Hindawi

Journal of Pharmaceutics
Volume 2018, Article ID 7916368, 7 pages
https://doi.org/10.1155/2018/7916368

Research Article
In Vitro and In Vivo Quality Evaluation of Glibenclamide
Tablets Marketed in Addis Ababa, Ethiopia

Haile Kassahun,1,2 Kaleab Asres,2 and Ayenew Ashenef 2

1
Department of Pharmacy, College of Health Sciences, Wollo University, P.O. Box. 1145, Dessie, Ethiopia
2
Department of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, College of Health Sciences,
Addis Ababa University, P.O. Box. 1176, Addis Ababa, Ethiopia

Correspondence should be addressed to Ayenew Ashenef; [email protected]

Received 14 May 2018; Accepted 26 June 2018; Published 18 July 2018

Academic Editor: Srinivas Mutalik

Copyright © 2018 Haile Kassahun et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Good quality drugs fulfilling the regulatory parameters and produced per the current good manufacturing (CGMP) standards
are very critical for best therapeutic outcome in patient therapy. Hence, this study assesses quality as well as physicochemical
bioequivalence of five brands of glibenclamide tablets marketed in Addis Ababa using in vitro and in vivo methods. Friability,
disintegration, dissolution, and assay for the content of active ingredients were evaluated using the methods described in the British
Pharmacopeia (2009) and United States Pharmacopeia (2007). All the brands of glibenclamide tablets complied with the official
specification for hardness, friability, disintegration, and assay. Difference factor (f1) values were less than 15 and similarity factor (f2)
values were greater than 50 for all products of glibenclamide. The hypoglycemic effect of different products of glibenclamide tablets
was evaluated on normoglycemic mice. The in vivo studies indicated that there is no significant difference in percent reduction of
blood glucose level between the brands of glibenclamide and the innovator product (p > 0.05). Hence, based on the in vivo results
and in vitro dissolution studies, the brands might be substituted with the innovator product in clinical practice.

1. Introduction Bioequivalence studies for generic products are essential to

ensure the absence of any significant difference in the rate
Good quality medicines are a prerequisite for a successful and extent to which the active ingredients become available at
treatment. Drug quality is currently receiving a growing the site of drug action administered under similar route and
international attention. Over the past decade, there has been conditions [5]. Generic drug products must satisfy the same
an increase in public awareness of the existence of coun- standards of quality, efficacy, and safety as those applicable
terfeit and substandard drugs which have been increasingly to the innovator product [6]. Bioavailability or bioequiva-
reported in developing countries where drug regulations lence studies may involve both in vivo and in vitro studies
are less effective or totally absent [1]. Use of poor quality [7].
products may lead to therapeutic failure, increased morbidity Glibenclamide (also known as glyburide) is an oral
and mortality, erosion of public confidence in health care, hypoglycemic agent of the sulphonylurea group widely used
unexpected side effects, and antimicrobial resistance [2]. in the treatment of type II diabetes mellitus (DM) [8]. It
The introduction of generic drug products from multiple lowers blood glucose concentration by stimulating the release
sources into the health care delivery system of many develop- of insulin from the pancreatic beta cells [9]. Globally, there
ing countries has been accompanied by a variety of problems are several generics of glibenclamide tablets available within
of which the most critical is the widespread distribution the drug delivery system after the expiration of patent on
of fake and substandard drug products [3]. To assist in the innovator brand. Studies that deal about comparative in
substitution of branded innovator product with generics vitro quality evaluation of generics of glibenclamide tablets
for affordability and at the same time to achieve therapeu- of different countries have been published. El-Sabawi et al.
tic efficacy, bioequivalence studies become important [4]. [10] studied five generics of glibenclamide tablets available in
2 Journal of Pharmaceutics

Table 1: Detailed description of products of glibenclamide tablets included in the study.

