Statistical modeling in pharmaceutical research and developmentPV. Viji
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Statistical modeling in pharmaceutical research and development , Statistical Modeling , Descriptive Versus Mechanistic Modeling , Statistical Parameters Estimation , Confidence Regions , Non Linearity at the Optimum , Sensitivity Analysis , Optimal Design , Population Modeling
cosmetics - regulatory : Regulatory provisions related to cosmetics PV. Viji
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REGULATORY PROVISIONS RELATED TO COSMETICS , REGULATORY PROVISIONS RELATING TO IMPORT OF COSMETICS , Application for registration certification for import cosmetics , Grant of registration certificate , Standards for imported cosmetics , REGULATORY PROVISIONS RELATING TO MANUFACTURE OF COSMETICS , REQUIREMENTS OF FACTORY PREMISES FOR MANUFACTURE OF COSMETICS , LOAN LICENCE
This document presents a summary of gastrointestinal (GI) simulation and model construction for predicting oral drug absorption. It discusses various compartmental models that can be used for GI simulation, including CAT, ADAM, Grass, and GITA models. Commercial software packages for GI simulation are also listed, such as GastroPlus, INTELLIPHARM PKCR, SimCYP, PK-Sim, IDEA, Cloe PK, and Cloe HIA. The document then focuses on using GastroPlus software to construct two models to simulate the oral absorption of the drug Nimesulide and compare the predicted pharmacokinetic parameters to observed in vivo data. Model 2 provided a better fit to the in vivo observations by accounting
Computational modelling of drug disposition lalitajoshi9
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computational modelling of drug disposition is the integral part of computer aided drug design. different kinds of tools being used in the prediction of drug disposition in human body. This topic in the CADD explains the details about the drug disposition, active transporters and tools.
REGULATORY AND INDUSTRY VIEWS ON QbD, SCIENTIFICALLY BASED QbD- EXAMPLES OF A...Ardra Krishna
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The pharmaceutical Quantity by Design (QbD) is a systemic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quantity risk management.
QbD has been adopted by U.S Food and Drug Administration (FDA) for the discovery, development and manufacture of drugs.
Quality- by- design (QbD) is a concept introduces by the International Conference on Harmonization (ICH) Q8 guidelines.
ACTIVE TRANSPORT- hPEPT1,ASBT,OCT,OATP, BBB-Choline Transporter.pptxPawanDhamala1
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The document discusses various transporters involved in active transport of drugs including hPEPT1, ASBT, OCT, OATP, and the BBB-choline transporter. Pharmacophore and QSAR models have been developed for many of these transporters based on in vitro data to understand their substrate binding requirements. These models can assist in predicting the effects of transporters on drug absorption, distribution, and excretion during drug development.
review of guidelines for herbal cosmetics by private bodies like cosmos with ...MoidulIslam17
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review of guidelines for herbal cosmetics by private bodies like cosmos with respect to preservatives, emollients, foaming agents, emulsifiers and rheology modifiers.
Statistical modeling in pharmaceutical research and developmentPV. Viji
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Statistical modeling in pharmaceutical research and development , Statistical Modeling , Descriptive Versus Mechanistic Modeling , Statistical Parameters Estimation , Confidence Regions , Non Linearity at the Optimum , Sensitivity Analysis , Optimal Design , Population Modeling
cosmetics - regulatory : Regulatory provisions related to cosmetics PV. Viji
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REGULATORY PROVISIONS RELATED TO COSMETICS , REGULATORY PROVISIONS RELATING TO IMPORT OF COSMETICS , Application for registration certification for import cosmetics , Grant of registration certificate , Standards for imported cosmetics , REGULATORY PROVISIONS RELATING TO MANUFACTURE OF COSMETICS , REQUIREMENTS OF FACTORY PREMISES FOR MANUFACTURE OF COSMETICS , LOAN LICENCE
This document presents a summary of gastrointestinal (GI) simulation and model construction for predicting oral drug absorption. It discusses various compartmental models that can be used for GI simulation, including CAT, ADAM, Grass, and GITA models. Commercial software packages for GI simulation are also listed, such as GastroPlus, INTELLIPHARM PKCR, SimCYP, PK-Sim, IDEA, Cloe PK, and Cloe HIA. The document then focuses on using GastroPlus software to construct two models to simulate the oral absorption of the drug Nimesulide and compare the predicted pharmacokinetic parameters to observed in vivo data. Model 2 provided a better fit to the in vivo observations by accounting
Computational modelling of drug disposition lalitajoshi9
Â
computational modelling of drug disposition is the integral part of computer aided drug design. different kinds of tools being used in the prediction of drug disposition in human body. This topic in the CADD explains the details about the drug disposition, active transporters and tools.
REGULATORY AND INDUSTRY VIEWS ON QbD, SCIENTIFICALLY BASED QbD- EXAMPLES OF A...Ardra Krishna
Â
The pharmaceutical Quantity by Design (QbD) is a systemic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quantity risk management.
QbD has been adopted by U.S Food and Drug Administration (FDA) for the discovery, development and manufacture of drugs.
Quality- by- design (QbD) is a concept introduces by the International Conference on Harmonization (ICH) Q8 guidelines.
ACTIVE TRANSPORT- hPEPT1,ASBT,OCT,OATP, BBB-Choline Transporter.pptxPawanDhamala1
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The document discusses various transporters involved in active transport of drugs including hPEPT1, ASBT, OCT, OATP, and the BBB-choline transporter. Pharmacophore and QSAR models have been developed for many of these transporters based on in vitro data to understand their substrate binding requirements. These models can assist in predicting the effects of transporters on drug absorption, distribution, and excretion during drug development.
review of guidelines for herbal cosmetics by private bodies like cosmos with ...MoidulIslam17
Â
review of guidelines for herbal cosmetics by private bodies like cosmos with respect to preservatives, emollients, foaming agents, emulsifiers and rheology modifiers.
Optimization technology and screening design sathish h tSatishHT1
Â
This document discusses various design of experiment methodologies including screening designs and optimization designs. It provides examples of factorial designs, response surface designs like central composite designs and Box-Behnken designs, and three-level full factorial designs. It also gives an example of using a fractional factorial design to screen critical processing parameters in a wet granulation coating process and selecting a three-level full factorial design to optimize two factors, blending speed and time, in a dry mixing process to investigate their interactive and quadratic effects on the response.
The document describes electrosomes, which are a novel surface display system composed of enzymes attached to a scaffoldin protein. This allows for multiple electron release from fuel oxidation. In the anode, an ethanol oxidation cascade is assembled using alcohol dehydrogenase and formaldehyde dehydrogenase enzymes attached to the scaffoldin. In the cathode, copper oxidase is attached for oxygen reduction. The electrosomes provide advantages as a fuel cell and drug delivery system by catalyzing chemical energy conversion to electricity and providing controlled drug release.
Cleansing and care needs for face eyelid lips hands feet nail scalp neck bodyRahul Krishnan
Â
This document provides information on various skin, eye, lip, nail, and scalp care products. It discusses cleansers, face washes, moisturizers, fairness creams, and other cosmetic products. It also covers ingredients and formulations for lipsticks, lip balms, lip gloss, lip liner, eye shadows, mascara, eye liner, and other eye and lip care products. The document is intended to educate readers on cleansing and care needs for different areas of the face and recommendations for appropriate cosmetic products.
Computational modeling of drug dispositionPV. Viji
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Computational modeling of drug disposition , Modeling techniques , Drug absorption , solubility , intestinal permeation , Drug distribution , Drug excretion , Active Transport , P-gp , BCRP , Nucleoside transporters , hPEPT1 , ASBT , OCT , OATP , BBB-choline transporter
Formulation Building blocks: Building blocks for different product formulatio...PRAJAKTASAWANT33
Â
Building blocks for different product formulations of
cosmetics/cosmeceuticals. Surfactants - Classification and application. Emollients,
rheological additives: classification and application.
This document discusses various compendial methods for drug dissolution testing. It begins by defining dissolution as the process where a solid substance solubilizes in a solvent, transferring mass from the solid surface to the liquid phase. It then describes the seven USP dissolution apparatus types and their applications for testing different drug products like tablets, capsules, modified release formulations and transdermal systems. The document provides details on factors that influence dissolution test design and the principles of operation for each apparatus type.
