It is defined as “the predictive mathematical model that describes the relationship between in vitro property (such as rate & extent of dissolution) of a dosage form and in vivo response (such as plasma drug concentration or amount of drug absorbed)”.
It is defined as “the predictive mathematical model that describes the relationship between in vitro property (such as rate & extent of dissolution) of a dosage form and in vivo response (such as plasma drug concentration or amount of drug absorbed)”.
Biopharmaceutics Classification System (BCS) & Waiver of BioequivalenceAjaz Hussain
Graduate Lecture at the University of Maryland (August 2012). Learning Objective: Identify and explain how future regulatory applications of BCS may be realized in the context of ‘Quality by Design’.
Updated July 2013.
I wish to thank all the viewers of my Slideshare presentation of the development and application of the US FDA’s BCS Guidance 2000. Over 11K views have been recorded making this the 2nd highest viewed presentation. FDA is expected to issue a revised BCS draft guidance in the next few weeks. Expected changes include the following:
1. Addition of ‘very rapid’ dissolution criteria (>85% in 15 minutes)
2. Change permeability boundary from 90% to 85%
3. Change the pH solubility range from 1 – 7.5 to 1 – 6.8
4. Possibility of changing paddle speed from 50 to 75 rpm.
5. Additional topics / clarification on FDCs (Fixed Dose Combinations), ODTs (Orally Disintegrating Tablets), MR (Modified Release) products.
6. Update the list of model drugs.
7. Strengthen GI stability requirement.
United State Pharmacopoeia (USP)The establishment of a rational relationship between a biological property, or a parameter derived from a biological property produced by a dosage form, and a physicochemical property or characteristic of the same dosage form.
Food and Drug Administration (FDA) definitionIVIVC is a predictive mathematical model describing the relationship between an in vitro property of a dosage form and a relevant in vivo response. Generally, the in vitro property is the rate or extent of drug dissolution or release while the in vivo response is the plasma drug concentration or amount of drug absorbed.
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".
A review on waiving in vivo bioequivalence tests or Biovaiwer, with a case review on the biowaiver monograph on Ibuprofen by H. POTTHAST, J.B. DRESSMAN, H.E. JUNGINGER, K.K. MIDHA, H. OESER, V.P. SHAH,
H. VOGELPOEL, D.M. BARENDS
in J Pharm Sci 94:2121–2131, 2005
Explaining different approaches to waive different BCS class medicines based on their solubility and permeability, as is described by FDA and WHO
BCS Guideline for solubility and Dissolution.pptxImdad H. Mukeri
Briefly explanation of The Biopharmaceutics Classification System (BCS) of drug substance
and its solubility in the pH range of 1–7.5, absorption or intestinal membrane permeability
Biopharmaceutics Classification System (BCS) & Waiver of BioequivalenceAjaz Hussain
Graduate Lecture at the University of Maryland (August 2012). Learning Objective: Identify and explain how future regulatory applications of BCS may be realized in the context of ‘Quality by Design’.
Updated July 2013.
I wish to thank all the viewers of my Slideshare presentation of the development and application of the US FDA’s BCS Guidance 2000. Over 11K views have been recorded making this the 2nd highest viewed presentation. FDA is expected to issue a revised BCS draft guidance in the next few weeks. Expected changes include the following:
1. Addition of ‘very rapid’ dissolution criteria (>85% in 15 minutes)
2. Change permeability boundary from 90% to 85%
3. Change the pH solubility range from 1 – 7.5 to 1 – 6.8
4. Possibility of changing paddle speed from 50 to 75 rpm.
5. Additional topics / clarification on FDCs (Fixed Dose Combinations), ODTs (Orally Disintegrating Tablets), MR (Modified Release) products.
6. Update the list of model drugs.
7. Strengthen GI stability requirement.
United State Pharmacopoeia (USP)The establishment of a rational relationship between a biological property, or a parameter derived from a biological property produced by a dosage form, and a physicochemical property or characteristic of the same dosage form.
