Quality Assessment of some Povidone-Iodine Pharmaceutical Preparations

 

Suha Alnaeb, Youssef Alahmad, Saleh Trefi2*

1Department of Pharmaceutical Chemistry and Drug Quality Control, Faculty of Pharmacy,

Al-Baath University, Homs, Syria

2Department of Pharmaceutical Chemistry and Drug Quality Control, Faculty of Pharmacy,

Aleppo University, Aleppo, Syria

*Corresponding Author E-mail: salehtrefi@yahoo.com

 

ABSTRACT:

The aim of the present work was to determine the active pharmaceutical ingredient of samples of povidone-iodine solutions 10% (topical solution and vaginal douche), which were obtained from market in Syria (A, B, C) for povidone-iodine 10% topical solution and (D, E, F) for povidone-iodine 10% vaginal douche and one solution produced by Mundipharma Company (Betadine 10% topical solution and Betadine 10% vaginal douche), which used as a reference. The research included control of solutions pH and free iodine concentration. In addition, the factors affecting stability of previous solutions and control stability of samples during the date of validity were studied. The results obtained showed that only 50% of the samples evaluated were within the iodine concentration range required. For povidone-iodine 10% topical solution, sample (A) was the closest to Betadine 10% topical solution, which had the highest level. Study revealed significant difference between local companies, where (A) had the best bactericidal effect. In addition, stability study of samples revealed that 50% of samples showed a significant decrease in iodine content in the second year of validity. For povidone-iodine 10% vaginal douche, the sample (E) was the closest to Betadine 10% vaginal douche, which had the highest level. Study revealed significant difference between local companies, where (E) had the best bactericidal effect. In addition, stability study of samples revealed that 50% of samples showed a significant decrease in iodine content in the second year of validity. The pH values of the local samples solutions were within the range (1.5-6.5) of activity and stability.

 

KEYWORDS: Povidone-Iodine solutions, quality control.

 

 


INTRODUCTION:

PVP-Iodine was introduced to the pharmaceutical market as an antiseptic agent in the 1950`s and is as effective as iodine itself against a broad spectrum of disease-causing microorganisms1,2. Iodophors are complexes of iodine and a solubilizing agent or carrier, which acts as a reservoir of the active “free” iodine3. The term free iodine means the amount of iodine in the solution, while available iodine indicates that the product is free from iodine reservoir. Free iodine concentration is the greatest chemical and microbiological factor in iodosphore activity. PVP-Iodine is a stable chemical complex of polyvinylpyrrolidone (PVP), which itself has no microbicidal activity4 and elemental iodine5,6.

 

This combination increases iodine solubility and provides reservoir of long-lasting release. An antiseptic is a type of disinfectant, which destroys or inhibits the growth of micro-organisms on living tissues without causing injurious effects when applied to surfaces of the body or to exposed tissues. Povidone-iodine is one of the few topical antimicrobial shown to be effective against bacteria, several viruses, fungi, spores, protozoa, amoebic cystsand reduces surgical wound infections significantly4,7,8,9,10. The antimicrobial action of iodine is rapid, but the exact mode of action is unknown. Iodine rapidly penetrates into microorganisms11 and attacks key groups of proteins (in particular the free sulfur amino acids cysteine and methionine3,12), nucleotides, and fatty acids3,13, which culminates in cell death3. Less is known about the antiviral action of iodine, but no lipid viruses and parvoviruses are less sensitive than lipid enveloped viruses14. Similarly, to bacteria, it is likely that iodine attacks the surface proteins of enveloped viruses, but they may also destabilize membrane fatty acids by reacting with unsaturated carbon bonds15. Numerous in vivo studies made over approximately 35 years, as well as the widespread clinical use of products containing PVP-I, indicate the efficacy of PVP-I as a therapeutic agent for both humans and animals. Some of the publications supporting the clinical effectiveness of PVP-I are reviewed such as skin disinfection, pre-surgical skin preparation, treatment of wounds, topical applications (burns, ulcers), gynecological applications, dental and oral use and veterinary medicine. In our study, we will focus on skin disinfection and gynecological applications. PVP-Itopical solution (10% PVP-I containing 1% available iodine) is effective for ridding and preventing infections, including those with severe ulceration16,17. In addition vaginal douche containing 10% PVP-Iodine has been reported effective in the treatment of vaginal infections18,19. It can be used as a topical and therapeutic agent for the treatment of birth-canal infections and for various forms of vaginitis .PVP-I may interfere with thyroid function tests and systemic effects. Precautions must be taken in pregnancy, breastfeeding, broken skin, and renal impairment. The effective pH-range of PVP-Iodine is between 1.5 to 6.520 with an optimum between pH 3 to 6. PVP-Iodine can be stored in powdered form without significant iodine loss. Samples kept for three years at 65 C in glass stoppered bottles without tape or seal showed only 0.5% maximum loss of available Iodine. The product should, however, be protected from light and moisture. There are some factors affecting efficacy of PVP-I solutions such as organic and inorganic pollutants which reduce the efficacy of PVP-I21,22, the pH value (3-6)23, the temperature which increases the efficacy of PVP-I at 32 C°24, antiseptic`s concentration and time of exposure25,26. In addition there are some factors affecting stability of PVP-I solutions during the date of validity such as existence of some excipients or metal electrodes in the pharmaceutical formulation of povidone-iodine solution which may interact with PVP-I and reduce its concentration, water hardness used in manufacturing, the pH value appropriate for stability, storage and conservation conditions. Povidone-iodine is a 2-pyrrolidinone-1-ethenyl homopolymer compound with iodine27. It contains no less than 9.0% and no more than 12.0% of available iodine27. It is a water and alcohol soluble compound and practically non-soluble in chloroform.

