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					Comparative Invitro Study of Ibuprofen Tablets Used as Anti-inflammatory and
Analgesics in Niger Delta Areas, Nigeria.
              a             a                a                           b
NWIDU, L.L , OVEH, B , OKORIYE, T AND VAIKOSEN, N.E.
                  a
Department of         Pharmacology & Toxicology;    b
                                                        Department of Pharmaceutical Chemistry, Faculty of

Pharmacy, College OF Health Sciences, Niger Delta University, Wilberforce Island , Bayelsa State, Nigeria.




Corresponding Author:
Lucky Legbosi Nwidu
P.O. Box 10935 Port Harcourt, Nigeria,
E-mail:menelucky@yahoo.com
GSM NO +234 803 3417 432
Abstract
The number of different brands of Ibuprofen 400mg from retail pharmacies in Niger Delta
Areas is on the increase. Generic substitution or interchangeability of one brand for the
other and obtaining the same therapeutic effects is difficult for health care providers and
consumers. Most patients from experience have learnt that one brand is efficacious than
the others and insist on demand of a brand with perceived efficacy. The purpose of this
study therefore is to carry out a comparative invitro study of six brands of Ibuprofen
400mg to elucidate compliance or deviation from standards stipulated in official
monograph.
Six (6) brands were randomly selected from different pharmacy outlets. The parameters
assessed are uniformity of weight, friability, crushing strength, and chemical assay of the
tablets. Disintegration was tested according to the British Pharmacopoeia. Dissolution
behaviors of the different brands of ibuprofen were studied using USP apparatus.
Chemical assay of ibuprofen content was done using titrimetry and HPLC analysis.

The physicochemical results reveal all the six brands failed the BP 1998 specification for
acceptable uniformity of weight but all passed the friability test and only one sample
exceed the disintegration time limit by 222.2%. The estimation of the active drug content
with different instrumental technique gave different results. With titrimetry, sample A, B
and E failed the BP 1998 specification of Ibuprofen tablet .All the sample passed
chemical assay content of active drug test with HPLC and the dissolution test with the
USP dissolution apparatus as specified in official monograph.
The mechanical and release profiles of Brand E, B and C have comparable properties
showing the suitability of generic substitution and could also serve as first line drugs
when Ibuprofen 400mg is prescribed. However, pharmacological and clinical studies are
needed to corroborate this assertion.




\
Key words: Generic substitution, mechanical profile, release profile, Ibuprofen.
 INTRODUCTION
Ibuprofen is extensively used as anti-inflammatory, analgesics and antipyretic1 to treat the
increasing surge of chronic rheumatoid arthritis and lupus erythematosus which is
common in the cold and damp deltaic environment. The chaotic drug distribution in
Nigeria2,3 favours the dumping of various brands of ibuprofen 400mg from multiple
spurious sources. Health care givers and consumers often end with confusion on which
brand to patronized, prescribed or dispensed to achieve the desired therapeutic efficacy.
Both physician and pharmacist are been confronted with the problem of generic
substitution4 Generic substitution or interchangeability of proprietary drugs are influenced
by factors such as cost, efficacy, prescription, aesthetic packaging and recently the
embodiment of NAFDAC number on packaging5. Patients and physicians evaluate the
efficacy of drugs purchased in term of the likelihood of relief, the degree of relief, and the
persistence of relief of symptoms6.
These factors guide subsequent demand pattern especially of OTC products. Drugs that
are pharmaceutical equivalents from different sources have been noted to produce
variable clinical responses. Pharmaceutical equivalents may not be therapeutically
equivalent because they are affected by factors such as variation in inert ingredients,
plants from different parts of the world, international buy outs and diversification which
allow the combination of questionable ingredients in generic production, shifting sources
of supply within batches of production, deliberate changed in the formula originally
submitted to regulatory agencies7.