Food and Drug Administration (FDA) definitionIVIVC is a predictive mathematical model describing the relationship between an in vitro property of a dosage form and a relevant in vivo response. Generally, the in vitro property is the rate or extent of drug dissolution or release while the in vivo response is the plasma drug concentration or amount of drug absorbed.
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".
A review on waiving in vivo bioequivalence tests or Biovaiwer, with a case review on the biowaiver monograph on Ibuprofen by H. POTTHAST, J.B. DRESSMAN, H.E. JUNGINGER, K.K. MIDHA, H. OESER, V.P. SHAH,
H. VOGELPOEL, D.M. BARENDS
in J Pharm Sci 94:2121–2131, 2005
Explaining different approaches to waive different BCS class medicines based on their solubility and permeability, as is described by FDA and WHO
BCS Guideline for solubility and Dissolution.pptxImdad H. Mukeri
Briefly explanation of The Biopharmaceutics Classification System (BCS) of drug substance
and its solubility in the pH range of 1–7.5, absorption or intestinal membrane permeability
2.Sagar Goda Biological classification system (BCS); its significance on diss...Sagar Goda
This presentation provides a detailed information about Biopharmaceutics classification system(BCS) and its significance on dissolution study as well as its application in dosage form development.
Pharmacy presentation about BCS classification its criteria.Biowaiever and its conditions .permeability studies in vivo,invitro,in situ.mpharmacy b pharmacy pharmaceutics
biopharmaceuticals classification system and biowaiverRavish Yadav
The all the content in this profile is completed by the teachers, students as well as other health care peoples.
thank you, all the respected peoples, for giving the information to complete this presentation.
this information is free to use by anyone.
The study of absorption, distibution,metabolism,excretio of drug and their relationship to pharmacological response. In simple word ; what the body dose to the drug. Linear pharmacokinetics.In the pharmacokinetic parameter for drug would not change when difference dose or multiple dose of drug is given. Non linear pharmcokinetics-if any deviation cause linear pharmacokinetics called non linear, mixed, capacity – limited kinetics.
Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a prescription, from a healthcare professional, as compared to prescription drugs , which may be sold only to consumers possessing a valid prescription.
OTC drugs are selected by a regulatory agency to ensure that they are ingredients that are safe and effective when used without a physician's care.
To develop the skills of making the new marketing strategies for a product and to ensure the appropriate selling price of drug in the market and to distinguish the difference in the price of same drug from different brands, and to compare them with the DPCO prices.
A sale is the exchange of a commodity or money as the price of a good or a service. Sales is activity related to selling or the amount of sold goods or services in a given time period.
Antibiotics are powerful medicines that fight bacterial infections.
Antibiotics are effective against all microbes except viruses.
The major problem associated with use of antibiotics is Antibiotic Resistance. Resistance occurs when bacteria change in some way that reduces or eliminates the effectiveness of drugs, chemicals, or other agents designed to cure or prevent infections. The bacteria survive and continue to multiply causing more harm.
Antimalarial drugs are used to prevent and cure malaria.
Artemisinins are rapid acting blood schizonticidal antimalarials against chloroquinine resistant malaria.
Herbs have been used for centuries to treat a variety of medical illnesses. Many of the uses have come from folklore or cultural traditions.
Herbal teas can be a good alternative or addition to pharmaceuticals for some patients .
There are so many ways that our immune systems can be overwhelmed ... it's in our air, our water, our food, our workplace, our stress. This blend of organic and wild herbs is not only helpful but comforting, strengthening and tasty.
There are many antibiotics, which are safe as well as effective in a specified condition but are less effective in other condition. e.g. Many physicians prescribe azithromycin for the treatment of urinary tract infections but it is required in very high dose, on the other hand other antibiotics are proved to be effective in a comparative lower dose for treatment of same condition
Marketing and sales differ greatly, but have the same goal. Selling is the final stage in Marketing, which also includes Pricing, Promotion, Place and Product. A marketing department in an organization has the goals of increasing the desirability and value to the customer and increasing the number and engagement of interactions between potential customers and the organization.
