The document discusses several physicochemical properties of drugs that influence drug absorption, including drug solubility, particle size, polymorphism, salt form, lipophilicity, pKa, and stability. It focuses on how the pH-partition hypothesis relates drug pKa and lipophilicity to gastrointestinal (GI) pH and passive drug absorption across the GI epithelium. The pH-partition hypothesis states that only the unionized, lipid-soluble form of a drug can passively diffuse across membranes. The document also notes limitations of this hypothesis and discusses how dosage form characteristics like disintegration time and excipients can impact drug absorption.
includes different mechanism involved in the absorption of the drug s into the systemic circulation. different factors affecting absorption including characters of drugs and different dosage forms. bioavailability of different dosage forms
A brief presentation on the factors affecting bioavailability of drugs along with a quick overview on what is bioequivalence, clinical equivalence, therapeutic equivalence, chemical equivalence and pharmaceutical equivalence.
Biopharmaceutic considerations in drug product design and In Vitro Drug Produ...PRAJAKTASAWANT33
Introduction, biopharmaceutic factors affecting drug bioavailability, rate–limiting steps in drug absorption, physicochemical nature of the drug formulation factors affecting drug product performance
Bioavailability and Bioequivalence studyMcpl Moshi
Bioavailability and Bioequivalence study, BCS is a scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability.
It is a drug development tool that allows estimation of solubility, dissolution and intestinal permeability affect that oral drug absorption.
Biopharmaceutic considerations in Drug Product DesignRiaz Islam
Drug product Design remain one of the most challenging aspects in formulation development. But nowadays formulation strategies have been far more successful in improving the bioavailability of the compounds with poor solubility, poor dissolution rate, and poor chemical stability in acidic environment. This article begins with a brief discussion on Physical and Chemical Properties of the Drug Impacting Oral Absorption. This article also reviews the Factors Contributing to Poor Aqueous Solubility. and a brief relationship between Physicochemical Properties and Drug Delivery System.
includes different mechanism involved in the absorption of the drug s into the systemic circulation. different factors affecting absorption including characters of drugs and different dosage forms. bioavailability of different dosage forms
A brief presentation on the factors affecting bioavailability of drugs along with a quick overview on what is bioequivalence, clinical equivalence, therapeutic equivalence, chemical equivalence and pharmaceutical equivalence.
Biopharmaceutic considerations in drug product design and In Vitro Drug Produ...PRAJAKTASAWANT33
Introduction, biopharmaceutic factors affecting drug bioavailability, rate–limiting steps in drug absorption, physicochemical nature of the drug formulation factors affecting drug product performance
Bioavailability and Bioequivalence studyMcpl Moshi
Bioavailability and Bioequivalence study, BCS is a scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability.
It is a drug development tool that allows estimation of solubility, dissolution and intestinal permeability affect that oral drug absorption.
Biopharmaceutic considerations in Drug Product DesignRiaz Islam
Drug product Design remain one of the most challenging aspects in formulation development. But nowadays formulation strategies have been far more successful in improving the bioavailability of the compounds with poor solubility, poor dissolution rate, and poor chemical stability in acidic environment. This article begins with a brief discussion on Physical and Chemical Properties of the Drug Impacting Oral Absorption. This article also reviews the Factors Contributing to Poor Aqueous Solubility. and a brief relationship between Physicochemical Properties and Drug Delivery System.
Ruchi rawat, romit vaishnav presentation on ph partitionRuchiRawat13
basic concept,digram showing drug transfer from membrane, ph partition throry, deviations,drug pka and GI ph, equations on weak acid and weak base, deviations from ph-partition theory.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
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hematic appreciation test is a psychological assessment tool used to measure an individual's appreciation and understanding of specific themes or topics. This test helps to evaluate an individual's ability to connect different ideas and concepts within a given theme, as well as their overall comprehension and interpretation skills. The results of the test can provide valuable insights into an individual's cognitive abilities, creativity, and critical thinking skills
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This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Travis Hills' Endeavors in Minnesota: Fostering Environmental and Economic Pr...Travis Hills MN
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Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
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Slides from:
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Track: Artificial Intelligence
https://www.etran.rs/2024/en/home-english/
The ability to recreate computational results with minimal effort and actionable metrics provides a solid foundation for scientific research and software development. When people can replicate an analysis at the touch of a button using open-source software, open data, and methods to assess and compare proposals, it significantly eases verification of results, engagement with a diverse range of contributors, and progress. However, we have yet to fully achieve this; there are still many sociotechnical frictions.