Also, most drugs have been noted to lose potency on the shelf, so Pharmaceutical
companies increase the strength so that as the drug ages, it will still provide a therapeutic
level 6. This means the patients who use the drugs soon after production when the dose
may be stronger may be getting an overdose7. There is a risk that a generic substitution
could result in a change in serum concentration; such a change may lead to significant
adverse effects or loss of benefits. There is a risk that response to a drug may change if
different generics are substituted8, 9.
Ibuprofen 400mg is one of the low cost and most commonly available mulitisource and
branded pharmaceutical products in the Niger Delta dispenstories, pharmacies, and
chemist. Bioavailability problems have not been reported with Ibuprofen, but it is
increasingly becoming relevant as interdividual preferences and prescription of one brand
and rejection of substituted pharmaceutical equivalent is on the increase. However,
clinical differences or serious bioequivalence problems have been observed with some
drugs such as paracetamol, prednisolone, estrogen, levodopa, and phenytoin tablets 10, 11,
12, 13

Many developing countries are rattling with widespread distribution and marketing of
substandard and or counterfeit drugs due to lack of effective means of monitoring the
quality of generic drug products in circulation12, 14.The apex health authority, the World
Health Organisation, have formulated specific guidelines for registration, assessment,
quality control and assurance, marketing and regulatory framework for generic
pharmaceutical products. These have led various health jurisdictions to formulate and
adopt official compendia such as BP, USP, AP, EP etc15, 16 which provide the protocol for
achieving the global aspiration. In Nigeria this has led to the establishment of regulatory
agency such as the National Agency of Food and Drug Control and Administration
(NAFDAC) for the regulation, control and administration of the quality of food and drugs
in Nigeria.
Pharmaceutical equivalents are expected to have equivalent efficacy, safety and quality as
stipulated in pharmacopoeia or official monograph12.Most often preliminary
pharmaceutical analysis of generic products on the market reveals non-compliance of
physicochemical parameters and chemical contents to official monograph Work of this
nature has been carried out on other drugs such as prednisolone, estrogen, levodopa,
phenytoin, carbamazepine, and paracetamol; etc 10, 11, 12, 13 ,14.This present study is
expected to predict in vivo bioavailability through invitro dissolution and chemical
content analysis which correlate with inter-individual responses. This in vitro study is
expected to compare the physical and chemical properties of six different brands of
Ibuprofen 400mg marketed in the Niger Delta, whether there is any conformity with
official monograph.
This study will guide providers and consumers of health services in rational drug use
when ibuprofen is indicated for therapy.
Material and Method:
Six brands of Ibuprofen 400mg (A-F) were purchased from retail Pharmacies in the Niger
Delta Region, Nigeria. The Product information with respect to brand name, country of
origin, date of manufacture, expiry date, batch No., Regulatory Authority Registration No.
(NAFDAC.No) as shown in Table 1.

Physical parameters evaluated:
(i) Weight uniformity test-Twenty tablets selected at random was weighed individually
and the average weight was calculated to estimate the weight uniformity. The percentage
deviation of each tablet from the average weight was calculated.
(ii).Disintegration test: The disintegration times of six tablets per brands were
determined in distils water at 37 ±0.50C using the disintegration apparatus (Eweka
Apparabetau, Germany).The determination was done in duplicates and the average
calculated. The BP 1993 was the Official standards used.
(iii) Crushing strength test: Five tablets per brand were determined using Strong Cobb
hardness tester ( ) .The load required to break the tablet into two halves was estimated.
(iv) Friability test: Ten was subjected to the combined effects of abrasion and shock
using a D7859 Roche Friabilator (Haltingent, Germany) rotating at 25rpm for four
minutes dropping the tablets a height of 6 inches. The weight loss was determined as a
percentage of the initial weight
(v).Dissolution Test The dissolution test was executed on the tablets using Distek 2000
dissolution test apparatus (USA) fitted with basket rotated at 50 rpm. 34.7ml of 0.2M
NaOH was added to 50ml monobasic potassium phosphate buffer solution (pH 7.2) and
made up to 900ml with distil water. This was poured into the vessel and maintained at
37± 0.5oC. One tablet from each brand was placed in the basket and lowered into the
vessel enclosing the dissolution medium.5ml were withdrawn at time intervals and put
back with fresh dissolution medium. The samples were filtered and diluted approximately
with 0.2M NaOH and the absorbance of the medium solution measured at about
266nm.This was subtracted from the absorbance of 280 nm of standard reference sample
of Ibuprofen .The amount dissolve at 60minutes was obtained from each brand. The
determination was done in triplicate.
Assay of Active ingredient:
The assay was carried out using titrimetric methods and the highly sensitive High
Performance Liquid Chromatography17 (HPLC Agilent 1100 series, USA) .For the
Titrimetry methods, standard procedure using 1998 BP was followed. With the HPLC,
twenty tablets from each brand were weighed and powdered. An accurately weighed
portion of the powder, equivalent to about 1200mg of Ibuprofen, to a suitable container,
100.0ml of internal standard solution was added and shaken for 10 minutes.
 For those brand sample that are sugar coated, 20 tablets equivalent to 1200mg of
Ibuprofen, in a container was added to an accurately measured volume of internal