Brand Manufacturer Batch Number Mfg. date Exp. date

Betanase Cadila Health Care Limited (India) GM3429 12/2012 11/2016
Daonil Sanofi Aventis (France) 3AP9A 03/2013 03/2015
Glamide Cadila Pharmaceuticals PLC (Ethiopia) D12010BX75 09/2012 08/2016
Glitisol Remedica Ltd. (Cyprus) 52994 10/2012 10/2017
Melix Lagap SA ( Switzerland) B050 05/2011 04/2016

Jordan market and reported that they exhibited dissolution Switzerland), hardness tester (Schleuniger, 2E/205, Switzer-
profiles that are significantly different from each other and land), friability tester (ERWEKA, TAR 20, Germany), dis-
from that of the original Daonil. In addition, Elhamili et al. integration apparatus (CALEVA, G.B. Caleva Ltd., UK),
[11] evaluated three brands of glibenclamide tablets available dissolution apparatus (ERWEKA, DT600, Germany), UV-
in Libyan market and reported that all products were within Visible Spectrophotometer (Single beam Spectrophotometer,
the British Pharmacopeia (BP) specifications. CM2203, Belarus), filter paper (diameter 110, lot ER0692-1,
The increasing use of glibenclamide tablets in clinical Schleicher and Schell, Germany), Vacuum filter (Scientific
practice necessitates the need to monitor and ascertain Laboratories Supplies, Germany), glucometer (Prodigy Dia-
the quality of the various brands available in the drug betes care LLC, USA), PH meter (Mettler Toledo, Switzer-
market. Oral glibenclamide is widely used in Ethiopia with land), and HPLC-UV (Shimadzu Corporation, C18 stainless
several new brands introduced into the Ethiopian market steel column (15 cm x10 mm), UV-VIS detector, Japan).
in recent years. Variety of drugs in circulation often put
clinicians and pharmacists into difficult situation of choice 2.4. Experimental Animals. Swiss albino mice of either sex
for the possibility of interchangeability among brands [12, weighing 21- 30 g and age 5-6 weeks were obtained from the
13]. Use of substandard products may lead to poor blood Department of Biology, Addis Ababa University. All animals
glucose control, thus causing life threatening complications. were housed in an air-conditioned room. They were offered
Despite the widespread presence of non-insulin dependent standard pellets and water ad libitum. The animals were
diabetes mellitus (NIDDM) in Ethiopia and extensive use conditioned one week prior to the experiments.
of glibenclamide, there are no reports on the bioavailability
and bioequivalence of the various brands in the country. 2.5. Methods. Drug quality assessment experiments were
Hence, the present study was carried out to assess the quality done using pharmacopeial procedures described in the
and physicochemical bioequivalence of glibenclamide tablets USP/NF XXIV, 2000 [14], USP/NF 25, 2007 [15], and BP, 2009
available in Addis Ababa, Ethiopian market. [16].

2. Materials and Methods 2.5.1. Hardness Test. The hardness of each tablet was deter-
mined by selecting six tablets randomly using a hardness
2.1. Materials. Different brands of 5 mg glibenclamide tablets tester. Each tablet was placed between two anvils and force
were bought from various pharmacy retail outlets in Addis was applied to the anvils, and the crushing strength that
Ababa, Capital city of Ethiopia. All the brands used were causes the tablet to break was recorded. Crushing strength of
within their shelf life at the time of study. The detailed average of six tablets was recorded.
descriptions for these products are presented in Table 1.
Standard glibenclamide was obtained from Ethiopian Food,
Medicines and Health care Administration and Control 2.5.2. Friability Test. Ten tablets from each brand were
Authority (EFMHACA) and is of United States Pharma- weighed using an analytical balance. Tablets were placed in
copoeia (USP) reference standard. All chemicals used were the drum of the friability tester and subjected to rotation
of analytical grade. at 25 revolutions per minute (rpm) for four minutes (100
times). Then, tablets were dedusted and weighed. The weights
2.2. Reagents and Solvents. The chemicals and reagents used were compared with their initial weights and then percentage
to perform the experiments were the following: monobasic friability was calculated based on the weight difference
ammonium phosphate (FARMITALIA CAROERBA, Italy), obtained.
sodium hydroxide (BDH limited, Poole, England), HPLC
grade acetonitrile (BDH Laboratory Supplies, England), 85% 2.5.3. Disintegration Time. Disintegration time test is carried
phosphoric acid (Riedel-de Haen, Germany), potassium out according to USP/NF (2007) specification. Six tablets
phosphate monobasic (Fisher Scientific, USA), HPLC grade were placed in a disintegration tester filled with distilled water
methanol (Park Scientific Limited, UK), and distilled water. at 37±0.5∘ C. The tablets were considered as completely disin-
tegrated when all the particles have passed through the wire
2.3. Instruments/Equipment. The following instruments were mesh. This time was recorded in minutes as disintegration
used for the experiments: analytical balance (Mettler Toledo, time.
Journal of Pharmaceutics 3

