Alyahawi et al.

Universal Journal of Pharmaceutical Research

Available online on 15.9.2018 at http://ujpr.org

Universal Journal of Pharmaceutical Research
An International Peer Reviewed Journal
Open access to Pharmaceutical research
©2018, publisher and licensee UJPR, This is an open access article which permits unrestricted non commercial
use, provided the original work is properly cited
Volume 3, Issue 4, 2018

RESEARCH ARTICLE

QUALITY CONTROL ASSESSMENT OF DIFFERENT BRANDS OF

CIPROFLOXACIN 500 MG TABLETS IN YEMEN
Ali Alyahawi1*, Abdulmajed Alsaifi2
1
Department of Pharmacy, Al-Razi University, Republic of Yemen.
Department of Chemistry, Sana’a University, Republic of Yemen.
2

ABSTRACT
Ciprofloxacin is a fluorinated 4-quinolone or fluoroquinolone antibacterial with a wider spectrum of activity than nalidixic acid
and more favorable pharmacokinetics allowing its use in systemic infections. It has been used in the treatment of a wide
range of infections. Many different brands and dosage forms of Ciprofloxacin hydrochloride are available in the Sana'a
market that places health practitioners in a dilemma of drug substitution in case of non-availability of a particular brand.
The aim of the present study was to evaluate the quality control of five brands of Ciprofloxacin hydrochloride tablets marketed and
commonly prescribed in Sana'a city. The results and findings of the present study will be interpreted and discussed.
Five brands of Ciprofloxacin hydrochloride tablets (500 mg) were purchased from the retail pharmacy outlets and their
pharmaceutical quality were assessed by using in-vitro tests as per the British Pharmacopoeia (BP) and unofficial standards as
recommended by the manufacturers. The assessment of tablets included the evaluation of uniformity of weight, friability, hardens,
disintegration time, dissolution test and assay content by UV spectrophotometric method. All brands passed USP and BP standards
in- vitro quality control tests prescribed for the tablets except hardens test but the all products were satisfactory for hardness.
The results indicated that the overall quality of all tested Ciprofloxacin hydrochloride tablets brands was satisfactory as they met
the requirements of the official and unofficial quality control tests.
Keywords: Ciprofloxacin HCl, dissolution, disintegration, friability, hardness, quality control.

Article Info: Received 18 August 2018; Revised 26 August; Accepted 3 September, Available online 15 September 2018
Cite this article-
Ali Alyahawi, Abdulmajed Alsaifi. Quality control assessment of different brands of ciprofloxacin 500 mg
tablets in Yemen. Universal Journal of Pharmaceutical Research. 2018; 3(4): 31-36.
DOI: https://doi.org/10.22270/ujpr.v3i4.180
Address for Correspondence:
Dr. Ali Alyahawi, Department of Pharmacy, Faculty of Medical Sciences, Al-Razi University, Republic of
Yemen. E-mail: alyahawipharm@yahoo.com.

INTRODUCTION to the safety, effectiveness and acceptability of the

product”5.
Ciprofloxacin is a synthetic flouroquinolone derivative
with broad spectrum antibacterial activity1. It is widely
used in the treatment of urinary tract infections, lower
respiratory tract infections, bacterial diarrhoea, skin
and soft tissue infections, bone and joint infections,
gonorrhea, and in surgical prophylaxis2. In most of the
cases, it would appear that for treatment of above said
infections, physicians prescribe ciprofloxacin as a first
choice of drug. Ciprofloxacin (CIP) is flouroquinolone Figure 1: Chemical structure of ciprofloxacin.
with fluorine at position 6 of naphthyridine ring. The
chemical structure of ciprofloxacin is shown in Figure Also, quality control is the part of Good Manufacture
13. Quality control is all measures designed to ensure Practice (GMP) that is concerned with sampling,
the output of uniform batches of drugs that conform to specifications, testing, documentation and release
established specifications of identity, strength, purity, procedures which ensure that the necessary and
and other characteristics4. According to pharmaceutical relevant tests are actually carried out and that the
manufacturers association of U.S. “quality is the sum materials are not released for use, not products released
of all the factors which contribute directly or indirectly

