INTRODUCTION:
Malaria is considered to be the
most prevalent vector-borne disease worldwide and is currently endemic in 97
countries [1]. Despite being preventable and treatable,
malaria continues to be a life-threatening disease resulting in high levels of
morbidity and mortality. Malaria is estimated to cause between 660,000 and over
a million deaths every year and in 2012 there were an estimated 207 million
cases of malaria [2]. Worldwide estimated
malaria mortality rates between 2000 and 2012 fell by 42% across all age groups
and by 48% amongst children under five years old [3].
However, the pace of this decrease slowed between 2011 and 2012 [3].
Africa is now at a critical
stage in the struggle against a disease that saps its development. Without
intervention, the crisis will deepen. But if national and global commitment and
support for the Roll Back Malaria initiative can be put into action on the
ground, then the devastation being wrought by malaria can be reversed [4].
Artemisinin combination therapy (ACT) is now the
treatment of choice for uncomplicated Plasmodium falciparum malaria [5, 6] . Malaria endemic
countries have switched to artemisinin-based
combination therapy (ACT) for the treatment of acute, uncomplicated Plasmodium falciparum
malaria [7] The fixed dose combinations (FDCs) are strongly
recommended over the blister packs to reduce the potential use of monotherapy [8]. FDCs are pre-ferred to loose tablets because
fewer tablets are involved and patient adherence can be improved [9].
Accordingly, all ACTs, except artesunate + sulphadoxine-pyrimethamine have been developed as FDCs.
Since the efficacy of the ACT is partly dependent on the efficacy of its
partner drug, there is a need to develop multiple ACTs. In Africa such as artemether- lumefantrine [10],
artesunate-amodiaquine [11], pyronaridine-artesunate [12] dihydroartemisinin
- piperaquine [13] . Poor-quality antimalarials
have been a severe under-recognised public health
problem, reducing the effectiveness of these drugs and threatening current
treatment policies. There are three main types of poor-quality medicines;
degraded, substandard and counterfeit. The WHO defines counterfeit drugs as
those that are ‘deliberately and fraudulently mislabeled with respect to
identity and/or source’, and may include those with the correct ingredients or
with the wrong ingredients, without active ingredients, with insufficient
active ingredients or with fake packaging [14]. Substandard drugs
are produced with inadequate attention to good manufacturing practices and may
have contents and/or dissolution times outside accepted limits, due to poor
quality control [15]. In addition, degraded formulations may result
from exposure of good-quality medicines to light, heat and humidity [16].
There is an increasing concern that a major impediment to malaria control is
the poor quality of antimalarial medicines.
Counterfeiting is one of the oldest and most profitable occupations [17]. However, even today, it remains difficult
to detect, investigate or quantify. The World Health Organization (WHO)
estimated that nearly half of the global pharmaceutical market is occupied by
counterfeit drugs [18]. Recent estimates
suggest that nearly 800 fake drug types [19]
are within the legitimate pharmaceutical market structure, and globally there
is a massive increase in counterfeit or falsified drug sales to over US$75
billion in 2010, an increase of more than 92% from 2005 [20]
. Poverty, weak economies, poor regulatory systems, short supply, and the
rising cost of therapeutic agents have created a corresponding increase in
production of fake drugs because of the huge profit margin [21]
. Both substandard and counterfeit drugs are serious problems, and remain
as one of the most neglected public health issues [22],
where counterfeiting is mounting to more than 60% in Third World countries [23].
WHO estimates about 60% of purchased counterfeited products did not have any
active pharmaceutical ingredient (API), 17% contain too much or too little API,
whilst another 16% contain the wrong ingredients altogether [24].
In this research, we report the electronic and Fourier transform infrared
spectroscopic characterization of dicomponent antimalarial drugs sold in Nigeria drug stores.
