Dependence of drug absorption on ph and drug protonation almost all drugs can be classified as. Ppt drug absorption powerpoint presentation free to. In the case of an organic acid, it can also take two forms. Is the phpartition theory still valid to predict oral. Lecture 3 drug absorption 9 sep 2006 cell membrane. The solute is mixed with water and the organic solvent such as octanol. This work is dedicated to its experimental determination. Partition coefficient in drug discovery and development, lipophilicity is usually expressed by the partition between water and octan1ol. Brodie proposed the partition theory to explain the influence of gi ph and drug pka on the extent of drug transfer or drug absorption. Phase volume and partitioning effects on drug delivery from. Scribd is the worlds largest social reading and publishing site. Haspi medical math 3 ph and drug absorption application of logarithms objectives hsfle.
Pharmacy pharmaceutics sims college of pharmacy, m angaldas n agar, guntur. Why the partition coefficient of ionic liquids is concentrationdependent. A high partition coefficient implies that the drug is highly lipophilic. Apr 21, 2018 ph partition hypothesis presented by zahid husain m.
Effects of salinity, ph and temperature on the octanolwater. What is the lipidwater partition coefficient of a drug. That is, they must be able to demonstrate that the new drug is better. Quaternary ammonium compounds are ionized at all phs but are readily absorbed from the gi tract. Partition and distribution coefficients absorption of drugs there are a number of ways that drugs are absorbed,1 but the most common route is passive. Phase volume and partitioning effects on drug delivery. Definition it is defined as the process of movement of unchanged drug from the site of administration to the systemic circulation. For exponential models, express as a logarithm the solution to abct d where a, c and d are numbers and the base is 10. This can be understood clearly as a sub topic of ph partition hypothesis factors affecting gastrointestinal absorption of drugs. Phase volume and partitioning effects on drug delivery from topical emulsions sui yuen e. Explain how bioavailability can impact drug response and product selection. Pdf s available in description find your topic and download the pdf 1 repetitive iv injection multiple dosage regimen bioph. The partition coefficient, abbreviated p, is defined as a particular ratio of the concentrations of a solute between the two solvents a biphase of liquid phases, specifically for unionized solutes, and the logarithm of the ratio is thus log p. Consequently, when assessing photosensitivity of a pharmaceutical product, it is necessary to consider the formulation as a whole and not just the drug itself 36.
Compare the roles of passive diffusion and carriermediated transport in drug absorption. Is the phpartition theory still valid to predict oral absorption of drugs. We have applied the ph partition theory to drug absorption, later we will use this theory to describe drug reabsorption in the kidney. This book has been conceived as an introduction to pharmacokinetics for phar. Calculating partition coefficients of peptides by the. A valid and reasonable research can be conducted without any hypothesis. Dissolution is generally defined as a process by which a solid substance is solubilized into the solvent to yield a solution.
An additional problem is that excipients in the formulation socalled photosensitizers may absorb radiation and transfer this absorbed energy to the drug causing its degradation. A selforganized data visualization tool based on the flux function was mined for the promising. Importance of partition coefficient in formulation development. Lecture03 drug absorption and distribution dependence of. Is the ph partition theory still valid to predict oral absorption of drugs. How would we rationalize the absorption of aspirin and nsaids which are almost ionized at ph 7 with partition. This informs the hologenome theory of evolution with the holobiont. Contents of the powerpoint on ph partition theory include. E ffect of particle size,ph partition hypothesis and dissolution rate on bioavailability of drugs presented by j. Wafik gouda the rate of absorption of poorly soluble drugs is dissolution ratelimited. Ultimately, ph can affect dissolution or how much drug will be dissolved. On the other hand, bases become positively electric charged in acid fluids, since they receive a proton. Aug 12, 2017 it is usually expressed as the oilwater partition coefficient and it is a measure of the relative solubility of a solute in an organic phase vs water.
