factors influencing drug absorption

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FACTORS INFLUENCING DRUG ABSORPTION PRESENTED BY:- GUIDED BY:- TARUN POKHARIYAL Mr. AJAY KUMAR TIWARI M.PHARM.(1 st SEM.) LECTURER DEPT. OF pharmaceutics JAIPUR NATIONAL UNIVERSITY JAIPUR DATE:-15 NOV.2011

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Page 1: Factors influencing drug               absorption

FACTORS INFLUENCING DRUG ABSORPTION

PRESENTED BY:- GUIDED BY:-TARUN POKHARIYAL Mr. AJAY KUMAR TIWARIM.PHARM.(1st SEM.) LECTURER DEPT. OF pharmaceutics JAIPUR NATIONAL UNIVERSITY JAIPUR DATE:-15 NOV.2011

Page 2: Factors influencing drug               absorption

(A). PHARMACEUTICAL FACTORS:-I. PHSICOCHEMICAL PROPERTIES OF DRUG:-1. DRUG SOLUBILITY AND DISSOLUTION RATE disintegration dissolution permeation

across mem.

Maximum absorbable dose (MAD) is used to correlate drug absorption Ka= intrinsic absorption rate constantSgi=solubility of drug in GI fluidVgi=volume of GI fluid present. tr= residence of drug in GI

Solid dosag

e form

Solid drug

particles

Drug in solution at absorption

site

Drug in

the body

MAD= Ka Sgi Vgi tr

Page 3: Factors influencing drug               absorption

BIOPHARMACEUTICS CLASSIFICATION SYSTEM:-CLASS I DRUG:- high solubility and high permeability eg. diltiazemCLASS II DRUG:-low solubility and high permeability eg.nifedipine.CLASS III DRUG:-high solubility and low permeability eg. Insulin.CLASS IV DRUG:-low solubility and low permeability eg. taxol

Page 4: Factors influencing drug               absorption

THEORIES OF DRUG DISSOLUTION:-DISSOLUTION IS THE MASS TRANSFER FROM SOLID SURFACE TO THE LIQUID PHASE.Theories:-1.Diffusion layer model/film theory

2.danckwerts’s model/penetration theory

3.Interfacial barrier model/limited solvation theory

Page 5: Factors influencing drug               absorption

DIFFUSION LAYER MODEL/ FILM THEORY:-

Page 6: Factors influencing drug               absorption

The rate of dissolution is given by Noyes and Whitney:

Where,dc/dt= dissolution rate of the drugK= dissolution rate constantCs= concentration of drug in stagnant layer

Cb= concentration of drug in the bulk of the solution at time t

dc dt = k (Cs- Cb)

Page 7: Factors influencing drug               absorption

Modified Noyes-Whitney’s Equation -

dC dt

Where, D= diffusion coefficient of drug. A= surface area of dissolving solid. Kw/o= water/oil partition coefficient of drug. V= volume of dissolution medium. h= thickness of stagnant layer. (Cs – Cb )= conc. gradient for diffusion of drug.

DAKw/o (Cs – Cb ) Vh

Page 8: Factors influencing drug               absorption

This is first order dissolution rate process, for which the driving force is concentration gradient.

This is true for in-vitro dissolution which is characterized by non-sink conditions.

The in-vivo dissolution is rapid as sink conditions are maintained by absorption of drug in systemic circulation i.e. Cb=0 and rate of dissolution is maximum.

Page 9: Factors influencing drug               absorption

Under sink conditions, if the volume and surface area of the solid are kept constant, then

dC dtThis represents that the dissolution rate is constant under sink conditions and follows zero order kinetics.

K

first order dissolution under non-sink condition

zero order dissolution under sink condition

Time

Con

c. o

f dr

ug

Page 10: Factors influencing drug               absorption

Danckwert’s model/Penetration or surface renewal Theory :-

Dankwert takes into account the eddies or packets that are present in the agitated fluid

which reach the solidliquid interface, absorb the solute by diffusion and carry it into the bulk of solution.These packets get continuously replaced by new ones and expose to new solid surface each time, thus the theory is called as surface renewal theory.

Page 11: Factors influencing drug               absorption

III. Interfacial barrier model/Double barrier or Limited solvation theory :-

The concept of this theory is explained by following equation-

G = Ki (Cs - Cb)

Where,G = dissolution rate per unit area,Ki = effective interfacial transport constant.