A drug can be given three possible operational definitions:
A chemical substance that affects the processes of the body or mind;
Any chemical compound used on or administered to humans or animals as an aid in the diagnosis, treatment or prevention of disease, or other abnormal condition, for the relief of pain or suffering, or to control or improve any physiologic or pathologic state.
A substance used recreationally for its effects on the central nervous system.
In the present era, the pharmaceutical industry is growing enormously and number of drugs are available for treatment of a specific disease or condition.
Determination of rationality of the prescribed drugs in the specific condition.
Determination of rationality of the dosing frequency.
It has been scientifically proved that antibiotics prescribed in pediatric patients may lead to severe consequences, as their intestinal flora is not well developed to mark the effect of drug.
There are many antibiotics, which are safe as well as effective in adults but may cause serious adverse effects in pediatrics. E.G. Ofloxacin is an antibiotic used to treat numerous infections in children but is having lesser safety in children, still it is among one of the highly used drugs in pediatrics in india.
A tablet press is a mechanical device that compresses powder into tablets of uniform size and weight. A press can be used to manufacture tablets of a wide variety of materials, including pharmaceuticals, illicit drugs such as MDMA, cleaning products, and cosmetics. To form a tablet, the granulated material must be metered into a cavity formed by two punches and a die, and then the punches must be pressed together with great force to fuse the material together.[1]
A tablet is formed by the combined pressing action of two punches and a die. In the first step of a typical operation, the bottom punch is lowered in the die creating a cavity into which the granulated feedstock is fed. The exact depth of the lower punch can be precisely controlled to meter the amount of powder that fills the cavity. The excess is scraped from the top of the die, and the lower punch is drawn down and temporarily covered to prevent spillage. Then, the upper punch is brought down into contact with the powder as the cover is removed. The force of compression is delivered by high pressure compression rolls which fuse the granulated material together into a hard tablet. After compression, the lower punch is raised to eject the tablet
The use of herbal drugs for the prevention and treatment of various health ailments has been in practice from time immemorial. Generally it is believed that the risk associated with herbal drugs is very less, but reports on serious reactions are indicating to the need for development of effective marker systems for isolation and identification of the individual components.Standards for herbal drugs are being developed worldwide but as yet there is no common consensus as to how these should be adopted. Standardization, stability and quality control for herbal drugs are feasible, but difficult to accomplish. Further, the regulation of these drugs is not uniform across countries. There are variations in the methods used across medicine systems and countries in achieving stability and quality control. The present study attempts to identify the evolution of technical standards in manufacturing and the regulatory guideline development for commercialization of herbal drugs.
Keywords: survey was conducted to obtain primary data on challenges faced during production, commercialization, and marketing approval for traditional or herbal drugs in India and abroad. Responses were collected from companies by email, telephone, and in-person interviews and were analyzed to draw appropriate conclusions.The use of plants, parts of plants and isolated phytochemicals for the prevention and treatment of various health ailments has been in practice from time immemorial. It is estimated that about 25% of the drugs prescribed worldwide are derived from plants and 121 such active compounds are in use. Of the total 252 drugs in WHO's essential medicine list, 11% is exclusively of plant origin The use of plants, parts of plants and isolated phytochemicals for the prevention and treatment of various health ailments has been in practice from time immemorial. It is estimated that about 25% of the drugs prescribed worldwide are derived from plants and 121 such active compounds are in use. Of the total 252 drugs in WHO's essential medicine list, 11% is exclusively of plant origin .
Jatin an overview of sunscreen regulations in the worldjatin singla
Various types of traditional medicine (TM) and medical practices referred to as complementary or alternative medicine (CAM), have been increasingly used in both developing and developed countries. One of the major components of the WHO Traditional Medicine Strategy is to promote the integration of TM and CAM into national health care systems where appropriate. Development of national policy and regulations are an essential indicator of the level of integration of such medicine within a national health care system.
The use of medicinal plants is the most common form of traditional medication worldwide. Regulation of herbal medicines is a key means of ensuring safety, efficacy and quality of herbal medicinal products. WHO has been receiving an increasing number of requests from governments for guidance on how to regulate herbal medicines.