Hypothesis formulation is not a necessary but an important step of the research. May 20, 2011 very few studies have investigated the pharmacokinetics and pharmacodynamics of nph insulin in type 2 diabetes 1,2. Prediction of partition coefficients and permeability of. Absorptionexcipientph classification gradient maps. These partition between the gas and the particle phase. The more acidic a solution the greater the hydrogen ion concentration and the lower the ph. When a drug company wishes to introduce a new drug, they must.
Absorption kinetics of regular and isophane nph insulin. This was followed by the development of the long acting nph insulin in the 1940s. This process is fundamentally controlled by the affinity between the solid substance and the solvent and consists of two consecutive steps. Pharmacokinetics and pharmacodynamics of therapeutic doses. Introduction phpartition theory drug pka and gastrointestinal ph lipophilicity and drug absorption deviations from the ph partition theory a unifying hypothesis conclusion references drug absorption. Ph partition definition of ph partition by medical dictionary. The concentration ratio concentration of drug in gastric juice divided by concentration in plasma depends on the dissociation constant of the drug. Pharmacokinetics and pharmacodynamics of therapeutic doses of. These studies have provided valuable information that is limited, however, by a short period of observation 1216 h and by the comparison of nph with only one longacting insulin analog, either glargine or detemir.
Experimental determination of the partitioning coe cient. The oilwater partition coefficient of drugs is widely accepted as a key parameter in drug design. It is defined as the process of movement of unchanged drug from the site of administration to systemic circulation. Drug absorption is defined as the process of movement of unchanged drug from. Therefore, as a model for a drug traversing through the body to its site of action, the relative potency of the drug, expressed as log 1c, where c is the concentration of the drug that produces some standard biological effect, was related by hansch et als to its lipophilicity by the parabolic expression shown in equation 2. In almost all cases, drugs must also have a certain degree of lipid solubility to move around leave and enter capillaries, enter and leave cells. The partition coefficient the lipophilicity of an organic compound is usually described in terms of a partition coefficient, log p, which can be defined as the ratio of the concentration of the unionized compound, at equilibrium, between organic and aqueous phases. Parenterally administered drugs are secreted directly into the gastric juice. Pharmacokinetics is the science of the kinetics of drug absorption, distribution, and elimination i.
Hypothesis can be one and it can be as many as possible. View notes lecture03 drug absorption and distribution from neu 365d at university of texas. Brodie proposed the ph partition theory to explain the influence of gi ph and drug pka on the extent of drug transfer or drug absorption. Lecture 3 drug absorption 9 sep 2006 free download as powerpoint presentation. Drugs must have some ability to dissolve in water to move around be absorbed, reach sites of action. Effect of certain formulation factors on the dissolution. To this end, a new measurement technique for compoundspeci c analysis of organic aerosol was used. The physiologically and pharmacologically relevant structure is, of course, the bilayer lipid membrane, but until now there has been no convenient means of measuring the partition coefficients of small. Ultimately, membrane permeability is a key determinant of drug absorption, distribution. Structural determinants of drug partitioning in surrogates of phosphatidylcholine bilayer strata.
Estimation of tissuetoplasma partition coefficients used in. Effect of certain formulation factors on the dissolution and. Received 8 january 1990 modified version received 1 june 1990 accepted 26 july 1990. The coefficients are usually determined using a bulk octanol phase to represent the lipid. The compoundspeci c gastoparticle partitioning can be described with the temperaturedependent partitioning coe cient. Ph partition definition of ph partition by medical.
Keenan, and caroline gauchottelindsay international journal of environmental science and development, vol. Effect of particle size, dissolution and ph partition hypothesis. Effect of certain formulation factors on the dissolution and absorption of drugs. Describe two types of drug interaction and explain how they might affect drug response and safety. Director clinical pharmacology program september 30, 2010 office of clinical research training and medical education.
