M.pharm (Pharmaceutics) Molecular Pharmaceutics (NTDS) unit 1 part 1 Targeted Drug Delivery Systems: Concepts, Events and biological process involved in drug targeting.
The document describes electrosomes, which are lipid vesicles containing ion channel proteins that allow ion transport. Electrosomes consist of two compartments - an anode displaying enzymes for ethanol oxidation and a cathode displaying an oxygen-reducing enzyme. Enzymes containing dockerin modules are attached to cohesin sites on scaffoldin proteins and displayed on yeast cell surfaces. This allows electron transfer through enzymatic cascades for high fuel cell power output. Electrosomes show potential as drug delivery carriers by controlling drug release and targeting tissues selectively.
Virtual clinical trials offer advantages over traditional trials such as improved patient comfort, convenience and confidentiality. They utilize technologies like apps and online platforms to remotely collect data from trial participants from start to finish. While offering benefits, virtual trials also carry risks regarding patient privacy, operational challenges, and technical or cultural barriers. Ideal virtual trials would generate necessary data with minimal burden, foster ongoing relationships to better understand conditions, and engage providers in a complementary way. Emerging technologies like social media, mobile devices, remote monitoring, and electronic patient reporting can help promote virtual trials by automating data collection and enabling remote participation. Physiologically-based modeling using software like GastroPlus can help predict food effects on drug absorption by simulating gastrointestinal conditions
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.
ROLE OF DOSAGE FORM IN GASTRO-INTESTINAL ABSORPTION Ankit Malik
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.
Computational modelling of drug disposition lalitajoshi9
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.
M.pharm (Pharmaceutics) Molecular Pharmaceutics (NTDS) unit 1 part 1 Targeted Drug Delivery Systems: Concepts, Events and biological process involved in drug targeting.
The document describes electrosomes, which are lipid vesicles containing ion channel proteins that allow ion transport. Electrosomes consist of two compartments - an anode displaying enzymes for ethanol oxidation and a cathode displaying an oxygen-reducing enzyme. Enzymes containing dockerin modules are attached to cohesin sites on scaffoldin proteins and displayed on yeast cell surfaces. This allows electron transfer through enzymatic cascades for high fuel cell power output. Electrosomes show potential as drug delivery carriers by controlling drug release and targeting tissues selectively.
Virtual clinical trials offer advantages over traditional trials such as improved patient comfort, convenience and confidentiality. They utilize technologies like apps and online platforms to remotely collect data from trial participants from start to finish. While offering benefits, virtual trials also carry risks regarding patient privacy, operational challenges, and technical or cultural barriers. Ideal virtual trials would generate necessary data with minimal burden, foster ongoing relationships to better understand conditions, and engage providers in a complementary way. Emerging technologies like social media, mobile devices, remote monitoring, and electronic patient reporting can help promote virtual trials by automating data collection and enabling remote participation. Physiologically-based modeling using software like GastroPlus can help predict food effects on drug absorption by simulating gastrointestinal conditions
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.
ROLE OF DOSAGE FORM IN GASTRO-INTESTINAL ABSORPTION Ankit Malik
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.
Computational modelling of drug disposition lalitajoshi9
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.
ACTIVE TRANSPORT- hPEPT1,ASBT,OCT,OATP, BBB-Choline Transporter.pptxPawanDhamala1
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.
The document discusses various drug delivery systems including niosomes, aquasomes, and phytosomes. Niosomes are vesicles composed of non-ionic surfactants that can encapsulate medications and offer advantages over liposomes such as lower cost and greater stability. Aquasomes are three-layered nanoparticle structures consisting of a ceramic core coated with an oligosaccharide film that can deliver fragile molecules while maintaining their integrity. Phytosomes utilize phospholipids to surround active herbal constituents, improving their absorption and bioavailability compared to traditional herbal extracts.
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
Tumour targeting and Brain specific drug deliverySHUBHAMGWAGH
The document discusses tumor targeting and brain specific drug delivery. It provides an introduction to targeted drug delivery and outlines strategies for tumor targeting including passive targeting via the enhanced permeability and retention effect, active targeting using ligands, and triggered drug delivery responsive to microenvironment changes. It also discusses challenges of drug delivery to the brain posed by the blood-brain barrier and factors that affect crossing it, as well as diseases related to the brain and strategies to enhance brain-specific drug delivery.
computer aided formulation developmentSUJITHA MARY
The document discusses optimization techniques used in computer aided formulation development. It defines optimization as choosing the best alternative while considering all influencing factors. Optimization techniques help minimize experimental trials, reduce costs and save time compared to traditional trial and error methods. The document describes various experimental design approaches like factorial designs, response surface methodology and mixture designs that are used to optimize formulations. It also discusses simultaneous techniques like evolutionary operations and simplex method as well as sequential techniques like mathematical modeling and search methods. Optimization is important for developing formulations with desired performance and ensuring reproducible, large-scale manufacturing.