Table 2: Results of hardness, friability, disintegration tests, and chemical assay of different brands of glibenclamide tablets included in the
study.

Hardness (N) Friability Disintegration Assay (%W/W

Drug Product Brand
±SD (%) time ±SD (Min) ±SD)
Betanase 65.83±6.79 0.224 2.83±0.25 101.05±0.16
Daonil 81.66±4.5 0.106 1.43±0.14 95.53±0.54
Glibenclamide 5 mg Glamide 50.3±2.65 0.289 1.36±0.09 100.68±1.83
Glitisol 85.5±3.39 0.105 6.44±0.44 104.33±0.04
Melix 101.66±3.38 0.126 2.29±0.19 97.32±0.65

2.5.4. Chemical Assay. Assay of glibenclamide was done solution was diluted with phosphate buffer to 100 ml to
using BP (2009) method by high pressure liquid chro- obtain 0.01 mg/ml of the working standard solution. Finally,
matography (HPLC) equipped with UV/VIS detector, a C18 from the resulting solution, 16, 20, 24, 28, 32, and 36 ml
stainless steel column (15 cm x10 mm). The mobile phase were pipetted out separately into 50 ml volumetric flask
composition was a mixture of acetonitrile and 1.36 % w/v and was made to volumes to get a concentration range of
solution of potassium dihydrogen orthophosphate (previ- 0.0032, 0.004, 0.0048, 0.0056, 0.0064, and 0.0072 mg/ml,
ously adjusted to pH 3.0 with 85 % orthophosphoric acid) respectively. The absorbance was measured at 226 nm using
in a ratio of 47:53, with flow rate of 1.5 ml/min. The sample UV-Visible Spectrophotometer.
injection volume was 20 𝜇l and the wavelength was set at 300
nm. 2.5.6. Test for Hypoglycemic Effect. Different studies on
antidiabetic activity of plant extracts in normoglycemic rats
Sample Preparation. Twenty tablets were weighed and pow- have been conducted [17, 18] and in the present study, the
dered. A quantity of the powdered tablets containing 5 mg of method described by Saidu et al. [17] was followed to study
glibenclamide was mixed with a mixture of 2 ml of water and the hypoglycemic effect of products of glibenclamide on
20 ml of methanol with the aid of ultrasonic bath and filtered normoglycemic mice.
through a vacuum filter. Swiss albino mice of either sex were randomly housed in
stainless steel cages and were offered standard pellets with
Standard Preparation. Glibenclamide working standard (50 drinking water ad libitum. The animals were acclimatized
mg) was dissolved in 10 ml of methanol with the aid of for one week prior to the experiments. Then, the animals
ultrasonic bath for 20 min, sufficient methanol was added were divided into 6 groups of five mice each. Groups
to produce 50 ml of stock solution and finally the resulting (1-5) were treated with different brands of glibenclamide
solution was diluted to 200 ml with methanol. From the stock tablets (5 mg/kg p.o). Animals in group 6 received 90 %
solution, serial dilutions were made to obtain calibration Dimethyl Sulfoxide (DMSO) as a control. All groups were
concentrations of 181.8181 𝜇g/ml, 204.5454 𝜇g/ml, 227.2727 subjected to fasting for 16 h before the experiment. Powdered
𝜇g/ml, 250 𝜇g/ml, and 272.7272 𝜇g/ml. Equal volumes (20 glibenclamide tablets were dissolved in DMSO for oral
𝜇l) of the standard preparation and the assay preparation administration. Blood samples were collected at 0, 1, 2, 3, and
were separately injected into the HPLC system and then 4 h from each group by cutting the tail tip of the mice, then
the chromatograms were recorded and the peak areas were blood glucose level was measured using glucometer [19, 20].
obtained to be employed for amount calculation.
2.6. Data Analysis. Data obtained was treated using ORI-
2.5.5. Dissolution Test. The dissolution of glibenclamide GIN graphing and scientific analysis software program,
tablets was done according to the specification of USP/NF Microsoft Excel 2007 and Windows SPSS Version 20. Com-
XXIV, 2000 [14] using dissolution apparatus type II (paddle parison and statistical significance was determined by one-
apparatus) with the rate of 50 rpm at 37±0.5∘ C on six way analysis of variance (ANOVA). All data were analyzed at
tablets of each brand. 10 ml sample was withdrawn at 10, a 95 % confidence interval (P < 0.05).
20, 30, 45, and 60 min and an equivalent amount of fresh
dissolution medium was replaced. Filtered samples were then 3. Results and Discussions
appropriately diluted and absorbance readings were taken
with UV/Visible Spectrophotometer at wavelength of 226 3.1. Hardness and Friability Test. The mean hardness value of
nm. The concentration of each sample was determined from glibenclamide tablets is shown in Table 2. The results showed
calibration curve. The percent of drug release at each time was that the brands had mean hardness value within the range
calculated. of 50.3±2.65-101.66±3.38 N. Melix had the highest hardness
value (101.66±3.38 N) and Glamide had the lowest hardness
Standard Preparation. Stock solution of 100 𝜇g/ml was pre- value (50.3±2.65 N). A force of about 40 N is the minimum
pared by dissolving glibenclamide working standard (50 mg) requirement for satisfactory tablet hardness [21]. Hence,
in 500 ml of phosphate buffer pH 7.4. 10 ml of the resulting the tablets of all brands of glibenclamide had satisfactory
4 Journal of Pharmaceutics