ISSN: 2456-8058 31 CODEN (USA): UJPRA3

Alyahawi et al. Universal Journal of Pharmaceutical Research

for sale or supply, until their quality has been judged to percentage friability was obtained. Percentage
be satisfactory6. friability was calculated as:
A comprehensive evaluation, however, involves the W1– W2
determination of uniformity of weight, chemical Percentage friability = X100
W1
content, friability, hardness, and disintegration tests Disintegration Test
along with dissolution rate. Drugs that are chemically Six tablets from each brand were employed for this
and biopharmaceutically equivalent must be identical test in a freshly prepared medium, 0.1N HCl at 37 oC
in strength, quality, and purity. The content uniformity, using the BP disintegration apparatus. The
disintegration, and dissolution rates must be disintegration time was taken to be the time no particle
comparable7. remained on the basket of the system.
The United States Pharmacopoeia describes an HPLC Dissolution Test
method for CIPRO and CIPRO HCl assay in bulk, The dissolution test was carried out using USP
CIPRO injection, ophthalmic ointment, ophthalmic apparatus II (paddle method) 5 in 6 replicates for each
solution and tablets8. Despite most methods presented brand. The dissolution medium was 900 mL 0.1N
in official compendia are physicochemical assays, HCL which was maintained at 37±0.5oC. In all the
these methods do not represent the potency of experiments 5 mL of dissolution sample was
antimicrobials neither can predict the loss of activity. withdrawn at 0, 10, 20, and 30 min and replaced
The aim of the present study is to evaluate the quality with equal volume of dissolution medium to
of different brands of Ciprofloxacin tablets. maintain sink condition. The sampling times were
selected in due consideration for the short
MATERIALS AND METHODS disintegration times. Samples were filtered and
Materials assayed by ultraviolet spectrophotometry at 276 nm.
Comparative in-vitro quality control parameters The concentration of each sample was determined from
between six commercially available tablet different a predetermined calibration curve for ciprofloxacin
brands of ciprofloxacin were purchased from the retail hydrochloride.
pharmacies in Sana,a, Yemen. All brands were studied Data processing and analysis
through the evaluation of weight variation, drug After the completion of all test procedures data for all
content, hardness, friability, disintegration time and the individual tablets were recorded and separated on a
dissolution profile. All the tablet brands of different sheets according to the manufacturer. Finally,
ciprofloxacin were labeled to contain 500 mg of data were analyzed by using the above mentioned
ciprofloxacin per tablet and coded as A, B, C, D, and E mathematical formula and MS-Excel®, 2007.
(Table 1). The study was done by performing various
test procedures associated to assess the quality of RESULTS AND DISCUSSION
tablets. USP and British pharmacopoeia were used as General aspect
standard for the evaluation study. The present study was conducted to assess the quality
Methodology of 500 mg ciprofloxacin tablets marketed in Sana’a
Various analytical methods and tests are important for Yemen. To achieve this purpose, four different
the development and manufacture of pharmaceutical pharmaceutical companies (brands) A, B, C, D, and E
formulations. The evaluation was done according to were used (see table 1). They were obtained from
USP and BP standards. different retail pharmacies in Sana’a and then were
Weight Variation subjected to a number of tests. A quality control study
Twenty (20) tablets from each of the brands were is very important to evaluate tablet properties.
weighed individually using an analytical weighing Different quality control parameters (e.g., weight
balance. The average weight for each brand as well as variation, drug content uniformity, hardens, friability,
percentage deviations were calculated. disintegration time and dissolution tests) were
Drug content performed to determine the differences among various
The estimation of drug content for ciprofloxacin tablets conventional ciprofloxacin tablets that are available in
was performed by crushing three tablets and quantity the Yemeni drug market.
equivalent to 45 mg was taken and determined using Average Weight and Weight Variation:
0.1M HCl using UV spectrophotometer at about 276 Although the uniformity of weight does serve as a
nm, pointer to good manufacturing practice (GMP) as well
Hardness Test as amount of the active pharmaceutical ingredients,
A tablet was placed vertically on the Monsanto especially for reproducibility of the product which is
Hardness tester. The load was then applied along the very essential for mass production of any product.
radial axis of the tablet. The weight or load required for The average weight and weight variation of the
breaking the tablet was noted down. Similarly it was different brands of ciprofloxacin tablets tested are
done for 10 tablets. shown in Tables 3.1 and Fig.3.1. It was found that the
Friability average weight of different five brands tablets of
It was performed using Roche Friabilator, 10 tablets ciprofloxacin tablets ranged from 679.3 mg  2.63 %
were weighed and placed in apparatus. The apparatus (A brand) to 842.7 mg  3.58 % (E brand), while the
was rotated at a speed of 25 rpm. The apparatus was deviation from average weight for all product is not
made to rotate for 4 min. The tablets were reweighed more than 3.58 %. Therefore, all the five brands tested
(W2) and compared with their initial weights and in this study complied with the compendia