LEGAL PROTECTION OF INNOVATIVE USES OF COMPUTERS IN R & D.pptxTanvi Mhashakhetri
CONTENTS :
Introduction
Intellectual Property Rights
Patents
Patents on Algorithms
Patents on Human Interfaces
Patents on Machine-Machine Interfaces
Patents on Data Structures
Copyright
Protection of Databases
Trade Secrets
Enforcement of Rights
Conclusion
References
INTRODUCTION :
The days in which IP (intellectual property) strategists were separated into groups of pharmacologists (chemists or biologists) and other groups of computer scientists are slowly passing—in the same manner in which the technologies are increasingly overlapping in the scientific world.
Pharmacology patent lawyers had typically spent their training in the laboratory working with chemicals or using polymerase chain reaction (PCR) techniques; they understood how small molecular entities functioned and characterized sequences of RNA, DNA, and proteins.
Computer scientists, on the other hand, spent hours programming computers and later writing software and business method patents.
Just as understanding the application of computers in pharmacology presents a challenge for researchers in both fields, it also means that the IP specialists also need to combine strategies from both fields to obtain the best possible legal protection for innovation.
A few years ago a study carried out by the London-based consulting firm Silico Research reported that very few patent applications had been filed in bioinformatics.
The reasons cited in the study for the scarcity of patents included the fact that many current bioinformatics products merely combined existing data sources into a single product and the difficulty of proving infringement of software patents.
The United States Patent and Trademark Office (USPTO) recognized in 1999 that bioinformatics represented a special challenge and that same year created a special examination group—Art Unit 1631—to examine the increasing number of applications .
Since these studies were published, however, the growth in the number of bioinformatics patents seems to have stalled.
INTELLECTUAL PROPERTY RIGHTS
The term “ Intellectual property Rights” is used to describe the legal instrument for protecting innovation .
There are intellectual property issues associated with four elements of a software program:
Program function - whether the algorithm is performed by the hardware or the software,
External design - the conventions for communication between the program and the user or other programs,
User interfaces - the interactions between the program and the user,
Program code - the implementation of the function and external design of the program.
CONCLUSION
The use of computers in developing new pharmaceutical products is nowadays common place, and a number of tools and databases have been developed to improve their use. Although intellectual property rights have to date rarely been the subject of court cases.
• In silico (literally alluding the mass use of silicon for semiconductor computer chips) is an expression used to performed on computer or via computer simulation
• In silico tools capable of identifying critical factors (i.e. drug physicochemical properties, dosage form factors) influencing drug in vivo performance, and predicting drug absorption based on the selected data set (s) of input factors.
Virtual trial, Fed vs fasted state, In vitro dissolution & IVIC correlation ,...PawanDhamala1
The document discusses virtual clinical trials and their advantages over conventional clinical trials. It describes how emerging technologies like mobile apps, remote monitoring devices, and electronic data capture can enable various stages of clinical trials to be conducted virtually with participants' comfort and convenience in mind. Several case studies are presented, including one conducted by Sanofi using Facebook to recruit diabetes patients for a virtual trial testing a wireless glucose meter. The document also covers other topics like predicting food effects on drug absorption using physiologically-based modeling, and using such models to establish in vitro-in vivo correlations.
This document discusses computer aided formulation development and optimization techniques. It covers topics like optimization parameters, response surface curves, experimental designs, and factorial designs. Specifically, it defines optimization as making a design or system as effective as possible. It also describes types of experimental designs like factorial designs, which study the effects of varying multiple factors simultaneously. Full and fractional factorial designs are explained, with fractional designs requiring fewer runs by testing only a subset of the full factorial design combinations.
Cellular uptake of drugs can occur through passive diffusion of small molecules or active transport of larger particles via endocytosis, exocytosis, phagocytosis, or pinocytosis. Transport across epithelial barriers relies on passive diffusion, carriers, or endocytosis. Extravasation from blood vessels depends on permeability and physicochemical drug properties, while lymphatic uptake drains drug molecules from tissues. The reticuloendothelial system phagocytoses pathogens and debris from circulation and tissues.
Gastrointestinal absorption simulation using in silico methodology; by Dr. Bh...bhupenkalita7
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 summarizes strategies for brain-specific drug delivery by bypassing the blood-brain barrier (BBB). It discusses the anatomy and functions of the BBB and various invasive and non-invasive approaches to deliver drugs to the brain. Invasive approaches include temporary disruption of the BBB using osmotic or ultrasound techniques or direct injection into the brain or ventricles. Non-invasive methods involve chemical modifications like prodrugs or drug conjugates, use of nanoparticles, liposomes, or monoclonal antibodies to transport drugs across the BBB. The document also lists some marketed products and potential applications like treatment of neurodegenerative diseases, brain tumors, and infections.