During the last four years, many countries have established, or initiated the process of establishing national regulations regarding herbal medicines. WHO has been conducting a global survey on national policy on traditional medicine and on the regulation of herbal medicines; aiming to:
Collect updated and comprehensive information on TM/CAM policies and regulations of herbal medicines
Clarify the current situation, in each country, on the TM/CAM national policies and regulation of herbal medicines, and their major challenges on these particular area
Identify the specific needs on capacity building for TM/CAM policy development including establishment of regulations of herbal medicines, and the type of direct support WHO should provide to Member States
Monitor the impact of the WHO Strategy for Traditional Medicine in relation to present national policy and regulation on TM/CAM/herbal medicines.
validation is a technique of validating the final product either starting from the raw material or within the process, its all types cover the methods of validation and sequence in the product development.
How to Split Bills in the Odoo 17 POS ModuleCeline George
Bills have a main role in point of sale procedure. It will help to track sales, handling payments and giving receipts to customers. Bill splitting also has an important role in POS. For example, If some friends come together for dinner and if they want to divide the bill then it is possible by POS bill splitting. This slide will show how to split bills in odoo 17 POS.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
The Art Pastor's Guide to Sabbath | Steve ThomasonSteve Thomason
What is the purpose of the Sabbath Law in the Torah. It is interesting to compare how the context of the law shifts from Exodus to Deuteronomy. Who gets to rest, and why?
The Indian economy is classified into different sectors to simplify the analysis and understanding of economic activities. For Class 10, it's essential to grasp the sectors of the Indian economy, understand their characteristics, and recognize their importance. This guide will provide detailed notes on the Sectors of the Indian Economy Class 10, using specific long-tail keywords to enhance comprehension.
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Students, digital devices and success - Andreas Schleicher - 27 May 2024..pptxEduSkills OECD
Andreas Schleicher presents at the OECD webinar ‘Digital devices in schools: detrimental distraction or secret to success?’ on 27 May 2024. The presentation was based on findings from PISA 2022 results and the webinar helped launch the PISA in Focus ‘Managing screen time: How to protect and equip students against distraction’ https://www.oecd-ilibrary.org/education/managing-screen-time_7c225af4-en and the OECD Education Policy Perspective ‘Students, digital devices and success’ can be found here - https://oe.cd/il/5yV
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
2. INTRODUCTION
• IVIVC can be used in the development of new pharmaceuticals to reduce
the number of human studies during the formulation development.
• In recent years, the concept and application of the in vitro-in vivo
correlation (IVIVC) for pharmaceutical dosage forms have been a main
focus of attention of pharmaceutical industry, academia, and regulatory
sectors.
• IVIVC could also be employed to establish dissolution specification and to
support and/or validate the use of dissolution methods.
3. DEFINITIONS
• Acc. to FDA:
It is defined as a predictive mathematical model describing
the relationship between an in-vitro property(rate or extent of drug
dissolution or release) of a dosage form and an in vivo response(plasma
drug concentration or amount of drug absorbed.)
• Acc. To USP:
The establishment of the relationship b/w a biological
property, or a parameter derived form a biological property produced
from a dosage form, and a physicochemical property of same dosage
form.
4. CORRELATION LEVELS
• Level A correlation: Highest category of correlation and represent a point
to point relationship b/w in-vitro dissolution rate and in-vivo input rate of
the drug from the dosage form. Percent of drug absorbed may be
calculated by means of model dependent technique such as Wagner-
Nelson Procedure or Loo-Riegelman method or by Model independent
numerical deconvolution.
5. CORRELATION LEVELS(contd.)
• Level B correlation: In this level of correlation, the mean in-
vitro dissolution time(MDT vitro) of the product is compare to
either mean in vivo residence time MRT or in vivo dissolution
time (MDT vivo). It uses all of the in vivo or in vitro data and
not to be considered a point to point correlation.
6. CORRELATION LEVELS(contd.)
• Level C Correlation: In this level one dissolution time point ( t50% , t90%, etc) is
compare to one mean pharmacokinetic parameter such as AUC, tmax or cmax. It is
weakest level of correlation as partial relationship b/w absorption and
dissolution is established and represents a single point correlation and
doesn’t reflect the entire shape of plasma drug conc. curve.
