A Prospective study on the Drug prescribing pattern of Antibiotics in the Ears, Nose and Throat department of a Tertiary Care Hospital

 

Susan Isaac1, S. Jayakumari2*, Sree Lekshmi R. S.

School of Pharmaceutical Sciences, Vels Institute of Science Technology and Advanced, Studies [VISTAS], VELS University, Chennai, India.

*Corresponding Author E-mail: nisajayaa@gmail.com

 

ABSTRACT:

Aim and objective: ENT infections are the most commonly occurring problems around the globe and for which antibiotics are prescribed frequently. The aim of the study was to explore the antibiotic prescribing patterns used in the ENT conditions by analyzing the prescriptions. Methods and materials: A prospective study was conducted in 100 patients who visited the in-patient and out- patient of ENT department over a period of six months. Results: Among 100 patients, male predominance was more than females. The highest numbers of patients were from the age group of 18-65 years. Most commonly diagnosed conditions were acute sinusitis, chronic suppurative otitis media, tonsillitis, pharyngitis. Cefuroxime and Amoxicillin/ clavulanate were mostly prescribed among out- patients and Cefotaxim, Gentamicin, Cefuroxime among in- patients. Majority of the out-patient prescription contained single antibiotic, whereas in- patient prescription included the use of single, double and triple antibiotics. Oral agents were predominant in the out-patient prescription, whereas parenteral route was preferred in the in-patients. The WHO/INRUD core prescribing indicators showed relatively higher number of drugs per prescription. Most of drugs were prescribed by its generic name. It also highlighted good adherence to the formulary listed drugs by the physicians. Conclusion: The present study showed good prescribing patterns such as prescribing drugs by their generic name and adherence to formulary. However, there is a need to reduce the act of polypharmacy. The data presented here will be useful in future in promoting rational use of drugs.

 

KEYWORDS: ENT infections, antibiotics, prescribing pattern, Outpatient, Inpatient.

 


INTRODUCTION:

According to the American Academy of Otolaryngology, ENT is a medical subspecialty department which deals with the diagnosis and management of patients with diseases/disorders of the ears, throat as well as structures of nose and face. Ear, nose, and throat (ENT) diseases are the most common causes of hospital visits globally and are responsible for absenteeism from school and work and unnecessary medical care, and at times associated with serious consequences.1,2 Some of the most common ENT infections known to occur are tonsillitis, pharyngitis, sinusitis, adenoiditis, acute and chronic suppurative otitis media (CSOM), epiglottitis, laryngitis and infections of the ear canal.

 

 

Antibiotics are the key drugs for treatment of infections. Nevertheless, many antibiotics are prescribed for viral infections.3 The results of the various studies based on the antibiotic use showed that in about 40% of all consultations for rhino-pharyngitis had antibiotics prescribed. Antibiotics were prescribed in more than 90% of cases of pharyngitis irrespective of the age of the patient.4 Such irrational use of antibiotics often results in increased frequency of adverse drug reactions, suboptimal therapy, therapeutic failure, polypharmacy and most importantly, the emergence of antibiotic resistance5. Thus, it is imperative to monitor, evaluate, and suggest modifications in the practitioner's prescription habits, so as to make patient care reasonable and effective.6 Requirements for rational use of drugs will be fulfilled if the process of prescribing is appropriately followed. Prescription pattern monitoring study (PPM) is a tool for assessing the prescribing, dispensing and distribution of drugs. The main aim of PPMS is to facilitate rational use of medicine.7 The International Network for the Rational Use of Drugs (INRUD) which was established in 1989 so as to promote the rational use of drugs in developing countries. Various indicators were developed by INRUD in collaboration with WHO that provided objective indices to allow for assessment of drug use practices8. Hence, the present prospective study was conducted with the aim of evaluating prescribing pattern of antibiotics used in ENT infections in patients of outpatient (OPD) and inpatient (IPD) departments at the tertiary care hospital.

 

METHODOLOGY:

Study site:

The study was carried out in the ENT OPD and IPD of a tertiary care hospital.

 

Study population:

The study population consists of 100 patients satisfying the inclusion criteria.

 

Inclusion criteria:

All patients attending the ENT IPD and OPD, irrespective of age and gender.

 

Exclusion criteria:

Patients unwilling to co-operate, pregnant and lactating women were excluded.

