PHARMACEUTICAL EQUIVALENCE STUDIES ON SOME LOCALLY MANUFACTURED BRANDS OF PARACETAMOL SOLD IN KUMASI

ABSTRACT
Paracetamol (acetaminophen), N-(4-Hydroxyphenil)-acetamide an over-the-counter analgesic, antipyretic and anti-inflammatory drug is a widely used drug. There are numerous generics of Paracetamol tablets available within the health delivery system in Ghana and globally. This study sought to determine the pharmaceutical equivalences between some selected brands of Paracetamol produced locally and compared to one imported brand from England. Thirteen brands of Paracetamol tablets plus one imported brand (M&A Pharmachem, England) were purchased from licensed pharmacies within Kumasi. Samples were all immediate-release conventional, oral dosage forms and were coded to avoid bias. Pharmacopoeial and non-pharmacopoeial tests such as friability, thickness, hardness, uniformity of diameter, uniformity of weight, disintegration time, in vitro dissolution testing and assay were used to assess the pharmaceutical equivalence of the various brands of Paracetamol tablets. The paddle method was used for the dissolution testing. UV spectroscopy was used for the assay analysis of all the brands of Paracetamol tablets sampled. All brands complied with the official specifications for identification, diameter, thickness and hardness. PLE, PMA, PPH, and POC passed all the test conducted on it. However brands PSA, PTA and PDA passed majority of the tests and failed the test for assay. Brands PAS, PMG, and PAN failed the dissolution rate test and assay. Brand PKI also failed the test for disintegration and dissolution. PAE failed the weight uniformity test but passed the other tests. PAR performed poorly by failing the test for friability, weight uniformity and assay. Statistically all brands are different from the standard in at least one test. Only Brands PLE, PPH and POC are pharmaceutically equivalent to the standard (PMA) and may be used as alternatives if they proved to be bioequivalent.


CHAPTER ONE 
1.1 Introduction
Paracetamol (acetaminophen), N-(4-Hydroxyphenil)-acetamide an over-the-counter analgesic, antipyretic and anti-inflammatory drug is a widely used drug, though its mechanism of action is not yet confirmed. (Ababa et al., 2014). It has been proposed that the analgesic mechanisms action of Paracetamol which involves prostaglandins (PGs), has a controversial result of inhibiting the central Cyclo-oxygenases (COX-1, COX-2, and COX-3) (Smith, 2009).

In the proximal small bowel, Paracetamol is well absorbed and this enables it to bypass any significant first pass metabolism that occurs in the liver. It is estimated that the oral bioavailability of Paracetamol in adults is between 63-89%. Approximately 90 % of the therapeutic doses of Paracetamol which is absorbed in the liver is metabolized by sulphation and glucouronidation to form non-toxic metabolites, which are then excreted in the urine(Ababa et al., 2014).

Peak plasma concentration (Cmax) of Paracetamol is usually achieved at approximately 45 minute. The distribution of volume is between 0.7 L/kg and 1L/kg and it is usually eliminated by the kidney (Shep et al ., 2010). Paracetamol bound less to plasma protein than the salicylates, even though the amount bound varies from 20 to 50 %. (Ababa et al., 2014). Side effects associated with Paracetamol are rare, usually transient. (Oscier et al., 2007). However; increased sweating, severe diarrhea, nausea and vomiting, loss of appetite, severe abdominal pain, stomach cramps, tenderness and pain in the upper abdomen or swelling, could all be attributed to signs of overdose ( Koppert et al., 2006).

The health delivery system in Ghana and globally consist of lots of generics brands of drugs especially Paracetamol tablets. They are usually preferred and recommended for use by practitioners because they are cheaper as compared to the innovator products. The quality of Generic drug should be good enough, so that it can be compared to that of the innovator product despite the price. Drugs that are therapeutically and pharmaceutically equivalent are the only drug that qualifies to be called generics and can therefore be interchanged with the innovator products. Determining the chemical and biopharmaceutical equivalence of a drug is the first stage as well as very important step in establishing the therapeutic equivalence of any drug product (Olaniyi et al., 2001). Some parameters that are used to determine Drugs that are biopharmaceutically and chemically equivalent are; the drugs must be identical in quality, purity, strength, active ingredient release profile and it must also be in the same dosage form as well as same route of administration.