MATERIALS AND METHODS:
Different
brands of dicomponent
antimalarial drugs were purchased from
different Nigerian drug stores. There inscriptions were removed and they were
labeled A, B, C and D respectively. The UV- visible spectra of the antimalarial drugs in solution were scanned between 200 –
800 nm on a Perkin Elmer model spectrum BX using chloroform as solvent. The Infrared spectra of the antimalarial drugs were carried out using FT-IR
spectrometer by Perkin Elmer (Model Spectrum BX) equipped with caesium widow (4000-350cm-1) in KBr pellets. Interpretations of the spectra were made.
RESULTS:
The
electronic and Fourier transform infrared spectra of the malarial drugs
(labeled A, B, C, D) are presented in Figures 1-8 respectively.
DISCUSSION:
In
the electronic spectrum (Figure1), the electronic absorption band at 192.63 nm
has been assigned σ → σ * transitions since this transitions
occurred in the vacuum ultraviolet region < 200 nm. The absorption bands
222.38, 281.02 and 318.65 nm were assigned π → π *, since these
transitions occurred in the ultraviolet region. The suggested chromophores are C=C, C=N and S=O. In the FTIR spectrum of
sample A, (Figure 2), the vibration frequencies 1155.24 and 1313.12 cm-1
have been assigned ν(S=O). The frequencies 3456.58, 3381.78 have been
attributed to ν(N-H) stretch. The vibration frequency 1081.94 cm-1
have been attributed to ν(R-O-R) functionality. 833.29 cm-1 frequency has
been assigned to ν(R-Cl), 1595.29 cm-1 was
attributed to ν(C=C) ring stretch. Aliphatic C-H stretch was found at
2952.38 cm-1 in the spectrum.
The
electronic spectrum of Sample B (Figure 3) showed absorption at 199.94 nm. This
absorption was assigned σ → σ * transitions because it occurred
in the vacuum region < 200 nm. The bands 206.70, 232.80, 287.83 and 306.93
nm were assigned π → π * transitions. The possible chromophores in the antimalarial
drug that showed these absorptions are C=C, C=N and S=O. In the vibrational
frequency of the FTIR spectrum of sample B (Figure 4), 1152.44 and 1314.65 cm-1
were attributed to ν(S=O). 3241.41, 3462.18 and 3372.76 cm-1 wavenumbers have been assigned ν(N-H) stretch. R-O-R, R-Cl, ArC=C and aliphatic C-H stretch functional groups were
found at 1080.92 cm-1, 836.04 cm -1, 1591.46 cm-1
and 2946. 30 cm-1 respectively.
The
absorption band 205.75, 219.76 228.51, 244.26 and 320.40 nm which are in the
ultraviolet region (Figure 5) were assigned
π → π * transitions. The absorption band at 484.06 nm
appeared in the visible region. This band was assigned n→ π*. The
suggested chromphores
in the antimalarial drug for these electronic
transitions are C=C and C=N. The ν(OH), ν(R-O-R), ν(aliphatic
C-H), ν(C=N), ν(C-Cl) and ν(C-N)
functionalities appeared at 3350.14, 1037.76, 2929.97, 1644.75, 685.51 and
1037.76 cm-1 respectively (Figure 6).
The
electronic absorption bands 200.89, 207.99, 241.84, 256.55 and 272.54, 300.58,
330.73, 337.60 and 350.41 nm is present in the electronic spectrum shown in
Figure 7. The possible chromophores in the test drug
that might exhibit these bands C=C and C=N functional groups. These absorption
have been assigned π → π * transitions. The vibrational
frequencies in the FTIR of sample D (Figure 8) showed 3434.00, 1017. 79,
2931.24, 615.38, 1017.79, 3064.42 and 1126.76 cm-1 absorptions. These bands have been assigned
ν(OH), ν(R-O-R), ν(aliphatic C-H), ν(C-Cl) and ν(C-N),
ν(ArC-H) and ν(P=O) functional
groups respectively.
Based
on the electronic and Fourier transform infrared spectra, the following
structures (Figures 9 and 10) have been suggested for the dicomponent
antimalarial drugs.
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