 

Study period:

The study was carried out from October 2016 to March 2017 (6 months). The study was approved by the Institutional Review Board. An oral and written consent was obtained from the patients before their participation in the study.

 

Study design:

It was a prospective study. The relevant data on clinical symptoms, investigations, diagnosis and treatment were recorded on a customized data collection sheet and were analyzed using WHO/INRUD indicator.

 

Parameters for evaluation:

The parameters included were age and gender wise distribution, types of infections, types of anti- microbial prescribed, most commonly prescribed antibiotics, route of administration comparison of antibiotics prescribed as mono therapy and polytherapy, average number of drugs prescribed per prescription, drugs prescribed by generic name and drugs prescribed from the formulary.

 

RESULTS:

The study attended to observe the drug prescription pattern in patients suffering from ENT disease. Among 100 prescriptions, 60 prescriptions were collected from OP and 40 from IP.

 

In this study, the highest number of patients was from the age group of 18-65 years amounting to 75% from OP and 67.5 % from IP. The lowest percentage was of geriatric patients, that is, 8.3% from OP and 5% from IP as depicted in Fig. 1.

 

Fig. 1. AGE-WISE DISTRIBUTION

 

According to the gender wise distribution, 53.3% from OP and 60% from IP were males and 46.7% from OP and 40% from IP were females as shown in Fig. 2.

 

 

Fig. 2. GENDER WISE DISTRIBUTION

 

During the study, it was observed that 28 patients visited for treating ear infection, 25 for nose infections, 38 for throat infections and 10 for combination of ENT infections as depicted in Table 1.

 

Table 1. TYPES OF ENT INFECTIONS

 

ENT INFECTIONS

FREQUENCY OF INFECTIONS

OP

IP

EAR DISEASES

 

CSOM

11

9

 

AOM

3

1

 

OTOMYCOSIS

2

-

 

AURAL POLYP

1

-

 

OSTEOSARCOMA

-

1

NOSE DISEASES

 

 

ACUTE SINUSITIS

15

3

 

CHRONIC SINUSITIS

6

-

 

EPISTAXIS

1

-

THROAT

 

TONSILITIS

8

7

 

ADENOIDITIS

-

4

 

PHARYNGITIS

8

5

 

PHARYNGOTONSILITIS

-

1

 

MASTOIDITIS

-

1

 

PERITONSILLAR ABSCESS

-

4

COMBINED URTIs

 

URTI

3

4

 

PHARNGITIS+ CSOM

2

1

TOTAL

 

60

40


Table 2. TYPES AND FREQUENCY OF ANTIBIOTICS PRESCRIBED

CLASS OF ANTI MICROBIALS

ANTI MICROBIAL AGENTS PRESCRIBED

FREQUENCY OF PRESCRIBED ANTIBIOTICS IN OP

% OF ANTIBIOTIC CONSUMPTION

FREQUENCY OF PRESCRIBED ANTIBIOTICS IN IP

% OF ANTIBIOTIC CONSUMPTION

ANTI BACTERIALS

β-LACTAMS

PENICILLINS

 

 

 

 

AMOXICILLIN

5

8.06

-

 

AMOXICILLIN + CLAVULANIC ACID

15

24.1

2

3.77

AMOXICILLIN + CLOXACILLIN

3

4.83

-

 

AMPICILLIN

1

1.61

4

7.54

CEPHALOSPORIN

 

 

 

 

CEFUROXIME

19

30.64

10

18.86

CEFIXIME

3

4.83

-

 

CEFPODOXIME PROXETIL

3

4.83

 

 

CEFOTAXIME

1

1.61

21

39.62

MACROLIDES

AZITHROMYCIN

2

3.07

-

 

 

CLARITHROMYCIN

1

1.61

-

 

FLUOROQUINOLONES

CIPROFLOXACIN

5

8.06

2

3.77

LEVOFLOXACIN

1

1.61

-

 

NITROIMIDAZOLES

METRONIDAZOLE

-

 

3

5.66

AMINOGLYCOSIDES

GENTAMICIN

-

 

11

20.75

ANTI FUNGAL

AZOLES

CLOTRIMAZOLE

3

4.83

-

 

TOTAL

 

62

 

53

 

 