This document discusses regulatory provisions related to the manufacture of cosmetics in India. It notes that a license must be obtained from the state licensing authority to manufacture products like tooth powders, pastes, creams, lotions, shampoos, hair oils, emulsions, nail polishes, lipsticks, aerosols, colognes, hair dyes, and toilet soaps. The license application must be submitted along with a Rs. 6000 fee and Rs. 1500 inspection fee. It also outlines penalties for contraventions like importing or selling spurious, prohibited, or misbranded cosmetics, which can include imprisonment of up to 5 years and fines up to Rs. 10,000.
Problems of variable control in dissolution testing discusses issues that can affect the results of dissolution testing. Dissolution testing is important for characterizing drug release from oral solid dosages and ensuring bioavailability. However, variables like equipment alignment and agitation levels can increase variability in dissolution rates measured. Both the paddle and basket methods are sensitive to different issues like tilting, clogging, or air bubbles. No single method works best for all products, so selection depends on the specific drug formulation and optimizing test conditions.
The document discusses the use of computers in pharmaceutical formulation development. It provides examples of how experimental design techniques like factorial design and response surface methodology can be used to optimize emulsion and microemulsion formulations. Artificial neural networks can also model complex nonlinear relationships in formulations. Quality by design approaches involving design spaces and multivariable optimization are important. Computer tools can help optimize variables, ingredients, processing parameters, and define formulation robustness.
ROLE OF DOSAGE FORM IN GASTRO-INTESTINAL ABSORPTION Ankit Malik
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The document discusses how the dosage form impacts drug absorption in the gastrointestinal tract. It summarizes that solutions show the fastest and most complete absorption as they do not have dissolution problems. Suspensions also absorb relatively quickly due to their small particle size. Capsules and tablets must undergo dissolution and disintegration processes first. Coated tablets have an additional step of the coating dissolving or disrupting before drug absorption can occur. The dosage form selection can make over a 60-fold difference in a drug's absorption rate or extent.
This document describes electrosomes, which are a novel surface display system that allows multiple electron release from fuel oxidation using a scaffoldin protein and cascade of redox enzymes. Electrosomes consist of a hybrid anode with ethanol-oxidizing enzymes attached to scaffoldin and a hybrid cathode with an oxygen-reducing enzyme also attached to scaffoldin. This allows the electrosomes to function as both an anode and cathode in a biofuel cell. Characterization of the electrosomes showed they were able to catalyze the conversion of chemical energy from ethanol to electricity with high power outputs due to the enzymatic cascades in the anode. Potential applications of electrosomes include use in enzymatic fuel cells, drug targeting
Computers in pharmaceutical research and development, General overview, Brief...Manikant Prasad Shah
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This document discusses the history of computers in pharmaceutical research and development. It describes how computers first began to be used in the 1940s and the early pioneers in computational chemistry in the 1950s and 1960s. It outlines the advancements made in the field in the following decades, including the development of quantum chemistry models, molecular mechanics, and other approaches. The document emphasizes that computational chemistry experts now play an important role in drug discovery by maximizing the benefits of computer technologies.
MPH07 Computers in clinical development.pptxBhuminJain1
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My topic is computers in clinical development. There are various ways pf collecting data like pure paper based system, electronic based system and communication.
Gastrointestinal absorption simulation using in silico methodology; by Dr. Bh...bhupenkalita7
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This PPT includes a brief introduction of in silico models for simulation of GI absorption of drugs, principles involved in the dvelopment of computational models for in silico pharmacokinetic studies related to absorption of drugs from GI tract.
The document discusses the COSMOS standard for organic and natural cosmetics certification in Europe. Some key points:
- COSMOS sets certification requirements for organic and natural cosmetics products in Europe to use specific guidelines and signatures on packaging.
- There are four main COSMOS certification signatures: organic, natural, certified, and approved products. Companies must go through a six step process to gain approval for product labeling.
- Over 1,600 manufacturers across 45+ countries follow the COSMOS standard. It aims to promote principles like using organic farming ingredients and environmentally friendly production processes.
The document discusses several key concepts related to drug transport and absorption:
1) The pH partition hypothesis states that acidic drugs are absorbed from acidic solutions and basic drugs from alkaline solutions, though some exceptions exist due to the microclimate pH near the membrane surface.
2) Tight junctions form a virtually impermeable barrier between cells, composed of sealing strands that prevent fluid passage.
3) According to Fick's first law, passive diffusion of solutes is determined by concentration gradients and membrane permeability. For ionizable drugs, the uncharged form is more permeable. The pH partition hypothesis relates permeability to pH and the fraction of uncharged molecules.
The document discusses various topics related to drug dissolution testing and absorption:
1. It describes 7 common dissolution apparatus used for testing according to the USP and provides details on rotating basket (Apparatus 1) and paddle (Apparatus 2) methods.
2. It explains the levels of correlation (A, B, C) between in vitro dissolution data and in vivo drug absorption, with Level A being a point-to-point correlation and the highest level.
3. It introduces concepts like the permeability-solubility-charge state model and pH partition hypothesis which aim to understand efficient drug permeation across membranes based on factors like solubility and ionization state.
Optimization technology and screening design sathish h tSatishHT1
Â
This document discusses various design of experiment methodologies including screening designs and optimization designs. It provides examples of factorial designs, response surface designs like central composite designs and Box-Behnken designs, and three-level full factorial designs. It also gives an example of using a fractional factorial design to screen critical processing parameters in a wet granulation coating process and selecting a three-level full factorial design to optimize two factors, blending speed and time, in a dry mixing process to investigate their interactive and quadratic effects on the response.
The document describes electrosomes, which are a novel surface display system composed of enzymes attached to a scaffoldin protein. This allows for multiple electron release from fuel oxidation. In the anode, an ethanol oxidation cascade is assembled using alcohol dehydrogenase and formaldehyde dehydrogenase enzymes attached to the scaffoldin. In the cathode, copper oxidase is attached for oxygen reduction. The electrosomes provide advantages as a fuel cell and drug delivery system by catalyzing chemical energy conversion to electricity and providing controlled drug release.
Cleansing and care needs for face eyelid lips hands feet nail scalp neck bodyRahul Krishnan
Â
This document provides information on various skin, eye, lip, nail, and scalp care products. It discusses cleansers, face washes, moisturizers, fairness creams, and other cosmetic products. It also covers ingredients and formulations for lipsticks, lip balms, lip gloss, lip liner, eye shadows, mascara, eye liner, and other eye and lip care products. The document is intended to educate readers on cleansing and care needs for different areas of the face and recommendations for appropriate cosmetic products.
Computational modeling of drug dispositionPV. Viji
Â
Computational modeling of drug disposition , Modeling techniques , Drug absorption , solubility , intestinal permeation , Drug distribution , Drug excretion , Active Transport , P-gp , BCRP , Nucleoside transporters , hPEPT1 , ASBT , OCT , OATP , BBB-choline transporter
Formulation Building blocks: Building blocks for different product formulatio...PRAJAKTASAWANT33
Â
Building blocks for different product formulations of
cosmetics/cosmeceuticals. Surfactants - Classification and application. Emollients,
rheological additives: classification and application.
This document discusses various compendial methods for drug dissolution testing. It begins by defining dissolution as the process where a solid substance solubilizes in a solvent, transferring mass from the solid surface to the liquid phase. It then describes the seven USP dissolution apparatus types and their applications for testing different drug products like tablets, capsules, modified release formulations and transdermal systems. The document provides details on factors that influence dissolution test design and the principles of operation for each apparatus type.
This document discusses regulatory provisions related to the manufacture of cosmetics in India. It notes that a license must be obtained from the state licensing authority to manufacture products like tooth powders, pastes, creams, lotions, shampoos, hair oils, emulsions, nail polishes, lipsticks, aerosols, colognes, hair dyes, and toilet soaps. The license application must be submitted along with a Rs. 6000 fee and Rs. 1500 inspection fee. It also outlines penalties for contraventions like importing or selling spurious, prohibited, or misbranded cosmetics, which can include imprisonment of up to 5 years and fines up to Rs. 10,000.
Problems of variable control in dissolution testing discusses issues that can affect the results of dissolution testing. Dissolution testing is important for characterizing drug release from oral solid dosages and ensuring bioavailability. However, variables like equipment alignment and agitation levels can increase variability in dissolution rates measured. Both the paddle and basket methods are sensitive to different issues like tilting, clogging, or air bubbles. No single method works best for all products, so selection depends on the specific drug formulation and optimizing test conditions.