 

Figure 1 Chemical structure of Povidone Iodine27

 

MATERIALS AND METHODS:

Reagents and apparatus:

Sodium thiosulphate 0.1 N, Starch paste solution (1% in distilled water), Distilled water, Crison pH meter, volumetric flask, Erlenmeyer, beaker, burette, pipette.

 

Samples:

Four samples of povidone-iodine 10% topical solution(three samples collected from market in Syria (A, B, C) and one sample (Betadine 10% topical solution) produced by Mundipharma company), in addition four samples of povidone iodine solution 10% vaginal douche (three samples collected from market in Syria (D, E, F) and one sample (Betadine 10% vaginal douche) produced by Mundipharma company)were analyzed at the first and second year of validity. Three determinations in each sample were carried out considering as the end value the corresponding average.

 

Method:

The method recommended by the USP volumetric titration27 with sodium thiosulphate was used for the labelling of iodine present in povidone-iodine solution. To assay for available iodine- 5ml of povidone-iodine solution were placed in a 100ml Erlenmeyer flask. Titrate immediately with 0.1N sodium thiosulphate, adding 3ml of starch paste solution as an indicator until the end point was approached. In addition, CRISON pH meter was used to determine the pH of povidone-iodine solutions.

 

RESULTS:

The results obtained for povidone-iodine 10% topical solution were indicated in table (1). The results in table (1) showed that two of the samples analyzed are outside the range allowed. The percentage of the active ingredient of samples in table (1) were in sequence (116%-100.2%-83.7%-81.2%), (Betadine topical solution-A-B-C) in the first year of validity. In addition, stability study of samples revealed that 50% of samples showed a significant decrease in iodine content in the second year of validity, where the percentage of the active ingredient of samples in table (1) were in sequence (115.8%-100%-76.07%-60.6%), (Betadine topical solution -A-B-C) in the second year of validity. Whereas the iodine content of (Betadine 10% topical solution and sample A) remain approximately stable during the date of validity. The pH values of the local samples solutions were within the range (1.5-6.5) of activity and stability, which were all about the minimal values. Whereas Betadine 10% topical solution showed higher and more appropriate values to skin. In addition, the pH values of samples remain approximately stable during the date of validity.

 


Table 1: Iodine percent (w/v) determined in Povidone-Iodine 10% topical solutions.

Samples

First year of validity

 

Second year of validity

Iodine (w/v)

Free iodine %

SD

RSD

pH

(Mean ± SD)

Iodine (w/v)

Free iodine %

SD

RSD

pH

(Mean ± SD)

Betadine

1.16

116

0.013

0.011

5.3 ± 0.02

1.158

115.8

0.032

0.027

5.4 ± 0.03

A

1.002

100.2

0.1

0.099

2.46 ± 0.03

1

100

0.012

0.012

2.5 ± 0.1

B

0.837

83.7

0.025

0.029

2.2 ± 0.07

0.7607

76.07

0.055

0.073

2.3 ± 0.02

C

0.812

81.2

0.04

0.049

2.95 ± 0.06

0.606

60.6

0.065

0.107

3 ± 0.05

 