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Our observation is that multiple layers — hardware, operating systems, third-party libraries, software versions, input data, compile-time options, and parameters — are subject to variability that exacerbates frictions but is also essential for achieving robust, generalizable results and fostering innovation. I will first review the literature, providing evidence of how the complex variability interactions across these layers affect qualitative and quantitative software properties, thereby complicating the reproduction and replication of scientific studies in various fields.
I will then present some software engineering and AI techniques that can support the strategic exploration of variability spaces. These include the use of abstractions and models (e.g., feature models), sampling strategies (e.g., uniform, random), cost-effective measurements (e.g., incremental build of software configurations), and dimensionality reduction methods (e.g., transfer learning, feature selection, software debloating).
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Factors affecting drug absorption part ii
1. Dr. Nilesh S. Kulkarni
Associate Professor in Pharmaceutics
PES Modern college of Pharmacy For Ladies Moshi Pune
9/21/2021
2. Physicochemical properties of drug
1. Drug solubility and dissolution rate
2. Particle size and effective surface area
3. Polymorphism and amorphism
4. Pseudopolymorphism (hydrates/solvates)
5. Salt form of the drug
6. Lipophilicity of the drug
7. pKa of the drug and gastrointestinal pH
8. Drug stability
9. Stereochemical nature of the drug
PHARMACEUTICAL FACTOR
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3. Drug pKa and Lipophilicity and GI pH—pH Partition Hypothesis
- According to the pH-partition hypothesis, the gastrointestinal
epithelia acts as a lipid barrier towards drugs which are
absorbed by passive diffusion, and those that are lipid soluble
will pass across the barrier.
Brodie et al.
“The theory states that for drug compounds of molecular weight
greater than 100, which are primarily transported across the
biomembrane by passive diffusion, the process of absorption is
governed by:
dissociation constant (pKa) of the drug,
lipid solubility of the unionised drug (a function of drug Ko/w)
and The pH at the absorption site.
9/21/2021
4. Most drugs are weak electrolytes (weak acids or weak bases), their degree of
ionisation depends upon the pH of the biological fluid.
If the pH on either side on the membrane is different, then the compartment whose
pH favours greater ionisation of the drug will contain greater amount of drug, and
only the unionised or undissociated fraction of drug, if sufficiently lipid soluble, can
permeate the membrane passively until the concentration of unionised drug on
either side of the membrane becomes equal i.e. until equilibrium is attained.
The above statement of the hypothesis was based on the assumptions that:
1. The GIT is a simple lipoidal barrier to the transport of drug.
2. Larger the fraction of unionised drug, faster the absorption.
3. Greater the lipophilicity (Ko/w) of the unionised drug, better the absorption.
9/21/2021
5. Drug pKa and Gastrointestinal pH
The lower the pKa of an acidic drug, stronger the acid
i.e. greater the proportion of ionised form at a particular pH.
Higher the pKa of a basic drug, stronger the base
i.e. greater the proportion of ionised form at a particular pH.
The knowledge of pKa of drug and pH at the absorption site (or biological fluid), the
relative amount of ionised and unionised drug in solution at a particular pH and the
percent of drug ionised at this pH can be determined by Henderson-Hasselbach
equations:
9/21/2021
6. WEAK ACIDS
WEAK BASE
If there is a membrane barrier that separates the aqueous solutions of different pH such
as the GIT and the plasma, then the theoretical ratio R of drug concentration on either
side of the membrane can be given by equations derived by Shore et al:
WEAK ACIDS
WEAK BASE
9/21/2021
7. Drugs pKa pH/site of absorption
Very weak acids
e.g. Pentobarbital
Hexobarbital
>8
Unionized at all pH values; Absorbed along the
entire length of GIT
Moderately weak acids
e.g. aspirin
Ibuprofen 2.5 – 7.5
Unionized in gastric pH & ionized in intestinal pH;
better absorption from stomach
Stronger acids
E.g. disodium Cromogylate < 2.0
Ionized at all pH values; Poorly absorbed from GIT
Very weak bases
e.g. Theophylline
Caffeine
< 5.0
Unionized at all pH values; Absorbed along entire
GIT
Moderately weak bases
e.g. codeine 5 – 11
Ionized at gastric pH, unionized at intestinal pH;
better absorption from intestine.
