A Novel Polymeric Gel for Periodontitis

Various synthetic chemical agents have been evaluated over the years with respect
to their antimicrobial effect in oral cavity, however, all are associated with
various side effects and short residual time that prohibitis regular long term
use. Therefore in current research, attempts are being made to prolong residual
time and increase patient compliance by using sustained release drug delivery
system especially bioadhesive in nature without any side effects.

Present study included formulation of targeted Bioadhesive dental gel (injectable
system) containing Paan Oil (Piper betle L.), Tulsi Oil
(Ocimum sanctum L.) and Neem extract (Azadirachta indica
A. Juss.) . A clinical study was conducted to evaluate the efficacy
of a herbal polymeric gel (ingestable system) against Gingivitis and Dental
plaque. The results of the study suggested that this herbal bioadhesive gel
has significantly (p < 0.01) reduced the Gingival index and plaque index.

indica A. Juss., gingival index, plaque index. 

Introduction

            Dental diseases are recognized as a major public health problem, in civilized society. The prevalence of tooth decay, various dental diseases, and tooth loss are so great that a permanent healthy oral system in the body is almost impossible. Dental diseases are studied by oral examination of a particular section of the population and the incidence measured by the number of new cases occurring in a given period of time. Dental diseases attacks almost the entire population. In UK it is estimated that 99% of children under 12 years suffer from dental caries. Only two out of ten 5-year old have sound teeth according to the General Dental Council. In India also this dental disease attack almost the entire population.

Paan (piper betle L.) has been used in Indian subcontinent for thousands of years. It is intimately linked with the history, religion and cultural life of people of Indian subcontinent. Piper betle has strong antimicrobial activity towards all the food-borne pathogens. Betle has also showed better activity in aches and pains, especially nervous in origin. Betle has showed good effect in the treatment of gout, arthritis (pain and inflammation), orchitis. In ancient India, preparation and application of manure of the essential oil of piper betle has shown better effect in dental complaints.

Ocimum sanctum L. (Tulsi), queen of herbs, has been used in Indian
subcontinent for thousands of years as a household remedy. The analgesic and
anti-inflammatory activity of Tulsi (O.sanctum) has been evaluated (Singh S,
College of Pharmacy, Pushp Vihar). Tulsi (O.sanctum) has also showed better
activity against the enteric pathogens (Geeta, Vasudevan DM, Kandlaya R, Deepa
S, Ballal M, Department of Microbiology, Manipal Institute of Medical 
Sciences).

The analgesic activity of Ociumum sanctum (O.sanctum) is exerted both centrally as well as peripherally and involved an interplay between various neuro transmitter systems (Khanna and Bhatia, J.).

Azadirachta indica has been used in India and South Asia for thousands of years as the preferred tool for maintaining healthy teeth and gums. Brushing with Azadirachta indica twigs and chewing Azadirachta indica leaves and seeds after a meal has been the traditional dental care practice in this area. With available modern preparations, many people are now using commercial products that contain the same basic Azadirachta indica components. The antibacterial activity of Azadirachta indica has been evaluated and known from ancient times (Chaurasia and Jain, 1978 ; Chawla et al. 1994). Azadirachta indica has been considered to have various activity such as astringent, antiseptic, insecticidal, antiulcer and for cleaning of teeth in pyrrohoea and other dental diseases. Other than this, Azadirachta indica leaf extract showed superior antiviral and antihyperglycemic activity in vitro and in vivo on animal (Chattopadhyay, 1999 ; Parida et al., 2002). Leaves of Azadirachta indica has been in treatment of gingivitis and periodontis (Husain et al., 1992). Azadirachta indica has also showed better efficacy in the treatment of oral infection and plaque growth inhibition in treating periodontal disorders (Patel and Venkatakrishna, 1988). Azadirachta indica had shown good in vitro broad range antibacterial activity (Rao et al., 1986).

It appears to be a general opinion that by and large, herbals being natural products, are inherently safer  than the potent synthetic drugs which often produce undesirable side effects.

