Int. J. Drug Res. Tech. 2012, Vol. 2 (5), 407-410                ISSN   2277 - 1506

 

International Journal of Drug Research and Technology

   Available online at http://www.ijdrt.com

Original Research Paper

FORMULATION AND EVALUATION OF ERYTHROMYCIN DENTAL IMPLANTS FOR PERIODONTITIS

Sudeep Kothari*, G. Gnanaranjan and Preeti Kothiyal

Division of Pharmaceutical Sciences, S.G.R.R.I.T.S. Patel Nagar,

Dehradun, Uttarakhand-248001, India

ABSTRACT

Periodontitis is an inflammatory response to the overgrowth of anaerobic organisms in the subgingiva and if unchecked, results in the destruction of the bone and soft tissues supporting the tooth, which results in tooth loss. Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin. Erythromycin has antibacterial activity and is used in the treatment of superficial infections caused by organisms susceptible to Erythromycin. In present work dental implants were prepared by solvent casting technique using glass moulds. Implants were prepared by dissolving Ethyl cellulose alone and with copolymers (HPMC K4M, Sodium Alginate) in chloroform and dichloromethane (1:1) solution, using dibutyl phthalate and PEG400 as plasticizers. These formulated implants were then evaluated for different parameters like uniformity of thickness, uniformity of weight, tensile strength of the films, folding endurance and in vitro drug release.

Keywords: Erythromycin, In Vitro release, Periodontal insert, Controlled release.

INTRODUCTION

Periodontitis is an inflammatory response to the overgrowth of anaerobic organisms in the subgingiva and if unchecked, results in the destruction of the bone and soft tissues supporting the tooth, which results in tooth loss.1,2  As a pathologic condition of the periodontal disease, inflammation of gingival is observed at first. Then periodontal pocket is formed in the gingiva. Thereafter absorption of the alveolar bone progresses and a tooth is loosened. Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin. Erythromycin has antibacterial activity and is used in the treatment of superficial infections caused by organisms susceptible to Erythromycin. Pharmacological studies indicate that erythromycin has short biological half-life of 1.5 hours and eliminated rapidly. Erythromycin is easily inactivated by gastric fluid therefore orally administered formulations are given as enteric-coated.3

Gastrointestinal disturbances, such as diarrhea, nausea, abdominal pain, and vomiting, are very common. Allergic reactions range from urticaria

 to anaphylaxis. Cholestasis, Stevens–Johnson syndrome, and toxic epidermal necrolysis are some other rare side-effects that may occur. Conventional therapy based on scaling, root planning and surgical procedures with adjunction to systemic antibiotics have been proposed. But considering patient non compliance, systemic toxic effects and bacterial resistance a controlled drug delivery system is developed to maintain the drug in the periodontal pocket over a long period of time.

MATERIALS AND METHODS

Erythromycin was obtained as gift sample from Shrishti Biotec Pvt. Ltd., Paonta Sahib (H.P). Hydroxy propyl Methyl Cellulose (HPMC K4M), Sodium Alginate, PEG 400, dibutyl phthalate were obtained

 from CDH (P) Ltd., New Delhi. All other reagents used were of analytical grade.

Preparation of Implants Containing Erythromycin

Dental implants were prepared by solvent casting technique using glass moulds. Formulations were designed as shown in the Table1, in which Ethyl cellulose was taken as the main non biodegradable polymer in combination with different copolymers for each cast films. Films were prepared by dissolving Ethyl cellulose alone and with copolymers (HPMC K4M, Sodium Alginate) in chloroform and dichloromethane (1:1) solution, using dibutyl phthalate and PEG400 as plasticizers. Erythromycin was added in to the polymeric solution and mixed homogenously using magnetic stirrer in a closed beaker. After complete mixing the solution was taken and poured into the clean leveled glass moulds. The solvent was allowed to evaporate slowly by inverting a glass funnel with a cotton plug closed into the stem of the funnel at room temperature for 24 hours. After complete evaporation of solvent, cast films were obtained, which were then cut into pieces of 7×4 mm, wrapped in an aluminum foil and stored in a desiccator at room temperature in a dark place for further evaluation studies.

Table 1: Composition of different Erythromycin dental implants

Ingredients

F1

F2

F3

F4

Drug (mg)

120

120

120

120

Ethyl Cellulose (mg)

1100

1000

1100

1000

HPMC K4M(mg)

100

200

-

-

Sodium Alginate

-

-

100

200

Dibutyl phthalate (ml)

 

0.3

0.3

0.3

0.3

 PEG 400 (ml)

0.1

0.1

0.1

0.1

 

Evaluation of the Prepared Formulations3

Uniformity of thickness

Five  films  were  taken  from  each  batch  and  their  individual  thickness  was measured using micrometer screw gauge.

Uniformity of weight

 Five  films  were  taken  from  each  batch  and  their  individual  weights  were determined by using electronic balance.

Uniformity of drug content

 Five films were taken from each batch and individually dissolved in 5 ml of pH 6.8 phosphate buffer in a beaker and filtered it. 0.1 ml of the filtered solution was diluted to 10 ml with pH 6.8 phosphate buffer in a 10 ml volumetric flask. Three reading were taken using UV spectrophotometer at 232 nm.

Tensile strength of the films

Tensile strength of the films was determined by Universal strength testing machine. It consists of two load cell grips, the lower one is fixed and upper one is movable. The test film of specific size (4 × 1 cm2) was fixed between these cell grips and force was gradually applied till the film breaks. The tensile strength of the film was taken directly from the dial reading in kilograms.