Table 3: Time dependent drug release of different products of glibenclamide tablets.

Percent of drug release (W/W) ±RSD

sampling time (min)
Betanase Glitisol Glamide Melix Daonil
10 52.77± 0.18 60.25±0.031 38.95±0.09 44.94±0.04 51.89±0.028
20 60.06±0.003 62.67±0.032 46.93±0.2 54.85±0.006 53.64±0.012
30 62.18 ±0.02 64.5±0.018 50.99±0.1 67.5 ±0.067 56.79± 0.06
45 64.65 ±0.28 67.358±0.01 54.57±0.07 70.13± 0.04 60.698±0.02
60 66.45± 0.01 70.34±0.019 58.88±0.08 73.16±0.035 61.57 ±0.072

hardness. Similarly, the percent weight loss of the tablets after The results for the mean percentage label claim of the dif-
friability test is shown in Table 2. The results showed that ferent brands of glibenclamide tablets are depicted in Table 2.
all the brands of glibenclamide tablets had friability values The products were assayed according to the method outlined
ranging from 0.105-0.106%. The lowest and highest friability in BP (BP, 2009). BP (2009) states glibenclamide tablets
have been obtained for Glitisol (0.105) and Glamide (0.289). should contain not less than 95.0 % and not more than 105.0
According to USP (2007), percent friability value of tablets % of the stated amount. As indicated in Table 2, all products
should be less than 1%. Thus, all brands passed the friability fulfilled the pharmacopeial standards for percentage content
specification. of active ingredient.
Hardness or crushing strength of tablets is an important The highest percentage content was obtained for Glitisol
parameter which helps to assess the resistance of the tablet (104.33 %), while the least drug content was obtained for
to breakage under condition of storage, transportation, and Daonil (95.53 %). Tablets contain specific amount of active
handling [22]. It is, therefore, important that tablets are ingredient with allowable variable limit and assay of tablet
of optimum hardness [23]. Friability test is closely related ensures the amount of active ingredient which is indicative of
to tablet hardness and is designed to evaluate the ability its efficacy and stability of the product. Statistical comparison
of the tablet to withstand abrasion in coating, packaging, for drug content indicates that with 95 % confidence interval,
handling, and transporting and other manufacturing pro- there is significant difference in the drug content between
cesses [24]. Generally, adequate tablet hardness as well as Daonil and all other brands of glibenclamide (P<0.05).
reasonable friability is required for consumer acceptance
[25]. 3.4. Dissolution Test. Five different products of glibenclamide
tablets were studied, with Daonil being the innovator. To
3.2. Disintegration Test. The mean disintegration time for compare the dissolution profiles, dissolution curve (based
the different brands of glibenclamide tablets is shown in on mean percentages of drug released) of test and innova-
Table 2. The results showed that all brands passed the dis- tor products were combined and depicted in Table 3 and
integration test according to USP (2007), which specifies 30 Figure 2.
min for uncoated and film coated tablets. All products of From Figure 2, it can be seen that all products, including
glibenclamide tablets had mean disintegration time of less the innovator product (Daonil), did not release significant
than 5 min except Glitisol. The rapid disintegration time percentage of the drug within the first 30 min. In fact,
