Bioavailability of drug through iv,im

Bioavailability of Drugs through IV & IM Routes

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

2. 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

3. “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

4. Bioavailability of a drug from it’s dosage form depends upon 3 major factors : Pharmaceutical factors Patient related factors Route of administration

5. Biological fluids used for determination of Bioavailability : Plasma Urine Saliva CSF Bile

6. Bioavailability Measurement:

7. DRUG ROUTES : Intravenous Injection : 100 % bioavailability Onset of action is very rapid Irritant drugs to the tissues can be given intravenously

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

9. IV and IM administration Dosing Sampling at Pre-determined Time intervals Bio-analytics Conc. vs time profiles

10. Concentration versus Time Profiles One-Compartment Model Assumes body as one compartment 1 Two-Compartment Model Central 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

11. 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

12. 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

13. Pharmacokinetic Studies Key Measurements AUC Area under the concentration- time curve C max Maximum concentration A difference of greater than 20% in C max or the AUC represents a significant difference between the study and reference compounds T max Time to maximum concentration Study Compound Reference Compound Time Concentration C max T max AUC

14. Peak serum concentration of selected oral, IM and IV antibiotics Class of Antibiotics Oral IM IV Natural Penicillin ++ -- ++++++ Aminopenicillin + ++ +++ Chloramphenicol ++ + +++ Sulfonamides + NA + Rifampin + NA ++

15. 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

16. 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.

17. HPLC Instrumentation : Solvent Reservoir Pumps Injection System Columns Detectors Data Processing Waste

18. PUMP: COLUMNS:

19. Flow Diagram :

20. 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 ).

21. Applications of HPLC: Pharmaceutical Applications Environmental Applications Applications in Forensics Applications in Clinical Tests

22. 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.

23. 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 , . D rug Bioavailability edited by Han van de Waterbeemd , Bernard Testa

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