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RESEARCH ARTICLE
Publications trends of different routes of administration,
oral dosage forms and conventional tablets during 1980-2012: A pilot study
using PubMed search tool
Farah Hamad Farah1*, RanaMohd. Fareed Sammour2
and Abdul-Azim Ahmed Ali3
1Department
of Pharmaceutics, College of Pharmacy and Health Sciences, Ajman University of
Science and Technology, UAE
2Department
of Pharmaceutics, Dubai Pharmacy College, UAE
3Department
of Pharmaceutics, College of Pharmacy and Health Sciences, Ajman University of
Science and Technology, UAE
Corresponding Authors E-mail: f.hamad@ajman.ac.ae
The
main objectives of this study is to record, analyze, and compare the trend of
published scientific research articles conducted on different routes of
administrations, various oral dosage forms and conventional tablets,
during 1980-2012 and try to explain possible reasons leading to such
trend.
In this study, PubMed, has been used as a
search tool for published scientific articles, using different keywords related
to different routes of administrations, various oral dosage forms and
conventional tablets.
Analysis of the searched published
articles, showed almost a regular increasing annual publication pattern of the
oral route compared to other routes. The domination of the oral route may be
due to the access-ability, convenience and safety of this route compared to
other routes. The percutaneous route was ranked second. This is may be
attributed to the invention of transdermal devices or patches during 1980s,
that drew a lot of attention from researchers through
years succeeding 1980. The increase in the publication percentage growth rate
for parenteral route, during 19881992, may be attributed to research focusing
on recombinant DNA technology needed to develop new biotechnology drug
products, where most of these drugs are orally inactive and are thus taken
parenterally. The annual number of published articles for intraocular,
intranasal, pulmonary, rectal and vaginal routes showed low profiles throughout
the period of study. Published articles on different oral dosage forms
indicated that tablets are superior, reflecting the diversity of modifications
that can be applied to such dosage forms.
The annual number of published articles for
syrups and suspensions kept very low profile, which indicates that oral liquid
dosage forms, pose no formulation modification challenges for scientists to
add.Published articles on different conventional tablets including chewable,
effervescent, sublingual and immediate release tablets showed that chewable and
effervescent tablets, exhibit very low
total publication numbers
throughout the period of study, while immediate release tablets were rankedtop.
KEYWORDS: Pub Med search tool, trends, routes of
administration, oral dosage forms.
INTRODUCTION:
Very few or even rare publications have
focused on recording and analyzing the trend or pattern of published scientific
research articles on different routes of administrations and various oral
dosage forms [1 and 2 ]. PubMed that comprises over 22 million
citations for biomedical literature from MEDLINE, life science journals, and
online books, has been applied as a search tool for published scientific
articles, using different keywords related to the above mentioned topics.
Different routes of administrations covered
in this study include; oral, parenteral, pulmonary, topical, intraocular,
intranasal, rectal and vaginal routes. The oral route is considered most
desirable and preferred method of administering therapeutic agents for their
systemic effects, mainly because of patient acceptance, convenience in
administration, and cost-effective manufacturing process, with an acceptable
level of safety to the patient [3]. The market value of
pharmaceuticals as classified by routes of administration has been ranked as
follow: oral ($ 24.1billion), pulmonary ($ 20 billion), nasal ($ 8.2billion),
injections ($ 6.6billion), percutaneous ($ 5.7billion), trans-mucosal ($
0.4billion) and other routes ($ 10 billion). A recent data monitor report
suggested a shift in the market share away from oral to injectable drugs, where
the annual sales of injectable is
expected to increase by about 49 billion
dollars by 2014 [4]. The oral drug delivery market was valued at $49
billion in 2010, and is forecast to grow at a compound average growth rate of
11.3% until reaching $97 billion by 2017. The market is expected to show this
increase due to continuing upswing in demand for innovative oral drugs [5].
Oral dosage forms covered in this study
include; tablets, capsules, suspensions and syrups. In addition, the survey
further covered various types of conventional tablets including chewable,
effervescent, sublingual and immediate release tablets.
METHODS:
Study design
PubMed has been used as a standard website
to search for scientific articles that have been published during 1980-2012.
Using different key words, the search was classified and confined to three main topics namely routes
of administration oral dosage forms and conventional tablets, which are then
subdivided to different groups.
Key words used in PubMed search
key words used in PubMed search for routes
of administration include, oral dosage forms, parenteral, pulmonary route,
topical route, intraocular drugs, intranasal drugs, rectal drugs and vaginal
drugs. Key words used for oral dosage forms are, oral tablets, oral capsules,
oral suspensions and syrups. Whereas Key words used for conventional tablets
include, chewable tablet, effervescent tablet, sublingual tablet and immediate
release tablet.
Data analysis
Data extracting
According to the key words listed above,
all relevant published articles during 1980-2012 were collected, classified and
tabulated on annual bases. The total number of published articles, and
publication percentage growth rates were determined and tabulated.