The document discusses the use of computers in pharmaceutical formulation development. It provides examples of how experimental design techniques like factorial design and response surface methodology can be used to optimize emulsion and microemulsion formulations. Artificial neural networks can also model complex nonlinear relationships in formulations. Quality by design approaches involving design spaces and multivariable optimization are important. Computer tools can help optimize variables, ingredients, processing parameters, and define formulation robustness.
ROLE OF DOSAGE FORM IN GASTRO-INTESTINAL ABSORPTION Ankit Malik
Â
The document discusses how the dosage form impacts drug absorption in the gastrointestinal tract. It summarizes that solutions show the fastest and most complete absorption as they do not have dissolution problems. Suspensions also absorb relatively quickly due to their small particle size. Capsules and tablets must undergo dissolution and disintegration processes first. Coated tablets have an additional step of the coating dissolving or disrupting before drug absorption can occur. The dosage form selection can make over a 60-fold difference in a drug's absorption rate or extent.
This document describes electrosomes, which are a novel surface display system that allows multiple electron release from fuel oxidation using a scaffoldin protein and cascade of redox enzymes. Electrosomes consist of a hybrid anode with ethanol-oxidizing enzymes attached to scaffoldin and a hybrid cathode with an oxygen-reducing enzyme also attached to scaffoldin. This allows the electrosomes to function as both an anode and cathode in a biofuel cell. Characterization of the electrosomes showed they were able to catalyze the conversion of chemical energy from ethanol to electricity with high power outputs due to the enzymatic cascades in the anode. Potential applications of electrosomes include use in enzymatic fuel cells, drug targeting
Computers in pharmaceutical research and development, General overview, Brief...Manikant Prasad Shah
Â
This document discusses the history of computers in pharmaceutical research and development. It describes how computers first began to be used in the 1940s and the early pioneers in computational chemistry in the 1950s and 1960s. It outlines the advancements made in the field in the following decades, including the development of quantum chemistry models, molecular mechanics, and other approaches. The document emphasizes that computational chemistry experts now play an important role in drug discovery by maximizing the benefits of computer technologies.
MPH07 Computers in clinical development.pptxBhuminJain1
Â
My topic is computers in clinical development. There are various ways pf collecting data like pure paper based system, electronic based system and communication.
Gastrointestinal absorption simulation using in silico methodology; by Dr. Bh...bhupenkalita7
Â
This PPT includes a brief introduction of in silico models for simulation of GI absorption of drugs, principles involved in the dvelopment of computational models for in silico pharmacokinetic studies related to absorption of drugs from GI tract.
The document discusses the COSMOS standard for organic and natural cosmetics certification in Europe. Some key points:
- COSMOS sets certification requirements for organic and natural cosmetics products in Europe to use specific guidelines and signatures on packaging.
- There are four main COSMOS certification signatures: organic, natural, certified, and approved products. Companies must go through a six step process to gain approval for product labeling.
- Over 1,600 manufacturers across 45+ countries follow the COSMOS standard. It aims to promote principles like using organic farming ingredients and environmentally friendly production processes.
The document discusses several key concepts related to drug transport and absorption:
1) The pH partition hypothesis states that acidic drugs are absorbed from acidic solutions and basic drugs from alkaline solutions, though some exceptions exist due to the microclimate pH near the membrane surface.
2) Tight junctions form a virtually impermeable barrier between cells, composed of sealing strands that prevent fluid passage.
3) According to Fick's first law, passive diffusion of solutes is determined by concentration gradients and membrane permeability. For ionizable drugs, the uncharged form is more permeable. The pH partition hypothesis relates permeability to pH and the fraction of uncharged molecules.
The document discusses various topics related to drug dissolution testing and absorption:
1. It describes 7 common dissolution apparatus used for testing according to the USP and provides details on rotating basket (Apparatus 1) and paddle (Apparatus 2) methods.
2. It explains the levels of correlation (A, B, C) between in vitro dissolution data and in vivo drug absorption, with Level A being a point-to-point correlation and the highest level.
3. It introduces concepts like the permeability-solubility-charge state model and pH partition hypothesis which aim to understand efficient drug permeation across membranes based on factors like solubility and ionization state.
In vitro dissolution, Alternative Methods.pptxPrachi Pandey
Â
In vitro dissolution and drug release testing provides important information about drug product performance. There are several methods for testing, including sink and non-sink methods as well as natural convection, forced convection, and continuous flow/through methods. Key factors in testing include the dissolution medium, apparatus used, sampling timepoints, and analytical methods for quantifying the amount of drug released over time. Dissolution and drug release profiles are important for understanding and comparing the in vivo behavior and therapeutic effectiveness of different drug product formulations.
Dissolution method and ivivc by ranjeet singhRanjeet Singh
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The document discusses dissolution testing methods for oral drug formulations. It describes dissolution as a mass transfer process involving interactions at solute-solute, solute-solvent, and solvent-solvent interfaces. Official dissolution testing methods specified by regulatory agencies include the rotating basket, paddle, flow-through, reciprocating cylinder, paddle over disk, rotating cylinder, and reciprocating disk methods. Non-official methods described for specific dosage forms include the rotating bottle method for sustained release formulations and dialysis systems for poorly soluble drugs. The document also discusses the importance of establishing in vitro-in vivo correlations to ensure batch uniformity and aid new drug development.
This document discusses dissolution testing apparatus and validation. It begins with an introduction to dissolution testing, its importance, and factors that affect dissolution. It then describes the various USP apparatus for dissolution testing and theories of dissolution. The remainder of the document outlines the validation process, including qualification phases, protocols, and maintenance. Validation establishes evidence that a process will consistently produce quality products meeting specifications.
The document presents information on the development of dissolution methods. It discusses the processes involved in dissolution testing of solid oral dosage forms including that the drug must be released and dissolve in GI fluids to be absorbed. It also outlines factors that affect dissolution tests such as the apparatus, dissolution fluid, and process parameters. The document provides details on apparatus selection and types, as well as key elements of developing a dissolution method such as ensuring it is discriminatory, robust, and correlated to in vivo outcomes. Steps involved in method development like degassing, sinkers, agitation, sampling, and cleaning are also summarized.
This document discusses in-vitro dissolution testing and drug release. It defines dissolution as the process where a solid substance is solubilized in a liquid solvent. Dissolution is the rate determining step for drug absorption if the drug is highly soluble. The document then covers various theories of dissolution, types of in-vitro dissolution testing models and apparatuses, and factors that can affect drug dissolution and release such as drug properties, formulation components, and test conditions.
Dissolution testing is an important quality control tool for assessing drug release from solid oral dosage forms. Key factors that influence dissolution include solubility, permeability, dissolution rate, and drug release kinetics. The document discusses the importance of dissolution testing and outlines various parameters to consider like sink conditions, selection of media, rpm, and apparatus type. It also covers topics like intrinsic dissolution, biowaiver requests, and dissolution testing for modified release formulations. Overall, the document provides a comprehensive overview of the dissolution testing process and parameters.
The document discusses invitro dissolution testing of drugs. It defines dissolution rate and invitro dissolution tests as tests used to measure the rate and extent of dissolution of a drug from its formulation under specified conditions. Key factors in designing dissolution tests include the apparatus used, dissolution medium properties, and process parameters. Common apparatuses include basket, paddle, reciprocating cylinder, and flow-through cell methods. Dissolution testing provides important information on a drug's in vivo performance and quality control.
This document discusses in vitro dissolution, which is the process by which a solid substance dissolves in a solvent to form a solution. It describes the various processes involved in dissolution of solid dosage forms and defines intrinsic dissolution rate. It also provides the mathematical equations to describe dissolution processes under sink and non-sink conditions. The document then discusses various compendial dissolution apparatus and methods specified in different pharmacopoeias including rotating basket, paddle, reciprocating cylinder, flow-through cell methods. It also covers alternative dissolution testing methods like rotating bottle, peristalsis and Franz diffusion cell methods. Finally, the document discusses problems of variable control in dissolution testing and provides an overview of in vitro-in vivo correlation (IVIVC
Formulation and evaluation of TDDS sheets.pptxomkarmandlik678
Â
Shweta Rokade presented on formulation and evaluation of transdermal drug delivery systems (TDDS). TDDS, also known as patches, are designed to deliver drugs across the skin. The basic components of TDDS include a polymer matrix containing the drug, permeation enhancers, pressure sensitive adhesives, backing laminates and release liners. Drugs suitable for TDDS have specific properties like extensive first-pass metabolism. TDDS were evaluated through physicochemical tests, in vitro studies of drug release and skin permeation, and in vivo studies using animal and human models.