ISSN: 2456-8058 32 CODEN (USA): UJPRA3

Alyahawi et al. Universal Journal of Pharmaceutical Research

specification for uniformity of weight which states that compressed to very hard tablet tend to cap or laminate
for tablets weighing more than 324 mg, weight of not on attrition losing their crown part. Therefore, another
more than 2 tablets should not differ from the average measure of the tablet strength, its friability is often
weight by more than 5%9. Thus, all brands passed the measured. The loss due to abrasion is a measure of the
weight uniformity test set by USP. Also, the results tablet friability. The average values of friability of the
indicate the use of different excipients with different different brands of ciprofloxacin tablets tested shown
weights. in table 3 and figure 5. The average values of friability
Content Uniformity (Assay) ranging from 0.01 % (D brand) to 0.37 % (B brand).
Every unit of tablet should contain the amount of drug The friability was less than 0.5 %, indicating that it is
substance equivalent to its label amount. For the within the compendia limits, which showed that the
evaluation of content, assay should be performed. The tablets possess good mechanical strength. Also, this
weight variation test is simplified and alternative to showed that all the brands could withstand abrasion
content uniformity test to assure therapeutic utility10 without loss of tablet integrity, and the causes of high
and is an indicator of variations in the drug content11. friability were taken in consideration during
The average chemical content (assay) values of the manufacturing the tablet. Namely tablets compressed
different brands of ciprofloxacin tablets tested shown with larger force tend to have slightly lower friability
in Table 2 and Figure 3. The results of the assay of compared with the ones compressed with smaller
chemical content of ciprofloxacin tablets showed that force21. The pharmacopoeia states that the friability
the active content of all the brands were between value of tablets should be less than 1% and as such all
98.102.2990 % (A brand) and 101.400.3778% (E the brands of ciprofloxacin had passed this friability
brand) of the labeled amount specified for specification20.
ciprofloxacin tablets. A and B brands were chemically Disintegration Time
equivalent because they had chemical content not less Tablet disintegration time is one of the very important
than 90 % and not more than 100% (w/w)12. According physicochemical properties in solid dosage forms. The
to the United State Pharmacopoeia13, ciprofloxacin disintegration test measures the time required for
tablets should contain not less than 90 % and not more tablets to disintegrate into particles. This is a necessary
than 110 % of ciprofloxacin tablets. The results condition for dissolution and could be the rate-
indicated that although different manufacturer determining step in the process of drug absorption. The
formulates the different brands are under the BP/USP average values of disintegration of the different brands
specification14. Furthermore, all the brands of the of ciprofloxacin tablets tested shown in table 3 and in
tablets passed the test for the content of ciprofloxacin figure 6. The results of disintegration time (min) of
tablets. All these brands fall within the British ciprofloxacin tablets were ranging from 1.41 min (A
Pharmacopoeia Specification of 95 % – 105 %15. and D brans) to 4.15 min (E brand). All brands of the
Hardness Test ciprofloxacin tablets passed the pharmacopoeia22
The crushing strength of the tablets is an essential standard which stipulates a disintegration time of not
criterion in the determination of the ability of the more than 15 minutes for uncoated tablets, while USP
tablets to resist chipping, abrasion or breakage under specification for disintegration is 30 min both for
conditions of storage, transportation and handling uncoated and film coated tablets. All the brands were
before storage16. Hardness, which is now more complied with the both BP and USP specifications. All
appropriately called crushing strength of the tablet is the brands were complied with the both BP and USP
determined to make adjustments to the pressure in the specifications. The rapid disintegration time exhibited
tablet press17. It can also influence other parameters by all the brands might be due to type and amount of
such as friability and disintegration18. disintegrant used in the formulation. All the
The average values of hardness of the different brands disintegration times had fallen within the acceptable
of ciprofloxacin tablets tested shown in table 3 and range.
figure 4. Average hardness was found in the range of Dissolution Test
20.03 kg/cm2 (A brand) to 31.535 kg/cm2 (E brand). The process of dissolution plays a vital role in
The results indicated that all brands of ciprofloxacin liberation a drug from its dosage form and making it
tablets were not in the limit range of between 4 to 10 available for subsequent gastrointestinal absorption.
kg/cm2 stated17,19. Where all brands were greater than So, dissolution analysis of pharmaceutical solid dosage
20 kg/cm2. The hardness of the tablets showed that all forms is a very important test of product quality and it
brands gave the highest crushing strength. can be used as a sensitive method for differentiating
Hardness is referred to as non-compendial test. The between formulations of the same therapeutic agent23-
24
hardness or crushing strength assesses the ability of .
tablets to withstand handling without fracturing or Drugs with poor dissolution profile will not be
chipping. It can also influence other parameters such as available in the body system to elicit therapeutic
friability and disintegration. Normally, a force of about effect25. Also, the dissolution study was carried out to
4 kgs is the minimum requirement for satisfactory determine the resistance of the materials the acidic
tablets20. Therefore, the tablets of all products were environment of the stomach and their suitability as
satisfactory for hardness. enteric coating materials. The drug release study is a
Friability Test measure of the amount of the drug released into the
Tablet hardness is not the absolute indicator of the dissolution medium with time. This study gives an idea
tablet strength since some formulations when of amount of drug available for absorption after oral