TABLE 3. COMMONLY PRESCRIBED CLASS OF ANTIBIOTICS

CLASS OF DRUGS

FREQUENCY

% CONSUMPTION

β-LACTAMS

87

75.65%

MACROLIDES

3

2.60%

FLUOROQUINOLONES

8

6.95%

NITROIMIDAZOLES

3

2.60%

AMINOGLYCOSIDES

11

9.56%

AZOLES

3

2.60%

TOTAL

115

100%

 

 

 

TABLE 4.  PATTERN OF ANTIBIOTIC USE: SINGLE V/S MULTIPLE THERAPY

OUT- PATIENT

AMA’s Prescribed

No. of prescription

%

Single drug

57

95%

Two AMAs

3

5%

TOTAL

60

100%

IN- PATIENT

AMA’s Prescribed

No. of prescription

%

Single drug

22

59.45%

Two AMAs

13

35.13%

Three AMAs

2

5.40%

TOTAL

37

100%


 

TABLE 5. DISTRIBUTION PATTERN OF AMAS FOR SPECIFIC DISEASE

DISEASE DIAGNOSED

A

M

O

X

AMOX

+ CLAV

AMOX+ CLOX

A

M

P

C

E

F

U

R

C

E

F

I

C

E

F

P

O

C

E

F

O

T

A

Z

I

C

L

A

R

C

I

P

R

O

L

E

V

O

M

E

T

R

O

G

E

N

T

C

L

O

T

T

O

T

A

L

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

CSOM

-

2

-

-

9

2

-

5

1

-

5

1

1

3

-

29

AOM

-

-

-

1

1

-

-

-

-

-

1

-

-

-

-

3

OTOMYCOSIS

-

-

-

-

-

-

-

-

-

-

 

-

-

-

2

2

AURAL POLYP

-

-

-

-

 

-

-

-

-

-

1

-

-

-

-

1

OSTEOSARCOMA

-

-

-

-

1

-

-

1

-

-

-

-

-

1

-

3

ACUTE SINUSITIS

2

10

-

-

8

-

-

-

-

-

-

-

-

-

-

20

CHRONIC SINUSITIS

-

3

-

-

3

-

-

-

-

-

-

-

-

-

-

6

EPISTAXIS

-

-

-

-

1

-

-

-

-

-

-

-

-

-

-

1

TONSILITIS

3

3

1

1

1

-

-

9

-

-

-

-

-

5

-

23

ADENOIDITIS

-

-

-

3

1

-

-

-

-

-

-

-

-

1

-

5

PHARYNGITIS

-

1

-

1

7

1

2

1

-

-

-

-

-

-

-

13

PHARYNGO-TONSILITIS

-

-

-

-

-

-

 

1

-

-

-

-

1

-

-

2

MASTOIDITIS

-

-

-

-

-

-

-

1

-

-

 

-

-

1

-

2

PERITONSILLAR ABSCESS

-

-

-

-

-

-

-

2

-

-

-

-

1

2

-

5

URTI

-

1

-

-

1

-

1

3

1

1

-

-

-

-

-

8

PHARNGITIS+ CSOM

-

-

-

-

2

-

-

-

-

-

-

-

-

-

-

2

TOTAL

5

20

1

6

25

3

3

18

2

1

7

1

3

13

2

 

 

 

Table 6. WHO/INRUD CORE PRESCRIBING INDICATORS.

WHO PRESCRIBING INDICATORS

CURRENT STUDY VALUE

WHO REFERENCE VALUE

Average number of drugs per prescription

3.8

1.6 – 1.8

Percentage(%) of injectables prescribed

12%

<10%

Percentage(%) of drugs prescribed by generic name

87.4%

100%

Percentage(%) of drugs prescribed from hospital formulary

98%

100%

 


The frequency of antibiotics prescribed in both IP and OP is depicted in Table 2. As illustrated in Table 3, 75.65% were β-lactams, 2.60% macrolides, nitroimidazoles and azoles (anti- fungal), 6.95% fluoroquinolones and 9.56% amino glycosides. As shown in Table 4, out of 100 prescriptions included in the study, 95% prescriptions from OP and 59.45% from IP had single antibiotic, 5% from OP and 35.13% from IP prescriptions had two antibiotics, whereas only 5.40% IP prescriptions had three antibiotics. The overall distribution pattern of AMAs used for specific disease in IP and OP is depicted in Table 5.

