Formulation factors affecting drug absorption & bioavailability

1. ManipalCollegeofPharmaceuticalSciences(MCOPS)
F O R M U L AT I O N FA C TO R S
A F F E C T I N G D R U G
A B S O R P T I O N
P R E S E N T E D B Y : S H I K H A Y. S I N G H
U N D E R T H E G U I D A N C E O F : D R V A M S H I K R I S H N A T
D E P A R T M E N T O F P H A R M A C E U T I C S
R E G I S T R A T I O N N O . 1 6 0 6 1 7 0 0 9

2. CONTENT
1. Introduction
2. Manufacturing variables
3. Pharmaceutic ingredients
4. Nature and type of dosage form
5. Conclusion
6. References
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3. INTRODUCTION
• A drug injected intravascularly directly enters systemic circulation & exerts its
pharmacological effects
• If intended to act systemically, such drugs can exert their pharmacological actions only
when they come into blood circulation from their site of application
• Majority of drugs are administered extravascular only
• Absorption is an important step
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4. MANUFACTURING/PROCESSING
VARIABLES
Variables
Manufacturing
processes
Excipients
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5. MANUFACTURING PROCESSES
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 Manufacturing processes that influence drug dissolution are
1. Compression force
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6. 2. Method of Granulation
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7. PHARMACEUTIC
INGREDIENTS/EXCIPIENTS
 Despite their inertness & utility in the dosage form, excipients can influence
absorption of drug
 More number of excipients in a dosage form, the more complex it is & greater
potential for absorption & bioavailability problems
 Excipients are added to ensure
1. Stability
2. Uniformity
3. Functionability
4. Bioavailability
5. Acceptability
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8. 1. VEHICLE
 Absrption depend to a large extent on its miscibility with biological fluids
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9.  Diluents are commonly added to tablet (and capsule) formulations if the required
dose is inadequate to produce the necessary bulk
 Eg of drug-diluent interaction resulting in poor bioavailability is that of tetracycline &
DCP
2. DILUENTS
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Diluents
Organic Inorganic

10. 3. BINDERS & GRANULATING AGENTS
 Promote cohesive compacts before & after compression
 Eg polymeric materials like starch, cellulose derivatives, acacia, PVP, etc
4. COLOURANTS
 Very low concentration of water-soluble dye inhibitory effect on dissolution
 Dye molecules get adsorbed onto the crystal faces & inhibit drug dissolution
 E.g. brilliant blue retards dissolution of sulfathiazole
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11. 5. LUBRICANTS
 To aid flow of granules
 To reduce interparticle friction
 Sticking of particles to dies & punches
 Eg Hydrophobic in nature (several metallic stearates & waxes)
6. COATINGS
 Deleterious effect of various coatings on drug dissolution from a tablet dosage form
is enteric coat > sugar coat > nonenteric film coat
 e.g. Shellac coated tablets, on prolonged storage, dissolve more slowly in the GIT
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12. 7. DISINTEGRANTS
 Agents overcome cohesive strength of tablet & break them up on contact with water
which is an important prerequisite to tablet dissolution
 These are hydrophilic in nature eg MCC
 Mechanism
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13. 8. BUFFERS
 They create right atmosphere for dissolution e.g. buffered aspirin tablets
 Buffer containing potassium cations inhibit the drug absorption e.g. vitamin B2 &
sulphanilamide
9. SURFACTANTS
 They may enhance or retard drug absorption
1. Promotion of wetting & dissolution of drugs
2. Better membrane contact of drug for absorption
3. Enhanced membrane permeability of the drug
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14. 10. SUSPENDING AGENTS/VISCOSITY IMPARTERS
 Hydrophilic polymers like vegetable gums, semisynthetic gums & synthetic gums
 Stabilize drug particles by reducing their rate of settling & by increasing viscosity of
the medium they also affect palatability & pourability of solution dosage forms
 Eg Na-CMC complex amphetamine increases drug absorption
11. CRYSTAL GROWTH INHIBITORS
 Eg crystal growth inhibitors like PVP & PEG inhibit conversion of a high energy
metastable polymorph into stable
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15. 12. COMPLEXING AGENTS
 These agent alters stability, solubility, molecular size, partition coefficient & diffusion
coefficient
 Pharmacologically inert & must dissociate either at the absorption site or following
absorption into the systemic circulation
Complexation has been used to enhance drug absorption are:
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Enhanced dissolution through formation of a soluble complex e.g. ergotamine tartarate-caffeine complex
Enhanced lipophilicity for better membrane permeability e.g. caffeine-PABA complex
Enhanced membrane permeability e.g. enhanced GI absorption of heparin

16. NATURE & TYPE OF DOSAGE FORM
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17. SOLUTIONS
 Solutions is most rapidly absorbed
 Drug dissolution is absent
 Factors influencing absorption of solution are:
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18. EMULSIONS
 Superior to suspensions in administering
poorly aqueous soluble lipophilic drugs
 Absorption increases 3 fold over its aqueous
suspension
 Factors influencing drug absorption of emulsion
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Surface area
Interfacial tension
Droplet size
Surfactants
Lipophilicity
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19. SUSPENSIONS
 Drug dissolution which is generally rapid due to the large surface area of the
particles
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20. POWDERS
 Though powders are superior to tablets & capsules
 They are not in use nowadays due to handling &
palatability problems
 Factors to be considered in the absorption of drug
from powders are
particle size
Polymorphism
wettability
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21. CAPSULES
 Powders & granules are administered in hard gelatin
capsules whereas viscous fluids & oils in soft elastic
shells
 Factors of importance in case of hard gel-
Drug particle size
Density
Polymorphism
Intensity of packing
Influence of diluents & excipients
 Factors of importance in case of soft gel-
Between the drug & the diluent
Between drug & gelatin shell
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22. TABLETS
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• Compressed Tablets > Film Coated Tablets > Sugar Coated Tablets > Enteric
Coated Tablets > Sustained Release Products
Factors to be considered in the absorption of drug from tablets
are
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23. CONCLUSION
• Absorption plays an major role to attain the desired therapeutic action with minimal
side effects at the given period of time
• Formulation factors influencing drug absorption helps us to focus on formulating
drug with proper attainment of permeability of drugs to systemic circulation at given
time
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24. REFERENCES
1. Brahmankar D.M., Jaiswal S.B., First edition, “Absorption of Drugs”
Biopharmaceutics and Pharmacokinetics – A treatise, Vallabh Prakashan, Delhi 1995,
page no. 27-77
2. Shargel L., Andrew B.C., Fourth edition “Physiologic factors related to drug
absorption” Applied Biopharmaceutics and Pharmacokinetics, Prentice Hall
International, INC., Stanford 1999, Page No. 99-128
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ANY QUERIES???
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