INTRODUCTION:

The gel is the state that remains between liquid and firm stage. The solid component consists of a three-dimensional network of interlinked molecules that immobilizes the liquid phase.¹The in-situ gel effect is focused on drug formulation fluid solution and transformed into a semi-solid mucoadhesive². Also, its mucoadhesive property prevents it from getting washed by salivary fluid inside the buccal cavity. In past few years, there has been a growing concern in water-soluble polymers that can shape gels after introduction to the delivery site. Compared to other polymers, these so-called in-situ gelling polymers are extremely advantageous because, unlike very powerful gels, they can be readily transferred to the drug absorption location in liquid phase. Hydrogels are the polymeric materials with three-dimensional networks that have received considerable exposure in biomedical areas as transports of drugs, proteins, cells and others because of their excellent biocompatibility.⁴

Because of the present busy life system even in common man dental diseases are most wide spread chronic disorders.^5-6Periodontal disease refers to a group of problems that arise in the sulcus, the crevice between the tooth and gum. The common causative organisms include Actinobacillus actinomcetemcomitans as a pathogen responsible for juvenile periodontitis, and Staphylococcus aureus are responsible for adult periodontal disease.⁷

Site specific therapy for periodontitis has three potential advantages, it decreases drug doses, increased drug concentration at the site of infection and reduce systemic side effects such as gastrointestinal distress.⁸Periodontal disease treatment with a localized drug delivery system aims at delivering therapeutic agent at enough level inside the periodontal pocket and at the same time minimizing the side effects associated with systemic drug administration. Thus, it increases patient compliance.⁹

In-situ gel drug distribution approaches:

There are mainly four widely specified methods used to trigger the development of biomaterials in-situ gel: Physiological stimuli, physical modifications in biomaterials and chemical reactions.

I. Formation on the basis of physiological stimuli:

a) Thermally trigged system:

There are three primary approaches in the engineering of a thermo-responsive sol-gel polymer scheme. For convenience, temperature-sensitive hydrogels are classified into negative thermo-sensitive, positive thermo-sensitive, and thermally reversible gels.^10,11

a) pH triggered systems:

Another in-situ gel development dependent on physiological stimuli is that gel formation is caused by modifications in pH. All pH-sensitive polymers comprise of acidic or basic groups that either accept or release protons in reaction to ambient pH modifications.¹²

II. In-situ formation based on physical mechanism:

a) Swelling:

When material absorbs water from the surrounding atmosphere and expands to create desired space, in-situ development may also happen. One such material is myverol 18-99 (mono-oleate glycerol), which is a polar lipid that swells in water to create crystalline phase formations of lyotropic liquid.¹³

b) Diffusion:

This technique includes the diffusion of the solvent from the polymer fluid into the nearby tissue, resulting in precipitation or polymer matrix solidification.¹⁴

III. Formation on the basis of chemical reactions:

In this technique, the chemical reactions resulting in in-situ gelation may require precipitation of inorganic solids from supersaturated ionic solutions, enzymatic procedures, and photo-initiated procedures.

a) Ionic crosslinking:

In presence of various ions, Polymers may undergo phase transition. Some polysaccharides fell into the category of ion-sensitive materials, while k-carrageenan produces rigid, brittle gels in response to tiny amounts of K⁺, i-carrageenan builds elastic gels primarily in the existence of Ca^{2 +}.^15,16

b) Enzymatic cross-linking:

In-situ development catalyzed by natural enzymes has not been extensively researched, but appears to have certain benefits over chemical and photochemical methods. Cationic pH-sensitive polymers that contain immobilized insulin and glucose oxidase may expand in reaction to blood glucose levels that release pulsating insulin.¹⁷

c) Photo-polymerisation:

Photo-polymerization is widely used to form biomaterials in-situ. Reactive macromer or monomer or initiator solution and implementation of electromagnetic radiation used to create gel can be introduced into a tissue location. Acrylate or similar polymerizable functional groups are typically used on the individual monomers and macromers as the polymerizable groups because they undergo rapid photo-polymerization in the presence of an appropriate photo initiator.^18,19

Anatomy and physiology of periodontal disease:

Periodontitis:

Periodontitis is used to define certain diseases which have the effect of gum, ligaments, alveolar tissue and dental tissue degeneration and inflammation.^20,²¹While bacteria are the main cause of periodontal disease, periodontal disease alone cannot be caused by the occurrence of microbial pathogenic variables.^22,21

MATERIALS AND METHODS:

Selection and procurement of drugs and excipients^23-25

Table no. 1: Materials procurement.

