– Comparative Bioavailability Studies of Paracetamol Brands In Humans –
Download Comparative Bioavailability Studies of Paracetamol Brands In Humans project materials: This project material is ready for students who are in need of it to aid their research.
ABSTRACT
The comparative bioavailabilities (bioequivalence) of five generic brands ofparacetamol were compared in six (6) healthy male volunteers. The aim was to studywhether the generic brands are bioequivalent to the standard brand.
The study was carried out following oral administration of 1g of each brand afterwash-out period of two weeks. The concentration of paracetamol in the saliva sampleswere determined using UV – spectrophotometer.
The pharmacokinetic parameters for bioavailability evaluation Cmax, Tmax and AUC were determined. The values ofreference tablet panadol® was Cmax 48.50 ± 21.82 µg/ml, Tmax 1 ± 0.41 (hr), AUC238.13 ± 12.4 µg/ml/hr,
while test brand XA was Cmax31.50 ± 16.83 µg/ml, Tmax 0.5 ±0.25 (hr), AUC 117.93 ± 8.10µg/ml/hr, XB Cmax50.0±17.39µg/ml, Tmax0.50 ±0.25(hr), AUC 202.0 ± 12.56 µg/ml/hr, XC Cmax42.0 ± 17.39µg/ml, Tmax1 ± 0.41 (hr),
AUC 192.63 ± 10.07µg/ml/hr, XD Cmax50.0 ± 15.82µg/ml, Tmax1±0.41 (hr), AUC256.13 ±11.51µg/ml/hr and XE Cmax5.3 ± 2.4 µg/ml, Tmax3±1.07 (hr), AUC 27.03 ±
1.34 µg/ml/hr.
Reference ratio of three generic brands XB, XC and XD were bioequivalentto the standard brand because their limits lies within the bioequivalent range of 0.8 –1.25 or 80% – 125% confidence limits with panadol® while the other two brands XAand XE were not within these bioequivalence range with panadol®.
TABLE OF CONTENTS
Declaration – – – – – – – – ii
Certification – – – – – – – – iii
Dedication – – – – – – – – iv
Acknowledge – – – – – – – – v
Abstract – – – – – – – – vi
Table of contents – – – – – – – vii
List of Table – – – – – – – – viii
List of figures – – – – – – – – ix
List of appendices – – – – – – – x
Abbreviation – – – – – – – – xi
CHAPTER ONE: INTRODUCTION
1.1 Bioavailability, Bioequivalence and Generic drugs – – – 1
1.2 Generic drugs – – – – – – – – 2
1.3 Bioavailability – – – – – – – 2
1.4 Absolute bioavailability – – – – – – 3
1.5 Comparative bioavailability – – – – – – 3
1.6 Factors affecting bioavailability – – – – – 4
1.7 Assessment of bioavailability – – – – – 6
1.8 Bioequivalence – – – – – – – 7
1.9 Assessment of Bioequivalence – – – – – 7
1.9.1 Pharmacokinetic criteria – – – – – – 8
1.9.2 Statistical criteria – – – – – – – 8
CHAPTER TWO: LITERATURE REVIEW
2.1 Paracetamol – – – – – – – – 11
2.1.1 History – – – – – – – – 11
2.1.2 Chemistry of paracetamol – – – – – – 11
2.1.3 Absorption and Bioavailability – – – – – 12
2.1.4 Distribution – – – – – – – – 13
2.1.5 Dosage form performance – – – – – – 13
2.1.5.1 Excepient and manufacturing variation – – – – 13
2.1.5.2 Risk for bioequivalence caused by excepient
and manufacturing parameters – – – – – 16
2.1.5.3 Patients risks associated with Bioavailability – – – – 16
2.1.6 Comparative Bioavailability and plasma paracetamol profiles of panadol suppositories in children – – – – 16
CHAPTER THREE:MATERIALS AND METHODS
3.1 Materials – – – – – – – 18
3.1.2 Glass wares – – – – – – 19
3.1.3 Equipments – – – – – – – 20
3.1.4 Reagents – – – – – – – 20
3.2 In-vitro studies – – – – – – – 20
3.2.1 Identification test – – – – – – – 20
3.2.2 Assay – – – – – – – – 21
3.2.3 Disintegration test – – – – – – – 21
3.2.4 Dissolution test – – – – – – – 21
3.2.5 Preparation of standard samples – – – – – 22
3.2.5.1 Preparation of paracetamol solution – – – – 22
3.2.5.2 Preparation of dissolution medium – – – – – 22
3.3 In-vitro studies – – – – – – – 22
3.3.1 Protocols of study – – – – – – – 23
3.3.2 Analytical methods — – – – – – – 23
3.3.3 Extraction methods – – – – – – – 23
3.3.4 Calibration curve – – – – – – – 24
3.3.5 Data handling – – – – – – – 26
CHAPTER FOUR: RESULTS AND DISCUSSION
4.1 In-vitro studies – – – – – – – 27
4.1.1 Identification test – – – – – – – 27
4.1.2 Assay – – – – – – – – – 27
4.1.3 Disintegration time for paracetamol tablets – – – – 27
4.1.4 Dissolution profile for paracetamol tablets – – – – 28
4.2 In-vitro studies – – – – – – – 28
4.2.1 Calibration curve – – – – – – – 28
4.2.2 Pharmacokinetics – – – – – – – 31
4.3 Conclusion – – – – – – – – 44
References – – – – – – – – 46
REFERENCES
Abernethy DR, Greenblatt DJ, Divoll M, Ameer B, Shader RI. (1982). differential effect of cimotidine on drug oxidation (antipyrine and Iorazepam): Prevention of acetaminophen toxicity by cimetidine AM J Pharm Exp Theraput 224: 508- 513.
Ameer B, Divoll M, Abernethy DR, Grunblatt DJ, Shorgel L, (1983) Absolute and relative bioavailability of oral acetaminophen preparations. J Pharm Sci 72:955-958.
American Hospital Formulary Service (1994). Drug information. Bethesda: America society of Hospital Pharmacists 1328p.
Arana A, Morton NS, Hansen TG. (2001). Treatment with paracetamol in infants.Acta Anaethesiol scand 45:20-29.
Bababola CP, Oladimeji FA, Femi – Oyewo MN (2001). Correlation between in vitro and in vivo parameters of commercial paracetamol tablets. Afri J Med Med Sci 30:275-280.
Bailey DN, Briggs JR (2004). The binding of acetaminophen, lidocaine and valproic acid to human milk. Am J Clin Pathol 121:754- 757.
Be the first to comment