The document discusses validation of dissolution apparatus. It begins with an introduction to dissolution testing and factors affecting dissolution. It then covers the various theories of dissolution and describes the common USP dissolution apparatus. The remainder of the document focuses on validation, including equipment validation, validation phases, protocols, and revalidation. It emphasizes establishing documented evidence to ensure dissolution apparatus will consistently produce reliable results.
This document provides an overview of dissolution testing and the factors that influence drug dissolution. It defines dissolution and describes the intrinsic dissolution process. It also discusses the various apparatus used for dissolution testing according to pharmacopeial specifications, including the basket, paddle, reciprocating cylinder, and flow-through cell. The key factors affecting dissolution are also summarized, such as drug properties, apparatus parameters, and media properties.
This document discusses solubility and dissolution of solids in liquids, which are important processes in pharmaceutical solutions. It describes dissolution as a process where a substance goes into solution. Solubility is defined as the capacity of a solute to dissolve in a pure solvent. The document then discusses key steps in the dissolution process including removal of drug molecules from the solid state, formation of solvent cavities, and accommodation of drug molecules into the cavities. It presents the Noyes-Whitney equation, which describes dissolution rate in terms of surface area, concentration gradient, and diffusion coefficient. Finally, it notes that quality control dissolution testing is required by the FDA to ensure batch-to-batch uniformity of pharmaceutical formulations.
Bioavailability & Bioequivalence ppt, Objectives, Improving bioavailability, Assessment of bioavailability, Urinary excretion studies, Blood serum studies, in vitro drug dissolution testing, need for dissolution testing, in vitro drug dissolution testing models, Bioequivalence, Therapeutic equivalence, Types of bioequivalence studies, Pharmacokinetic studies, Methods to enhance dissolution rate.
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
PPT on Alternate Wetting and Drying presented at the three-day 'Training and Validation Workshop on Modules of Climate Smart Agriculture (CSA) Technologies in South Asia' workshop on April 22, 2024.
EWOCS-I: The catalog of X-ray sources in Westerlund 1 from the Extended Weste...SĂŠrgio Sacani
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Context. With a mass exceeding several 104 Mâ and a rich and dense population of massive stars, supermassive young star clusters
represent the most massive star-forming environment that is dominated by the feedback from massive stars and gravitational interactions
among stars.
Aims. In this paper we present the Extended Westerlund 1 and 2 Open Clusters Survey (EWOCS) project, which aims to investigate
the influence of the starburst environment on the formation of stars and planets, and on the evolution of both low and high mass stars.
The primary targets of this project are Westerlund 1 and 2, the closest supermassive star clusters to the Sun.
Methods. The project is based primarily on recent observations conducted with the Chandra and JWST observatories. Specifically,
the Chandra survey of Westerlund 1 consists of 36 new ACIS-I observations, nearly co-pointed, for a total exposure time of 1 Msec.
Additionally, we included 8 archival Chandra/ACIS-S observations. This paper presents the resulting catalog of X-ray sources within
and around Westerlund 1. Sources were detected by combining various existing methods, and photon extraction and source validation
were carried out using the ACIS-Extract software.
Results. The EWOCS X-ray catalog comprises 5963 validated sources out of the 9420 initially provided to ACIS-Extract, reaching a
photon flux threshold of approximately 2 Ă 10â8 photons cmâ2
s
â1
. The X-ray sources exhibit a highly concentrated spatial distribution,
with 1075 sources located within the central 1 arcmin. We have successfully detected X-ray emissions from 126 out of the 166 known
massive stars of the cluster, and we have collected over 71 000 photons from the magnetar CXO J164710.20-455217.
Microbial interaction
Microorganisms interacts with each other and can be physically associated with another organisms in a variety of ways.
One organism can be located on the surface of another organism as an ectobiont or located within another organism as endobiont.
Microbial interaction may be positive such as mutualism, proto-cooperation, commensalism or may be negative such as parasitism, predation or competition
Types of microbial interaction
Positive interaction: mutualism, proto-cooperation, commensalism
Negative interaction: Ammensalism (antagonism), parasitism, predation, competition
I. Mutualism:
It is defined as the relationship in which each organism in interaction gets benefits from association. It is an obligatory relationship in which mutualist and host are metabolically dependent on each other.
Mutualistic relationship is very specific where one member of association cannot be replaced by another species.
Mutualism require close physical contact between interacting organisms.
Relationship of mutualism allows organisms to exist in habitat that could not occupied by either species alone.
Mutualistic relationship between organisms allows them to act as a single organism.
Examples of mutualism:
i. Lichens:
Lichens are excellent example of mutualism.
They are the association of specific fungi and certain genus of algae. In lichen, fungal partner is called mycobiont and algal partner is called
II. Syntrophism:
It is an association in which the growth of one organism either depends on or improved by the substrate provided by another organism.
In syntrophism both organism in association gets benefits.
Compound A
Utilized by population 1
Compound B
Utilized by population 2
Compound C
utilized by both Population 1+2
Products
In this theoretical example of syntrophism, population 1 is able to utilize and metabolize compound A, forming compound B but cannot metabolize beyond compound B without co-operation of population 2. Population 2is unable to utilize compound A but it can metabolize compound B forming compound C. Then both population 1 and 2 are able to carry out metabolic reaction which leads to formation of end product that neither population could produce alone.
Examples of syntrophism:
i. Methanogenic ecosystem in sludge digester
Methane produced by methanogenic bacteria depends upon interspecies hydrogen transfer by other fermentative bacteria.
Anaerobic fermentative bacteria generate CO2 and H2 utilizing carbohydrates which is then utilized by methanogenic bacteria (Methanobacter) to produce methane.
ii. Lactobacillus arobinosus and Enterococcus faecalis:
In the minimal media, Lactobacillus arobinosus and Enterococcus faecalis are able to grow together but not alone.
The synergistic relationship between E. faecalis and L. arobinosus occurs in which E. faecalis require folic acid
The cost of acquiring information by natural selectionCarl Bergstrom
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This is a short talk that I gave at the Banff International Research Station workshop on Modeling and Theory in Population Biology. The idea is to try to understand how the burden of natural selection relates to the amount of information that selection puts into the genome.
It's based on the first part of this research paper:
The cost of information acquisition by natural selection
Ryan Seamus McGee, Olivia Kosterlitz, Artem Kaznatcheev, Benjamin Kerr, Carl T. Bergstrom
bioRxiv 2022.07.02.498577; doi: https://doi.org/10.1101/2022.07.02.498577
Discovery of An Apparent Red, High-Velocity Type Ia Supernova at đł = 2.9 wi...SĂŠrgio Sacani
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We present the JWST discovery of SNâ2023adsy, a transient object located in a host galaxy JADES-GS
+
53.13485
â
27.82088
with a host spectroscopic redshift of
2.903
Âą
0.007
. The transient was identified in deep James Webb Space Telescope (JWST)/NIRCam imaging from the JWST Advanced Deep Extragalactic Survey (JADES) program. Photometric and spectroscopic followup with NIRCam and NIRSpec, respectively, confirm the redshift and yield UV-NIR light-curve, NIR color, and spectroscopic information all consistent with a Type Ia classification. Despite its classification as a likely SNâIa, SNâ2023adsy is both fairly red (
ďż˝
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) despite a host galaxy with low-extinction and has a high CaâII velocity (
19
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km/s) compared to the general population of SNeâIa. While these characteristics are consistent with some Ca-rich SNeâIa, particularly SNâ2016hnk, SNâ2023adsy is intrinsically brighter than the low-
ďż˝
Ca-rich population. Although such an object is too red for any low-
ďż˝
cosmological sample, we apply a fiducial standardization approach to SNâ2023adsy and find that the SNâ2023adsy luminosity distance measurement is in excellent agreement (
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) with
Î
CDM. Therefore unlike low-
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Ca-rich SNeâIa, SNâ2023adsy is standardizable and gives no indication that SNâIa standardized luminosities change significantly with redshift. A larger sample of distant SNeâIa is required to determine if SNâIa population characteristics at high-
ďż˝
truly diverge from their low-
ďż˝
counterparts, and to confirm that standardized luminosities nevertheless remain constant with redshift.