Sr.No	Ingredients	Supplier	Company
1.	Ofloxacin	Rajesh chemicals, Mumbai.	Ozone international, Mumbai.
2.	Poloxamer 407	Rajesh chemicals, Mumbai.	Ozone international, Mumbai.
3.	Gellan gum	Marine hydrocolloids, Kochi Kerala.	Marine hydrocolloids, Kochi Kerala.
4.	Methyl paraben	Rajesh chemicals, Mumbai.	Loba chemie, Mumbai.
5.	Propyl paraben	Rajesh chemicals, Mumbai.	Loba chemie, Mumbai.
6.	Sodium citrate	Rajesh chemicals, Mumbai.	Loba chemie, Mumbai.
7.	Monopotassium phosphate	Rajesh chemicals, Mumbai.	Ozone international, Mumbai.
8.	Disodium phosphate	Rajesh chemicals, Mumbai.	Loba chemie, Mumbai.

Table no. 2: List of instruments.

Sr. No	Instruments	Manufacturer
1.	Electronic balance	Shimadzu
2.	Sonicator	Shimadzu
3.	UV spectrophotometer	Jasco(V-630)
4.	Magnetic stirrer	Remi Instrument Ltd.
5.	Viscometer	Brookfield LVDE-E
6.	Franz diffusion cell apparatus	Shimadzu
7.	IR spectrophotometer	Shimadzu japan (IR200)

Methods:

1. Preformulation Study:

Preformulation experiments such as melting point determination and compatibility tests have been performed as per the procedure. FT-IR compatibility study was conducted to detect feasible interactions between drug and polymer used as per standard procedure.²⁶

2. Identification of pure drug:

Is done by performing the solubility study and melting point determination.

Drug and excipient compatibility study:

FT-IR spectroscopy:

The spectral measurements of the Fourier transform infrared (FT-IR) were recorded using an IR spectrophotometer at ambient temperature. The spectrum of drug ofloxacin was evaluated for drug quality. FT-IR was also used as a parameter to determine the incompatibility of any drug-polymer. Mixtures of drug- polymers (ofloxacin, poloxamer 407) were prepared in 1:1 ratio and analyzed by FT-IR spectroscopy.^27-34

3. Determination of UV and λ max of ofloxacin:

Standard calibration curve of ofloxacin:

10 mg of ofloxacin dissolved in 100 ml mixture of phosphate buffer (pH 6.8) to obtain concentrations ranging 5, 10, 15, 20 and 20 µg/ml respectively. The absorbance of solution was measured at 295 nm using UV Visible Spectrophotometer and the results were recorded. The graph of calibration was plotted as x-axis concentration and y-axis absorption.^35,36

4. Characterization of poloxamer 407:

a) Solubility determination: Poloxamer 407 solubility has been verified in distilled water.

b) Viscosity determination: Viscosity was evaluated using brookfield viscometer 3 times w/v poloxamer 407 alternative in distilled water.

c) pH determination: Digital pH meter determines pH.³²

5. Characterization of gellan gum:

a) Solubility determination: Solubility of gellan gum was checked in cold distilled water.

b) Viscosity determination: By using brookfield viscometer 3 % w/v gellan gum solution in hot distilled water.