standard solution, sufficient to obtain an assay preparation containing about 12mg of
ibuprofen per ml, and about 15 glass beads and shaken until the tablets are completely
disintegrated. This was centrifuge and the supernatant clear solution obtained was use in
the assay preparation.
This was subjected to Liquid chromatography by separately injection of equal volumes
(about 5 µL) of the standard preparation, the assay preparation, and the 4-
isobutylacetophenone standard solution into the Chromatograph, the chromatograms was
recorded including the responses of the major peaks and the quantity, in mg of ibuprofen
C13H1802 in each tablet was calculated by the formula
                       100(C/W) (RU/RS)
 where C=concentration mg/ml of USP ibuprofen RS in the standard preparation; A is the
average weight, in mg, of a Tablet; W is the weight in mg of tablet powder taken to
prepare the assay preparation; and RU/RS are the ratios of the ibuprofen peak response to
the valerophane peak response obtained from the Assay preparation and the standard
preparation, respectively.


The data for weight uniformity test, friability, crushing strength, disintegration and
dissolution times of the various brands of Ibuprofen was analysed using mean ± standard
deviation.

The results of the country of origin, pharmaceutical manufacturing company, expiry dates
and the availability of NAFDAC NO are given in Table 1.Out of the six brands of
Ibuprofen studied two brands A and D are not registered with NAFDAC.All the sample
used were within the shelf life at the time of investigation. Four of the brands originated
from India, One from Germanys and one from Nigeria.
The result of the physico chemical properties of the tablets is presented in Table 2.All the
brands A-F failed BP specification for acceptable uniformity of weight as all the tablets
deviated by more than twice 5%, the percentage stipulated by the British Pharmacopoeia
(BP) 1988.The significance of this parameter is to ensure that the tablets in each batch are
with appropriate size range15.
All the brands pass or meet the criteria for friability specify in USP 1990, as all the tablets
have percentage loss on weight of 15 or less. The crushing strength friability Ratio
(CSFR) shows the tablet with greater strength: F (264)>D (240) >.C (165) >B (56.6) >E
(13.05) >A (1.15).
The relative hardness was in this order: 3.3, 5.22, 5.28, 5.66, 6.6, and 9.6 KgF and
corresponding disintegration time in minutes are 7.12, 2.08, 14.93, 3.43, 14.87, and 53.33
for brand A, E, F, B, C, and D respectively. Brand E which is the only uncoated tablet has
the lowest disintegration time of 2.08 minutes than all other brands that are coated tablets.
Brand B of the coated tablet give the least disintegration time and Brand D has the highest
disintegration time of 14.87 minutes.
The results of the assay of chemical content using titrimetric and HPLC analysis and the
dissolution time to determine the amount of Ibuprofen present in each formulation are in

