Create
Learn
Share

Factors Affecting Absorption

rename
allelipraise's version from 2017-09-28 03:43

Factors Affecting Absorption

Question Answer
Factors Affecting AbsorptionPhysiological/Formulation/Pharmacological/Pathological
Cell Membranethe barrier that separate the inside of the cell from the outside
Composition(Cell Membrane)Lipids, CHONs, Lipoproteins and Polysaccharides
Dynamic Lipoid Sievecarrier molecules shuttle back and forth across the membranes through microscopic aqueous pores or channels
Selective Permeability(Properties of Membranes)permits the rapid passage of some chemicals while retarding or preventing passage of others
CANNOTIonic, polar, CHONs, CHON-bound drug and macromolecules_______cross easily
CANlipid-soluble, unionized, nonpolar, low MW_____cross easily
Properties of Membranes • Surface Tension • Electrical Properties
Blood Brain BarrierPrevents many polar materials from entering the brain
Renal tubulesReabsorption
Blood capillaries and renal glomerular membranesAllow non-polar and polar molecules to pass through
memorize

Physiological Factors

Question Answer
Passive diffusionTransfer occurs from a region of higher concentration to a region of lower concentration
Passive diffusionOccurs in skin, mouth cavity, stomach, small intestine, large intestine, rectum
Carrier-mediated TransportCarriers in the lipoprotein membranes of the intestinal epithelial cells shuttle solutes from the mucosa to the serosa
Active Transport(Carrier Mediated Transport)Transports uphill against a concentration or an electrochemical potential gradient
Active Transport(Carrier Mediated Transport)transport that requires energy
Active Transport(Carrier Mediated Transport)Thiamine, niacin, riboflavin, vitamin B6, pyrimidine bases, testosterone, estradiol, Fe2+, Ca2+ , amethyldopa, 5-fluorouracil
Sodium Pump(Active Transport)Special Type of Active Transport that Utilizes not a carrier but a wave of electrons through a pore
Facilitated Transport(Carrier Mediated Transport)Passive movement of molecules or ions down a concentration gradient
Facilitated Transport(Carrier Mediated Transport)Does not require energy• Occurs in small intestines • Vitamin B12
Convective Transport(Carrier Mediated Transport)Pore or Paracellular Transport
Convective Transport(Carrier Mediated Transport)(trans-endothelial channels)Transport across tight or narrow junctions between cells
Convective Transport(Carrier Mediated Transport)Small molecules (MW 150); chainlike molecules (MW 400); Inorganic and organic electrolytes, ionized sulfonamide
Vesicular TransportProcess of engulfing particles or dissolved materials by a cell
Vesicular Transport(Types)Exocytosis/Endocytosis=Pino/Phagocytosis
Ion-pair FormationDrugs link up with an oppositely charged ion forming a neutral molecule which diffuses easily across membranes
Ion-pair FormationQuaternary ammonium compounds, sulfonates
Transporters proteinsp-glycoprotein
Transporters proteinsATP-dependent pumps which aid the refflux of drug molecules from the cell
Transporters proteinsreduces the efficacy of some pharmaceutical drugs
Gastrointestinal PhysiologyStomach/Small and large intestine
Gastrointestinal Physiology (Small Intestine)Duodenum/Jejenum/Ileum
Stomachpouch-like structure lined with a relatively smooth epithelial surface
Stomachpouch-like structure lined with a relatively smooth epithelial surface
Small Intestinemost important site for drug absorption in the GIT
Duodenumcarrier-mediated transport
Jejunumdietary constituents
IleumVitamin B12 and bile salts
Small IntestineVery large epithelial surface area due to the presence of villi and microvili
Large intestineless irregular mucosa than small intestine
Large intestineReserve area for the absorption of drugs that have escaped absorption because of their physicochemical properties of their dosage form
Gastrointestinal Blood FlowThe higher the blood flow the better the absorption
Gastrointestinal Blood FlowDuodenum has a large network of capillaries and lymphatic vessels
Gastrointestinal pH• Determines extent of ionization of drugs and where drug is best absorbed • Quick estimate to determine ionized and unionized state
Gastric EmptyingGenerally, drugs are better absorbed in the small intestine than in the stomach therefore INCREASING the rate of stomach emptying will promote drug absorption
Gastrointestinal MotilityThe slower the intestinal motility the better the absorption of drugs
Gastrointestinal Motility(Importance)• Dissolution of slowly soluble drugs • metabolism by microbial flora
Physiological Factors(Food)Generally, food retards transit
Physiological Factors(Food)Generally, better absorption in fasted state and with a larger volume of water
Physiological Factors(Food)NOT always predictable
Physiological Factors(Microbial Flora)Aerobic and anaerobic microorganisms may metabolize some drugs
memorize

Fick’s Law of Diffusion

Question Answer
Fick’s Law of Diffusion(Passive diffusion)rate of diffusion across a membrane is proportional to the difference in drug concentration on each side of the membrane
dQ/dt rate of drug diffusion
Ddiffusion rate constant
Asurface area of absorbing surface
Klipid-water partition coefficient
hthickness of membrance
Cpconc. of drug in plasma
Ctconc. of drug in tissue
memorize