Graphical presentation
Bar-graphs of the annual number of
published articles, the total number of published articles, and the peak year
for the number of published articles were constructed. In addition graphs of
the total number of published articles and publications percentage growth rates
were plotted.
The multiple year publications percentage
growth rates (publication growth rate) calculation
The multiple year publications percentage
growth rates for the routes of administration and oral dosage forms were
calculated according to the following formula [6]:
{[End value/start value]1/y-
1}Χ100
All the years were divided into groups,
each 4 years is considered as a one group, so(y) is 4.The end value is number
of publications in fourth year, while
the start value is number of publications in first year.
RESULTS AND DISCUSSION:
Among various routes of administration, the
total number of published articles during the period of study (1980-2012)
showed a clear domination of the oral route over other routes (fig 1and 2). The
annual number of published articles, for the oral route, showed almost a
regular increasing annual pattern compared to other routes (fig 1).
The peak year for the oral route published
articles was 2010 (fig 3). Such results are expected, due to the versatility of
oral dosage forms as well as convenience and safety of this route compared to
other route. The total number of articles published during the period of
study for percutaneous route, indicated
that this route is the second best to the oral route (fig1and 2).The reasons
for such popularity of percutaneous route may be attributed to the invention of
transdermal devices or patches during 1980s, that drew a lot of attention form
researchers through years succeeding 1980, due to their convenience, safety and
their possible avoidance of disadvantages and barriers encountered with oral
medications[7,8,9].
Compared to other routes, the publication growth rate of the
oral route was somewhat consistent throughout the period of study, whereas
parenteral route showed an inconsistent pattern with a sharp decline of
publication growth rate during 1984-1988 and then regain pace during 1988-1992
(fig 4).The increased growth rate during this period may be attributed to the
production of a number of new biotechnology drug products using recombinant DNA
technology, where most of these drugs are orally inactive
and are thus taken parenterally[10].The
total number of articles published during the period of study for parenteral route, indicates that this route is ranked third after the oral and
percutaneous routes(fig 1and 2).This is because parenteral products have
limited use due to their specific characters, compared to other convenient
routes such as oral or topical routes.
The pulmonary route, though traditionally
being used to treat asthma and other chronic obstructive pulmonary diseases,
have recently become of increasing interest for systemic delivery of drugs,
where new dispersible formulations and drug aerosol delivery devices for
inhale-able peptides, proteins such as insulin , and various small molecules
have been introduced [11]. For the pulmonary route, the annual
number of published articles showed a steady increase during the entire period
of study especially during 1998-2012, with
maximum publication number of
1552 in 2003 (fig 3). The total number of articles published during the period
of study for pulmonary route, indicates that this route is ranked fourth after oral, percutaneous,
and parenteral routes (fig 1and 2).The publications growth rate was12% during
the period 19841988, although it declines clearly during recent years
2004-2012 (fig 4).The increase in the publications growth rate during
19841988, may be attributed to the introduction of new dispersible
formulations and drug aerosol delivery devices for inhale-able peptides,
proteins and various small molecules [11].
The annual number of published articles for
intraocular, intranasal, rectal and vaginal routes showed low profiles
throughout the period of study (fig1and 2). Despite the limited uses of the
intraocular route compared to other routes such as oral route, the annual
number of published articles during the period of study, was somewhat
progressively but slowly increasing reaching its maximum number of more than
1000 articles in 2011(fig 3). The reason for this increase can be attributed to
the invention of ophthalmic inserts delivery systems in the mid-1980s that have
encouraged researchers to further investigate techniques of modifying drug
release rates from such devices. Large number of publications have since
appeared on the use of viscofying agents and bio-adhesives to extend retention
of such delivery systems in the eye [12,13,14]. The publications
number of intranasal route was low at 1980, but From 1985-2012, but exhibited a
progressively slowly increasing pattern during 1985-2012 with a maximum
publication number in 2011 (fig 3). The publication growth rate during this
period was ranging between 510% (fig 5).
For the rectal route, the number of
published articles was around 200 in 1980, then showed slight increase in 1985
and 1995 keeping almost the same pace during 1995-2000 and showed another increase in 2001, reaching a peak in
2011 (fig 3).The growth rate for this route was around 15% at the beginning of
1980s but it decreased to negative
values throughout the period of study (fig 5).