The present study was planned to develop and formulate a mucoadhesive biodegradable
gel in such a way that the beneficial effects are utilized to the maximum extent
and at the same time formulation problems such as degradation, bitter taste,
storage, dosage accuracy, incompatibility etc. are eliminated or minimized.
Qualities like prolonged release effects, quick onset, patient compliance, cost
effectiveness are the main targets of proposed work.

{mospagebreak title= Material and Methods }

Material and Methods

Biodegradable polymer carbopol 974 P (0.15%) for the preparation of the gel was procured from Noveon Inc., Cleveland, USA. Herbs like Ocimum sanctum L. (O.S.), Piper betle L., Azadirachta indica A. Juss. collected from the Botanical Garden of NBRI, Lucknow. Essential oil from O.S. and piper betle was collected after a few hours of hydrodistillation by Clevenger's apparatus.

Mature leaves and bark of three different Azadirachta indica trees were collected from Biomass Research Centre, Banthara of National Botanical Research Institute, Lucknow and LLRM Medical College, Meerut, India and dried under controlled parameters. The botanical identification of the leaves were done by        Dr. AKS Rawat, Senior Scientist, Head Deptt. of Pharmacognosy, NBRI, Lucknow, India.

Extract was prepared by treating 95% ethanol using kinematica polytran homogenizer (Kinematica AG, PT 6000). Ethanol extract thus obtained was filtered and concentrated up to dryness by Rotory Evaporator (Laborota 4000, Heidolph) under reduced pressure. Concentrated ethanolic extract was dissolved in propylene glycol, which was used as solvent and extract of 5% concentration was prepared.

The polymer carbopol 974 P (0.15%) was dispersed in aqueous phase containing 5% alcoholic extract of Azadirachta indica. The dispersion was then stirred for 1 hour using magnetic stirring bar at room temperature, eventually 1 M NaOH was added to neutralize the sample to pH 7.4. The gel was then allowed to equilibrate for at least 16 hours at room temperature after incorporating all essential oil (Betle oil, Oscimum oil). The pH of the gel was again measured and when needed adjusted to pH 7.4. Sorbitol 20% of sweetner and amaranth red colour to fulfill the organoleptic  properties of the final formulation.

Rheological measurement was conducted by measuring viscosity by Brookefield synchro electric viscometer. The spindle No. 4 was employed at different rpm and dial reading measured.

Stability study was conducted to evaluate the consistency of the Gel over a period of 2 months by keeping the formulation at different conditions (4ºC, 7ºC and room temperature) and measured the viscosity of the Gel formulation at regular interval.

The study indicated that the viscosity of the carbopol 974P Gel did not change
significantly throughout the stability period under the specified conditions.

{mospagebreak title= Results and Discussion}

Clinical evaluation for gingivitis :

Clinical evaluation of the carbopol herbal Gel on selected subjects with different grade of gingivitis was carried out with the help of a dentist in the Subharti Dental College, Meerut and at Department of Dental Surgery, LLRM Medical College, Meerut.

Gingival health status was recorded by Loe & Silness (1963)gingival index :

0                   
Normal gingival

1                   Mild
inflammation, slight change in colour, slight edema, no bleeding on palpation.

2                    Moderate
inflammation, redness, edema, and glazing bleeding on probing.

3                   
Severe inflammation marked redness and edema, ulceration, tendency to spontaneous
bleeding.

Before starting the clinical trial gingivitis health status was recorded. After that gel was applied on lower anterior inflamed gingiva and the Gel was given to subjects in a glass container, which was sufficient for fourteen days twice daily application. The subjects were advised to keep gel preparation at a cool and safe place and to keep container tightly closed after use.

Patients were advised to apply given gel once in the morning and second time in the evening with the help of cotton pellets for one week. During this period, patients were advised to continue their usual prophylactic procedure. After one week, gingivitis scores were recorded on the proforma by Loe and Silness method. Subjects were advised to apply the same gel for another one week. After second week, gingivitis was again recorded by the same method.