Table 2: Iodine percent (w/v) determined in povidone-iodine10%vaginal douche solutions.

samples

First year of validity

 

Second year of validity

Iodine (w/v)

Free iodine %

SD

RSD

pH

(Mean ± SD)

Iodine (w/v)

Free iodine %

SD

RSD

pH

(Mean ± SD)

Betadine

1.03

103.06

0.05

0.019

1.36 ± 0.07

1.015

101.52

0.02

0.091

1.4 ± 0.22

D

0.725

72.5

0.051

0.07

2.2 ± 0.03

0.534

53.4

0.05

0.093

2.3 ± 0.15

E

1.001

100.1

0.13

0.21

5.35 ± 0.2

0.99

99

0.19

0.19

5.5 ± 0.01

F

0.471

47.1

0.033

0.07

1.5± 0.096

0.427

42.7

0.06

0.14

1.49 ± 0.05

 


The results obtained for povidone-iodine 10% vaginal douche were indicated in table (2).The results in table (2) showed that two of the samples analyzed are outside the range allowed. The percentage of the active ingredient of samples in table (2) were in sequence (103.06%-72.5%-100.1%-47.1%), (Betadine vaginal douche-D-E-F) in the first year of validity. In addition, stability study of samples revealed that 50% of samples showed a significant decrease in iodine content in the second year of validity, where the percentage of the active ingredient of samples in table (2) were in sequence (101.52%-53.4%-99%-42.7%), (Betadine vaginal douche-D-E-F). Whereas the iodine content of (Betadine 10% vaginal douche and sample E) remain approximately stable during the date of validity. The pH values of the samples were within the range (1.5-6.5)20 of activity and stability, which were all about the minimal values. In addition, the pH values of samples remain approximately stable during the date of validity.

 

DISCUSSION:

Povidone-iodine solutions 10% must contain between 85-120% of iodine20.The higher level of free iodine was accompanied with increase of inhibition diameter and rapidity of bactericidal effect. According to the results obtained there are some factors affecting stability of povidone-iodine solutions during the date of validity. It was probably that factors that affect the stability of PVP-I solutions were related to errors in the stage of manufacturing and pharmaceutical formula such as existence of some excipients or metal electrodes in the pharmaceutical formulation of povidone-iodine solution which may interact with PVP-I and reduce its concentration or water hardness used in manufacturing, where samples were saved during the study period by room temperature. The results of our study were compared with a study conducted by et al Nidaa Moussa etc28, where the spectral method was used to calibrate PVP-I 10% preparations. The results of our study were closely correlated with the results of Nidaa Moussa, where the percentage of iodine in Betadine 10% topical solution was 116% while it was 115.07% in Nidaa's study. In addition our study was also compared with a study conducted by et al Andrea Lorenzo etc29, where redox titration was used to calibrate PVP-I 10% preparations and the results showed that 50% of samples were out of quality control. Therefore the simple and low cost method used in our study allows us to control most of PVP-I preparations simply without the need to use organic solvents harmful to the environment.

 

CONCLUSION:

It is possible to conclude that 50% of samples (10% topical solution and 10% vaginal douche) PVP-I solutions under quality control of povidone-iodine solution normally used as antiseptic to clean surgical areas do not perform in agreement with USP. It is extremely important for such solutions to fulfil their antiseptic effects efficiently to contain the levels of iodine required.

 

This research intends to carry out periodical control of povidone-iodine solutions. Thus, a simple and low cost method which allows to trace the quality control of product used is suggested. It was observed that there are obvious errors in the manufacture of povidone-iodine solutions, 10% (topical solution and vaginal douche) that affecting efficacy. A strict fulfillment of storage, manufacturing and conservation conditions of povidone-iodine solution is suggested to avoid post operating infections and the consequent re-hospilization of the patient.

 

ACKNOWLEDGEMENT:

The authors would like to acknowledge Shahba Med Company for disinfectants and consultations, Dr Mostafa Jabas in Aleppo University Hospital, Aleppo and Al-Baath University for gifting of raw materials and supporting the research.

 

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Received on 25.04.2019           Modified on 23.05.2019

Accepted on 30.06.2019         © RJPT All right reserved

Research J. Pharm. and Tech. 2019; 12(12): 5963-5966.

DOI: 10.5958/0974-360X.2019.01035.7