Immersive Learning That Works: Research Grounding and Paths ForwardLeonel Morgado
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We will metaverse into the essence of immersive learning, into its three dimensions and conceptual models. This approach encompasses elements from teaching methodologies to social involvement, through organizational concerns and technologies. Challenging the perception of learning as knowledge transfer, we introduce a 'Uses, Practices & Strategies' model operationalized by the 'Immersive Learning Brain' and âImmersion Cubeâ frameworks. This approach offers a comprehensive guide through the intricacies of immersive educational experiences and spotlighting research frontiers, along the immersion dimensions of system, narrative, and agency. Our discourse extends to stakeholders beyond the academic sphere, addressing the interests of technologists, instructional designers, and policymakers. We span various contexts, from formal education to organizational transformation to the new horizon of an AI-pervasive society. This keynote aims to unite the iLRN community in a collaborative journey towards a future where immersive learning research and practice coalesce, paving the way for innovative educational research and practice landscapes.
CLASS 12th CHEMISTRY SOLID STATE ppt (Animated)eitps1506
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Description:
Dive into the fascinating realm of solid-state physics with our meticulously crafted online PowerPoint presentation. This immersive educational resource offers a comprehensive exploration of the fundamental concepts, theories, and applications within the realm of solid-state physics.
From crystalline structures to semiconductor devices, this presentation delves into the intricate principles governing the behavior of solids, providing clear explanations and illustrative examples to enhance understanding. Whether you're a student delving into the subject for the first time or a seasoned researcher seeking to deepen your knowledge, our presentation offers valuable insights and in-depth analyses to cater to various levels of expertise.
Key topics covered include:
Crystal Structures: Unravel the mysteries of crystalline arrangements and their significance in determining material properties.
Band Theory: Explore the electronic band structure of solids and understand how it influences their conductive properties.
Semiconductor Physics: Delve into the behavior of semiconductors, including doping, carrier transport, and device applications.
Magnetic Properties: Investigate the magnetic behavior of solids, including ferromagnetism, antiferromagnetism, and ferrimagnetism.
Optical Properties: Examine the interaction of light with solids, including absorption, reflection, and transmission phenomena.
With visually engaging slides, informative content, and interactive elements, our online PowerPoint presentation serves as a valuable resource for students, educators, and enthusiasts alike, facilitating a deeper understanding of the captivating world of solid-state physics. Explore the intricacies of solid-state materials and unlock the secrets behind their remarkable properties with our comprehensive presentation.
The debris of the âlast major mergerâ is dynamically youngSĂŠrgio Sacani
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The Milky Wayâs (MW) inner stellar halo contains an [Fe/H]-rich component with highly eccentric orbits, often referred to as the
âlast major merger.â Hypotheses for the origin of this component include Gaia-Sausage/Enceladus (GSE), where the progenitor
collided with the MW proto-disc 8â11 Gyr ago, and the Virgo Radial Merger (VRM), where the progenitor collided with the
MW disc within the last 3 Gyr. These two scenarios make different predictions about observable structure in local phase space,
because the morphology of debris depends on how long it has had to phase mix. The recently identified phase-space folds in Gaia
DR3 have positive caustic velocities, making them fundamentally different than the phase-mixed chevrons found in simulations
at late times. Roughly 20 per cent of the stars in the prograde local stellar halo are associated with the observed caustics. Based
on a simple phase-mixing model, the observed number of caustics are consistent with a merger that occurred 1â2 Gyr ago.
We also compare the observed phase-space distribution to FIRE-2 Latte simulations of GSE-like mergers, using a quantitative
measurement of phase mixing (2D causticality). The observed local phase-space distribution best matches the simulated data
1â2 Gyr after collision, and certainly not later than 3 Gyr. This is further evidence that the progenitor of the âlast major mergerâ
did not collide with the MW proto-disc at early times, as is thought for the GSE, but instead collided with the MW disc within
the last few Gyr, consistent with the body of work surrounding the VRM.
(June 12, 2024) Webinar: Development of PET theranostics targeting the molecu...Scintica Instrumentation
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Targeting Hsp90 and its pathogen Orthologs with Tethered Inhibitors as a Diagnostic and Therapeutic Strategy for cancer and infectious diseases with Dr. Timothy Haystead.
(June 12, 2024) Webinar: Development of PET theranostics targeting the molecu...
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Alternative method of dissolution in-vitro in-vivo correlation and dissolution profile comparison
1. Alternative method of Dissolution
Meeting dissolution requirements
Performance of drug product
Dissolution profile comparison
by-
Sahil Suleman
M. Pharm (2st Sem)
2. CONTENTS
Introduction
Dissolution Methods
Alternative Methods Of Dissolution Testing
Meeting Dissolution Requirements
Problems Of Variable Control In Dissolution Testing
Performance Of Drug Products: In Vitroâin Vivo Correlation
Dissolution Profile Comparisons
3. DISSOLUTION
⢠Dissolution is a dynamic process by which solid solutes dissolve in a solvent to yield a
solution. Mass transfer of drug from solid into solvent.
⢠Dissolution rate may be defined as the amount of substances that goes into solution per
unit time under standard conditions of temperature, pressure and solvent composition.
⢠A drug is expected to be released from the solid dosage forms (granules, tablets, capsules
etc.) and immediately go into molecular solution.
⢠Dissolution is the rate determining step for hydrophobic, poorly aqueous soluble drugs.
For instance : Griseofulvin, Spironolactone.
5. Rotating Bottle Method
⢠Used mainly for controlled-release beads.
⢠For this purpose the dissolution medium may be easily changed, such as from simulated
gastric juice to simulated intestinal juice.
⢠The equipment consists of a rotating rack that holds the sample drug products in bottles.
⢠The bottles are capped tightly and rotated in a 37¹0.5°C temperature bath. At various
times, the samples are removed from the bottle, decanted through a 40-mesh screen, and
the residues are assayed.
⢠An equal volume of fresh medium is added to the remaining drug residues within the
bottles and the dissolution test is continued.
6. ⢠A dissolution test with pH 1.2 medium
for 1 hour, pH 2.5 medium for the next
1 hour, followed by pH 4.5 medium for
1.5 hours, pH 7.0 medium for 1.5 hours,
and pH 7.5 medium for 2 hours was
recommended to simulate the condition
of the gastrointestinal tract.
⢠Used between 10 and 60 rpm.
⢠The main disadvantage is that this
procedure is manual and tedious.
7. Simulated gastric fluid is a solution that simulates the composition and pH of
gastric juice. The reagent is sterilized by 0.2 Âľm filtration.
Simulated gastric juice is prepared by dissolving pepsin (1 g), gastric mucin (1.5
g), and NaCl (8.775 g) in 1 L distilled water with pH of 1.3 adjusted using 6 N
HCI.
Simulated Intestinal fluid composition â
1.725mL of KCl, 0.025mL of KH2PO4, 3.125mL of NaHCO3, 7.375mL of NaCl,
0.1mL of MgCl2.6H2O and 0.125mL of (NH4)2CO3
8. Intrinsic Dissolution Method
⢠Most methods for dissolution deal with a finished drug product.
⢠Sometimes a new drug or substance may be tested for
dissolution without the effect of excipients or the fabrication
effect of processing.
⢠The dissolution of a drug powder by maintaining a constant
surface area is called intrinsic dissolution.
⢠Intrinsic dissolution is usually expressed as mg/cm2/min. In one
method, the basket method is adapted to test dissolution of
powder by placing the powder in a disk attached with a clipper
to the bottom of the basket.
9. Peristalsis Method
⢠The peristalsis method attempts to simulate the hydrodynamic conditions of the
gastrointestinal tract in an in vitro dissolution device.
⢠The apparatus consists of a rigid plastic cylindrical tubing fitted with a septum and
rubber stoppers at both ends.
⢠The dissolution chamber consists of a space between the septum and the lower stopper.
⢠The apparatus is placed in a beaker containing the dissolution medium.
⢠The dissolution medium is pumped with peristaltic action through the dosage form.
10. Schematics of the peristaltic
dissolution assembly. Plastic
tubing is used to connect the
combined Y-shaped connectors to
the two hypodermic needles at the
top of the disintegrating chamber
and the outlet-inlet connectors of a
Brewer pipetting pump assembly
equipped with a 50 mL syringe
11. Diffusion Cells
⢠Static and flow-through diffusion cells are used to characterize in vitro drug release and drug
permeation kinetics from topically applied dosage form or transdermal drug product.