Einstein's Relation

Question Answer
Einstein's Relation Explains that the time required for diffusion increases with the square of the distance
∆xdisplacement or distance travelled
D diffusion rate constant
memorize

Formulation Factors

Question Answer
Formulation Factors• Physicochemical Properties • Dosage Form
Drug SolubilityStatic (equilibrium) property in a saturated solution
Drug Solubilitydissolution of solute in solvent to give a homogenous system
Partition coefficientis defined as a ratio of the drug concentration in the oil phase to the drug concentration in the aqueous phase
Partition coefficient• Hydrophilic Drugs* • Hydrophobic Drugs*
Extent of ionizationDependent on the pKa of weak electrolyte and the pH of the solution
Extent of ionizationfraction of a weak electrolyte (acid or base) that dissociates in solution
Chemical VariationSalt formation, ester formation
Chemical VariationTo provide slower dissolution, slower absorption and longer duration of action
Chemical VariationSelected for greater stability, less local irritation at the absorption site or less systemic toxicity
Weak acidswater-soluble forms are K+ and Na+ salts
Weak basewater-soluble forms are HCl, SO4, citrate, gluconate, tartrate, succinate
PolymorphismAbility of drug to exist in more than one crystalline forms
Polymorphism(Crystalline)definite identifiable shape
Polymorphism(Amorphous)no definite structure
MP, BP, dissolution rateDifferent polymorphs have different physical properties
PolymorphismInsulin, Pen G
ChiralityAbility of the drug to exist as optically active stereoisomers or enantiomers
chiral drugsused as RACEMIC mixtures
differently pharmacokinetically and pharmacodynamicallyenantiomer behave
HydratesAffects dissolution rate
Anhydrousmore soluble than hydrated
Hydrates/solvated drugsadded with water or an organic solvent, respectively
Complex FormationReversible or irreversible association of two or more interacting molecules or ions
Complex Formation(chelate)complex that typically involves a ring-like structure formed by the interaction between a partial ring of atoms and a metal
Complex FormationUsually alters physical and chemical characteristics of a drug
Complex Formationtetracycline• Theophylline- ethylelenediamine complex • Drug-cyclodextrin complex/ Complex Formation /Drug - protein complex*
memorize

Section 6

Question Answer
Noues-Whitney EquationDrug Solubility Equation
dC/dtdrugdissolutionrate
DDiffusion rate constant(cm2s-1).
A surface area of drug (cm2)
hthickness of the diffusion or stagnant layer liquid film (cm).
Cs Saturation solubility of the drug in stagnant layer (mg.cm-3).
Cb concentration of drug in bulk solution (mg.cm-3).
memorize

Section 7

Question Answer
Partition coefficientunitless and is defined as a ratio of the drug concentration in the oil phase to the drug concentration in the aqueous phase
C[octanol]the molar concentration of the organic compound in the octanol phase
C[water]the molar concentration of the organic compound in water .
memorize

Section 8

Question Answer
Henderson–Hasselbalch equationWeak acid/base
memorize

Liquid Dosage Forms

Question Answer
Rate limiting stepis the rate of gastric emptying
A drug in hydro-alcoholic solutions has good absorption but may tend to formfinely divided precipitates in the lumen of GIT
Viscositymay interfere with dilution and mixing with GIT contents
EmulsionsInherently unstable
Emulsifierprevents coalescence and maintains the integrity of the individual droplets
SuspensionsFinely divided powder dispersed in viscous medium
memorize

 

Question Answer
Conventional oral dosage formsRate-limiting step is dissolution
Modified-release formsRate-limiting step is liberation
Hard Shell Capsulesfilled with a powder blend and Contents should not be subjected to high compression forces
Soft Shell Capsulescontain a non-aqueous solution, a powder or a drug suspension with a vehicle that is water-miscible (PEG) or hydrophobic (vegetable oil)
TabletsSolid dosage form containing the drug and excipients and usually compressed into a solid mass
Coated Tabletscoating must breakdown quicky
Types of coated tabletsSugar/Film Coater
Modified Release TabletsHave altered rate or timing of drug release
memorize

Transdermal Drug Delivery Systems

Question Answer
Components of transdermalocclusive impermeable backing/Formulation matrix/Adhesive Layer
Occlusive impermeable backingPrevents in sensible water loss from the skin/Enhances permeation of the skin by the drug
Formulation matrixMaintains the drug concentration within the device
Adhesive layerEnsures drug contact with the skin and continued drug delivery
memorize

TARGETED (SITE-SPECIFIC) DRUG DELIVERY SYSTEMS

Question Answer
TARGETED (SITE-SPECIFIC) DRUG DELIVERY SYSTEMSSystems that place the drug at or near the receptor site by complexing with a carrier that recognizes the target
memorize

INSERTS, IMPLANTS AND DEVICES

Question Answer
Inserts / implants / devicesDrug is impregnated into a biodegradable or non- biodegradable material and inserted in the body
Inserts / implants / devicesDrug is released slowly for localized or systemic effect
memorize

Drugs Affect the motility of the GIT

Question Answer
Drugs Affect the motility of the GITDecreased GI motility by TCA and antipsychotics
Drugs Affect the motility of the GITReduced stomach acid secretion by anticholinergics
Drugs Affect the motility of the GITSome drugs interfere with the absorption of other drugs
memorize