COMPUTER SIMULATIONS IN PHARMACOKINETICS & PHARMACODYNAMICSsagartrivedi14
Computer simulations in pharmacokinetics and pharmacodynamics can model the whole organism, isolated tissues, and individual organs. Whole organism simulations use lumped-parameter models that represent the body with a small number of differential equations, or physiological models that use more differential equations to describe organs in detail. Isolated tissue and organ simulations often use distributed blood tissue exchange models for organs like the heart and liver. These simulations aim to integrate organ-specific models with whole-body models to improve predictive capabilities in areas like pharmacokinetics.
Computational modeling of drug dispositionPV. Viji
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
This document discusses using computer-aided modeling to simulate gastrointestinal absorption and predict oral drug bioavailability. Dynamic models can predict drug absorption rates and plasma concentration profiles. Such models can help evaluate formulations, screen compounds, and predict absorption when traditional methods are limited. The document describes how GastroPlus software simulates drug movement through the GI tract and how models are constructed and verified. It also discusses using models to predict food effects and establish in vitro-in vivo correlations to evaluate bioequivalence.
This document discusses gastrointestinal absorption simulation presented by Arzoo Sekhani. It provides background on in silico gastrointestinal absorption modeling using the Advanced Compartmental Absorption and Transit (ACAT) model in GastroPlus software. The theoretical background section describes the processes considered in the ACAT model, including drug transit, dissolution, absorption and metabolism in GI tract compartments. The model construction section discusses parameter selection and optimization to simulate nimesulide absorption, comparing two models based on different assumptions about nimesulide transporter interactions and solubility. Simulation results from both models were compared to clinical data to identify the most accurate model.
ACTIVE TRANSPORT- hPEPT1,ASBT,OCT,OATP, BBB-Choline Transporter.pptxPawanDhamala1
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.
The document discusses various drug delivery systems including niosomes, aquasomes, and phytosomes. Niosomes are vesicles composed of non-ionic surfactants that can encapsulate medications and offer advantages over liposomes such as lower cost and greater stability. Aquasomes are three-layered nanoparticle structures consisting of a ceramic core coated with an oligosaccharide film that can deliver fragile molecules while maintaining their integrity. Phytosomes utilize phospholipids to surround active herbal constituents, improving their absorption and bioavailability compared to traditional herbal extracts.
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
Tumour targeting and Brain specific drug deliverySHUBHAMGWAGH
The document discusses tumor targeting and brain specific drug delivery. It provides an introduction to targeted drug delivery and outlines strategies for tumor targeting including passive targeting via the enhanced permeability and retention effect, active targeting using ligands, and triggered drug delivery responsive to microenvironment changes. It also discusses challenges of drug delivery to the brain posed by the blood-brain barrier and factors that affect crossing it, as well as diseases related to the brain and strategies to enhance brain-specific drug delivery.
computer aided formulation developmentSUJITHA MARY
The document discusses optimization techniques used in computer aided formulation development. It defines optimization as choosing the best alternative while considering all influencing factors. Optimization techniques help minimize experimental trials, reduce costs and save time compared to traditional trial and error methods. The document describes various experimental design approaches like factorial designs, response surface methodology and mixture designs that are used to optimize formulations. It also discusses simultaneous techniques like evolutionary operations and simplex method as well as sequential techniques like mathematical modeling and search methods. Optimization is important for developing formulations with desired performance and ensuring reproducible, large-scale manufacturing.
LEGAL PROTECTION OF INNOVATIVE USES OF COMPUTERS IN R & D.pptxTanvi Mhashakhetri
CONTENTS :
Introduction
Intellectual Property Rights
Patents
Patents on Algorithms
Patents on Human Interfaces
Patents on Machine-Machine Interfaces
Patents on Data Structures
Copyright
Protection of Databases
Trade Secrets
Enforcement of Rights
Conclusion
References
INTRODUCTION :
The days in which IP (intellectual property) strategists were separated into groups of pharmacologists (chemists or biologists) and other groups of computer scientists are slowly passing—in the same manner in which the technologies are increasingly overlapping in the scientific world.
Pharmacology patent lawyers had typically spent their training in the laboratory working with chemicals or using polymerase chain reaction (PCR) techniques; they understood how small molecular entities functioned and characterized sequences of RNA, DNA, and proteins.
Computer scientists, on the other hand, spent hours programming computers and later writing software and business method patents.