 

As depicted in Fig. 3 and Fig. 4, out of 53 antibiotics prescribed in the IP prescription, 69 % were administered through parenteral route, 27% through oral and 4% through topical route. On a contrary, out of 62 antibiotics prescribed in the OP prescription, 95% were given orally and 5% were given for topical administration. Using the WHO/INRUD core prescribing indicator, the average number of drugs per prescription was calculated, which showed a relatively higher value indicating polypharmacy.

 

 

Fig. 3: ROUTE OF ADMINISTRATION OF ANTIBIOTICS IN OP

 

 

 

Fig. 4: ROUTE OF ADMINISTRATION OF ANTIBIOTICS IN IP

About 12% injectables were encountered. 87.4% of drugs were prescribed by its generic name. 98% adherence to the hospital formulary was a noteworthy finding in this study as illustrated in Table 6.

 

DISCUSSION:

The present analysis comprises of a survey of antibiotics prescribed for the treatment of ear, nose and throat (ENT) infections. As a common practice, ENT infections are treated empirically to cover the most likely pathogens and the expected outcome is to treat as specifically as possible.

 

The current statistics show that, great numbers of the patients were in the age group of 18–65 years and the lowest percentages were of the elderly, indicating the prevalence of ENT infections more among adults. Similar findings were also reported in the study conducted by Ain et al1. On observing the gender wise distribution, it was found that percentage of males suffering from ENT infections was more than females in both OP as well as in IP department, which might be due to the occupational reasons. Similar result was found in previous surveys conducted in various countries.1,9,10,11,12 In the study conducted, among the out- patients, most of the hospital visits constituted for acute sinusitis, followed by CSOM, and that followed by tonsillitis and pharyngitis. Among the in- patients, majority were hospitalized for CSOM, tonsillitis, pharyngitis, peritonsillar abscess, and adenoiditis. Out of 100 prescriptions collected, all the infections were treated with different anti- microbial agents. Among 62 antibiotics prescribed in the OP, Cefuroxime was found to be most commonly prescribed antibiotic (30.64%), followed by Amoxicillin/clavulanate (24.1%). In a comparative study between Cefuroxime axetil and Amoxicillin/clavulanate conducted by Dan C Henry et al 13, it was found that that Cefuroxime axetil is as effective as Amoxicillin/clavulanate in the treatment of acute sinusitis. Also newer fluoroquinolones proved no benefit when compared with that of β-lactams.14 It is observed that Ciprofloxacin was prescribed only for CSOM (Table 5). In a study conducted by Abu baker K. et al15 on pattern of drug utilization in the treatment of CSOM, the most commonly prescribed class of antibiotics were the Quinolones (44.5%). H. S. Rehan, in his study, reported that Amoxicillin is the most commonly prescribed antibiotic for tonsillitis; followed by Azithromycin.16 In a study conducted to evaluate the clinical efficacy and tolerability of Cefixime by Dreshraj Sh et al17, treatment with Cefixime was successful in 100% patients suffering from AOM, 83.3% with acute sinusitis. A total of 53 antibiotics were prescribed in the in-patients. Majority of the prescriptions included Cefotaxim (39.62%) closely followed by Gentamicin (20.75%), Cefuroxime (18.86%). It is notable that 95% of out- patients received single antibiotic and the rest 5% received 2 antibiotics. Whereas, among in- patients, 59.45% received single antibiotic, 35.13% patients received double and 5.40% received triple antibiotic therapy. Similar findings were reported in the study conducted by Das et al.18 In the present study, the routes of administration of AMA administered among out- patients were found to be 90% and 10% topical administration. In IP, 69% were found to be given orally, 27% via intravenous route and 4% topical administration. Shankar et al12 in his study reported 48.9% of AMAs were prescribed by the parenteral route. Using the WHO/INRUD core prescribing indicator, it was found that the average number of drugs prescribed per prescription was relatively high (3.18) indicating polypharmacy. Encounter with injectables were also comparatively high (12%). About 87.4 % of drugs prescribed were in their generic name, which is in contrast with other studies reporting a higher use of brand names.1,15,16. However, the study highlighted that 98% of drugs prescribed were from the hospital formulary list. This infers adherence to formulary by the physicians and that if the formulary is well updated, disseminated and reinforced, further antibiotic use may be improved.19  Also, in a study conducted on ‘how to improve antibiotic use’, stated that close international cooperation involving international guidelines, agreements, monitoring and feedback of information, and implementation programmes.20 The study was carried out for a period of 6 months therefore, seasonal variations in disease and prescribing patterns were not considered. Further, the study population was low and the study was confined to only one hospital.