Table 3.Using Titremetry, based on USP 1999 specification of active ingredient content
 of 97-103% of label claim ,brand A, B, and E failed the test and using HPLC all the
brands, A-F meet BP 1998 active drug content of Ibuprofen of 95-105%.The dissolution
test results comply with USP dissolution time of 60 minutes as not less than 80% of the
labeled amount of ibuprofen was dissolved.
 The present study was carried out to evaluate the physicochemical properties of different
brands of Ibuprofen tablets having the same labeled content to determine the
pharmaceutical equivalence so as to prescribed generic substitution. The uniformity of
weight which ensure that the tablets in each batch are within appropriate particle size
range failed the BP 1998 standards as brands A-F of the tablets deviated by more than
twice the percentage deviation for all the brands. Uniformity of weight gives indication of
content uniformity which elucidates the potency of the tablets 18,19. However this is
affected by granules size distribution, poor mixing, and flow ability of granulation20, 21
.All the brands show good friability properties as all have percentage loss on weight of
less than or equal to 1%.They will withstand shock and abrasion without crumbling
during transportation, packaging , handling, and dispensing22. Tabalon the only uncoated
brand that was expected to have the highest friability than the coated tablets have a
friability of 0.4 while Troge has the highest friability of 1.0.There was no discriminatory
relationship between hardness and friability. The tablet strength and weaknesses is
indicated by crushing strength CS, and friability, F respectively. The mechanical strength
of Ibuprofen 400mg obtained from ratio CS/F shows that the higher the ratio the stronger
the tablets. From the results the crushing strength friability Ratio (CSFR) are: F (264)>D
(240) >.C (165) >B (56.6) >E (13.05) >A (1.15).The higher the value the more excellent
the mechanical properties of the brand. There was no correlation between relative
hardness and disintegration time. This could be as result of type of binder, type of
disintegrant, compressional pressure during formulations, particle size of granules,
diluents, glidants, lublicants which have been documented as variables which affect
disintegration time 23, 24. Since disintegration is the rate determining step in drug
absorption, the type and proportion of excipients used by different manufacturers may
influence disintegration and dissolution parameters and consequently interbrand
bioavailability and interindividual preferences25, 26. All the brands except C disintegrate in
less than 15 minutes, and meet the BP1998 standards for disintegration which is not more
than 15 minutes for uncoated tablets .The quality and quantity of disintegrant could
determine the rapidity of disintegration27,. The mechanical and release prophile of the
various brands was balance as some tablets with high crushing strength has low
disintegration time.

The assay of chemical content executed by different instrumental methods give different
results .With the titrimetric methods none of the sample meet the BP 1998 standards.
Brand C, D and F had the stated amount of Ibuprofen in the tablets, having between 98.2
and 103.6% while brands A, B and F failed having more than the stated amount of
Ibuprofen content. Poor formulation techniques, incorrect weighing, mixing errors and
increase in strength by drug companies to carter for loss of potency on the shelves are
factors that affect chemical content assay 28, 29.

This titrimetric method involved the use of indicator and five out of the six brands are
color coated which could affect the end point. However the only uncoated colourless
brand, E, Tabalon, gave an increase in strength than BP standard. With HPLC all the
brands, A-F, meet the BP1998 standard. Thus instrumental techniques even within the
same laboratory could give different results. On the basis of titrimetry half of the entire
samples would have been rejected but with more sensitive, highly efficient and qualitative
technique, HPLC, the entire sample was observed to pass the assay of chemical content.
The dissolution test is indicative of the amount of drug released into the dissolution media
with time30 The USP 1990 stipulates that within 60 minutes not less than 80% of
Ibuprofen should be release into dissolution medium. All the brands A-F pass this test
with the uncoated brand having the highest dissolution rate of between 91.6-92.8% in 60
minutes. Other brands that are coated give dissolution rates which are as follows:
B>D>C>F>A. This contra pose to the disintegration time which is as follows: A < F< B<
C< D. However it was noted that brand D which may probably contain a strong adhesive
binder and compressed with high compression force disintegrate with the highest
disintegration time of 53 minutes than other brands. The dissolution rate was expected to
be below standard but this was probably balance with disintegrant with high solubility as
its dissolution rate was high than expected. These formulation maneuvers often results to
none correlation between evaluated parameters 31, 32.