exhibited by all the brands might be due to type and amount Betanase, Glitisol, and Melix released more than 60 % drug
of disintegrant used in the formulation. Glitisol showed the within 30 min and Glamide and Daonil released about 50 %
longest disintegration time (6.44±0.44) which correlates with drug within 30 min.
its low friability and high hardness values. Similarity factor (𝑓2) and difference factor (f1), model
Tablet disintegration is a prerequisite to dissolution and independent parameters, derived from the dissolution pro-
subsequent absorption of the drug from its dosage form. files were calculated to compare dissolution profiles of the
A drug incorporated in a tablet will be released rapidly as different products of glibenclamide tablets [27].
the tablet disintegrates. The rate of disintegration affects the
󵄨 󵄨
dissolution and subsequently the therapeutic efficacy of the ∑𝑛𝑡=1 󵄨󵄨󵄨𝑅𝑡 − 𝑇𝑡 󵄨󵄨󵄨
𝑓1 = ( ) × 100, (1)
medicine [12]. Different formulation factors are known to ∑𝑛𝑡=1 𝑅𝑡
affect results in disintegration test. The type and amount of
excipients used in tablet formulation as well as the manufac-
turing process are all known to affect both the disintegration [ 100 ]
𝑓2 = 50 × log10 [ ], (2)
2
and dissolution parameters [26]. √1 + ∑𝑛𝑡=1 (𝑅𝑡 − 𝑇𝑡 ) /𝑛
[ ]
3.3. Chemical Assay. The assay determines the concentration where Rt and Tt are the cumulative percentage of dissolved
of the active pharmaceutical ingredient in a sample. The assay drug for the reference and test formulation at time t, respec-
was done by using HPLC. Samples were injected and the tively, and n is the number of time points. According to these
averages of the peak areas were calculated. Representative guides, generally, f1 values up to 15 (0–15) and f2 values greater
peaks are shown in Figure 1. than 50 (50–100) ensure similarity or equivalence of the two
Journal of Pharmaceutics 5

Table 4: Similarity and difference factors of glibenclamide products.

Products Betanase Glamide Glitisol Melix

f1 7.56 12.04 14.24 14.02
f2 65.912 55.695 54.26 52.61

Chromatogram of Glibenclamide standard Chromatogram of Daonil tablets

Chromatogram of Glamide tablets Chromatogram of Betanase tablets

Chromatogram of Melix tablets Chromatogram of Glitisol tablets

Figure 1: Typical HPLC chromatogram’s obtained in the assay.

dissolution profiles [28]. f1 and f2 values were calculated 3.5. In Vivo Studies
between the test products and reference product (Daonil) and
are illustrated in Table 4. 3.5.1. Hypoglycemic Effect of Glibenclamide Tablets on Normo-
As shown in Table 4, the f1 values are found to be less glycemic Mice. Quantification of pharmacologic effect is one
than 15 and f2 values are greater than 50 for all products possible way to assess a drug’s bioavailability. This method is
of glibenclamide which shows similarity or equivalence of based on the assumption that a given intensity of response is
the dissolution profiles. Therefore, this confirmed similarity associated with a particular drug concentration at the site of
between all products of glibenclamide compared with the action [7].
innovator product (Daonil) and indicated that the release of Tmax after oral administration of glibenclamide in mice
glibenclamide from all products was similar to the reference. is 2 h [29]. As shown in Table 5, Glamide (45.99 %) showed
6 Journal of Pharmaceutics

Table 5: Percent reduction in blood glucose level of normoglycemic mice for glibenclamide products.