Folding endurance

The folding endurance of the films was determined by repeatedly folding the film at the same place up to 300 times till it broke or folded, which is considered satisfactory to reveal good film properties. This test was carried out on all the films.5

In vitro drug release

Static dissolution method reported in the literature was adopted. Films of known weight and dimensions (size of 7×4 mm2) were placed separately into small test tubes containing 1 ml of pH 6.8 phosphate buffer. The test tubes were sealed with aluminum foil and kept at 37°C for 24 hours.  The buffer was drained off and replaced with fresh 1 ml of pH 6.8 phosphate buffer after 24 hours. The concentration of drug in the buffer was measured at 232 nm. The procedure was repeated for 10 days.6

RESULTS

In the present study, efforts were taken for designing and evaluating Erythromycin dental implant. Formulations were designed in which Ethyl cellulose was taken as the main non biodegradable polymer in combination with different copolymers (HPMC K4M, Sodium Alginate) for each cast films. Films were prepared by dissolving Ethyl cellulose alone and with copolymers (HPMC K4M, Sodium Alginate) in chloroform and dichloromethane (1:1) solution, using dibutyl phthalate and PEG400 as plasticizers.

The physicochemical evaluation data presented in table2. The prepared implants were evaluated for the thickness using micrometer screw gauge. The average of three readings were taken; the mean thickness and standard deviation were calculated. The low standard deviation of the measured thickness of all the 4 formulations may indicate uniform distribution of drug and excipients in prepared implants.

Table 2: Physicochemical characteristics of dental implants containing Erythromycin

Implants

 

Thickness (mm) ± SD

n = 3

Weight

(mg) ± SD

n = 3

Drug Content (%) ± SD

n = 3

Tensile Strength

(Kg) ± SD

n = 3

Folding Endurance

F1

0.412 ± 0.028

10.2 ± 0.008

94.1 ± 0.026

1.56 ± 0.006

228

F2

0.446 ± 0.032

10.6 ± 0.036

97.8 ± 0.045

1.75 ± 0.052

212

F3

0.422 ± 0.041

9.9 ± 0.024

89.4 ± 0.032

1.68 ± 0.062

199

F4

0.401 ± 0.060

10.3 ± 0.03

96.3 ± 0.053

1.81 ± 0.02

205

 

It was found to be in the range of 0.401 ± 0.060 to 0.446 ± 0.032. The weight of all the implants were found to be in the range of 9.9 ± 0.024 to 10.6 ± 0.036. The uniformity of weight of the film indicates good distribution of the drug, polymer and plasticizer.

Table 3: In vitro release profile of Erythromycin implants

Time

(Days)

% Drug Release

F1

F2

F3

F4

0

0

0

0

0

1

32.16

30.38

37.8

33.22

2

64.42

61.52

68.46

66.96

3

71.59

74.18

77.19

80.32

4

78.94

81.91

85.41

89.27

5

86.2

89.62

93.51

94.36

6

94.91

93.31

99.75

98.3

7

99.88

99.32

-

-

For various formulations, the % drug content was found to vary between 89.4 ± 0.032 % to % 97.8 ± 0.045. Tensile strength of the implants were found in the range of 1.56 ± 0.006 to 1.81 ± 0.02. The folding endurance was measured for all formulations manually. It was found in between 199 to 228. The release profile of the formulations is shown in the figure 1. The periodontal implants prepared with HPMC K4M released the drug completely in 7 days.

 

 

 

            

 

 

Figure 1: In vitro release profile of Erythromycin implants

 

The release of the drug from the formulation F1and F2 was found to be 99.88 % and 99.32 release in 6 days. The release of drug from formulations F3 and F4 was found to be 99.75% and 98.3% at the end of 6 days respectively.

CONCLUSION

Dental implants containing Erythromycin were prepared. In vitro characterization studies revealed that erythromycin can be incorporated in a slow release device for the treatment of periodontitis. The formulations (F1 and F2) containing Erythromycin , ethyl cellulose and HPMC K4M as polymer satisfied required pharmaceutical characteristics of implants and was found promising. The Erythromycin dental implant would be able to offer benefits such as increasing residence time, prolonging drug release, reducing frequency of administration, and there by may help to improve patient compliance.

REFERENCES           

1.      Sunil, Agarwal; Venkatesh, M and Udupa, N (2004), “Controlled drug delivery systems for periodontitis”, The Pharm. Review, 61-82.

2.      Pandit, JK (2004), “Targeted Devices For Periodontal Disease”, Ed. by N K Jain, Controlled and novel drug delivery, CBS Publishers and distributors, Vol. 2, 130.

3.      http//en.wikepida.org.wiki/erythromycin, Accessed 2009.

4.      Knaig, JL and Goodmann, H (1962), J Pharma Sci., 5, 77.

5.      Khanna, R; Agrawal, SP and Ahuja, A (1997), “Preparation and evaluation of buccal films of clotrimazole for oral Candida infections”, Indian J Pharm Sci., 59, 299-305.

6.      Mastiholimath, VS; Dandagi, PM; Gadad, AP; Patil, MB; Manvi, FV and Chandur, VK (2006), “Formulation and evaluation of ornidazole dental implants for periodontitis”, Indian J. Pharm sci., 68(1), 6871.