The mechanical and release profiles of these brands of Ibuprofen is quite revealing. Brand
E, B and C have comparable properties showing the suitability of generic
interchangeability and could also serve as first line drugs when Ibuprofen is Prescribed.
This study could assist health care providers and consumers confronted with multisource
branded product range in rational drug selection and substitution without compromise of
efficacy, safety and cost. This study could be complemented with pharmacological and
clinical studies to elucidate other factors influencing interindividual preferences for
different brands of Ibuprofen 400mg in Niger Delta region of Nigeria.
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Md, USP29-NF24pp1100-1102


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Table1: Country of Origin, Pharmaceutical Manufacturing Company, Expiry   dates
and NAFDAC No. of six brands of Ibuprofen 400mg Tablets
                    Country of
                    origin
Brand of Ibuprofen & Pharm.      Date       of Expiry                     *NAFDAC
400mg               Company      manufacture Date          Batch No.      Reg. NO.
A.Troge,            Germany      08/2004       07/2008     TR1303/29      Nil.
                    Hamburg                                83-01

B Brustan-N,       India,       05/2004       04/2007      9121297        04-0694
                   Ranbaxy

C. Medrofen        India,       07/2004       06/2008      MP-029         04-3761
                   Medrel
                   Pharm.
D. Dexprofen,      India,       12/2004       11/2007      DT-19          NIL
                   Mancare

E. Tabalon         Nigeria,     01/2005       01/2010      E-089          04-0758
                   NGC

F. Nalfen forte    India,       11/2004       10/2007      NF-43          04-4298
                   MAAN
                   Pharm
*
NAFDAC: National Agency for Food and Drug Administration and Control
           Table 2: Physico chemical Properties of six brands of Ibuprofen 400mg Tablets.
Brands         of Weight                         Friability Crushing         Crushing      Disintegration
Ibuprofen          Uniformity                                Strength        Strength           Time
400mg              Test , mg        Thickness                                Friability       (Minutes)
                                       mm                          Kgf       Ratio
                   Mean±SD)                       % Loss (Mean±SD)           (CSFR)       (Mean±SD)
A. Troge           613±9.5 *        6.76±0.20       1.00     3.3 ±1.15       1.15         7.12±0.05
B.Brustan-N        1017±19.3*       5.16±0.10       0.10     5.66±0.12       56.6         3.43±0.13
C.Medrofen         909±46.7*         5.4±0.24       0.04     6.6±0.55        165          14.87±0.06
D.Dexprofen        1093±9.7*        6.64±0.07       0.04     9.6±2.10        240          53.33±1.18
E.Tabalon          658±15.4*        5.83±0.09       0.40     5.22±0.08       13.05        2.08±0.05
F.Nalfen forte     948±19.2*        5.27±0.38       0.02     5.28±0.48       264          14.93±0.53
           *Failed to meet BP specification
    Table 3: Active drug content and Dissolution parameters
Brand of Ibuprofen           HPLC              TITREMETRIC      % Dissolved
   400mg tablets             % w/w                    % w/w     at 60 minutes
                         (Mean ± SD)             ( Mean ± SD)
A.Troge                     99.8±0.2               *106.2±2.0     85.2±0.2
B.Brustan-N                 99.4±0 3               *118.5±2.0     89.1±0.5
C.Medrofen                  97.1±0.5                100.5±4.2     87.2±0.3
D.Dexprofen                 99.5±0.2                 96.2±2.0     88.3±0.4
E.Tabalon                  100.3±0.2               *109.2±0.1     92.2±0.6
F.Nalfen forte              98.2±0.7               103.6±0.01     86.3±0.3
    *Failed to meet BP Specification

				
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