ISSN: 2456-8058 33 CODEN (USA): UJPRA3

Alyahawi et al. Universal Journal of Pharmaceutical Research

administration. Drugs with poor dissolution profile will 6. World Health Organization and Cairo University, Guidelines
not be available in the body system to elicit therapeutic for good manufacturing practice of pharmaceuticals in Egypt,
Faculty of pharmacy, Cairo University, Central
effect25.
administration of pharmacy, WHO, Cairo, 1994.
The average values of dissolution of the different 7. Dressman JB, Amidon GL, Reppas C, Shah VP. Dissolution
brands of ciprofloxacin tablets tested shown in table 3 testing as a prognostic tool for oral drug absorption:
and graphically in Figure 7. The obtained dissolution immediate release dosage forms. Pharm Res.1998; 15(1):
content at 30 minutes was found to be ranged from 11–22.
96.48 1.168 % to 100.151.4314%. All brands of 8. The US Pharmacopeia, 30 editions, The US Pharmacopeial
Convention, Rockville, 2007.
ciprofloxacin tablets showed more than 90 % drug
9. Ngwuluk NC, lawal K, Olorunfemi PO, Ochekpe NA. Post-
release after 30 minutes. At 30 mins, all the brands market in vitro bioequivalence study of six brands of
released more than the pharmacopoeia (USP 30, NF ciprofloxacin tablets/caplets. Sci. Res. Essay. 2009; 4: 298-
25) requirement of 70% active pharmaceutical 305.
ingredient20. All the brands of the ciprofloxacin 10. Lachman L, Liberman H, Kanig J. The Theory and Practice
hydrochloride tablets complied with the official of Industrial Pharmacy; Third Edition: 293-345, 346-373.
specification for content uniformity having between 11. Aulton M. Pharmaceutics: The Science of Dosage Form
Design. International Student Edition: 304-321, 347-668.
92-104% as stipulated by the USP. This might be as a 12. The United States Pharmacopoeial Convention, United States
result of strict adherence to good manufacturing Pharmacopoeia 30. Acetaminophen. The United States
practice in the process of manufacturing these tablets. Pharmacopoeial Convention, Rockville. USA, 2006.
13. Bradoo R, Shahani S, Deewan B, Sudarshan S. Fast
CONCLUSION dissolving drug delivery system. J Am Med Assoc India,
From the present study, it was clearly demonstrated 2001; 4 (10): 27-31.
14. Willard-Hobart H, Merritt Jr Lynne L, Dean John A (1974)
that all five brands of the ciprofloxacin hydrochloride Instrumental Methods of Analysis. (5th edn), Von Nostrand,
tablet comply with BP and USP specifications for University of Michigan.
in vitro quality control tests of uniformity of weight, 15. Milton AS, Wendlandt SA. Possible role for prostaglandin
uniformity of content, friability, disintegration time, E1 as a modulator of temperature regulation in the central
and dissolution except hardens test for five brands. The nervous system of the cat. J Physiol. 1970; 207:76–7.
USP and BP specification of maximum hardens value 16. Davidson AG. Ultraviolet-visible absorption
spectrophotometry. In Beckett AH, Stenlake JB, (4th edn),
of 10 kg/cm2, where the lower value of hardens is
Practical Pharmaceutical chemistry. CBS Publishers and
20.03 kg/cm2 and the value is 31.535 kg/cm2. But distributors, New Delhi. 2002; 275-278.
Hardness is referred to as non-compendial test. 17. Rawlins EA. Bentley’s text book of pharmaceutics, Bailliere
Finally, bioequivalence studies are essential and Tindal publisher, 1977; 8th ed., 289-290.
important. Also such studies may be more important in 18. Tanjinatus SO, Md. Ahsanul Haque, Irin Dewan, Islam A.
developing countries where counterfeit and comparative in vitro dissolution study of some
substandard drugs have become a major challenge to ciprofloxacin generic tablets under bio waiver conditions
by RP-HPLC. Int J Pharm Sci Res. 2011; 2(12): 3129-3135
health care services. 19. Ali HM, Homeida MMA, Ford J, Truman CA, Roberts CJC,
Badwan AA. Int J Pharm. 1988; 42:155-159.
CONFLICT OF INTEREST 20. The United State Pharmacopoeia. USP 30 - NF25, the
The authors declare that they have no competing official compendia of standards 2007, 1755 – 1759.
interests. 21. Perioli L, Ambrogi V, Angelici F, Ricci M and Giovagnoli S,
Development of Mucoadhesive Patches for Buccal
Administration of Ibuprofen. J Con Rel. 2004; 99: 73-82.
REFERENCES
22. British Pharmacopoeia. Her majesty’s Stationery office,
1. Tripathy KD: Sulfonamides, cotrimoxazole and qunolones,
University Press Cambridge. 2002, Vol. 1 and 2.
In: Essentials of Medical Pharmacology. Jaypee Brothers
23. Hsu H, Ayres JW. Chlorpheniramine dissolution and relative
Medical Publishers (P) Ltd, New Delhi, India. 2003; 5: 646-
urinary exerction from commercial products. J Pharm Sci.
652.
1989; 78(10): 844-47.
2. Hervey SC: Antimicrobial drugs, In: Gennaro AR, Editor,
24. Bruntion LL. The pharmacological Basis of Therapeutics.
Remington’s Pharmaceutical Sciences, Mack Publishing
Gilman AG, Ra TW, Nies AS and Taylor P (ed),
Company, Eston, Pennsylvania 18042.1991; 18: 1163-1241
pergamon press. Singapore, Edition 8. 1991: 926-928.
3. Qureshi MN, Inayat UR Raahman, Gul Akhtar Marwat.
25. Giri TK, Parveen N, Thakur D, Alexander A, Badwaik AH,
Comparative analysis of Ciprofloxacin in different
Tripathi DK. In vitro Evaluation of Commercially Available
Pharmaceutical products by High Performance Liquid
Enteric Coated Tablet Containing Diclofenac Sodium. Int J
Chromatography. Sci Tech Dev. 2010; 31 (1): 69-73.
Res Pharm Biomed Sci. 2012; 3 (2):875 – 881.
4. World Health Organization, Guidelines for developing
national drug policies, Geneva, 1988
5. Verpoorte R, Mukherjee PK. GMP for botanicals: regulatory
and quality issues on phytomedicines. Business Horizons;
2003; 1:60.