⢠The Franz diffusion cell is a static diffusion system that is used for characterizing drug
permeation through a skin model.
⢠The source of skin may be human cadaver skin or animal skin (e.g.., hairless mouse skin).
Anatomically, each skin site (e.g., abdomen, arm) has different drug permeation qualities.
⢠The skin is mounted on the Franz diffusion cell system.
⢠The drug product (e.g.., ointment) is placed on the skin surface and the drug permeates across
the skin into a receptor fluid compartment that may be sampled at various times.
12. ⢠The Franz diffusion cell system is useful for comparing in vitro drug release profiles
and skin permeation characteristics to aid in selecting an appropriate formulation that
has optimum drug delivery
FRANZ DIFFUSION CELL
13. MEETING DISSOLUTION REQUIREMENTS
According to CFR (21CFR 343.90), a drug product application should include the
specifications necessary to ensure the identity, strength, quality, purity, potency, and
bioavailability of the drug product, including, and acceptance criteria relating to, dissolution
rate in the case of solid dosage forms.
For dissolution acceptance criteria, the following points should be considered:
14. 1. The dissolution profile data from the pivotal clinical batches and primary (registration)
stability batches should be used for the setting of the dissolution acceptance criteria of
the product (i.e., specification-sampling time point and specification value).
⢠A significant trend in the change in dissolution profile during stability should be
justified with dissolution profile comparisons and in vivo data in those instances where
the similarity testing fails.
2. Specifications should be established based on average in vitro dissolution data for each
lot under study, equivalent to USP Stage 2 testing (n = 12).
3. For immediate-release formulations, the last time point should be the time point where
at least 80% of drug has been released.
⢠If the maximum amount released is less than 80%, the last time point should be the
time when the plateau of the release profile has been reached. Percent release of less
than 80% should be justified with data (e.g.., sink conditions information).
15. 4. For extended-release formulations, a minimum of three time points is recommended to
set the specifications.
⢠These time points should cover the early, middle, and late stages of the release profile.
The last time point should be the time point where at least 80% of drug has been
released.
⢠If the maximum amount released is less than 80%, the last time point should be the time
when the plateau of the release profile has been reached.
5. The dissolution acceptance criterion should be set in a way to ensure consistent
performance from lot to lot, and this criterion should not allow the release of any lots
with dissolution profiles outside those that were studied clinically
16. PROBLEMS OF VARIABLE CONTROL IN DISSOLUTION
TESTING
⢠Dissolution testing involves various steps such as solidâliquid mass transfer, particle erosion,
possible particle disintegration, particle suspension, and particleâliquid interactions.
⢠It is complicated by other factors such as shear stress distribution as a function of tablet
location within the apparatus, and the location of the tablet upon its release inside the apparatus.
⢠Depending on the particular dosage form involved, the variables may or may not exert a
pronounced effect on the rate of dissolution of the drug or drug product.
⢠Variations may occur with the same type of equipment and procedure.
17. ⢠The centering and alignment of the paddle is critical in the paddle method.
⢠Turbulence can create increased agitation, resulting in a higher dissolution rate.
⢠Wobbling and tilting due to worn equipment should be avoided. The basket
method is less sensitive to the tilting effect.
⢠However, the basket method is more sensitive to clogging due to gummy materials.
⢠Pieces of small particles can also clog up the basket screen and create a local non-
sink condition for dissolution.
⢠Dissolved gas in the medium may form air bubbles on the surface of the dosage
form unit and can affect dissolution in both the basket and paddle methods.
⢠Small variations in the location of the tablet on the vessel bottom caused by the
randomness of the tablet descent through the liquid are likely to result in
significantly different velocities and velocity gradients near the tablet
18. The Reynolds number is calculated with this equation:
Where,
Re is the Reynolds number,
is the density of the fluid,
v is the velocity of the fluid flow,
d is the diameter of the pipe, and
Âľ is the viscosity of the fluid.Âľ
19. PERFORMANCE OF DRUG PRODUCTS: IN VITROâIN
VIVO CORRELATION
⢠For CR or ER formulation - dissolution is the rate-limiting step, hence it is possible to
establish a relationship between the release of the drug in vitro and its release in vivo or its
absorption into the systemic circulation.
⢠If such correlation exists, then one is able to predict the plasma concentration time profile of a
drug from its in vitro dissolution.
⢠Usually such a correlation is developed with two or more formulations with different release
characteristics. (Recommended- 3 or more formulations)
⢠If the dissolution of the drug is independent of the dissolution conditions (such as apparatus
agitation rate, pH, etc), then it is possible to establish such a correlation with only one
formulation
20. ⢠The establishment of a predictive IVIVC also enables us to decrease the number of in
vivo studies needed to approve and maintain a drug product on the market resulting in an
economic benefit as well as a decreased regulatory burden.
⢠It also enables to set clinically meaningful dissolution specifications based on the
predicted plasma concentration time profile.
⢠There are two ways in evaluating the predictability of the correlation:
1. Internal predictability refers to the ability to predict the pharmacokinetic profile
of the formulations that were used to develop the correlation;
2. External predictability refers to the ability to detect the profile of a lot or
formulation that was not used to develop the IVIVC.
21. Categories of In VitroâIn Vivo Correlations
1. Level A Correlation
2. Level B Correlation
3. Level C Correlation
a) Dissolution rate versus absorption rate.
b) Percent of drug dissolved versus percent of drug absorbed.
c) Maximum plasma concentrations versus percent of drug dissolved in vitro.
d) Serum drug concentration versus percent of drug dissolved.
e) Biopharmaceutic Drug Classification System
4. Multiple level C correlation
22. LEVEL A CORRELATION
⢠Highest level of correlation and represents
a point-to-point (1:1) relationship between
an in vitro dissolution and the in vivo
input rate of the drug from the dosage
form.
⢠Level A correlation compares the percent
(%) drug released versus percent (%) drug
absorbed.
⢠The percentage of drug absorbed can be
calculated by the Wagnerâ Nelson or Looâ
Riegelman procedures or by direct
mathematical deconvolution.
Advantages-
⢠A point-to-point correlation is developed.
⢠In vitro dissolution profile can serve as a
surrogate for in vivo performance.
⢠A change in manufacturing site, method of
manufacture, raw material supplies, minor
formulation modification, and product
strength using the same formulation can be
justified without the need for additional
human studies.
⢠Enables the in vitro dissolution test to become
meaningful and clinically relevant quality
control test that can predict in vivo drug
product performance
23. % drug dissolved in-vitro
% drug
Absorbed
in-vivo
LEVEL A CORRELATION
24. WAGNER NELSON METHOD
⢠The Wagner Nelson method can be used to calculate the absorption rate
constant when the absorption process follows zero-order or first-order.
⢠The model also generates AUCs (Areas Under the Curve) and rate of
absorption values.
⢠This method estimates the loss of drug from the GI over time, whose slope
is inversely proportional to ka.
⢠After a single oral dose of a drug, the total dose should be completely
accounted for the amount present in the body, the amount present in the
urine, and the amount present in the GI tract.
⢠Dose (D0) is expressed as follows:
25. LOOâRIEGELMAN
⢠Used to calculate the relative amount absorbed as a function of time from
plasma concentration data which follow a two-compartment open model.
⢠After oral administration of a dose of a drug that exhibits two-compartment
model kinetics, the amount of drug absorbed is calculated as the sum of the
amounts of drug in the central compartment (Dp), in the tissue compartment
(Dt), and the amount of drug eliminated by all routes (Du).
Ab = Dp + Dt + Du
27. LEVEL B CORRELATION
⢠Level B correlation utilizes the principle of statistical moment in which the mean
in-vitro dissolution time is compared to either the mean residence time (MRT) or
the mean in-vivo dissolution time (MDT).
⢠Level B correlation uses all of the in vitro and in vivo data, but is not a point-to-
point correlation.
⢠Different profiles can give the same parameter values.
⢠The Level B correlation alone cannot justify formulation modification,
manufacturing site change, excipient source change, batch-to-batch quality, etc.
28. MRT(Mean residence time) represents the average time a molecule stays in the body.
The MRT is calculated by summing the total time in the body and dividing by the number of
molecules.
AUMC is obtained from a plot of product of plasma drug concentration and time (i.e. C.t) versus time
t from zero to infinity. Mathematically, it is expressed by equation:
AUC is obtained from a plot of plasma drug concentration versus time from zero to infinity.