c) pH determination: Digital pH meter determines pH.³²

6. Formulation of in-situ gel of ofloxacin:

Thermo reversible gels of ofloxacin were prepared using cold method. In-situ gels were prepared using thermosensitive polymer poloxamer 407 and mucoadhesive polymer carbopol 934. The poloxamer 407 vehicles used throughout this study were composed of 18 % w/v of poloxamer 407 until a clear solution was obtained. Poloxamer 407 was slowly added in cold water with continuous agitation and the formed mixtures were stored overnight at 4 ⁰C. Carbopol 934 was also kept overnight to allow sufficient swelling. Slowly added the carbopol solution to poloxamer solution with continuous agitation. To the above mixture added specified quantity of drug and mixed well. The mixtures were kept overnight at 4 ⁰C to effect complete hydration.³⁸ The compositions of prepared formulations were shown in Table 1.

Evaluation of Formulations:

a) pH of the gel:

pH of formulation was determined by pH meter.

b) Viscosity measurement:

The viscosity reading was determined by using electronic viscometer (Brookfield LVDV-E). The in-situ gel formulation was taken in a beaker and maintained at room temperature. The measurements were carried out using spindle no. 62 at the speed of 50rpm in the sample, the viscosity was measured at 10 min.³⁷

c) In-vitro gelling capacity (Gel strength):

To study the in-vitro gelling capacity of prepared formulations, simulated saliva is used. 2 ml of simulated saliva was placed in a 15 ml borosilicate glass test tube and maintained at 37± 2 ⁰C. 1ml of formulation to be evaluated was added with a 1 ml pipette. The formulation was added in such a way that places the pipette at the surface of fluid in test tube and was released slowly. As the formulation comes in contact with the simulated saliva it was immediately converted to a stiff gel like structure. The gelling capacity was evaluated on the basis of stiffness of formed gel and time it remains as such. The in-vitro gelling capacity was given three grades (+) gelation after few minutes, dispersed rapidly, (++) gelation immediate, remains for few hours and (+++) gelation immediate, remains for an extended period.

Syringeability:

All ready formulations were transmitted to an identical 5 ml plastic syringe positioned at a steady quantity (1 ml) with 21 gauge needle. The solutions that were easily passed from the syringe were called passes and difficult to pass were called failures.³⁹

e) Determination of drug content:

The formulation was thoroughly stirred for 2–3 min. 1 ml of the formulation was taken to a 50ml volumetric flask with a pipette. 25 ml of pH 6.8-simulated saliva was introduced. With the help of a glass rod, the formed gel was totally broken, followed by strong shaking until the formed gel was fully dispersed to provide a clear solution. The final volume was adjusted with simulated saliva to 50 ml. The solution obtained was filtered through Whatman filter paper. 1 ml of this solution was transferred to a 10 ml volumetric flask and the volume was adjusted with simulated saliva and the drug concentration was determined at 295 nm using UV-Visible Spectrophotometer.³⁸

f) Gelation studies (Gelation time/temperature):

1. Gelation time:

2 ml of the formulation was put in 15 ml borosilicate glass test tube for measuring gelation time. This test tube was put in water bath kept at 37±2 °C. Gelation time was observed when the test tube was inverted.

2. Gelation Temperature:

10 ml of the sample solution as well as a magnetic bead were placed in a 30 ml transparent vial in a digital water bath at low temperature. In the sample setting, a thermometer was put. The solution was heated with the continuous stirring at lower rpm at a rate of 1°C/min. The temperature was determined as the temperature of the gelation at which the magnetic bead stopped moving due to gelation.⁴⁰

g) In-vitro % DR studies:

The study of drug release in vitro was performed using franz diffusion apparatus using Phosphate buffer pH 6. The receptor chamber was loaded with a dissolved medium of 20 ml. The pretreated egg membrane was mounted on the chamber of the donor. In the donor chamber, 1ml of formulation was placed. The entire assembly of diffusion was then placed in the magnetic stirrer. 2 ml of aliquots were thoroughly removed from the franz diffusion device at predetermined period intervals and evaluated spectrophotometrically at 295 nm. The medium was immediately replaced by the same volume of fresh phosphate buffer maintained at 37± 2 °C.^41-43

h) Stability studies:

The stability studies were carried out to determine the physical and chemical stabilities of prepared formulations. The optimized formulation was kept in air tight container covered with aluminium foil at refrigerated temperature, 4 ⁰C for a period of 3 months. The formulation was evaluated visually and for its gelation behaviour, viscosity, drug content and in vitro drug release.

