This document discusses factors that influence the availability of biopharmaceutical drugs. It covers physicochemical factors like particle size, solubility, pH, and viscosity that affect dissolution and absorption of drugs. Physiological factors like route of administration, blood flow, and dosage form are also discussed. Specific routes like intramuscular, subcutaneous, and intrathecal injection are examined in terms of how they impact drug absorption rates. Considerations for peptide and protein delivery are also reviewed. The document provides an overview of important concepts regarding drug availability from different administration approaches.

1. Biopharmaceutical
Factors Influencing
Drug Availability
Presented By-
Akhil S. Raut
Department Of Quality Assurance

2. Contents
 Introduction
 Physiochemical factors
 Physiologic factors
 Dosage form consideration
 Drug absorption and bioavailability
 Intramuscular injection
 Subcutaneous injection
 Bio-pharmaceutics of intrathecal injection
 Parentral administration of peptide and
proteins
 Parentral drug delivery system

3. Introduction
 For a therapeutic activity, the drug
molecule must be available to the site of
action.
 The several factors influence the therapeutic
effect of drug such as,
 Physicochemical properties of drug and
dosage form
 Biological characteristics of patient

4. Biopharmaceutic
 It is defined as, “The study of the
relationship between the physical
and chemical properties of the drug
and it’s dosage form and the biologic
effects observed following the
administration of the drug in the
dosage form.”

5. Bioavailability
 Bioavailability is defined as rate and extent of
absorption of unchanged drug from it’s dosage
form and become available at the site of action.
Drug availability from parentral dosage forms, is that
availability represents the amount of intact drug that
reaches the systemic circulation.

6.  Selection of route of administration
 Choice of the dosage regimen
 Choice of the specific drug analogue
 Use of other drug in therapeutic regimen
 Selection and preparation of the
formulation, including both active and
inactive ingredients
Therapeutic response to a given drug can be
controlled by,

7. Fig- drug absorption
from solid dosage form

8. Physicochemical influence
on bioavailability
 Dissolution rate
 “the process by which a drug in a solid
form goes into solution is termed
dissolution.
It is a slowest
step which affect
absorption of drug
at site .

9. Time
Bloodlevel
MEC
1
2
3
Fig:- Hypothermic blood levels versus time curve

10.  The factors and their effect on dissolution rate are easily
recognised by applying following equation,
Dissolution = K. D. S(CS – C)
Where,
C- concentration of drug in the solution at time t
CS –equilibrium solubility of the solute at the experimental
temperature
S- surface area of solid drug
D- diffusion coefficient of drug
K - constant
Several factors can influence the dissolution rate of drugs in
pharmaceutical dosage forms.

11.  As a particle size decreases there is increase in
absorption of drug. Similarly increase in particle
size result in prolongation of absorption.
 Absorption of procaine penicillin G suspension by
intramuscular route
Particle size
Particle size
(um)
Average blood levels
Units/ml
150-250 1.37
105-150 1.24
58-105 1.54
35-38 1.64
<35 2.40
1-2 2.10

12. Solubility
 By altering the solubility, dissolution rate can
be increased or decreased.
 Polymorphism is a factor which affect the
solubility of a drug.
 Crystalline form is more stable, other
polymorphic forms are less stable and have
greater solubility.
 Ex. Novobiocin and chloramphenicol

13. pH
 Altering the solubility of drug that are
either weak acids or weak bases.
 The solubility of drugs can be appreciably
increased in this diffusion layer
 PH of the diffusion layer is different from
the other body fluids
 The PH of the diffusion layer may have
an extremely important influence on drug
solubility and dissolution rate with other
routes of administration

14. Viscosity
 The effect of dissolution rate on drug
absorption is the viscosity of the parentral
solution or suspension
 The viscosity of the solution or fluid in
which a drug dissolves can affect the
dissolution rate by altering the diffusion
coefficient.
 High the viscosity, diffusion coefficient of
drug is reduced

15. Partition coefficient and
lipid solubility
 Before reaching to systemic circulation
drug should cross biological membrane
 Biologic membranes are highly complex
structure that are primarily composed of
lipids and proteins.
 Drugs should have lipophilic
characteristics to penetrate the biologic
membrane