Percent reduction in blood glucose level (mg/dl) ± SD

Brand
1h 2h 3h 4h
Betanase 31.55±9.52 36.27±14.69 30.15±6.07 30.4±16.56
Daonil 17.14±10.98 40.58±11.65 50.71±9.54 33.81±18
Glamide 43.16±13.87 45.99±20.65 46.7±15.43 50.38±7.4
Glitisol 40.57±10.9 44.62±9.48 47.53±5.81 52.22±3.28
Melix 33.93±23.33 38.77±11.16 37.92±7 37.29±8.83

80 of manufacturing these tablets, effective control activities

70 of EFMHACA, and the proper storage of these drugs by
wholesalers, retailers, and pharmacies.
60
percent drug release

50
4. Conclusion
40
This study assessed quality as well as physicochemical bioe-
30
quivalence of five brands of glibenclamide tablets marketed
20 in Addis Ababa using in vitro and in vivo methods. The study
10 confirmed that brands of glibenclamide tablets complied
with the official specification for hardness, friability, assay,
0
and disintegration. The f1 values were less than 15 and f2
−10 values were greater than 50 for all products of glibenclamide.
0 10 20 30 40 50 60 This suggests that release of the drug from all products of
Time (min) glibenclamide is similar to the innovator product. In addition,
Betanase Melix In vivo studies of the products of glibenclamide tablets
Glitisol Daonil indicated that there is no significant difference in percent
Glamide reduction of blood glucose level between Daonil and the
Figure 2: Dissolution profiles of different products of glibenclamide
other brands (p > 0.05). Hence, based on the in vivo results
tablets. and in vitro dissolution studies, any of the glibenclamide
products might be substituted with the innovator product in
clinical practice.

highest percent reduction in blood glucose level at Tmax while Data Availability
the least was observed for Betanase with 36.27 % at Tmax (2
h). The data used to support the findings of this study are
Statistical analysis was conducted using Dunnett’s t-test included within the article.
and it was found that, at 95% confidence interval, there was
no significant difference in the percent reduction of blood Conflicts of Interest
glucose level between Daonil and Glitisol, between Daonil
and Melix, and between Daonil and Betanase at l h (p >0.05), All authors in this manuscript did not have any conflicts of
while Glamide was significantly different from the innovator interest to declare.
product. Glamide showed highest reduction in blood glucose
level compared to the innovator product. At 2 h (Tmax Acknowledgments
value) and 4 h, there was no significant difference between
Daonil and all the other brands of glibenclamide (p >0.05), The authors are so grateful to the Ethiopian Food, Medicine
suggesting that the serum blood glucose profiles generated by and Health Care Administration and Control Authority
the reference tablets were comparable to those produced by (EFMHACA) for donating standard and for providing lab-
the test products. Hence, based on in vivo results and in vitro oratory facility for this research work. They are also grateful
dissolution studies, the brands might be substituted with the to staff members of EFMHACA, Quality Control Directorate,
innovator product in clinical practice. for allowing using their laboratory. Finally, they would like
From both in vitro and in vivo studies, it was shown that to acknowledge Addis Ababa University for sponsoring this
there are minor variations among the generic products of study. Addis Ababa University funded this research though
glibenclamide tablets. Despite that, all the studied gliben- its graduate student research support programme. Haile
clamide tablets distributed in the Ethiopian market are of Kassahun wants to thank Wollo University for the offer of
good quality products. This might be as a result of strict study leave to accomplish his graduate studies at Addis Ababa
adherence to good manufacturing practice in the process University (AAU).
Journal of Pharmaceutics 7