 

CONCLUSION:

To conclude, the prescribing pattern of antibiotics and adherence to the hospital formulary by the physicians in the hospital under review is encouraging. However, there is a considerable scope in reducing the number of drugs prescribed per patient. Continuing education on rational use of drugs and development of update and easy to use treatment guidelines/ formulary for common diseases is suggested. In our future attempt, we plan to study the effect of regulatory and educational interventions on drug use pattern in the management of ENT infection.

 

ABBREVIATIONS:

CSOM= chronic suppurative otitis media

AOM= acute otitis media

URTI= upper respiratory tract infection.

OP=outpatient

IP= inpatient

AMA: anti- microbial agent

 

REFERENCES:

1.      Ain MR, Shahzad N, Aqil M, Alam MS, Khanam R. Drug utilization pattern of antibacterials used in ear, nose and throat outpatient and inpatient departments of a university hospital at New Delhi, India. J Pharm Bioallied Sci. 2010; 2(1):8-12.

2.      Geneva, Switzerland: World Health Organization; 2004. Burden of illness and management options.

3.      Kenealy T, Arroll B. Antibiotics for the common cold and acute purulent rhinitis; Cochrane database systematic review.2013

4.      Needham A, Brown M, Freeborn S. Introduction and audit of general practice antibiotic formulary. J R Coll Gen Pract. 1988; 38:166–7.

5.      Mst. Marium Begum, Md. Sahab Uddin, M. Sohanur Rahman, Most. Akhlatun Nure, Rita Rani Saha, Taslima Begum, Rayhana Begum, Azharul Islam, Mahmuda Sultana, Rubaba Karim .Analysis of prescription pattern of antibiotic drugs on patients suffering from ENT infection within Dhaka Metropolis, Bangladesh. IJBCP, Vol 6, Issue 2,257- 264.

6.      Krishnaswamy K, Kumar BD, Radhaiah G. A drug delivery percept and practices. Eur J Clin Pharmacol. 1985; 29:363–70.

7.      Strom BL, Stephan EK, editors. Pharmacoepidemiology. 4th ed. Wiley-Blackwell: John Wiley and Sons, English; 2005.

8.      Laporte JR, Porta M, Capella D. Drug utilization studies: A tool for determining the effectiveness of drug use. Br J Clin Pharmacol. 1983; 16:301–4.

9.      Serena Pradhan, Akhilesh Chandra Jauhari.A study of antibiotics used in adult respiratory disorders in Kathmandu and Bhaktapur. Nepal Med Coll J. 2007 Jun;9(2):120-4.

10.   Khan FA, Nizamuddin S, Salman MT. Patterns of prescription of antimicrobial agents in the Department of Otorhinolaryngology in a tertiary care teaching hospital. Afr. J. Pharm. Pharmacol. 2011; 5:1732-8.

11.   Yadav P, Kanase V, Lacchiramka P, Jain S. Drug utilization trends in ENT outpatient department in a Teaching hospital. Int J Pharm Biol Sci. 2010; 1:153-60.

12.   Shankar PR, Upadhyay DK, Subish P, Dubey AK, Mishra P. Prescribing patterns among paediatric inpatients in a teaching hospital in western Nepal. Singapore Med J. 2006 Apr; 47(4):261-5.

13.   Dan C. Henry, Austin Sydnor Jr, Guy A. Settipane, James Alien, Scott Burroughs, Margaret M. Cobb, H. Preston Holley . Comparison of cefuroxime axetil and amoxicillin/clavulanate in the treatment of acute bacterial sinusitis. Clin Ther. 1999 Jul;21(7):1158-70

14.   Drosos E. Karageorgopoulos, Konstantina P. Giannopoulou, Alexandros P. Grammatikos, George Dimopoulos, Matthew E. Falagas. Fluoroquinolones compared with β-lactam antibiotics for the treatment of acute bacterial sinusitis: A meta-analysis of randomized controlled trials. CMAJ. 2008 Mar 25; 178(7):845-54.