Stronger bases
e.g. Guanethidine > 11
Ionized at all pH values; Poorly absorbed from GIT
9/21/2021
9. Total aqueous solubility, ST, of an IONISABLE DRUG is an important factor in the passive
absorption of drugs.
It is defined as the SUM OF CONCENTRATION OF IONISED DRUG IN SOLUTION AND
CONCENTRATION OF UNIONISED DRUG IN SOLUTION.
The solubility of unionised form of the drug is known as the intrinsic solubility of the
drug. If Sa is the intrinsic solubility of weakly acidic drugs and Sb that of weakly basic
drugs,
TOTAL AQUEOUS SOLUBILITY
ACIDS
BASE
9/21/2021
11. Lipophilicity and Drug Absorption
The degree of ionisation at a particular pH and that only the unionised drug, if
sufficiently lipid soluble, is absorbed into the systemic circulation.
if the drug exists in the unionised form, it will be poorly absorbed if it has poor lipid
solubility (or low Ko/w)
Systemic Circulation
GASTROINTESTINAL
TRACT
CELL
MEMBRANCE
9/21/2021
13. Limitations of the pH-partition hypothesis
1. Presence of virtual membrane pH
2. Absorption of ionised drug
3. Influence of GI surface area and residence time of drug
4. Presence of aqueous unstirred diffusion layer
PRESENCE OF VIRTUAL MEMBRANE pH
9/21/2021
14. PRESENCE OF AQUEOUS UNSTIRRED DIFFUSION LAYER
Aqueous Bulk Fluid of the GIT
Aqueous Unstirred Layer
Lipoidal Layer (Cell Membrane)
Blood
Limitations of the pH-partition hypothesis
9/21/2021
15. ABSORPTION OF IONISED DRUG
INFLUENCE OF GI SURFACE AREA AND RESIDENCE TIME OF DRUG
Limitations of the pH-partition hypothesis
9/21/2021
16. DRUG PERMEABILITY AND ABSORPTION
M = amount of drug absorbed
Peff = effective membrane permeability
A = surface area available for absorption
Capp = Apparent Luminal Drug Concentration
tres = residence time of Drug in GI lumen
The three major drug characteristics that determine the passive transport or
permeability of drugs across intestinal epithelium are
Lipophilicity of drug expressed as log P.
Polarity of drug which is measured by the number of H-bond acceptors and number of
H-bond donors on the drug molecule.
Molecular size.
9/21/2021
17. Rule of Five by LIPINSKI ET AL which is written as –
Molecular weight of drug ≤ 500
Lipophilicity of drug, log P ≤ 5
Number of H-bond acceptors ≤ 10
Number of H-bond donors ≤ 5
For a given drug, if any two of these values is greater than that specified above,
then oral absorption may be significant problem.
DRUG PERMEABILITY AND ABSORPTION
9/21/2021
18. Dosage form, dosage form related, pharmaceutical excipient
(Pharmaco Technical Factor)
1. Disintegration time (tablets/capsules)
2. Dissolution time
3. Manufacturing variables
4. Pharmaceutical ingredients (excipients/adjuvants)
5. Nature and type of dosage form
6. Product age and storage conditions
PHARMACEUTICAL FACTOR
9/21/2021
19. 1. Disintegration Time:
Coated tablets especially sugar coated have longer DT. DT is directly
proportional to the amount of binder present and the
compressional force of the tablet.
2. Manufacturing /Process variables:
Manufacturing process that affects the DT are :
a. Method of granulation.
b. Compressional force.
9/21/2021
20. 3. Pharmaceutical ingredients:
Excipients used to ensure the acceptability, physicochemical stability during the
shelf life, uniformity of composition and dosage, and optimum bioavailability
and functionality of the drug product.
a. Vehicles b. Diluents
c. Binder and granulating agents d. Disintegrants
e. Lubricants f. Coating
g. Suspending Agents h. Surfactants
4. Nature and type of Dosage form:
As a general rule, the bioavailability of a drug from various dosage form
decreases in the following order:
Solution > Emulsion > Suspension > Capsules > Tablets > Coated tablets > Enteric
Coated tablets > Sustained Release products.
9/21/2021