ISSN: 2456-8058 34 CODEN (USA): UJPRA3

Alyahawi et al. Universal Journal of Pharmaceutical Research

Table 1: Brands of Ciprofloxacin

Code Country of Strength Batch
Brand origin in mg number
A Yemen 500 12669
B Yemen 500 13219
C Yemen 500 1991
D India 500 1301
E India 500 FD3175

Table 2: Average weight, % deviation from average weight, content uniformity, and % deviation from content
uniformity of different brands of ciprofloxacin tablets.
Brands Average weight Content uniformity (%),
(mg) , % RSD % RSD
A 679.3 ±2.63 98.10 %±2.2990
B 758.3 ±1.07 101.3 % ±0.897544
C 809.6 ±1.57 101.34 %±3.264
D 812.5 ±1.70 100.30 %±3.607
E 842.7 ±3.6 101.40 %±0.3778

Figure 2: Comparison of different brands weight variation of different brands of ciprofloxacin tablets.

Figure 3: Comparison of assay content (Percent %) of different brands of ciprofloxacin tablets.

Table 3: Hardness (kg/cm2), % deviation from hardness, friability percent (%) , disintegration time (min),
dissolution (30 min), % deviation from dissolution of different brands of ciprofloxacin tablets.
Brands Hardness (kg/cm2) Friability Disintegration Dissolution (30 min),
% RSD (%) time (min) % RSD
A 20.03 ±14.397 0.36 1.41 99.33 ±2.03711
B 27.41 ±7.98681 0.37 3.16 100.15 ±1.4314
C 25.585 ±8.3994 0.12 3.51 98.15 ±1.796
D 23.35 ±8.16783 0.013 1.41 96.4 ±1.16786
E 31.535 ±7.37343 0.06 4.15 98.00 ±1.2712

ISSN: 2456-8058 35 CODEN (USA): UJPRA3

Alyahawi et al. Universal Journal of Pharmaceutical Research

Figure 4: Comparison of hardness of different brands of ciprofloxacin tablets.

Figure 5: Comparison of friability percent (%) for different brands of ciprofloxacin tablets.

Figure 6: Comparison of disintegration time (min) of different brands of ciprofloxacin tablets.

Figure 7: Comparison of dissolution test of different brands ciprofloxacin tablets.

ISSN: 2456-8058 36 CODEN (USA): UJPRA3