Table A shows that the effect of poly herbal carbapol gel on different grade of gingivitis for two weeks on all 10 subjects. The data indicated no reduction of gingival score on first week with gel formulation, but at the end of second week, data indicated 25.61% reduction in gingival score with a range of 6.01% to 46.58% which was statistically highly significant (p < 0.001).

Clinical evaluation for plaque :

The clinical evaluation of poly herbal carbapol gel assessed against dental plaque. Particulars of the individual, baseline plaque score and experimental plaque score were recorded on a specially designed proforma.

Plaque accumulation was recorded using Turesky-Gilmore-Glickman modification (1970) of Quingley-Hein Plaque Index System as follows :

0                        No
plaque

1                       
Separate flecks of plaque at cervical margin of tooth.

2                       
A thin continuing band of plaque (up to 1 mm) at cervical margin of tooth.

3                       
A band of plaque wider than 1 mm but covering less than one third of the crown
of the tooth.

4                        
Plaque covering at least one third but less than two third of the crown of the
tooth.

5                        
Plaque covering two third or more of the crown of the tooth. 

Table-B shows that segmentwise analysis, total baseline plaque score of upper
segment was found to range from, 2.74 to 3.69 with mean plaque score of 3.233
and experimental plaque score of upper segment ranged from 0.90 to 1.53. The mean
plaque score was found to be 1.208 and total plaque score reduction was 2.025
per surface, which was statistically highly significant (p < 0.001).

Analysis of lower segment showed that total baseline plaque score varied from
1.85 to 3.72 with mean plaque score of 2.814 and experimental plaque score ranged
from 0.69 to 1.57. The mean plaque score was found to be 1.705, hence, total
plaque score reduction was 1.709 per surface, which was statistically highly
significant (p < 0.001).

Conclusion

The present study confirms that use of poly herbal mucoadhesive biodegradable gel formulation can effectively treat dental plaque for longer duration without any adverse side effects and removal problem (as in case of Non biodegradable base). 

We are thankful to Prof. Shailendra Saraf, Dean, Faculty of Pharmacy,
Northern India  Engg. Cllege, Lucknow, Asst. Prof. R.S. Verma, Head,
Department of Pharamcy, Prof. P.K. Maheshwari, Head, Department of Periodontics
and Asstt. Prof. S.K.Bajpai, Department of Statistics (S.P.M.), L.L.R.M.
Medical College, Meerut, India for their immense support in successfully conducting
the clinical studies and their statistical calculations.

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Table A :     Baseline gingivial score of 10
subjects tested with herbal carbapol 974 Gel formulation.

First day gingivitis served as baseline gingivitis.

Experimental gingivitis after 15 days application of poly herbal carbopol
974 P gel formulation

Table B : Effect of herbal carbapol 974 Gel formulation on dental plaque
score in upper and lower segment of 10 subjects.

Three days old plaque served as baseline plaque.

Experimental plaque after 3 days application of poly herbal carbopol
974 P gel formulations

{mospagebreak title= About the Authors}

 Vibhu Sahani^(a), Shubhini Saraf*^(b)
and A.K.S. Rawat^(c).

(a)      Department of Pharmacy, L.L.R.M. Medical College,
Meerut-250004 U.P. (INDIA)  e-mail : vibhusahani@rediffmail.com

(b)     Faculty of Pharmacy , BBD National Institute
of Technology & Management, Lucknow U.P. (INDIA)

(c)      Department of Pharmacognosy, National Botanical
Research Institute, Lucknow U.P. (INDIA)

* Corresponding  Author :

Dr. Shubhini Saraf

Head, Faculty of Pharmacy,  B.B.D. National Institute of Technology 
& Management

Chinhut, Akhlesh Das Nagar, Lucknow, U.P. (INDIA)

Ph. 0522-2356855, Mob. 9415488410

E-Mail : sarafs@satyam.net.in