7. CORRELATION LEVELS(contd.)
• Multiple Level Correlation: It relates one or several pharmacokinetic
parameters of interest (cmax, AUC or any other suitable parameters) to the
amount of drug dissolved at several time points of the dissolution profile.
It should be based on at least three dissolution time points covering the
early, middle, and late stage of the dissolution profile.
• Level D Correlation: It is rank order and qualitative analysis and is not
considered useful for regulatory purposes. It is not formal correlation but
serve as an aid in the development of a formulation or processing
procedure.
9. Biopharmaceutics Classification System (BCS)
• The (BCS) has been developed to provide a scientific approach to allow for
the prediction of in vivo pharmacokinetics of oral immediate release (IR)
drug products by classifying drug compounds based on their solubility
related to dose and intestinal permeability in combination with the
dissolution properties of the dosage form.
10. BCS Classification
According to the BCS, drug substances are classified as
follows:
• Class I - High Permeability, High Solubility
• Class II - High Permeability, Low Solubility
• Class III - Low Permeability, High Solubility
• Class IV - Low Permeability, Low Solubility
11. BCS (Contd.)
• The BCS is a scientific framework for classifying drug substances based on
their aqueous solubility and intestinal permeability. When combined with
the dissolution of the drug product, the BCS takes into account three
major factors that govern the rate and extent of drug absorption from IR
solid oral dosage forms: dissolution, solubility, and intestinal permeability.
12. CLASS BOUNDARIES
• A drug substance is considered HIGHLY SOLUBLE when the highest dose
strength is soluble in < 250 ml water over a pH range of 1 to 7.5.
• A drug substance is considered HIGHLY PERMEABLE when the extent of
absorption in humans is determined to be > 90% of an administered dose,
based on mass-balance or in comparison to an intravenous reference
dose.
• A drug product is considered to be RAPIDLY DISSOLVING when > 85% of
the labeled amount of drug substance dissolves within 30 minutes using
USP apparatus I or II in a volume of < 900 ml buffer solutions.
13. The benefits of knowing the BCS category of a compound
• It can save both time and money—if the immediate -release, orally
administered drug meets specific criteria, the FDA will grant a waiver for
expensive and time-consuming bio-equivalence studies.
• The aim of the BCS is to provide a regulatory tool for the replacement of
certain BE studies by conducting accurate in vitro dissolution tests.
• Combined with the dissolution, the BCS takes into account the three
major factors governing bioavailability viz. dissolution, solubility and
permeability.
14. Key Parameters Controlling Drug Absorption
• Absorption number (An) :-
defined as the ratio of the mean residence time to
mean absorption time.
Radius of GI
Residence time in GI
( )
ABS
GI
GI
eff
T
T
T
R
P
An =
=
Effective permeability
Time required for complete absorption
15. Key Parameters Controlling Drug Absorption (contd.)
• Dissolution number (Dn) :-
defined as the ratio of mean residence time to
mean dissolution time.
( )
=
=
DISS
GI
GI
S
T
T
T
C
r
D
Dn
ρ2
3
Diffusivity
5x10-6
cm2
/s
Particle Radius
25 µm
Solubility
mg/mL
Density
1.2 mg/cm3
Residence time in GI
180 min
Time required forcomplete dissolution
16. Key Parameters Controlling Drug Absorption (contd.)
• Dose number (D0) :-
defined as the mass (Dose) divided by the product
of (uptake volume (250 ml) and solubility of drug).
=
S
Water
C
V
D
Do
Highest Dose Unit 250 mL
Solubility
17. Class I
• Class I drugs exhibit a high absorption number and a high
dissolution number. The rate limiting step is drug dissolution.
• If dissolution is very rapid, then gastric emptying rate becomes the
rate determining step.
• e.g. Metoprolol, Diltiazem, Verapamil, Propranolol.
18. Class II
• Class II drugs have a high absorption number but a low dissolution
number. In vivo drug dissolution is then a rate limiting step for
absorption except at a very high dose number. The absorption for
class II drugs is usually slower than class I and occurs over a longer
period of time.
