The Quality of Different Brand Paracetamol Suspension (Research Proposal Sample)

CHAPTER ONE
1.1 INTRODUCTION
Paracetamol is a medicine that is commonly used as an analgesic (pain reliever) and antipyretic (fever reducer). Paracetamol suspensions contain paracetamol or p-acetyl-N-aminophenol as an active pharmaceutical ingredient. The chemical name of paracetamol is p-acetyl-N-aminophenol and it is marketed as a generic drug under various brand names. CITATION Bru15 \l 1033 (Brune, 2015)
Figure 1: Structure of paracetamol
Paracetamol suspension is an over the counter drug use for management of fever and mild to moderate pain in infants and children. It is one of the most commonly use analgesic drug in the world. In Kenya, paracetamol is most prevalent (88.8%) analgesic medicine. In treatment of fever associated with malaria the ministry of health recommend that children under five years having axillary temperature of more than 37.5℃ or feeling very hot on examination be given antipyretic preferably paracetamol.
Paracetamol can be taken as a capsule, pill, or suspension. The idea is focused on paracetamol suspension a common painkiller for children aged 2 months to 15 years old, whose strength is determined by the dosage and active component content. The excess content of paracetamol in suspension can cause problems in the brain, blood, and kidneys. High content of paracetamol above the tolerance in suspension can cause acute hepatic necrosis because of depletion of glutathione and binding of excess reactive metabolite in vital cell constituents. Therefore, formulation of suspension require some accuracy to avoid the problem.CITATION For821 \l 1033 (Forrest, 1982)
The brand paracetamol suspension is made using paracetamol as the active pharmaceutical component, with excipients added to increase stability, bioavailability, and aid in the formulation of an accurate dose form, as well as to ensure safety during storage and usage. This includes Propylene glycol (solvent), glycerin (Co-solvent), citrates (buffering agent), sodium methyl paraben (preservative), ascorbic acid (antioxidant), sodium lauryl sulfate (surfactants), magnesium stearate (anti-forming agent), sodium methyl paraben (preservative), ascorbic acid (antioxidant), sodium lauryl sulfate (surfactants), magnesium stearate. Depending on the manufacturer, the excipient used may differ. Curamol Suspension, Skymol Suspension, Cetamol Suspension, and Panadol are some examples of brand names of paracetamol suspension. CITATION Abd12 \l 1033 (Abdullahu, 2012)
Figure 2: Paracetamol suspension
Paracetamol suspension is packaged in a brown sealed bottle that keeps moisture and oxygen out while also blocking UV rays. This is done to prevent the paracetamol in suspension from undergoing disintegration and the rate at which they degrade is determined by chemical structure, medication manufacture, ambient conditions, microbial contamination, and heat, light, oxygen, and water exposure. When paracetamol is broken down, it produces 4-aminophenol and other product, which has no biological significance. CITATION WuS121 \l 1033 (Wu S. Z., 2012)
To ensure effective marketing and safe oral administration of different brand of paracetamol it require analysis for biopharmaceutical and chemical equivalence. This ensure that generic paracetamol can be used interchangeably. From this observation, most generic paracetamol has raise issue of likelihood of unequal performance as stated by Rwandan Food and Medicine Administration. CITATION OCo19 \l 1033 (O'Connor, 2019)
Pharmaceutical test use in assessing chemical equivalence is assay content of active ingredient and the presence of 4-aminophenol. The aim of the work is to assess the quality of different brand of paracetamol suspension produce by different industries in Kenya by evaluating their chemical equivalence to correct market failure and used interchangeably.
1.2 OBJECTIVES
1.2.1 MAIN OBJECTIVE
The goal of this research proposal is to find out the compliance of different brand paracetamol suspension with their label claim that is produce by different Kenyan pharmaceutical companies.
1.2.2 SPECIFIC OBJECTIVES
a) To determine the presence of an active pharmaceutical ingredient in commercial brand paracetamol suspension produced in Kenya.
b) To determine if the content of the active pharmaceutical ingredient matches the label claim in commercial brand paracetamol suspension.
c) To determine the presence of 4-aminophenol, a disintegration product of paracetamol due to different environmental factors.
