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 !
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