Mathematically, it is expressed by equation:
29. MDT (The mean dissolution time ) can be calculated arithmetically the following equation:
where W(t) is the cumulative amount of drug dissolved at time t.
This equation is very useful, especially in cases where a correlation of in vitro and in vivo MDT
values is attempted.
In actual practice, an equivalent form of this equation is used to derive an estimate of MDT from
experimental dissolution data
where Wâ is the asymptote of the dissolved amount of drug and ABC is the area between the
cumulative dissolution curve and Wâ
30.
31. ⢠Not a point-to-point correlation.
⢠Establishes a single-point relationship between
a dissolution parameter (such as drug released
at a certain time ) and a pharmacokinetic
parameter of interest (such as AUC and Cmax).
⢠Useful for formulation selection and
development but has limited application.
⢠Multiple Level C correlation relates one or
several pharmacokinetic parameters of interest
to the amount of drug dissolved at several time
points of the dissolution profile.
⢠In general, if one is able to develop a multiple
Level C correlation, then it may be feasible to
develop a Level A correlation.
LEVEL C CORRELATION
Fig- Level C correlation showing the
relationship between the amount of drug
dissolved at a certain time and the peak plasma
concentration
32. Examples of Level C correlation:-
⢠Dissolution rate versus absorption rate.
⢠Percent of drug dissolved versus percent of drug
absorbed.
⢠Biopharmaceutic Drug Classification System
33. Dissolution Rate Versus Absorption Rate
⢠If dissolution is rate limiting,
faster dissolution - faster rate of appearance of the drug in the plasma.
correlation between rate of dissolution and rate of absorption may be established .
⢠The absorption rate is usually more difficult to determine than peak absorption time.
Therefore, the absorption time may be used in correlating dissolution data to
absorption data.
⢠In the analysis of in vitroâin vivo drug correlation, rapid drug dissolution may be
distinguished from the slower drug absorption by observation of the absorption time
for the preparation.
⢠The absorption time refers to the time for a constant amount of drug to be absorbed.
34. Fig- An example of correlation between time required for a given amount of drug to
be absorbed and time required for the same amount of drug to be dissolved in vitro
for three sustained-release aspirin products
35. Percent of drug dissolved versus percent of drug absorbed
⢠If a drug is absorbed completely after dissolution, a linear correlation may be obtained
by comparing the percentage of drug absorbed to the percentage of drug dissolved.
⢠In choosing the dissolution method, appropriate dissolution medium and slow
dissolution stirring rate is considered so that in vivo dissolution is approximated.
⢠Aspirin is absorbed rapidly, and a slight change in formulation may be reflected in a
change in the amount and rate of drug absorption during the period of observation.
⢠If the drug is absorbed slowly, which occurs when absorption is the rate-limiting step, a
difference in dissolution rate of the product may not be observed. In this case, the drug
would be absorbed very slowly independent of the dissolution rate.
36. Fig- An example of correlation between time
required for a given amount of drug to be absorbed
and time required for the same amount of drug to
be dissolved in vitro for three sustained-release
aspirin products
Fig- An example of continuous in
vivoâin vitro correlation of aspirin.
37. Biopharmaceutic Drug Classification System
⢠BCS is a predictive approach to relate certain physicochemical characteristics of a
drug substance and drug product to in vivo bioavailability.
⢠The BCS is not a direct in vitroâ in vivo correlation.
⢠For example, BCS Class I drugs- rapidly and mostly absorbed. (oral and IR)
⢠A BCS Class I drug (highly soluble & permeable) rapidly dissolves from the drug
product over the physiologic pH range of 1â7.4.
⢠Highly permeable drugs are drugs whose absolute bioavailability is greater than 90%.
⢠BCS only applies to oral immediate-release formulations and cannot be applied to
modified-release formulations or for buccally absorbed drug products.
38. MULTIPLE LEVEL C CORRELATION
⢠This level refers to the relationship between one or more pharmacokinetic parameters of
interest (Cmax,,AUC, or any other suitable parameters) and amount of drug dissolved at several
time points of dissolution profile.
⢠Multiple point level C correlation may be used to justify a biowaver provided that the
correlation has been established over the entire dissolution profile with one or more
pharmacokinetic parameter of interest.
⢠A multiple level C correlation should be based on atleast three dissolution time points
covering the early, middle, and last stages of the dissolution profile.
⢠The development of a level A correlation is also likely, when multiple level C correlation is
achieved at each time point at same parameter such that the effect on the in vivo performance
of any change in dissolution can be assessed.
39. DISSOLUTION PROFILE COMPARISONS
⢠Dissolution profile comparisons are used to assess the similarity of the dissolution
characteristics of two formulation or different strengths of the same formulation to decide
whether in vivo bioavailability/ bioequivalence studies are needed.
⢠The SUPAC-IR and SUPAC-MR provide recommendations to firms who intend, during
the post-approval period, to change
a) The components or compositions
b) The site of manufacture
c) The scale-up/scale-down of manufacture; and/or
d) The manufacturing (process and equipment) of the drug product.
For each type of change, these guidance list documentation (e.g., dissolution testing,
bioequivalence, etc) should be normally provided to support the change depending on the
level of complexity of the proposed change
40. ⢠For minor changes and some major changes for which in vivo bioequivalence is not
warranted, dissolution profile comparisons either in the proposed media or in multimedia
can be submitted to support the change.
⢠Dissolution profiles may be considered similar by virtue of overall profile similarity
and/or similarity at every dissolution sample time point.
⢠According to the FDA - three statistical methods for the evaluation of similarity:
1. Model-independent approach using a similarity factor;
2. Model-independent multivariate confidence region procedure; and
3. Model dependent approach
41. Model-independent approach
Difference factor (f1)
⢠The difference factor (f1) calculates
the percent (%) difference between the
two curves at each time point and is a
measurement of the relative error
between the two curves.
Similarity factor (f2)
⢠It is logarithmic reciprocal square root
transformation of the sum of squared
error and is a measurement of the
similarity in the percent (%) dissolution
between the two curves.
n - number of time points,
R - dissolution value of the reference batch at time t,
T - dissolution value of the test batch at time t
42. A specific procedure to determine difference and similarity :
1. Determine the dissolution profile of two products (12 units each) of the test and reference
products.
2. Using the mean dissolution values from both curves at each time interval, calculate the
difference factor (f1 ) and similarity factor (f2 ) using the given equations.
3. For curves to be considered similar, f 1 values should be close to 0, and f2 values should be
close to 100.
⢠Generally, f1 values up to 15 (0-15) and f2 values greater than 50 (50-100) ensure sameness
or equivalence of the two curves and, thus, of the performance of the test and reference
products.
⢠This model independent method is most suitable for dissolution profile comparison when
three to four or more dissolution time points are available.
43. Recommendations to be considered:
⢠The dissolution measurements of the test and reference batches should be made under
exactly the same conditions. The dissolution time points for both the profiles should be
the same (e.g.., 15, 30, 45, 60 minutes). The reference batch used should be the most
recently manufactured prechange product.
⢠Only one measurement should be considered after 85% dissolution of both the products.
⢠To allow use of mean data, the percent coefficient of variation at the earlier time points
(e.g.., 15 minutes) should not be more than 20%, and at other time points should not be
more than 10%.
⢠The mean dissolution values for R can be derived either from (1) last batch or (2) last two
or more consecutively manufactured reference batches.
44. Model Independent Multivariate Confidence Region Procedure
In instances where within batch variation is more than 15% CV, a multivariate model
independent procedure is more suitable for dissolution profile comparison.
Steps:
1. Determine the similarity limits in terms of multivariate statistical distance (MSD) based
on inter batch differences in dissolution from reference (standard approved) batches.
2. Estimate the MSD between the test and reference mean dissolutions.
3. Estimate 90% confidence interval of true MSD between test and reference batches.
4. Compare the upper limit of the confidence interval with the similarity limit. The test batch
is considered similar to the reference batch if the upper limit of the confidence interval is
less than or equal to the similarity limit.
45.
46. Model Dependent Approaches
Several mathematical models are described to fit dissolution profiles. To allow
application of models to comparison of dissolution profiles, the following procedures
are suggested:
1. Select the most appropriate model for the dissolution profiles from the standard,
prechange, approved batches. A model with no more than three parameters (such as
linear, quadratic, logistic, probit, and Weibull models) is recommended.
2. Using data for the profile generated for each unit, fit the data to the most
appropriate model.