• In vitro- In vivo correlation (IVIVC) is usually excepted for class I and
class II drugs.
• e.g. Phenytoin, Danazol, Ketoconazole, Mefenamic acid,
Nifedinpine.
19. Class III
• For Class III drugs, permeability is rate limiting step for drug
absorption. These drugs exhibit a high variation in the rate and
extent of drug absorption.
• Since the dissolution is rapid, the variation is attributable to
alteration of physiology and membrane permeability rather than the
dosage form factors.
• e.g. Cimetidine, Acyclovir, Neomycin B, Captopril.
20. Class IV
• Class IV drugs exhibit a lot of problems for effective oral administration.
Fortunately, extreme examples of class IV compounds are the exception
rather than the rule and are rarely developed and reach the market.
Nevertheless a number of class IV drugs do exist. e.g. Taxol.
21. Applications of BCS in oral drug delivery technology
• Once the solubility and permeability characteristics of the drug are known
it becomes an easy task for the research scientist to decide upon which
drug delivery technology to follow or develop.
22. CLASS I DRUGS
• The major challenge in development of drug delivery system for class I
drugs is to achieve a target release profile associated with a particular
pharmcokinetic and/or pharmacodynamic profile.
• Formulation approaches include both control of release rate and certain
physicochemical properties of drugs like pH-solubility profile of drug.
23. CLASS II DRUGS
• The systems that are developed for class II drugs are
based on micronisation, lyophilization, addition of
surfactants, formulation as emulsions and
microemulsions systems, use of complexing agents like
cyclodextrins.
24. CLASS III DRUGS
• Class III drugs require the technologies that address to
fundamental limitations of absolute or regional permeability.
Peptides and proteins constitute the part of class III and the
technologies handling such materials are on rise now days.
25. CLASS IV DRUGS
• Class IV drugs present a major challenge for development of
drug delivery system and the route of choice for
administering such drugs is parenteral with the formulation
containing solubility enhancers.
26. IN VITRO-DISSOLUTION
• Purpose of the in vitro dissolution studies in the early stage of
the drug development is to select the optimum formulation,
evaluate the active ingredient and excipient, and assess any
minor changes for drug products.
• For the ivivc perspective, dissolution is proposed to be a
surrogate of drug bioavailability.
27. Why do we study dissolution?
Disintegration Dissolution Absorption Drug in
the blood
and the
body
28. TYPES OF DISSOLUTION APPARATUS
Apparatus
Name
Apparatus 1 Rotating basket
Apparatus 2 Paddle
Apparatus 3 Reciprocating cylinder
Apparatus 4 Flow cell
Apparatus 5 Paddle over disk
Apparatus6 Cylinder
Apparatus7 Reciprocating disc
29. Apparatus 1 (ROTATING BASKET)
• In case of none-disintegrating dosage forms
this apparatus is superior to apparatus 2
since it constraints the dosage form in a
steady state fluid flow
• It is inferior for testing dosage forms which
contains gums due to clogging of screen
matrix
30. Apparatus 2 (ROTATING PADDLE)
• This apparatus is identical to apparatus
1 except that the paddle is substituted
for the rotating basket
• Frequently used for both disintegrating
and non-disintegrating dosage forms
31. Apparatus 3 (RECIPROCATING CYLINDER)
• One advantage of the reciprocating
cylinder is that the gastrointestinal
tract conditions can be easily
simulated, as it is easy to make time
dependent pH changes
• This apparatus is most suitable for
nondisintegrating (extended release) or
delayed release (enteric coated)
dosage forms
32. Apparatus 4 (FLOW CELL)
• The advantage of flow through cell
apparatus is the ability to test drugs of
very low aqueous solubility and the
ability to change the pH conveniently
during the test
33. Apparatus 5 (PADDLE OVER DISK)
• In paddle over the disc apparatus
the disc is placed and above that
the paddle is rotated .
• Mainly use in case of trandermal
preperations.
34. Apparatus 6 (CYLINDER)
• The cylinder method (Apparatus 6) for
testing transdermal preparation is
modified from the basket method
(Apparatus 1). In place of the basket, a
stainless steel cylinder is used to hold
the sample.