References [16] British Pharmacopoeia (BP), The Her Majesty’s Stationary

Office, vol. III, London, UK, 2009.
[1] K. Al-Tahami, “A comparative quality study of selected locally [17] A. Saidu, A. Mann, and S. Balogun, “The hypoglycemic effect
manufactured and imported medicines in Yemeni market,” of aqueous extract of the anacardium occidentale linn leaves
Yemeni Journal for Medical Sciences, vol. 4, pp. 6-6, 2010. grown in Nigeria on normoglycemic Albino Rats,” Journal of
[2] R. B. Taylor, O. Shakoor, R. H. Behrens et al., “Pharmacopoeial Emerging Trends in Engineering and Applied Sciences, vol. 3, no.
quality of drugs supplied by Nigerian pharmacies,” The Lancet, 2, pp. 302–308, 2012.
vol. 357, no. 9272, pp. 1933–1936, 2001. [18] S. O. Momoh, M. M. Yusuf, C. O. C. Adamu et al., “Evaluation
[3] B. Raheela, S. Gauhar, and S. B. S. Naqvi, “Pharmaceutical of the phytochemical composition and hypoglycaemic activity
evaluation of different brands of levofloxacin tablets (250 mg) of methanolic leaves extract of costus afer in albino rats,” British
available in local market of Karachi (Pakistan),” International Journal of Pharmaceutical Research, vol. 1, no. 1, pp. 1–18, 2011.
Journal of Current Pharmaceutical Research, vol. 3, no. 1, pp. 15–
[19] L. Nahar, F. Ripa, A. H. Zulfiker, and M. Rokonuzzaman, “Com-
22, 2011.
parative study of antidiabetic effect of Abroma augusta and
[4] N. C. Ngwuluka, K. Lawal, P. O. Olorunfemi, and N. A. Syzygium cumini on alloxan induced diabetic rat,” Agriculture
Ochekpe, “Post-market in vitro bioequivalence study of six and Biology Journal of North America (ABJNA), vol. 1, no. 6, pp.
brands of ciprofloxacin tablets/caplets in Jos, Nigeria,” Scientific 1268–1272, 2010.
Research and Essays, vol. 4, no. 4, pp. 298–305, 2009.
[20] M. Z. Zaruwa, J. Manosroi, T. Akihisa, W. Manosroi, and A.
[5] US Food and Drug Administration, Bioavailability and Bio- Manosroi, “Anti-diabetic activity of Anogeissus acuminata a
equivalence Studies for Orally Administered Drug Products - medicinal plant selected from the Thai medicinal plant recipe
General Considerations, US Food and Drug Administration, database MANOSROI II,” Wudpecker Journal of Medicinal
Guidance for Industry, Rockville, Md, USA, 2004, https://www Plants, vol. 1, pp. 11–18, 2012.
.fda.gov/downloads/drugs/guidance’s/ucm070124pdf.
[21] T. S. Oishi, Md. A. Haque, I. Dewan et al., “Comparative in
[6] M. A. Hassali, J. Thambyappa, F. Saleem, N. ul Haq, and H. Vitro Dissolution Study of Some Ciprofloxacin Generic Tablets
Aljadhey, “Generic substitution in Malaysia: Recommendations under Biowaiver Conditions by Rp-Hplc,” International Journal
from a systematic review,” Journal of Applied Pharmaceutical of Pharmaceutical Sciences and Research, vol. 2, no. 12, pp. 3129–
Science, vol. 2, no. 8, pp. 159–164, 2012. 3135, 2011.
[7] R. Chereson, Basic Pharmacokinetics: Bioavailability, Bioequiv- [22] M. A. Odeniyi, O. A. Adegoke, R. B. Adereti, O. A. Odeku,
alence and Drug Selection, 1996, http://www.scribd.com/doc/ and O. A. Itiola, “Comparative analysis of eight brands of
496701/basic-pharmacokineticsbioavaiabiltyy#scribd. sulfadoxine-pyrimethamine tablets,” Tropical Journal of Phar-
[8] M. Idries Amjad, E. Mohammed, E. Mahmoud, and E. Kamal, maceutical Research, vol. 2, no. 1, 2003.
“Interchangeability and Comparative Effectiveness between [23] C. O. Ogah and F. F. Kadejo, “Analysis of brands of gliben-