Just as understanding the application of computers in pharmacology presents a challenge for researchers in both fields, it also means that the IP specialists also need to combine strategies from both fields to obtain the best possible legal protection for innovation.
A few years ago a study carried out by the London-based consulting firm Silico Research reported that very few patent applications had been filed in bioinformatics.
The reasons cited in the study for the scarcity of patents included the fact that many current bioinformatics products merely combined existing data sources into a single product and the difficulty of proving infringement of software patents.
The United States Patent and Trademark Office (USPTO) recognized in 1999 that bioinformatics represented a special challenge and that same year created a special examination group—Art Unit 1631—to examine the increasing number of applications .
Since these studies were published, however, the growth in the number of bioinformatics patents seems to have stalled.
INTELLECTUAL PROPERTY RIGHTS
The term “ Intellectual property Rights” is used to describe the legal instrument for protecting innovation .
There are intellectual property issues associated with four elements of a software program:
Program function - whether the algorithm is performed by the hardware or the software,
External design - the conventions for communication between the program and the user or other programs,
User interfaces - the interactions between the program and the user,
Program code - the implementation of the function and external design of the program.
CONCLUSION
The use of computers in developing new pharmaceutical products is nowadays common place, and a number of tools and databases have been developed to improve their use. Although intellectual property rights have to date rarely been the subject of court cases.
• In silico (literally alluding the mass use of silicon for semiconductor computer chips) is an expression used to performed on computer or via computer simulation
• In silico tools capable of identifying critical factors (i.e. drug physicochemical properties, dosage form factors) influencing drug in vivo performance, and predicting drug absorption based on the selected data set (s) of input factors.
Virtual trial, Fed vs fasted state, In vitro dissolution & IVIC correlation ,...PawanDhamala1
The document discusses virtual clinical trials and their advantages over conventional clinical trials. It describes how emerging technologies like mobile apps, remote monitoring devices, and electronic data capture can enable various stages of clinical trials to be conducted virtually with participants' comfort and convenience in mind. Several case studies are presented, including one conducted by Sanofi using Facebook to recruit diabetes patients for a virtual trial testing a wireless glucose meter. The document also covers other topics like predicting food effects on drug absorption using physiologically-based modeling, and using such models to establish in vitro-in vivo correlations.
This document discusses computer aided formulation development and optimization techniques. It covers topics like optimization parameters, response surface curves, experimental designs, and factorial designs. Specifically, it defines optimization as making a design or system as effective as possible. It also describes types of experimental designs like factorial designs, which study the effects of varying multiple factors simultaneously. Full and fractional factorial designs are explained, with fractional designs requiring fewer runs by testing only a subset of the full factorial design combinations.
Cellular uptake of drugs can occur through passive diffusion of small molecules or active transport of larger particles via endocytosis, exocytosis, phagocytosis, or pinocytosis. Transport across epithelial barriers relies on passive diffusion, carriers, or endocytosis. Extravasation from blood vessels depends on permeability and physicochemical drug properties, while lymphatic uptake drains drug molecules from tissues. The reticuloendothelial system phagocytoses pathogens and debris from circulation and tissues.
Gastrointestinal absorption simulation using in silico methodology; by Dr. Bh...bhupenkalita7
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 summarizes strategies for brain-specific drug delivery by bypassing the blood-brain barrier (BBB). It discusses the anatomy and functions of the BBB and various invasive and non-invasive approaches to deliver drugs to the brain. Invasive approaches include temporary disruption of the BBB using osmotic or ultrasound techniques or direct injection into the brain or ventricles. Non-invasive methods involve chemical modifications like prodrugs or drug conjugates, use of nanoparticles, liposomes, or monoclonal antibodies to transport drugs across the BBB. The document also lists some marketed products and potential applications like treatment of neurodegenerative diseases, brain tumors, and infections.
COMPUTER SIMULATIONS IN PHARMACOKINETICS & PHARMACODYNAMICSsagartrivedi14
Computer simulations in pharmacokinetics and pharmacodynamics can model the whole organism, isolated tissues, and individual organs. Whole organism simulations use lumped-parameter models that represent the body with a small number of differential equations, or physiological models that use more differential equations to describe organs in detail. Isolated tissue and organ simulations often use distributed blood tissue exchange models for organs like the heart and liver. These simulations aim to integrate organ-specific models with whole-body models to improve predictive capabilities in areas like pharmacokinetics.
Computational modeling of drug dispositionPV. Viji
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
This document discusses using computer-aided modeling to simulate gastrointestinal absorption and predict oral drug bioavailability. Dynamic models can predict drug absorption rates and plasma concentration profiles. Such models can help evaluate formulations, screen compounds, and predict absorption when traditional methods are limited. The document describes how GastroPlus software simulates drug movement through the GI tract and how models are constructed and verified. It also discusses using models to predict food effects and establish in vitro-in vivo correlations to evaluate bioequivalence.