The various sources of generic drugs which have been introduced into the health care delivery system are to help improve access and affordability of life-saving drugs in many developing countries (Adegbolagun et al., 2007). Moreover this idea has been bedevilled by the introduction and widespread distribution of counterfeit and substandard drugs therefore compromising the quality of medicinal drugs being used in many developing countries. It is very difficult to distinguishing a degraded drug from substandard one, meanwhile this distinction is very important as the causes and remedies of these are different and must be investigated (Keoluangkhot et al., 2008). This revelation is therefore essential and helps reiterates the importance of monitoring the quality of drugs to be able to protect patients‟ health.


1.2 Problem Statement
In Ghana there is trade liberalization and this coupled with the boost in the local pharmaceutical manufacturing sector make entrepreneurs consider the pharmaceutical market as an easy means of making profits and also perceives it as an ordinary commodity market. Manufacturers desire to reap huge financial profits and this contribute to the general disregard of manufacturers to lay down rules by regulatory bodies like FDA resulting in quackery and faking.

The concept of quality assurance involves simple checks of the final products, such as test for appearance, colour, odour, identity, hardness, average weight or volume per unit.

The International Organization for Standardization (ISO) 8402-198, defines quality as “the -totality of characteristics and features of a product or service that bears its ability to satisfy stated or desired needs”. In order to fulfill these needs there should be a quality control mechanism in the production process. Certain critical measures are taken, and this usually includes sampling, testing samples, setting of specification, and analytical clearance .These are all considered by the quality control parameters of drugs and drug products and this ensures that the strength and purity of the drug, starting materials, intermediate, packaging materials and finished pharmaceutical products meet set standards to assure the identification, strength and purity of the drug are all validated (Ergetie et al., 2013). The efficacy and safety of all pharmaceutical dosage forms can be guaranteed only when the quality is reliable (Ahmed et al., 2012). The need therefore to ensure critically that generic drugs are pharmaceutically equivalent cannot be overemphasized in pharmaceutical manufacturing. Healthcare practitioners are always concerned with the need to select one product from several generic drug of the same active ingredients during the course of therapy.

1.3 Justification
World health organisation (WHO) has estimated that medicinal products on sale in various countries in Africa, parts of Latin America and Asia for consumption has about 30% of it been substandard and counterfeit (WHO, 2006). Generic and branded products can also be Counterfeit, counterfeiting can even be applied to products which have the correct ingredient or wrong ingredient, with insufficient active ingredient, without active ingredient, or with fake packaging (WHO, 1999). Meanwhile genuine drug products that do not meet all the quality specification claimed by their manufacturers upon laboratory testing are referred to as substandard drugs (Taylor et al., 2009).

Within the health delivery system globally as well as Ghana various types of generic Paracetamol tablets are available. There are evidences that products with the same amount of active ingredient sometimes show distinct differences in their therapeutic effects (Fujii et al., 2009). This therefore put Health practitioners in a dilemma when they have to do generic substitution. Paracetamol tablets usage as an over the counter (OTC) drug is in an increasing rate. It is also used in the clinical setting and this has made it very necessary to monitor and ascertain the quality attributes and the drug release proficiency of the various local brands of Paracetamol available on the Ghanaian market for purpose of generic substitution and also for quality control assessment.

1.4 General Objective
The broad objective of the research is to evaluate the pharmaceutical equivalence of some locally manufactured brands of Paracetamol tablets in Kumasi using a foreign brand as a reference.

1.5 Specific Objective
To achieve the broad objective, the following specifics will be pursued.

To sample some locally manufactured brands of Paracetamol tablets in Kumasi

To perform identification test on the brands of Paracetamol using Fourier Transmittance infrared spectroscopy (FTIR)

To determine the physicochemical equivalence of the Paracetamol tablet brands sampled using both compendia and non- compendia methods

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Item Type: Ghanaian Project Material  |  Attribute: 92 pages  |  Chapters: 1-5
Format: MS Word  |  Price: GH50  |  Delivery: Within 30Mins.
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