Micronized and Non-micronized Products of Glibenclamide clamide tablets in Lagos market,” Journal of Innovative Research
Tablets,” Sudan Journal of Medical Sciences, vol. 7, no. 3, pp. 153– in Engineering and Sciences, vol. 4, no. 2, pp. 466–471, 2013.
159, 2012.
[24] K. A. Kishore and P. Amareshwar, “Quality evaluation and com-
[9] A. Javaid, R. Hasan, A. Zaib, and S. Mansoor, “A comparative
parative study on tablet Formulations of different pharmaceuti-
study of the effects of hypoglycemic agents on serum elec-
cal companies,” Journal of Current Chemical & Pharmaceutical
trolytes in the diabetic patients.,” Pakistan Journal of Pharma-
Sciences, vol. 2, no. 1, pp. 24–31, 2012.
ceutical Sciences, vol. 20, no. 1, pp. 67–71, 2007.
[25] G. S. Hailu, G. B. Gutema, A. A. Asefaw et al., “Comparative
[10] D. El-Sabawi, S. Alja, and I. I. Hamdan, “Pharmaceutical
assessment of the physicochemical and in-vitro bioavailabil-
evaluation of glibenclamide products available in the Jordanian
ity equivalence of co-trimoxazole tablets marketed in Tigray,
market,” African Journal of Pharmacy and Pharmacology, vol. 7,
Ethiopia,” International Journal of Pharmaceutical Sciences and
no. 22, pp. 1464–1470, 2013.
Research, vol. 2, no. 12, pp. 3210–3218, 2011.
[11] A. Elhamili, J. Bergquist, M. El-Attug et al., “Pharmaceutical
[26] J. Muaz, L. K. Gazali, G. U. Sadiq, and G. M. Tom, “Comparative
evaluation of Type II oral antidiabetic agent,” International
in vitro evaluation of the pharmaceutical and chemical equiv-
Journal of Pharma Research & Review, vol. 3, no. 6, pp. 1–9, 2014.
alence of multi-source generic ciprofloxacin hydrochloride
[12] E. Osonwa Uduma, A. Agboke Ayodeji, C. Amadi Rosemary, O. tablets around Maiduguri metropolitan area,” Nigerian Journal
Ogbonna, and C. Opurum Christian, “Bioequivalence studies of Pharmaceutical Sciences, vol. 8, no. 2, pp. 102–106, 2009.
on some selected brands of ciprofloxacin hydrochloride tablets
[27] S. Dash, P. N. Murthy, L. Nath, and P. Chowdhury, “Kinetic
in the Nigerian market with ciproflox as innovator brand,”
modeling on drug release from controlled drug delivery sys-
Journal of Applied Pharmaceutical Science, vol. 1, no. 6, pp. 80–
tems,” Acta Poloniae Pharmaceutica. Drug Research, vol. 67, no.
84, 2011.
3, pp. 217–223, 2010.
[13] A. M. Olusola, A. I. Adekoya, and O. J. Olanrewaju, “Com-
[28] “US Food and Drug Administration, Center for Drug Eval-
parative evaluation of physicochemical properties of some
uation and Research. Guidance for industry: Dissolution
commercially available brands of metformin Hcl tablets in
testing of immediate release solid oral dosage forms,” 2017,
Lagos, Nigeria,” Journal of Applied Pharmaceutical Science, vol.
http://www.fda.gov/cder/Guidance/1713bp1.Pdf.
2, no. 2, pp. 41–44, 2012.
[14] The United State Pharmacopoeia (USP), National Formulary, [29] S. Mutalik and N. Udupa, “Formulation development, in vitro
M. D. Asian, Ed., USP 24/NF 19, United State Pharmacopoeial and in vivo evaluation of membrane controlled transdermal sys-
Convention, Rockville, Md, USA, 2000. tems of glibenclamide,” Journal of Pharmacy & Pharmaceutical
Sciences, vol. 8, no. 1, pp. 26–38, 2005.
[15] United States Pharmacopoeia (USP), National Formulary, vol.
1 of USP 30/NF 25, United States Pharmacopoeial Convention
Inc., Rockville, Md, USA, 2007.