3. A similarity region is set based on variation of parameters of the fitted model for
test units (e.g.., capsules or tablets) from the standard approved batches.
47. 4. Calculate the MSD in model parameters between test and reference
batches.
5. Estimate the 90% confidence region of the true difference between the
two batches.
6. Compare the limits of the confidence region with the similarity region. If
the confidence region is within the limits of the similarity region, the test
batch is considered to have a similar dissolution profile to the reference
batch.
48. DRUG PRODUCT STABILITY
⢠Product stability is usually determined by testing a variety of stability indicating attributes
such as drug potency, impurities, dissolution, and other relevant physicochemical
measures of performance as necessary.
⢠Stability studies are performed under well-controlled testing conditions and provide
evidence on how the quality of a drug product varies with time under the influence of a
variety of environmental factors such as temperature, humidity, oxygen, and light.
⢠The time period during which a drug product is expected to remain within the established
product quality specification under the labelled storage conditions is generally termed
âshelf-lifeâ(expiration period, expiry date, or expiration date).
ICH Q1A(R2)
49. CONSIDERATIONS IN THE DESIGN OFA DRUG PRODUCT
Biopharmaceutic Considerations
The essential elements include-
1. The physicochemical nature of the drug to be used, for example, salt and particle size;
2. The timing of these studies in relation to the preclinical studies with the drug;
3. The determination of the solubility and dissolution characteristics;
4. The evaluation of drug absorption and physiological disposition studies; and
5. The design and evaluation of the final drug formulation.
⢠The finished dosage form should not produce any additional side effects or discomfort
due to the drug and/or excipients.
⢠Ideally, all excipients - pharmacologically inactive ingredients in the final dosage form
50. Pharmacodynamic Considerations
⢠The therapeutic objective influences the design of the drug product, route of drug administration,
dose, dosage regimen, and manufacturing process.
⢠An oral drug used to treat an acute illness is generally formulated to release the drug rapidly,
allowing for quick absorption and rapid onset.
⢠If more rapid drug absorption is desired , then an injectable drug is formulated.
⢠Nitro-glycerine, is highly metabolized if swallowed, hence, a sublingual tablet formulation.
⢠To reduce unwanted systemic side effects - locally acting drugs (such as inhaled drugs)
⢠Advantage â drug can be delivered directly into the lungs.
⢠For the treatment of certain diseases, such as hypertension, chronic pain, etc, an extended or
controlled-release dosage form is preferred
51. Drug Substance Considerations
⢠The physicochemical properties of the drug substance are major factors.
⢠It include solubility, stability, chirality, polymorphs, solvate, hydrate, salt form, ionizable
behaviour, and impurity profile.
⢠They influence the type of dosage form, the formulation, and the manufacturing process.
⢠Physical properties of the drug such as intrinsic dissolution rate, particle size, and crystalline
form are influenced by methods of processing and manufacturing.
⢠If the drug has low aqueous solubility and an intravenous injection is desired, a soluble salt of the
drug may be prepared.
⢠Chemical instability or chemical interactions with certain excipients also affect the type of drug
product and its method of fabrication.
52. Pharmacokinetics of the Drug ⢠Clinical failures of about 50% of the
Investigational New Drug (IND) filings are
attributed to their inadequate ADME attributes.
⢠the integration of PK and PD allows for the
characterization of the onset, intensity, and
duration of the pharmacological effect of a drug
and its interaction to the mechanism of action.
⢠The degree of polymorphism can significantly
affect the drug metabolism and, therefore, the
pharmacokinetics and the clinical outcome of
the drug.
⢠Pharmacokinetic properties(ADME), of
the molecules being investigated as
potential drug candidates is a major factor.
⢠The data obtained from ADME studies
allow the development of a dose and
dosage regimen that are age appropriate
including avoidance of drugâdrug
interactions, food effect interactions, and
achieving an appropriate drug release rate.
53. Bioavailability of the Drug
⢠Dissolve > disintegrate > Absorb
⢠The stability of the drug in the gastrointestinal tract, is one consideration.
⢠Some drugs, (e.g.. penicillin G) are unstable in the acidic medium of the stomach > the
addition of buffer or the use of an enteric coating.
⢠Some drugs have poor bioavailability because of first-pass effects.
⢠If oral drug bioavailability is poor due to metabolism by enzymes in the GIT or in the liver,
then a higher dose may be needed (e.g.., Propranolol), or an alternative route of drug
administration, (e.g.., Nitro-glycerine).
⢠Incompletely absorbed drugs and drugs with highly variable bioavailability, under
unusual conditions (e.g.., change in diet or disease condition, drugâdrug interaction),
excessive drug bioavailability can occur leading to more intense pharmacodynamic
activity and possible adverse events.
⢠If the drug is not absorbed after the oral route or a higher dose causes toxicity > drug is
given by alternative route, and a different dosage form.
54. Dose Considerations
⢠Because of differences in pharmacokinetic parameters several patients, require individualized
dosing, therefore, the drug product must usually be available in several dose strengths.
⢠Some tablets are also scored for breaking, to allow the administration of fractional tablet doses.
⢠When pediatric studies are necessary, they must be conducted with the same drug and for the
same use for which they were approved in adults.
⢠Thus, specific dosing guidelines and useful dosage forms for pediatric patients are being
developed to optimize therapeutic efficacy and limit, or prevent serious adverse side effects.
⢠Renal or liver impairment > the drug metabolism or excretion process may be altered > requiring
smaller dose.
⢠For example, in case of renal insufficiency, phenobarbitone, which is mainly excreted by
the kidneys, should be given in smaller dose, and in case of patients with liver impairment,
morphine should be given in smaller dose.
⢠The size and the shape of a solid oral drug product are designed for easy swallowing.
⢠For example, many patients may find a capsule-shaped tablet (caplet) easier to swallow than
a large round tablet.
55. Dosing Frequency
⢠The dose is the amount of drug taken at any one time.
⢠This can be expressed as the wt. of drug, volume of drug solution, or some other quantity
(2 puffs).
⢠The dosage regimen is the frequency at which the drug doses are given. Examples - two
puffs twice a day, one capsule two times a day, etc.
⢠The total daily dose is calculated from the dose and the number of times per day the dose
is taken.
⢠If the drug has a short elimination half-life or rapid clearance > the drug is given more
frequently or in an extended release drug product.
⢠Simplifying the medication dosing frequency improves compliance.
⢠To minimize fluctuating plasma drug concentrations and improve patient compliance >
extended-release drug product may be preferred.
56. Patient Considerations
⢠The drug product and therapeutic regimen must be acceptable to the patient.
⢠Poor patient compliance may result from poor product attributes, such as difficulty
in swallowing, disagreeable odor, bitter medicine taste, or too frequent and/or
unusual dosage requirements.
⢠Orally disintegrating tablets and chewable tablets allow the patient to typically
take the medication without water.
⢠These innovations improve compliance, pharmacodynamic factors, such as side
effects of the drug or an allergic reaction, also influence patient compliance.
⢠Transmucosal (nasal) administration of antiepileptic drugs may be more
convenient, easier to use, just as safe, and is more socially acceptable than rectal
administration.
57. Route of Drug Administration
⢠The route of drug administration affects the bioavailability, thereby affecting the
onset, duration, and intensity of the pharmacologic effect.
⢠For IV delivery, the total dose of drug reaches the systemic circulation. However,
drug delivery by other routes result in only partial absorption, resulting in lower
bioavailability.
⢠In the design of a drug dosage form, the manufacturer must consider:-
1. the intended route of administration;
2. the size of the dose;
3. the anatomic and physiologic characteristics of the administration site, such
as membrane permeability and blood flow;
4. the physicochemical properties of the site, such as pH, osmotic pressure, and
presence of physiologic fluids; and
5. the interaction of the drug and dosage form at the administration site,
including alteration of the administration site due to the drug and/or dosage
form.
58. ⢠Pharmacodynamic activity of the drug at
the receptor site is similar with different
routes of administration, severe
differences in the intensity of the
pharmacodynamic response and the
occurrence of adverse events may be
observed.
⢠For example, isoproterenol has a
thousandfold difference in activity when
given orally or by IV injection.
⢠The use of novel drug delivery methods
could enhance the efficacy and reduce the
toxicity of antiepileptic drugs.
⢠Slow-release oral forms of medication or
depot drugs such as skin patches might
improve compliance and, therefore,
seizure control.
Doseâresponse curve to isoproterenol by
various routes in dogs