BIOAVAILABILITY OF DRUG THROUGH I/M, I/V ROUTE

Contents• Concept of Bioavailability• Factors of Bioavailability• Fluids for determination of Bioavailability• Bioavailability Measurement• IV & IM routes of administration• Pharmacokinetic Studies• Dtection method (HPLC)• Objective of Bioavailability

“The term Bioavailability is defined as a rate & extent (amount) of absorption of unchanged drug from its dosage form and become available at the site of action.”

• Absolute Bioavailability

• Relative Bioavailability

Bioavailability of a drug from it’s dosage form depends upon 3 major factors: Pharmaceutical factors

Patient related factors

Route of administration

Biological fluids used for determination of Bioavailability :

1.Plasma2.Urine3.Saliva4.CSF5.Bile

BIOAVAILABILITY MEASUREMENT:

Pharmacokinetic (Indirect )

1.Plasma level time studies

2.Urinary excretion studies

DRUG ROUTES :Intravenous Injection :

• 100 % bioavailability• Onset of action is very rapid• Irritant drugs to the tissues can be given intravenously

Intramuscular Injection :

• Injection is made deep into a large muscle• 75- <100% bioavailability• Absorption is rapid but uniform• Oily solutions…..retarded absorption• Painful

IV and IM administration

Dosing

Sampling at Pre-determined Time intervals

Bio-analytics

Conc. vs time profiles

Concentration versus Time Profiles

One-Compartment Model Assumes body as one compartment

1

Two-Compartment ModelCentral compartment (drug entry and elimination)Tissue compartment (drug distributes)

1 2

k

k

Dose

Dose

Broadly the concentration – time profiles can be viewed as two different ways

IM route• – Injection site• – Diluent• – Solubility of drug• – Concentration of drug• – Total surface area for

diffusion• – Blood flow to muscle

injected

Factors influencing absorption and bioavailability of medications

IV route

IV 100% bioavailability

Pharmacokinetic Studies• Parameters affected by mode of administration• – Absorption • – Bio-availability • – Peak serum concentration• – Time to peak serum

concentration

• Parameters unaffected by mode of administration

• – Half-life – Clearance• – Distribution• – Metabolism• – Protein binding

Pharmacokinetic StudiesKey Measurements

• AUC– Area under the concentration- time

curve• Cmax

– Maximum concentration– A difference of greater than 20% in

Cmax or the AUC represents a significant difference between the study and reference compounds

• Tmax– Time to maximum concentration

Study CompoundReference Compound

Time

Conc

entra

tion

Cmax

Tmax

AUC

Peak serum concentration of selected oral, IM and IV antibiotics

Class of Antibiotics

Oral IM IV

Natural Penicillin ++ -- ++++++

Aminopenicillin + ++ +++

Chloramphenicol ++ + +++

Sulfonamides + NA +

Rifampin + NA ++

Phamacokinetics of NSAIDs by IM & IV route of administration

Class NSAID Bioavailability % IV

Bioavailability (%) IM

Time to serum peak

Diclofenac Na 50-60 100 0.3

Ketorolac 100 100 0.5-1

HPLC (High Performance Liquid Chromatography) :Principle: Separation of a sample into its constituent parts because of the difference in the relative affinities of different molecules for the mobile phase and the stationary phase used in the separation.

HPLC Instrumentation :

• Solvent Reservoir • Pumps• Injection System • Columns • Detectors • Data Processing • Waste

PUMP:

COLUMNS:

FLOW DIAGRAM :

DATA PROCESSING :

USING SPECIFIC SOFTWARE, DATA IS PRESENTED IN THE FORM OF GRAPH. THE GRAPH DESCRIBES ABOUT QUALITATIVE DATA (RETENTION TIME) AND QUANTITATIVE DATA (AREA UNDER CURVE).

Applications of HPLC:

• Pharmaceutical Applications

• Environmental Applications

• Applications in Forensics

• Applications in Clinical Tests

OBJECTIVES OF BIOAVAILABILITY STUDIES : Development of new formulations.

Determination of influence of excipients, patient related factors and possible interaction with other drugs on the efficiency of absorption.

Control the quality of a drug product during the early stages of marketing in order to determine the influence of processing factors, storage, stability on drug absorption.

Primary stages of the development of a suitable dosage form for a new drug entity.

References :

• Chromatography by Dr. Haq Nawaz Bhatti (CH-7, Page 137)

• Journal of Clinical Pharmacology, 2001;41:1225-1231

• HPLC determination of acyclovir in human serum and its application in bioavailability study. J. Emami1, N. Bazargan1 and A. Ajami2 .

• http://laboratoryinfo.com/hplc/• Biopharmaceutics & pharmacokinetics,

D.M.Brahmankar, S.B.Jaiswal,.• Drug Bioavailability edited by Han van de

Waterbeemd, Bernard Testa

Thank

You !