This document discusses gastrointestinal absorption simulation presented by Arzoo Sekhani. It provides background on in silico gastrointestinal absorption modeling using the Advanced Compartmental Absorption and Transit (ACAT) model in GastroPlus software. The theoretical background section describes the processes considered in the ACAT model, including drug transit, dissolution, absorption and metabolism in GI tract compartments. The model construction section discusses parameter selection and optimization to simulate nimesulide absorption, comparing two models based on different assumptions about nimesulide transporter interactions and solubility. Simulation results from both models were compared to clinical data to identify the most accurate model.
Theoretical background on GastroPlus Simulation SoftwareArpitha Aarushi
this slides tells about Theoretical background on GastroPlus Simulation Software, basic ACAT model, and schematic diagram of compartment and sub compartment model.
Myself Omkar Tipugade , M - Pharm sem II , department of Pharmaceutics , today will upload presentation on Computational modeling in drug disposition .
Computational modeling in drug dispositionSUJITHA MARY
This document discusses computational modeling techniques for predicting drug disposition properties. It covers modeling approaches for drug absorption, distribution, and excretion. For absorption, it describes models for predicting solubility, intestinal permeability, and transporters. For distribution, it discusses models for volume of distribution, plasma protein binding, and blood-brain barrier permeability. For excretion, it summarizes models for hepatic and renal clearance. Current challenges include incorporating active transporters and generating predictive models from physiological understanding rather than empirical correlations.
This document summarizes computational modeling techniques for predicting drug absorption, distribution, and excretion properties. It discusses both quantitative and qualitative modeling approaches. For absorption, it describes models for predicting solubility, permeability, and factors like ionization state and transporters. For distribution, it covers volume of distribution, plasma protein binding, and blood brain barrier permeability modeling. For excretion, it discusses challenges modeling clearance but focuses on estimating clearance from in vitro data. The document provides examples of specific modeling tools and considers limitations of current approaches.
Rushikesh Shinde presented on computational modeling of drug disposition at Alard College of Pharmacy. The presentation discussed how modeling absorption, solubility, and intestinal permeation can help predict drug behavior in the body. Historically, drug candidates often failed in late-stage clinical trials due to issues related to metabolism, excretion, and toxicity, which computational modeling seeks to evaluate earlier in the drug development process. The presentation covered techniques like quantitative structure-activity relationship analysis and pharmacokinetic modeling to computationally simulate drug properties.
Computational modeling of drug disposition can help reduce drug development costs and failure rates. Key processes like absorption, distribution, metabolism, and excretion (ADME) can be modeled using various techniques. Drug absorption involves modeling solubility, which can be predicted using empirical or physiological approaches. Intestinal permeation, another key absorption process, can be modeled by simulating in vitro membrane permeation assays. Overall, computational modeling of ADME properties allows evaluation early in the drug development process to improve outcomes.
Computational modeling in drug dispositionHimal Barakoti
The document discusses computational modeling of drug disposition. It covers modeling of drug absorption, distribution, excretion, and active transport. For drug absorption, it describes modeling of solubility, intestinal permeability, and transporters involved. It also discusses modeling approaches for distribution processes like volume of distribution, plasma protein binding, and blood-brain barrier permeability. Current challenges include better incorporating the effects of active transporters in models. The document emphasizes that while computational models are useful for predicting drug properties, fully accounting for complex biological factors remains difficult.
This document discusses computational modeling techniques used in drug disposition modeling. It describes two main modeling approaches: quantitative approaches like pharmacophore modeling and docking studies; and qualitative approaches like QSAR and QSPR studies. It then discusses how these techniques can be applied to model key aspects of drug disposition, including absorption, distribution, and excretion. The key aspects of drug absorption, distribution, and excretion are also summarized.
This document discusses in silico modeling techniques for predicting drug absorption and pharmacokinetic properties. It covers two main modeling approaches: quantitative approaches like pharmacophore modeling and QSAR which use statistical analysis of molecular descriptors to correlate structure to properties, and qualitative approaches. Specific techniques covered include modeling solubility, intestinal permeability, and factors like transporters and ionization state that influence absorption. The goal is to use these computational models to predict absorption and other pharmacokinetic properties early in drug discovery to improve candidate selection and reduce late-stage clinical failures.
Bioavailability, Bioequivalence and BCS ClassificationVignan University
This document provides an overview of bioavailability, bioequivalence, and BCS classification. It defines key terms like bioavailability, absolute and relative bioavailability, and factors affecting bioavailability. Measurement methods like pharmacokinetic and pharmacodynamic approaches are discussed. Bioequivalence studies and their types are summarized. The six classes of BCS classification and its applications in drug development are highlighted in brief. In conclusion, the document notes that BCS classification provides guidance in drug formulation and review processes to reduce costs and time of approval.
