspended , from the arm of the tablet disintegration
apparatus and containing the dosage form in 150ml of distilled
water at 37°C.
The cell is raised or lowered 30times a min, into 150ml of distilled
water at same temperature.
Agitation by slight flexing and stretching of the dialysis membrane
as it enters and leaves the bath. Rotated at 60rpm.
.
49.
50. 7.DIFFUSION CELL
Static or flow through diffusion cells are used to characterize in-
vitro drug release and drug permeation kinetics from a topical drug
product eg: Ointment, cream or transdermal drug product.
The Franz diffusion cell is static diffusion system used to
characterize drug permeation through skin model.
The skin is mounted on the Franz diffusion cell and the drug
product is placed on the skin surface.
The drug permeates across the skin into a receptor fluid
compartment that may be sampled at various times.
This system is used for selection of appropriate formulation that
has optimum drug delivery.
53. Dissolution Testing methods For some
Drug Delivery Systems
A number of methods are used to conduct in-vitro evaluation
of controlled ocular drug delivery systems.
(a) Bottle method
In this method, dosage forms are placed in the culture
bottles containing phosphate buffer at pH 7.4.
The culture bottles are shaken in a thermostatic water bath
at 37°C.A sample of medium is taken out at appropriate
intervals and analyzed for drug contents.
40
Ocular Drug Delivery Systems
54. 41
b) Modified rotating basket method
In this method, dosage form is placed in a basket
assembly connected to a stirrer.
The assembly is lowered into a jacketed beaker
containing buffer medium.
The temperature of system is maintained at 37°C. A
sample of medium is taken out at appropriate time
55. Beaker method
The dosage form in this method is made to adhere at the bottom of the
beaker containing the medium and stirred uniformly using over head
stirrer.
Volume of the medium used for the studies varies from 50-500 ml and
the stirrer speed form 60-300 rpm.
Modified Keshary Chien Cell
A specialized apparatus was designed in the laboratory.
It comprised of a Keshary Chien cell containing distilled water (50ml) at
370 c as dissolution medium.
TMDDS (Trans Membrane Drug Delivery System) was placed in a glass
tube fitted with a 10# sieve at the bottom which reciprocated in the
medium at 30 strokes per min.
Samples are removed at appropriate time intervals and analyzed for
drug content.
Particulate Drug Delivery systems(MICROSPHERES)
57. DISSOLUTION ACCEPTANCE CRITERIA
STAGE Acceptance criteria
S1
No. of Dosage units
tested
6 No Dosage unit is
less then Q+5%
S2 6 Average Of 12
dosage units (S1+S2)
and no dosage unit is
S3 12(6+6+12=24)
less then Q-15%
Average of 24
dosage units >- And
not more than two
dosage units are less
than Q-15% and No
dosage unit is less46
than Q-25%
58. COMPARISON OF DISSOLUTION PROFILE
Difference factor (f1 Value)-
Define as calculate the % Difference between 2
curves at each time point and is a measurement of
the relative error between 2 curves.
f1= {[Σ t=1n |Rt-Tt|] / [Σ t=1n Rt]} ×100.
Values range from 0 to 15
47
59. Similarity Factor (f2 value)-define as
measurement of similarity in % Dissolution
between two curve.
Where Rtand Tt= cumulative % dissolved
for reference and test
Values range from 50(similar) to 100(Identical)
60. CONCLUSION:
By studying various factors influencing the rate of dissolution, we
can optimize type of dissolution method and the different
properties of the formulation.
To predict drug product performance it is essential to select
suitable dissolution method.
By conducting dissolution studies we can know the batch to batch
reproducibility.
In vitro Dissolution profile is used to estimate the In vivo behaviour of
the drug product.
The best available tool to atleast quantitatively assure about the
biological availability of drug from its formulation is its invitro
dissolution.
61. REFERENCES
D.M.Brahmankar, Biopharmaceutics and
pharmacokinetics- A Treatise; Vallabh Prakashan,
page no. 20–31.
Leon Shargel, Applied Biopharmaceutics &
Pharmacokinetics; 4thedition, page no. 132-136.
The Indian Pharmacist, February 2008,Page
no.10-12
62. United States Pharmacopoeia – 24, page no.: 1942
– 1951.
“Current perspectives in dissolution testing of
conventional and novel dosage forms”, by Shirazad
Azarmi, Wilson Roa, Raimar Lobenberg, Int. jou.
Of pharmaceutics 328(2007)12 – 21.
Alton’s pharmaceutics “ The design and
manufacturing of medicines”, by Michael E. Alton,
page no.: 21 – 22.