The low number of published articles for this route may be attributed to
the fact that the rectal route remains only an alternative to oral
administration and that its uses are limited to specific populations i.e.
pediatrics and some geriatrics[15]. In addition to problems
associated with patient acceptance and compliance, the need to refrigerate many
suppository bases and the inconvenience of dosing [16]. A literature
survey for the last 810 years suggested that rectal route has not received a
great deal of attention and relatively few articles have appeared in the
literature and new products have not captured a significant segment of the
pharmaceutical market[17,18]. The publication growth rate for the
vaginal route was low during1980-1992, but showed a maximum growth rate of
about 5% during 1992-1996 period (fig 5).Surprisingly enough, these results are
almost identical to the results obtained for the rectal route, reflecting the
resemblance of the two routes in their specialties in sites of applicationsand
population using them. The low number of published articles for this route may
be attributed to the fact that the vaginal route remains only an alternative to oral
administration and that its uses are limited to specific gender i.e. females.
Comparison
between published articles on different oral dosage forms reflects that tablets
are considered first in the ranking order, where the total number of
publications, during the entire period of study, exceeded 33000 articles
(fig
6 and 7). This figure is expected as it includes all types of tablets, both
conventional tablets and modified release tablets.
This
reflects the importance of this dosage forms for researchers, and the diversity
of modifications that can be applied to such dosage form to obtain various
modified release tablets. In addition oral tablets are considered convenient to
take, easy to prepare, safe, and can provide an exact dose compared to other
dosage forms. For capsules, the total number of publications, during the entire
period of study, exceeded 23000. This figure ranked capsules as second to
tablets in the ranking order of oral dosage forms (fig 6 and7). These results
reflect that both hard and soft gelatin capsules are still attracting
researchers as new excipients having superior qualities are used to enhance
drug release and bio-availability from capsules [19]. On the other
hand, syrups and suspensions are lagging behind in the ranking order of oral
dosage forms (fig 6 and 7). The annual number of published articles for syrups,
kept a very low profile, during the entire period of study (fig 6 and 7), with
a maximum published articles in 2003 of only 27 (fig 8).These figures locate
syrups in a trailing position compared to other oral dosage forms.
On
the other hand, the annual number of published articles for suspensions is
somewhat superior to syrups, where it was about 30 in 1980 and showed a
progressive increase during the period of study until it reached a maximum of
about 270 articles in 2012 (fig 8)These results indicate that oral liquid
dosage forms represented by syrups and suspensions, pose no formulation
modification challenges for scientists to add.
Some
commonly used conventional tablets were chosen in this research, including
chewable, effervescent, sublingual, and
immediate release tablets.The annual published articles for chewable and
effervescent tablets, showed very low pattern throughout the period of study,
with a maximum of only 11 in 1992 and 23 in 2011respectively (fig 9 and10). The
total number of publications, during the entire period of study, for chewable
and effervescent tablets were around 160 and 280 respectively (fig 10). This
reflects that both types of tablets drew little attention from researchers, as
no major formulation modifications can be added to such dosage forms.
On
the other hand, the annual published articles for sublingual tablets, showed
low pattern during 1980s and 1990s with a peak of 20 publications in 1993 and
gradually increasing from 2001till 2012, where it showed a maximum of about 48
publications in 2011 (fig 9,10 and 11).
The
total number of publications, during the entire period of study, for sublingual
tablets, was around 580 (fig 10). The increase in the annual publication number
during 2001till 2012, may be attributed to researchers interest to modify
sublingual formulations to obtain sustained drug release by adding
muco-adhesive polymers to formulate trans-mucosal sustained release products[20].
The annual published articles for immediate release tablets, showed very low
profile during 1980 till 2000, then started to increase gradually during
2001till 2012, with a sharp drop in 2008 and showing a maximum of about 70
publications in 2010 (fig 9 and10).The total number of publications, during the
entire period of study, for immediate release tablets was 700. This figure ranked immediate release
tablets at the top in the ranking order of conventional tablets (fig 11). These
results reflect that immediate release tablets are still attracting researchers
as new excipients having superior qualities such as super-disintegrants are
used as well as new techniques, such as temperature-controlled centrifugation
and freeze drying are applied to enhance drug release and bio-availability from
such dosage forms[21].
CONCLUSION:
Analysis
of the searched published articles, over the entire period of study
(1980-2012), has showed that the oral route of administration is ranked top in
attracting researchers, due to the access-ability, convenience and safety of
this route compared to other routes. The percutaneous route was ranked the
second. This may be attributed to the invention of transdermal devices or
patches during 1980s. Intraocular, intranasal, pulmonary, rectal and vaginal
routes all showed low publication profiles throughout the period of study.
Compared to other oral dosage forms,
tablets were superior, reflecting the diversity of modifications that can be
applied to such dosage forms. The annual number of published articles for
syrups and suspensions kept a very low profile, which indicates that oral
liquid dosage forms, pose no formulation modification challenges for scientists
to add.
Among different conventional tablets,
immediate release tablets were rank top, while chewable and effervescent
tablets, exhibited very low total publication numbers throughout the period of
study.
The
results obtained from this study indicate
how research aspects are annually moving, areas where researchers are
focusing, and trends of scientific research on routes of administrations, oral
dosage forms and conventional tablets.
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