I) In-vitro antibacterial study of optimized formulation:

The antimicrobial efficiency of optimized formulation was studied using microorganisms Staphylococcus aureus and Escherichia coli by agar well diffusion method. Nutrient agar medium was prepared and sterilized by autoclaving and inoculated with 0.1 ml of fresh overnight nutrient broth culture of each bacterium in separate flasks and were poured into sterile Petri plates. Allow them to solidify. After solidification cups were made on each plates with the help of sterile borer of 6 mm diameter. Poured appropriate amount of formulation and pure drug solution to the cups and incubated for 24 hrs. at 37 ⁰C. The diameters of the zones of inhibition were measured and compared with that of standard.³⁸

RESULT AND DISCUSSION:

1) Preformulation studies:

From the preformulation studies conducted, melting point of pure drug ofloxacin was found to be 254±0.42 ⁰C. The absorption maxima of ofloxacin were found to be 293nm.

2) Surface pH:

The pHs of all formulations were found within range 6.0- 7.2 and this pH range is suitable for insertion into periodontal pocket without any irritation.

3) Viscosity:

All the prepared formulations should have sufficient viscosity to be applied in the periodontium so that it will remain in the periodontal cavity to have sustained release of drug. The viscosity of formulations ranges from 281±3.60 - 743±11.37 cps.

4) Syringeability:

Results revealed that all formulation from F1 to F7 were syringeable at cold temperature.

5) Gelation temperature:

The sol- gel transition temperature of formulations is noted to find out their ability to form in-situ gel inside the oral cavity. The gelation temperature was found in the range of 33±1⁰C – 36.33±0.57⁰C.

6) Gelling time:

The time required for the solution to form gel is recorded in seconds. The gelling time was found to increase with increasing concentration of carbopol. The gelation time was found to be in the range 33±1.52 - 102±2.64 seconds.

7) In-vitro gelling capacity:

All the formulations except F6 and F7 showed immediate gelation and remained for few hours when come in contact with simulated saliva maintained at 37±2 ⁰C. Formulations F6 and F7 showed gelation after few minutes and were dispersed rapidly.

8) Drug content:

Drug content of the formulations were estimated using UV- visible spectrometer. The drug content was found in the range of 82.98±0.44 – 95.92±0.13%. The formulations exhibit fairly uniform drug content. Formulation F4 showed maximum drug content of 95.92 %.

9) In-vitro drug release:

The release studies of prepared in situ gelling systems were carried out up to 8 hrs using phosphate buffer (pH 6.8) and the cumulative percentage drug released was calculated. The release rate was found to increase with increasing concentration of carbopol 934 up to an optimum concentration and then found to be decreasing. Formulation F4 showed maximum drug release at the end of 8 hrs. The results of evaluation studies conducted were given in table 2 and 3. From the evaluation studies conducted on the prepared formulations one formulation was selected as the best formulation. Formulation F4 composed of 18 % w/v poloxamer and 0.2 % carbopol was selected as the optimized formulation. It has a gelation temperature of 36.33±0.57 ⁰C, gelling time of 67±1.52 sec and has drug content 95.92±0.13 %. The viscosity of F4 was found to be 527±4.58 and it showed cumulative drug release of 72.59 % at the end of 8 hrs. Further studies including drug release kinetics, in-vitro antibacterial studies and stability studies were conducted on formulation F4.