16.  Lipid solubility to drug absorption
concerns the drug molecule that are
either weakly acidic or weakly basic
 Un-ionised molecules have greater lipid
solubility and it can more readily
penetrate than ionised drug
 For weak acid
pH = pKa + log [un-ionized]
[ionized]
pH = pKa + log [ionized]
[un-ionized]
For weak base

17. Interaction between the
drug and dosage form
 Inert ingredients can affect availability of
active drug from the complete product
Active drug
Absorbed drug
Inert binding
agent
Drug
complex

18. Physiologic factors
 Route of administration
 Iv injection results in immediate and total
access of active drug molecules to the
body
 Intramuscular and subcutaneous routes
requires absorption step before drug can
access to the body

19. Blood flow
 After Sc injection, active drug is absorbed
by diffusion of the drug into capillary
network at absorption site
 Greater the blood flow at absorption site
greater is the absorption rate of the drug.
 Administration by oral route can also
influence the parentral absorption of
some drug

20. Dosage form
consideration
•Directly given to the systemic circulation
•Within 4 min. drug concentration reaches at
maximum after iv administration
•For a short biological half life drugs can not
achieved the concentration of drug for
sustained released
•For longer released continuous drip should be
allowed

21. Intramuscular and
subcutaneous injection
•It gives more sustained blood levels of drug
than intravenous route
•im & sc injection required an absorption step
before the drug reaches to the circulation
•Different dosage forms are..............
•Aqueous solution
•Aqueous suspension
•Oleogenous solution
•Oleogenous suspension

22. Formulation variables Effect of release
Solubility
in water
Particle
size
Total
amount
of drug in
doe
Rate Duration
of action
Constant Constant Increase Increase Unchange
d
Decrease Constant Decrease Decrease Unchange
d
Constant Decrease Constant Increase Decrease
Constant Increase Constant Decrease Increase
Increase Constant Constant Increase Decrease
Decrease Constant Constant Decrease Increase

23. Drug absorption and
bioavailability

24. From intramuscular injection
 Exact dose of drug can be administered
but rate of absorption may vary widely.
 Ex. Lidocaine levels were obtained in
plasma by giving injection in deltoid
muscles .
 Higher plasma levels obtained after
injection into the deltoid muscle than
injection into the buttock

26.  Many drugs with limited aqueous solubility
are often formulated in solution for parentral
administration through the used of ph and
alteration and organic co-solvents like.
 Propylene glycol, ethanol and low
molecular wt. polyethylene glycols.
 Crystals have a low rate of dissolution and
therefore drug is absorbed at low rate from
injection site,

27.  When drug is administered
intramuscularly the decrease in ph
results in conversion of the sodium salt to
the free acid and the precipitation of
phenytoin in interstitial water at the
injection site.
Ex. Phenytoin, is a insoluble drug the
preparation available for parental
administration is a propylene glycol and
alcohol aqueous solution adjusted to pH12.

28. From subcutaneous injection
 The vascularity in the region of
subcutaneous injection is poorer than
that of muscle tissue and may lead to
slower absorption
 Absorption rate may increase by applying
heat and decrease by adding
vasoconstrictor along with medication
 Absorption is done with capillaries or the
lymphatic system associated with site of
injection

29. Biopahrmaceutics of
intrathecal injection
 In this rote drug is directly given to the CSF
to achieve effective concentration, it also
associated with high incidence of side effect
 Injection of drug intrathecally accomplished
by way of lumber spinal cord, basal cisterns,
or lateral ventricles
 Factors such as solution volume and specific
gravity as well as the patient position
influence drug distribution within central
nervous system

30.  Vehicle solution pH and osmolarity
preservatives added physical state of the
drug addition of detergent and proteins all
have influence on patient tolerance to the
injected formulation

31. Parentral administration
of peptide and proteins
 To overcome the low bioavailability of
peptides through oral route interest will
be increased in administration of drug
through subcutaneous and intramuscular
route
 Sc or im administration may provide a
means to prolong systemic half-life and
therapeutic activity

32.  Factors which affect bioavailability of
peptides are
 Site of injection
 Use of absorption enhancers
 Chemical modification of the protein

33. Parentral drug delivery
system
 Liposomal encapsulation of drug
 It provides means to achieve systemic
sustained release or provide targeted
drug delivery while reducing
immunogenicity and systemic or local
adverse reaction

34. References
 Salvatore J. Turco, Sterile dosage form,
their preparation and clinical
application,4/E

35. Thank you..........
For patiently listening!