Page 12: Factors influencing drug               absorption

2. PARTICLE SIZE & EFFECTIVE SURFACE AREA OF DRUG:-TWO TYPES OF SURFACE AREA CAN BE DEFINED:-1.ABSOLUTE SURFACE AREA2.EFFECTIVE SURFACE AREA

3. POLYMORPHISM:- enantiotropic polymorph:-which can be reversibly change into another form by altering the temp.or pressure.Monotropic polymorph:-is the one which is unstable at all temp. and pressure.

Page 13: Factors influencing drug               absorption

Internal structure of a compound

noncrystallineCrystalline

Polymorph(single

molecule)

Molecular adduct

enantiotropic

monotropic

Nonstochiometric complexes

Stocheometric complexes

Organic solvates

Hydrates

Page 14: Factors influencing drug               absorption

5. drug pka and lipophilicity and gi Ph (PH PARTITION HYPOTHESIS):-This theory states for those drug compound of molecular weight greater than 100 which primariliy transported across the biomembrane by passive diffusion.Most drugs are weak electrolyte(weak acid or base)If the pH of either side of membrane is different than the compartment whose pH favours greater ionisation of drug will contain greater amount of drug and only unionised fraction of drug if sufficiently lipid soluble can permeate the membrane passively until the conc. Ofunionised drug on either side of membrane become equal.

4. Salt form of drug:-

Page 15: Factors influencing drug               absorption

6. DRUG STABILITY:- Degredation of drug into inactive form. Interaction with one or more different components

7. STERIOCHEMICAL NATURE OF THE DRUG:-

DOSAGE FORM(PHARMACOTECHNICAL) FACTORS:-1) DISINEGRATION TIME:-2) DISSOLUTION TIME:-3) MANUFACTURING VARIABLES:- *excipients and manufacturing process*EXCIPIENTS:-vehicle, diluents(filler),binder and granulating agents, disintegrants,lubricants,surfactants,viscosity imparters,buffers,complexing agents,ColorantsCrystal growth inhibitors.

Page 16: Factors influencing drug               absorption

MANUFACTURING VARIABLES:-*Method of granulation-wet granulation method is most conventional technique but limited.Most recent method is APOC(agglomerative phase of communition)

*Compression force:-*Intensity of packing of capsule contents-4.NATURE AND TYPE OF DOSAGE FORM5.PRODUCT AGE AND STORAGE CONDITION

Page 17: Factors influencing drug               absorption

PATIENT RELATED FACTORS:-1. AGE-2. GASTRIC EMPTYING:-the passage from stomach to

small intastine.Gastric emptying is first order process Gastric emptying rate:-is the speed at which the

stomach content empty into intestine. Gastric emptying time:-is the time required for

gastric content to empty into small intestine. Gastric emptying t1/2 is the time taken for half the

stomach content to empty.FACTORS EFFECTING GASTRIC EMPTYING:- VOLUME OF MEAL COMPOSITION OF MEAL PHYSICAL STATE AND VISCOSITY OF MEAL TEMP. OF MEAL

Page 18: Factors influencing drug               absorption

GI pH Electrolyte and osmotic pressure Body posture Emotional state Exercise Disease state Drug

3.INTESTINAL TRANSIT:-the passage of drug through intestine called as intestinal transit.

4.GIT Ph:- it influence absorption in various ways;-

Page 19: Factors influencing drug               absorption

a. Disintegrationb. Dissolutionc. Absorptiond. Stability

5.Disease state :-e. GIT diseasef. Cardiovascular diseaseg. Hepatic disease

6.BLOOD FLOW TO GIT:-

Page 20: Factors influencing drug               absorption

7.GASTROINTESTINAL CONTENT:-1. Food- drug interaction2. Fluid volume3. Interaction of drug with normal gi contents4. Drug –drug interaction

8. PRESYSTEMIC METABOLISM:-The loss of drug through biotransformation by such eliminating organs during its passage to systemic circulation is called first pass metabolism.Three types of systems:-5. Luminal enzyme (digestive and bacterial

enzyme)6. Gut wall enzyme7. Hepatic enzyme

Page 21: Factors influencing drug               absorption

THANK YOU