10) In-vitro antibacterial study:

The in-vitro antibacterial activity of optimized formulation (F4) against gram positive Staphylococcus aureus and gram negative Escherichia coli were carried out using test and standard preparations. The standard was pure drug of ofloxacin in distilled water. The study was carried out for 24 hrs using well diffusion technique. The antibacterial activity of formulation was confirmed by the formation of zone of inhibition of microbial growth around the well. Measured the zone of inhibition against each organisms and compared it with the standard. The zone of inhibition of test sample was similar to that of standard for both gram positive and gram negative organisms. This indicates that the prepared in-situ gel formulation has good antibacterial activity against Staphylococcus aureus and Escherichia coli. The test sample and standard sample shows a zone of inhibition of 52 mm and 45 mm for E. coli and 78 mm and 68 mm for Staphylococcus aureus respectively.

11) Stability studies:

The optimized in-situ gel formulation F4 was selected for the stability study and is stored at refrigerated temperature (4 ⁰C) for three months. The formulation showed good stability with no significant changes in the appearance, viscosity, gelation behavior, drug content and in-vitro drug release. From the stability study it was confirmed that the optimized formulation is stable at its storage temperature.⁴⁴

Table 3: Composition of in situ periodontal gel.

Sr. No	Formulation code	Poloxamer 407 (%w/v)	Carbopol 934 (%)	Drug (mg)	Distilled water upto (ml)
1	F1	18	0.05	100	20
2	F2	18	0.1	100	20
3	F3	18	0.15	100	20
4	F4	18	0.2	100	20
5	F5	18	0.25	100	20
6	F6	18	0.3	100	20
7	F7	18	0.35	100	20

Table 4. Gelation temperature and gelling time of formulations.

Sr. No	Formulation code	Gelation temperature (⁰C)	Gelling time (sec)
1	F1	34.33±0.57	33±1.52
2	F2	34±1	46.33±1.15
3	F3	33.66±0.57	59.66±1.52
4	F4	36.33±0.57	67±1.52
5	F5	35.33±0.57	76.33±1.52
6	F6	34±1	93±3.10
7	F7	33±1	102±2.64

values are mean ± sd, n=3

CONCLUSION:

The limitation of systemic therapy with antibiotics have evoked an interest in the development of in-situ periodontal gel containing ofloxacin whose flowing nature provides ease of administration before application and it's conversion into viscoelastic gel at physiological environment provides the sustained release of the drug for the required duration. The results indicate that the formulation of periodontal gel of Ofloxacin containing Poloxamer 407 and Carbopol 934 could be used as a potential drug delivery system to deliver the drug to periodontal pocket.

REFERENCES:

1. Nitin Gaikwad, Abhishek Pujari, Indrajeet Mane, Ganesh Vambhurkar, Pravin Honmane. Formulation and Evaluation of Hair gel containing Unani medicine. Asian Journal of Pharmaceutical Analysis. 2018; 8: 129-136.

2. Saudagar R. B., Sarika V. Khandbahale. In-situ Nasal Gel – A Review. Asian Journal of Research in Pharmaceutical Sciences. 2017; 7: 23-32.

3. Bajpai Vibha. In-situ gel nasal drug delivery system-A Review. International Journal of Pharmaceutical Sciences. 2014; 4: 577-80.

4. Aikawa K. Drug release from pH-response Polyvinylacetal diethyl aminoacetate hydrogel and application to nasal delivery. International Journal of Pharmacy. 1998; 168: 181-8.

5. Akshay Yadav, Shrinivas Mohite, Chandrakant Magdum. Preparation and Evaluation of Antibacterial Herbal Mouthwash against Oral Pathogens. 2020; 10: 149-152.

6. Bhardwaj TR, Kanwar M. Natural gums and modified natural gums as sustained release carriers. Drug Development and Industrial Pharmacy. 2000; 26: 1025-38.

7. Himanshu Bhusan Samal, Itishree Jogamaya Das, Niranjan Patta, P. N. Murthy. Design and Development of Dental Film Containing Aloe Vera for the treatment of Human Periodontal Diseases. Asian Journal of Pharmacy and Technology. 2015; 5: 273-280.

8. Chand P, Kothiyal P. In situ gel; Review. Indian Journal of Pharmaceutical and Biological Research. 2016; 4(2)11-19.

9. Chenite A, Chaput C. Novel injectable solution of chitosan from biodegradable gels in situ. Biomaterials. 2000; 21: 2155-61.