1.3 PROBLEM STATEMENT
The problem to investigate is the quality of different brand paracetamol suspension produced by Kenyan pharmaceutical manufacturers. According to some research, it is found that high content of paracetamol in suspension has some side effect on the liver and a report from Rwanda's drug authority (FDA), has stated that Kenyan-made paracetamol has some quality issues, and they have ordered an investigation. Health institutions in possession of Kenyan-branded paracetamol in Rwanda have been asked to stop dispensing medicine and return the drug to the supplier. Other research has been stated that the quality of paracetamol may be influence by chemical structure, medication manufacture, ambient conditions, microbial contamination, and heat, light, oxygen, and water exposure.
In Kenya, different generic drugs has likelihood of unequal performances, that is why they are sold at different prices, and they cannot be used interchangeably. For chemical equivalency, bioavailability and market status of different generic paracetamol. I intend to solve the problem by analyzing the content of active ingredient in different brand paracetamol suspension and determining the companies that make suspensions whose assay content of active ingredient does not match the label claim. In addition, convey the message to National Pharmacy and Poison Board to provide them with an appropriate formulation of paracetamol suspension as well as a better way of packing and sealing for pharmacovigilance.
1.4 JUSTIFICATION
The drug having more than one generic name require analysis for their chemical equivalency and bioavailability from some initial research done in Kenya at 2013 relating to paracetamol but for tablets it was found that out of ten brand analyzed one brand fail assay criteria of 90-110% label claim. Two batches marginally passed assay criteria at 90% two other at 91% and none was more than 95%. This might shed the light for possible non-chemical equivalency in paracetamol suspension. Significance of this work stems from the fact that it will help to narrow down side effects related to drug bioavailability caused by high or low active component content in paracetamol solution. It will also aid in determining the quality of various paracetamol brands available on the market both internally and externally.
1.5 HYPOTHESIS
The pharmaceutical companies in Kenya have the capacity to make paracetamol suspensions with different chemical equivalence and active ingredient are affected by environmental conditions.
CHAPTER TWO
2.1 LITERATURE REVIEW
2.1.1 Background
Paracetamol is a medicine that is commonly used as an analgesic (pain reliever) and antipyretic (fever reducer). Paracetamol suspensions contain paracetamol or p-acetyl-N-aminophenol as an active pharmaceutical ingredient. It have similar structure as aspirin and due to this they are recognize by the same enzyme. The enzyme, which are responsible for biosynthesis of prostaglandin, which are used in dilation of blood vessel, that cause pain in headache. Decrease in amount of prostaglandins help prevent in preventing headache and other pain like toothache, migraine headache, muscle aches, backache, period pain, join pain and also reduce fever of bacterial or viral origin. It suitable for most people including elderly and young children and due to that it has some side effects. The chemical name of paracetamol is p-acetyl-N-aminophenol and it is marketed as a generic drug under various brand names.
Harmon Northrop Morse created it in 1878 by reducing 4-aminophenol with acetic acid, and Vonmering utilized it clinically. In 1893, paracetamol did not appear commercially until 1950 in the United States and 1956 in Australia. . CITATION Bru15 \l 1033 (Brune, 2015)
Figure 3: Equation for the formation of paracetamol.
2.1.2 Bioavailability of paracetamol and its side effect
Paracetamol is classified as biopharmaceutics classification system, it is an acid with pKa of 9.0 it has a short life of about 2-3 hours, which necessitate frequent dosing. The ideal quantity of paracetamol in suspension is 120 mg/5 ml. Paracetamol is well absorbed from small bowel and is not subjected to significant fast pass metabolism in the liver, with oral bioavailability estimated at between 63-89%. Paracetamol is not significantly bound to plasma protein and has a volume distribution of 0.7-1 L/Kg and the analgesic and antipyretic occurs between 1-2 hour after peak plasma level. CITATION For822 \l 1033 (Forrest J. A., 1982)
The metabolism of paracetamol take place in the liver the whale estimations occur at most entirely through the kindly following absorption of therapeutic doses and almost all are broken down by glucoronidation and sulphonation to form non-toxic product and exerted in urine. The major metabolite being the sulphate and glucuronide conjugates the small fraction is change to highly reactive alkylating metabolite, which is inactivated with, reduced glutathione and excreted in the urine as cysteine and mercapturic acid conjugates. Large dose of paracetamol cause acute hepatic necrosis as a result of binding of...