1. The document discusses bioavailability and bioequivalence studies, which are important for determining the rate and extent of drug absorption from different formulations.
2. Key aspects of bioavailability studies include absolute and relative bioavailability, factors affecting bioavailability, and methods of measuring bioavailability through pharmacokinetic and pharmacodynamic approaches.
3. Bioequivalence studies aim to show that two products have identical plasma concentration time profiles and are therefore interchangeable. Different study designs like randomized and crossover designs are used to evaluate bioequivalence.
1. Various approaches can be used to predict the effect of food on drug absorption, including physiological factors, biorelevant dissolution methods, preclinical and clinical studies, Caco-2 cells, and in silico methods like physicochemical properties and physiologically-based pharmacokinetic modeling.
2. Physicochemical properties like aqueous solubility, dose to solubility ratio, and partition coefficient can provide qualitative predictions of food effects, and solubility has a strong negative correlation with the magnitude of food effects.
3. Physiologically-based pharmacokinetic modeling incorporates drug and physiological parameters to simulate absorption profiles under fasted and fed conditions and investigate variability, accounting for changes in stomach volume, pH, emptying
Martinez use of in silico models to support canine drug developmentCertara
The FDA's Dr. Marilyn Martinez discusses how biosimulation based approaches, such as PBPK modeling, can support developing safer, more effective medications for dogs.
The document provides an overview of the Biopharmaceutics Classification System (BCS). The BCS is a scientific framework used to classify drug substances based on their aqueous solubility and intestinal permeability. It includes four classes based on whether a drug is highly soluble/permeable, low soluble/high permeable, etc. The BCS is used to determine a drug's bioavailability and guide formulation approaches. It can help obtain a biowaiver for in vivo bioequivalence studies if a drug meets certain solubility and permeability criteria. While useful, the BCS has some limitations in predicting drug behavior due to challenges in determining permeability.
COMPUTATIONAL MODELING OF DRUG DISPOSITION.pptxPoojaArya34
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.
Historically, drug discovery has focused almost exclusively on efficacy and selectivity against the biological target.
As a result, nearly half of drug candidates fail at phase II and phase III clinical trials because of undesirable drug pharmacokinetics properties, including absorption, distribution, metabolism, excretion, and toxicity (ADMET).
The pressure to control the escalating cost of new drug development has changed the paradigm since the mid-1990s. To reduce the attrition rate at more expensive later stages, in vitroevaluation of ADMET properties in the early phase of drug discovery has been widely adopted.Many high-throughput in vitro ADMET property screening assays have been developed and applied successfully .
For example, Caco-2 and MDCK cell monolayers are widely used to simulate membrane permeability as an in vitro estimation of in vivo absorption.
These in vitro results have enabled the training of in silico models, which could be applied to predict the ADMET properties of compounds even before they are synthesized.
Computational Modeling of Drug Disposition bhupenkalita7
This document discusses in silico modeling techniques for predicting absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of drug candidates. It describes quantitative approaches like pharmacophore modeling and docking studies, as well as qualitative approaches like quantitative structure-activity relationship (QSAR) and quantitative structure-property relationship (QSPR) studies. Specific techniques are discussed for modeling various ADMET properties like solubility, permeability, plasma protein binding, blood-brain barrier penetration, and clearance. Transporters, ionization, and data quality are also mentioned as important factors. Commercial software packages are noted that can simulate these processes.
Computational modeling of drug dispositionArman Dalal
Computational modeling is used to predict drug absorption, distribution, metabolism, excretion and toxicity (ADMET) properties based on a drug's structure. Caco-2 and MDCK cell lines are used to simulate intestinal permeability for predicting oral absorption. Quantitative structure-activity relationship (QSAR) models correlate molecular descriptors with ADMET properties. Absorption models consider solubility, permeability through cell lines like Caco-2, and transporters. Distribution is reflected by volume of distribution, plasma protein binding and blood-brain barrier permeability. Excretion involves hepatic and renal clearance but current models cannot predict clearance directly from structure.
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
Mercurius is named after the roman god mercurius, the god of trade and science. The planet mercurius is named after the same god. Mercurius is sometimes called hydrargyrum, means ‘watery silver’. Its shine and colour are very similar to silver, but mercury is a fluid at room temperatures. The name quick silver is a translation of hydrargyrum, where the word quick describes its tendency to scatter away in all directions.
The droplets have a tendency to conglomerate to one big mass, but on being shaken they fall apart into countless little droplets again. It is used to ignite explosives, like mercury fulminate, the explosive character is one of its general themes.
