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.
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.
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.
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
For more Pharmaceutics Projects Click here
===================================================================Item Type: Ghanaian Topic | Size: 92 pages | Chapters: 1-5
Format: MS Word | Delivery: Within 30Mins.
===================================================================
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.