35. Apparatus 7 (RECIPROCATING DISK METHOD )
• In the reciprocating disk method for
testing transdermal products, a motor
drive assembly (Apparatus 7) is used to
reciprocate the system vertically, and
the samples are placed on disk-shaped
holders using cuprophan supports
36. DISSOLUTION MEDIUM
• Water or simulated gastric fluid(pH1.2) or intestinal
fluid( pH6.8 or 7.4) without enzyme, Buffer with a pH
range(4.5-7.5)
• For sparingly water soluble drugs surfactant may be added in
dissolved medium
37. SAMPLING TIME POINTS
Time Points
IR products
• Test duration : 15 to 60 minutes
Specifications
• Dissolution profile : sampling at 5-, 10-or 15-minute
intervals
38. SAMPLING TIME POINTS(contd.)
• Extended-Release Products
Test time : at least 3 test times
• Early time point : 1-2 hours : potential dose
dumping
• Intermediate time point : define the release
profile
• Final time point : show complete release of the
drug
39. IN VIVO ABSORPTION
• FDA requires in-vivo bioavailability test for NDA
• Bioavailability studies performed in young healthy male
volunteers. under some restriction conditions like :-
• fasting
• Non smoking
• No intake of other medications
40. APPROACHES FOR DETERMINING IN-VIVO ABSORPTION
Wagner-Nelson - One
compartment
Loo-Riegelman - Multi
compartment
Numerical Deconvolution - Both model
independent
method
41. BIOAVAILABILITY STUDIES FOR DEVELOPMENT
OF IVIVC
• A bioavailability study should be performed to characterize
the plasma concentration versus time profile for each of the
formulation.
• Bioavailability studies for IVIVC development should be
performed with sufficient number of subjects to characterize
adequately the performance of the drug product under study
42. EVALUATION OF PREDICTABILITY OF IVIVC
• An IVIVC should be evaluated to demonstrate that predictability of in vivo
performance of a drug product from its in vitro dissolution characteristics
is maintained over a range of in vitro dissolution release rates and
manufacturing changes
• Depending on the intended application of an IVIVC and the therapeutic
index of the drug, evaluation of prediction error internally and/or
externally may be appropriate.
43. EVALUATION OF PREDICTABILITY OF IVIVC
(contd.)
External predictability evaluation is not necessary unless the
drug is a narrow therapeutic index, or only two release rates
were used to develop the IVIVC, or, if the internal predictability
criteria are not met i.e. prediction error internally is inconclusive
44. INTERNAL PREDICTABILITY
All IVIVCs should be studied regarding internal
predictability. One recommended approach involves
the use of the IVIVC model to predict each
formulation’s plasma concentration profile (or Cmax
and/or AUC for a multiple Level C IVIVC) from each
respective formulation’s dissolution data.
45. EXTERNAL PREDICTABILITY
• Therefore, it may be important to establish the external
predictability of the IVIVC. This involves using the IVIVC to
predict the in vivo performance for a formulation with known
bioavailability that was not used in developing the IVIVC
model.
46. EXTERNAL PREDICTABILITY(contd.)
• Most important when using an IVIVC as a surrogate
for bioequivalence is confidence that the IVIVC can
predict in vivo performance of subsequent lots of the
drug product.
47. CONCLUSION
• IVIVC includes in vivo relevance to in vitro dissolution
specifications and can serve as surrogate for in vivo
bioavailability and to support biowaivers.
• Furthermore, IVIVC can also allow setting and validating of
more meaningful dissolution methods and specifications.
49. REFERENCES
• Venkateswarlu V. , “Biopharmaceutics and Pharmacokinetics”, edition
2004, PharmaMed press, Hyderabad.
• Brahmankar D.M., Jaiswal B. Sunil, “bipharmaceutics and
pharmacokinetics- a treatise”, first edition 1995, Vallabh prakashan, New
Delhi.
• Sharge leon , yu pc andrew, applied biopharmaceutics and
pharmacokinetics, third edition.