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
The skin is the largest organ and its health plays a vital role among the other sense organs. The skin concerns like acne breakout, psoriasis, or anything similar along the lines, finding a qualified and experienced dermatologist becomes paramount.
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
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Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
DECLARATION OF HELSINKI - History and principlesanaghabharat01
This SlideShare presentation provides a comprehensive overview of the Declaration of Helsinki, a foundational document outlining ethical guidelines for conducting medical research involving human subjects.
3. Concept of gastrointestinal simulation absorption studied using in silico methodology.
Biopharmaceutical characterization of drug or pharmaceutical product increased for
development and evaluation of in silico tools for identifying critical factors
Different parameter used for construction of model and sensitivity
predicted of pharmacokinetic responses
In silico model : experiment is one performed on
computer or via computer simulation
less
Investment
In Resources
Less Time
Required
More
Accurate
Prediction
Minimize Use
of Animal
No of
Experiments
More
Real world
Process
Simulation
process
Mathematical
model
Advantages of in silico modelling 3
4. Drug absorption from the gastrointestinal (GI) tract is a complex process depends
on large number of factors including drug physicochemical properties,
physiological factors, and formulation related factors .
Physiochemical
• Particle Size
• Surface Area
• Dissolution Rate
• Amorphism
• Polymorphism
• Drug Solubility
• Salt Form
• Lipophilicity
• pKa of Drug
• Drug Stability
Physiological
• Nature of cell
membrane
• Transport mechanism
• Gastric emptying rate
• pH of Git
• Surface area of Git
• Intestinal transit
• Blood flow
• Effect of food
Formulation
• Disintegration time
• Method of preparation
• Nature and type of
dosage
• Pharmaceutical
ingredients
• Storage conditions
4
5. Once the drug passes through the basolateral membrane of enterocytes, it reaches
the portal vein and liver, where it can undergo first pass metabolism. From the
liver, it goes into the systemic circulation from where the ACAT model is
connected to either a conventional PK compartment model or a physiologically
based PK (PBPK) disposition model
For the study of gastro intestinal simulation different model and softwares used
And this model works on given input parameter data
Modeling and simulation start from data collection. Mechanistic absorption
models require a number of input parameters, which can either be experimentally
determined or in silico predicted. The common approach is to use literature
reported values as initial inputs
5
6. Dynamic models that represent GI tract physiology in view of drug transit,
dissolution, and absorption.
Among these are the Advanced Dissolution, Absorption and Metabolism
(ADAM) model,
Compartmental Absorption Transit model
Grass model,
GI-Transit-Absorption (GITA) model,
Advanced CAT (ACAT) model
ADAM
ACAT
CAT
Grass
GITA
6
7. Available commercial software packages, for modelling such as
GastroPlus™ version 9.8.2,
SimCYP,
PK-Sim
®
,
IDEA™
Cloe
®
PK,
INTELLIPHARM
®
PKCR
www.Simulator.plus.com; www.Symcyp.com;
7
8. Original CAT model is semi-physiological absorption model is based on the
concept of the Biopharmaceutics Classification System (BCS). And prior
knowledge of GI physiology, and is modeled by a system of coupled linear and
nonlinear rate equations used to simulate the effect of physiological conditions on
drug absorption as it transits through successive GI compartments .
ACAT model of the human GI tract consists of NINE compartments linked in
series, each of them representing a different segment of the GI tract (stomach,
duodenum, two jejunum compartments, three ileum compartments, caecum, and
ascending colon).
These compartments are further subdivided into Unreleased Undissolved
Dissolved Absorbed
compartment
8
9. Fig no. 1 ACAT model interpretation of in vivo drug behavior 9
12. GastroPlus ACAT modelling requires a number of input parameters
• PK parameters
Clearance (CL),
Volume of distribution
Percentage of drug extracted in the oral
cavity, gut or liver, etc.),
• Formulation characteristics
Particle size distribution and
Density,
Drug release profiles for controlled-
release formulations
• Physicochemical properties
Solubility
Permeability
logP
pKa
Diffusion coefficient)
• Physiology parameters
Transit time
pH
Volume
Lenth
Radii of the
corresponding GI region
12
13. The rate of change of dissolved drug concentration in each GI compartment depends on
ten processes:
I. transit of drug into the compartment
II. transit of drug out of the compartment
III. release of drug from the formulation into the compartment
IV. dissolution of drug particles
V. precipitation of drug
VI. luminal degradation of drug
VII. absorption of drug into the enterocytes
VIII. exsorption of drug from the enterocytes back into the lumen
IX. absorption of drug into portal vein via paracellular pathway
X. exsorption of drug from portal vein via paracellular pathway.
13
14. GI simulation: general modeling and simulation strategy
Fig no. model construction and model exploration 14
15. RATE CONSTANT
Transfer rate constant (kt)
Associated with luminal transit, is determined from the mean transit time within each
compartment.