10. Inayathulla, Prakash Goudanavar, Ankit Acharya. Development and Evaluation of in-situ gel containing Linezolid and Diclofenac Sodium in the treatment of Periodontitis. Asian Journal of Pharmacy and Technology. 2020; 10: 20-26

11. Kant A, Reddy S. In situ gelling system- an overview. Pharmacologyonline 2011; 2: 28-44.

12. Kashyap N. Design and evaluation of biodegradable, biosensitive in situ gelling systems for pulsatile delivery of insulin. Biomaterials. 2007; 28: 2051-60.

13. Kumar S, Himmelstein K. Modification of in situ gel behaviour of carbopol solutions by hydroxypropylmethylcellulose. Journal of Pharmaceutical Sciences. 1995; 84:344-8.

14. Miyazaki S. In situ gelling gellan formulations as vehicles for oral drug delivery. Journal of Controlled Release. 1999; 60: 287-95.

15. Miyazaki S. In situ gelling xyloglucan formulations for sustained release ocular delivery of Pilocarpine hydrochloride. International Journal of Pharmacy. 2001; 229: 29-36.

16. Miyazaki S. Thermally reversible xyloglucan gels as vehicles fpr rectal drug delivery. Journal of Controlled Release. 1998; 56: 75-83.

17. Miyazaki S, Kawasaki N. Comparison of in situ gelling formulations for the oral delivery of cimetidine. International Journal of Pharmacy. 2001; 220: 161-8.

18. Motto F. In vitro assessment of new embolic liquids prepared from preformed polymers and water miscible solvents aneurysm treatment. Biomaterials. 2000; 21: 803-11.

19. Nirmal HB. In situ gel: new trends in sustained and controlled drug delivery system. International Journal of Pharmaceutical Technology and Research. 2010; 2(2): 1398-1408.

20. Cackrabarty S, Nath B. A review on oral in situ gel for periodontities. World Journal of Pharmaceutical Research. 2018; 7(11): 266-270.

21. Dr. Janhavi Manohar, Dr. Asha. Anti-protease activity of Lavender on Chronic Periodontitis patients – An ex-vivo study. Asian Journal of Pharmaceutical Research. 2020; 10: 95-100.

22. Dumitriu S. Hydrogels based on polysaccharides. In: Dumitriu S. Polysaccharides in medical applications. Marcel Dekker Inc, New York. 1996; 125-242.

23. Rawat S, Warade S. In situ gel formulation of ornidazole for the treatment of periodontal disease. Current Pharmaceutical Research. 2010; 1(1): 60-69.

24. Shaurya M, Shivamurthy R, Mohammed Gulzar A. Moxifloxacin in situ gel as an adjunct clinico-microbiological study. International Journal of Oral Health Sciences. 2018; 8(1): 19-25.

25. Harish NM, Prabhu P, Charyulu RN, Gulzar MA. Formulation and evaluation of in situ gels containing clotrimazole for oral candidiasis. International Journal of Pharmaceutical Sciences. 2009; 71(4): 421-427.

26. Gorle A, Yadav R. Formulation and evaluation of in situ gel containing ciprofloxacin hydrochloride in the treatment of periodontitis. Asian Journal of Pharmaceutical and Clinical Research. 2017; 10(6): 154-59.

27. Pujitha CH. Formulation and characterization of ofloxacin ophthalmic gel. Indian Journal of Pharmacy and Pharmacology. 2017; 4(2): 105-109.

28. Chandana Pasupuleti, Abdul Saleem Mohammed, Nuha Rasheed, Kathula Umadevi, Duggi Adilakshmi. Simultaneous Formulation, Estimation and Evaluation of Ofloxacin Microbeads. Asian Journal of Pharmaceutical Analysis. 2016; 6: 167-182.

29. Maha MA. Formulation in vitro characterization and clinical evaluation of curcumin in situ gel for treatment of periodontitis. Drug Delivery. 2017; 24(1): 133-42.