15.   Abubakar K., Abdulkadir R., Abubakar M. R., Ugwah-Oguejiofor J. C., Abubakar S. B., Pattern of Drug Utilization in the Treatment of Chronic Suppurative Otitis Media in a Tertiary Health Institution in Kaduna, Nigeria, Journal of Health Science, Vol. 4 No. 1, 2014, pp. 7-10.

16.   H. S. Rehan. Pattern of drug utilization in acute tonsillitis in a teaching hospital in Nepal. Indian J Otolaryngol Head Neck Surg. 2003 Jul; 55(3): 176–179.

17.   Dreshaj Sh Doda-Ejupi T Tolaj IQ Mustafa A Kabashi S Shala N Geca Nj ,Daka A, Basha N. Clinical role of Cefixime in community-acquired infections. Prilozi 2011, 32(2):143-155.

18.   Das BP, Sethi A, Rauniar GP, Sharma SK. Antimicrobial utilization pattern in outpatient services of ENT department of tertiary care hospital of Eastern Nepal. Kathmandu Univ Med J (KUMJ). 2005 Oct-Dec; 3(4):370-5.

19.   Dr Clayton John Fsadni, Dr Sarah Caruana Galizia. Clinicians’ adherence to local antibiotic guidelines for upper respiratory tract infections in the ear, nose & throat casualty department of a public general hospital. The Journal of the Malta College of Family Doctors. Volume 05 Issue 01 April 2016.

20.   Marlies E.J.L. Hulscher, Jos W.M. van der Meer, Richard P.T.M. Grol. Antibiotic use: How to improve it? Int J Med Microbiol. 2010 Aug; 300(6):351-6.

21.   Wal Pranay, Wal Ankita, Srivastava Rishabh, Rastogi Prateek, Rai Awani K. Antibiotic Therapy in Pediatric Patients. Research J. Pharm. and Tech. 3(1): Jan.-Mar. 2010; Page 118-120.

22.   G M. Vaishali, R.V. Geetha. The Superbug Threat. Research J. Pharm. and Tech. 8(3): Mar., 2015; Page 343-346.

23.   Aishwarya J. Ramalingam. History of Antibiotics and Evolution of Resistance. Research J. Pharm. and Tech. 8(12): Dec., 2015; Page 1719-1724.

24.   P. Geetha, M. Kousalya, S. Geetha Lakshmi, R. Gopi. Prescribing Pattern of Drugs Used For Respiratory Disease in Pediatric Patients at Private Hospital. Research J. Pharm. and Tech. 9(3): Mar., 2016; Page 251-256.

25.   A. Ramya, P. Geetha, P. Shanmugasundaram. Assessment of Appropriate use of Antibiotics in Paediatric Department of A Tertiary Care Teaching Hospital. Research J. Pharm. and Tech. 2017; 10(2): 381-384.

26.   Sreeja. M.K, Gowrishankar N.L, Adisha. S, Divya. K.C. Antibiotic Resistance-Reasons and the Most Common Resistant Pathogens – A Review. Research J. Pharm. and Tech. 2017; 10(6): 1886-1890.

27.   Shafinaz1, Juno J Joel, Vadish S Bhat, Angel Rose ER. Study on Drug Utilization Pattern of Antibiotics in Respiratory Tract Infections. Research J. Pharm. and Tech. 2019; 12(3): 1189-1192.

28.   Gurudharshini Natarajan, Madhumitha Muthusamy, Muthusaravanan Sivarama krishnan, Perianayaki Periasamy, Poornimmashree A, Kumaravel Kandaswamy. A Big Picture on Antimicrobial Strategies then and now. Research J. Engineering and Tech. 2017; 8(4): 361-364.

29.   Suresh A. Marnoor. A Review on Antimicrobial Resistance and Role of Pharmacist in tackling this Global Threat. Res. J. Pharm. Dosage Form. & Tech. 2017; 9(4): 143-146.

30.   Hisham A. Abbas, Ashraf A. Kadry, Ghada H. Shaker, Reham M. Goda. Resistance of Escherichia coli and Klebsiella pneumoniae isolated from different Sources to β-lactam Antibiotics. Research J. Pharm. and Tech. 2017; 10(2): 589-591.

 

 

 

 

 

 

Received on 13.05.2019           Modified on 18.06.2019

Accepted on 20.07.2019         © RJPT All right reserved

Research J. Pharm. and Tech. 2019; 12(12): 6001-6006.

DOI: 10.5958/0974-360X.2019.01041.2