Dissolution rate constant (kd)
For each compartment at each time step is calculated based on the relevant
formulation parameters and the conditions (pH, drug concentration, % fluid, and bile
salt concentration) in the compartment at that time.
Absorption rate constant (ka)
Depends on drug effective permeability multiplied by an absorption scale factor
(ASF) for each compartment
According to this model, as the ionized fraction of a compound increases, the
effective permeability decreases
15
16. Fig no. parameter and graph of comparison between model 1 and model 2
Case study
Nimesulide drug absorption
16
17. According to the obtained data, both Models 1 and 2 gave accurate predictions of
Nimesulide average plasma profile after oral administration
In both models , the percentage prediction errors for Cmax and area under the curve (AUC)
values were less than 10%
The largest deviation was observed for tmax
(PE of 21.25a/a and 15% in Model 1 and Model 2, respectively). Nevertheless, the predicted
values of 3.15 h (Model 1) and 3.4 h (Model 2)
Model 1 outcomes indicated involvement of influx transporters in nimesulide absorption,
while according to the Model 2 outcomes, the pH-surfactant induced increase in drug
solubility was a predominant factor leading to relatively rapid absorption in the proximal
intestine.
Conclusion :
17
18. Interpretation of the obtained data indicated that the approach applied in
Model 2 might be considered as more realistic, signifying that the related
absorption model more likely reflects nimesulide in vivo absorption. It was
also stressed that, in order to obtain meaningful in silico modeling, the
necessary input data have to be carefully selected and/or experimentally
verified.
Biowaiver :
the situations in which in vivo BE studies can be substituted with the relevant
in vitro data
biowaivers for IR drug products may be requested solely in the cases of highly
soluble and highly permeable substances (BCS class I) when the drug product
is (very) rapidly dissolving and exhibits similar dissolution profile to the
reference product
BCS class II drugs (eligible for biowaiver if the dose-to-solubility ratio at pH
6.8 is 250 mL or less and high permeability is at 85% absorbed)
18
19. Inter-subject variability may influence oral drug absorption is determined using
virtual trails
Virtual trials were performed on virtual 12 subjects (equal to the number of
subjects used in the clinical study), and the results were presented as mean Cp
vs. time profile with 90% confidence intervals
The Virtual Trial mode can also be used to conduct virtual BE studies on 25
subjects
values of the selected variables are randomly sampled from predetermined
distributions (defined as means with coefficients of variation (CV%) in
absolute or log space).
CV % values are usually estimated on the basis of previous knowledge or
analysis of literature data
results of the simulations are expressed as means and coefficients of variation
for the fraction of drug absorbed, bioavailability, t max, C max, and AUC
values
19
20. The presence of food may affect drug absorption via a variety of mechanisms ; By impacting
I. GI tract physiology (e.g. food- induced changes in gastric emptying time, gastric pH,
intestinal fluid composition, hepatic blood flow).
II. Drug solubility and dissolution
III. Drug permeation
For example lipophilic drugs often show increased systemic exposure with food due to
Improved solubilization in higher bile salt and lipid concentrations
To simulate food effect in human describes the kinetics of drug transit, dissolution, and
absorption on the basis of drug specific features such as permeability, biorelevant solubility,
ionization constant(s), dose, metabolism and distribution data, etc.
20
21. Dynamic models are able to predict both the fraction of dose absorbed and
the rate of drug absorption from gastrointestinal track .
Models can be utilized to explore mechanistic hypotheses and to help
define a formulation strategy
The effect of food on drug absorption or possible impact of intestinal
transporters and intestinal metabolism aslo explored
21
22. Abuasal, B.S., Bolger, M.B., Walker, D.K., and Kaddoumi, A. (2012) ‘In silico modeling for
the nonlinear absorption kinetics of UK-343,664: a P-gp and CYP3A4 substrate’, Mol.
Pharm., 9(3): 492–504.
Davis, T.M., Daly, F., Walsh, J.P., Ilett, K.F., Beilby, J.P., et al. (2000) ‘Pharmacokinetics and
pharmacodynamics of gliclazide in Caucasians and Australian Aborigines with type 2
diabetes’, Br. J. Clin. Pharmacol., 49(3): 223–30.
Norris, D.A., Leesman, G.D., Sinko, P.J., and Grass, G.M. (2000) ‘Development of
predictive pharmacokinetic simulation models for drug discovery’, J. Control Release, 65(1–
2): 55–62.
Welling, P.G. (1996) ‘Effects of food on drug absorption’, Annu. Rev. Nutr., 16:
383–415.
22