Slow dissolution results in incomplete, erratic and unpredictable absorption. Pharm pharmaceutics faculty of pharmacy, integral university, lucknow 2. It is usually expressed as the oilwater partition coefficient and it is a measure of the relative solubility of a solute in an organic phase vs water. Very few studies have investigated the pharmacokinetics and pharmacodynamics of nph insulin in type 2 diabetes 1,2. Partition coefficient p is the ratio of concentration of drug in noctanol phase divided by concentration of drug in aqueous phase. Effects of salinity, ph and temperature on the octanolwater partition coefficient of bisphenol a siriporn borrirukwisitsak, helen e. Flynn college of pharmacy, university of michigan, ann arbor, mi u. Drug absorption is defined as the process of movement of unchanged drug from the site of administration to systemic circulation. Characterization of absorption enhancers for orally. Fallacies concerning gastric drug absorption weakly acidic drugs absorbed only in the stomach ph partition hypothesis weakly basic drugs absorbed in the small intestine ph partition hypothesis gastric ph is always acidic in fact, most drug absorption occurs in the small intestine. For example, an amine type of drug can take two forms as shown to the right. Partition coefficients of drugs in bilayer lipid membranes. The drug molecule combine with carrier protein and then it transferred drug to the other side of membrane, there it leaves the molecule and come back to normal situation or form.
Effect of particle size, dissolution and ph partition. Effect of particle size,ph partition hypothesis and dissolution rate on bioavailability of drugs. Prediction of partition coefficients and permeability of drug. Jan 22, 2014 contents of the powerpoint on ph partition theory include.
The relationship between these two tissueplasma ratios is derived analytically for different routes of drug administration. The partition coefficient, p, of a drug is given by where drug octan1ol concentration of drug in octan1ol drug water concentration of drug in water a sample of the drug is shaken with a mixture of octan1ol and water and its concentration in each layer is determined. An important parameter in the development of pharmacokinetic models is the ratio of tissue drug concentration to the concentration of the drug in the arterial plasma or the effluent plasma. Twophase partition profiling of drugs and ionisable compounds ulmeanu plass, sorina. Estimation of tissuetoplasma partition coefficients used. Thus strong acids appear in gastric juice in negligible concentration, weak acids and weak bases in measurable amount and stronger bases in highest. Hypothesis formulation helps in formulating the research problem. Principles of drug absorption study guide by dtruong09 includes 84 questions covering vocabulary, terms and more. Ph partition theory of drug absorption is based on the assumption that the git is a simple lipid barrier to the transport of drugs and chemicals. Sparingly soluble drugs and the ph partition hypothesis. Thus strong acids appear in gastric juice in negligible concentration, weak acids and weak bases in measurable amount and stronger bases in highest concentration. The ph partition theory predicts the accumulation and oxicity. A free powerpoint ppt presentation displayed as a flash slide show on id. Quizlet flashcards, activities and games help you improve your grades.
Lecture03 drug absorption and distribution dependence. Drug discovery, design, and development pdf free download. Partition coefficient should not be confused with distribution constant in the physical sciences, a partition coefficient p or distribution coefficient d is the ratio of concentrations of a compound in a mixture of two immiscible phases at equilibrium. Absorption kinetics of regular and isophane nph insulin in. Lecture3 dependence of drug absorption on ph and drug. Guidancecomplianceregulatoryinformationguidancesucm070244. Effects of salinity, ph and temperature on the octanol. Department of pharmacology adapted from lectures of jeffrey l. Absorption kinetics of regular and isophane nph insulins were evaluated in seven normal fasted dogs by measuring serial serum concentrations of insulin and glucose following the subcutaneous administration of regular and nph insulins. Mechanism of absorption of drug by four ways the drug can be migrated. Pharmacokinetics drug disposition drug absorption, distribution and elimination general rules. Examples of infusion drugs that photodegrade drug absorption. The reason for this phenomenon is that acids become negatively electric charged in basic fluids, since they donate a proton.
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