30. https://www.drugbank.ca/drugs/DB01165.

31. https;//en.wikipedia.org/wiki/ofloxacin.

32. Ranch K. Ph.D. Thesis 2012 Pharm Technology, Chapter 2 Introduction, Shodhganga, 30.

33. Rakde A. In-situ gelling characteristics of Gellan gum at various simulated independent physiological conditions. Journal of Chemical and Pharmaceutical Research. 2015; 7(2): 819-29.

34. Hareesh KB, Mohammed GA, Narayan CR. Development and evaluation of in situ gels of moxifloxacin for the treatment of periodontitis. Indonesia Journal of Pharmacy. 2012; 23(3): 141-6.

35. Audumbar Mali, Santosh Jadhav, Rahul Gorad, Aamer Quazi, Ritesh Bathe, Manojkumar Patil, Ashpak Tamboli. Simultaneous UV Spectrophotometric Methods for Estimation of Cefixime Trihydrate and Ofloxacin in Bulk and Tablet Dosage form. Asian Journal of Pharmaceutical Research. 2016; 6: 100-106.

36. Chandana Pasupuleti, Abdul Saleem Mohammed, Nuha Rasheed, Kathula Umadevi, Duggi Adilakshmi. Simultaneous Formulation, Estimation and Evaluation of Ofloxacin Microbeads. Asian Journal of Pharmaceutical Analysis. 2016; 6: 167-182.

37. Priyanka Dhalkar, Shivrani Jagtap, Suraj Jadhav Mayuresh Redkar, Biradev Karande. Formulation and Evaluation of in-situ Gel Model Naproxen. Asian Journal of Pharmacy and Technology. 2019; 9: 204-207.

38. Rahana P, Dr. Sujit S. Nair. Formulation and evaluation of in-situ gel for the treatment of periodontal disease. World Journal of Pharmacy and Pharmaceutical Sciences. 2018; 7: 1308-17.

39. Dhabi MR, Nagori S. Formulation development of smart gel periodontal drug delivery system for local delivery of chemotherapeutic agents with application of experimental design. Drug Delivery. 2010; 17(7): 520-31.

40. Pandit NK, Kisaka J. Loss of gelation ability of pluronic F127 in the presence of some salts. International Journal of Pharmacy. 1996; 145: 129-36.

41. Borole P. Preparation and evaluation of in situ gel of levofloxacin hemihydrate of treatment of periodontal disease. International Journal of Pharma and Bio Sciences. 2013; 2(3): 185-96.

42. Bhimani DR, Patel JK, Patel VP, Detroja CM. Development and evaluation of floating in situ gelling system of clarithromycin. International Journal of Pharmaceutical Research and Development. 2011; 3: 32-40.

43. Himanshu G, Aarti S. Ion activated bioadhesive in situ gel of clindamycin for vaginal application. Int J Drug Deliv. 2009; 1: 32-40.

44. Ariyana A, David S, Irman E, Dan HB. Formulation and in vitro evaluation of alginate based metronidazole periodontal gel. Asian Journal of Pharmaceutical and Clinical Research. 2014; 7(1): 223-7.

Received on 22.06.2020 Modified on 11.10.2020

Research J. Pharm. and Tech. 2021; 14(9):4609-4614.

DOI: 10.52711/0974-360X.2021.00801

Sr. No	Formulation code	Surface pH	Viscosity (cps)	*In vitro* gelling capacity	Syringeability	Drug content (%)
1	F1	7.2	281±3.60	++	Pass	90.40±0.57
2	F2	7.1	342±7.09	+++	Pass	94.40±0.33
3	F3	7.0	435±9.64	++	Pass	91.95±0.31
4	F4	6.7	527±4.58	++	Pass	95.92±0.13
5	F5	6.5	592±7.09	++	Pass	95.11±0.31
6	F6	6.2	671±7.02	+	Pass	86.01±0.26
7	F7	6.0	743±11.37	+	Pass	82.98±0.44