INTRODUCTION:

Ficus racemosa also known as Ficus glomerata has various synonyms like Udumbara, Audumbar etc. Maharishi Charak has categorized Udumbara as Mutra Sangrahaniya (Anti-diuretic) herb. The fruits resemble the figs and are green when raw, turning orange, dull reddish or dark crimson on ripening.^1-3

Maharishi Sushruta has described the properties of the plant, like astringent, promotes callus healing in fractures (Bhagna Sandhaniya), alleviates Rakta-pitta, burning sensation and obesity, and useful in vaginal disorders. This plant has multiple pharmacological activities that include gastro-intestinal disorder, anti-diabetic, antioxidant, anti-diarrheal, anti-inflammatory, antipyretic activities. ^4-6

The fruit contains gluanol, hentriacontane, β-sitosterol,gluanol acetate, glucose, tiglic acid, esters of taraxasterol, lupeol acetate, friedelin, higher hydrocarbons, other tannins as main constituents.⁷As a result, the plant is also proven to be effective in the condition of Gastro-Esophageal Reflux Disease (GERD).

Gastro-retentive drug delivery systems (GRDDS) are those which extending the Gastric resident time of drug delivery systems in stomach. GRDDS offer several advantages including Controlled drug delivery, increased delivery of drugs for Local action in stomach, treatment of gastro-intestinal disorders such as GERD, site specific drug delivery, ease of administration and better patient compliance.^8-10

Raft forming system is one of the floating drug delivery systems retained in the stomach and is useful for drugs that are poorly soluble or unstable in intestinal fluids. This results in increased gastric residence time and better control of fluctuations in plasma drug concentration.¹¹The raft forming systems have been widely investigated as vehicles for prolonged drug delivery.Raft formation occurs due to one or a combination of different stimuli like pH change, temperature modulation and solvent exchange.¹²

Various pH dependent polymers are used which cause the formation of in situ gel in the system. Swelling of hydrogel increases as the external pH increases in the case of weakly acidic (anionic) groups, but decreases if polymer contains weakly basic (cationic) groups. pH sensitive polymer can be neutral or ionic in nature. The anionic networks contain negatively charged moieties, cationic networks contain positively charged moieties, and neutral networks contain both positive and negatively charged moieties. In the case of anionic polymeric network containing carboxylic or sulphonic acid groups, ionization takes place, as the pH of the external swelling medium rises above the pKa of that ionizable moiety.⁷

The current study was to formulate raft in situ gelling system of the extract of Ficus racemosa fruits with the objectives of better control and treatment of GERD associated disorders.

MATERIALS AND METHODS:

Materials:

The plant materials used in this study were fresh unripe fruits of Ficus racemosa were collected from the local regions of Solapur. Gellan gum, Hydroxy Propyl Methyl Cellulose was obtained as gift samples from Mediorals Pharma, Satara. Other chemicals were used of AR grade.

Collection and Authentication of Fruit Material:

The fruit was identified and taxonomically authenticated by comparing with herbarium From Department of Botany, D.B.F. Dayanand College of Arts and Science, Solapur. (The plant specimen number was K001039299, Catalogue No. 4549 Royal Botanic Garden)

Methods:

Preparation of Plant Extract:

The fresh unripe fruits of Ficus racemosa were washed thoroughly with distilled water, chopped into small pieces and dried in hot air oven at a range of 40 to 45°C for 3 to 4 days and in controlled conditions. The extraction of dried chopped pieces was carried out at 40- 45°C by Soxhlet extraction process using ethanol as solvent. The solution containing extract was kept for refrigeration at 4-5°C for recrystallization. The solid component was collected by filtration, dried and stored in a cool and dry place.²

Preparation of Standard Calibration Curve of Fruit Extract of Ficusracemosa:

Calibration curve of the extract was plotted using 0.1N Hydrochloric acid. The series of solutions were prepared and to get the concentration in the range of 10-50 µg/ml. The solutions were analyzed spectrophotometrically at 243 nm on double beam UV-Visible Spectrophotometer (Systronics 2201).

Preparation of in situ Raft:

To prepare raft formulations, 3²factorial design was employed using Gellan Gum and HPMC concentrations as dependent variables as shown in Table 1 and 2. Gellan Gum was dispersed in distilled water with continuous stirring. To this solution, Citric Acid and HPMC was added with vigorous stirring. Calcium Carbonate and Drug Extract was added slowly in the last stage. This was subjected to magnetic stirring until uniform dispersion was formed.^13-17

Table 1: Factorial Design of Polymers for Raft Formulation

Factor Code	Factor	-1	0	+1
X1	Gellan Gum	1 gm	1.5 gm	2 gms
X2	HPMC	0.25 gm	0.5 gm	0.75 gm

Table 2: Formulation of in situ Raft

Formulation code	Drug Extract(gm)	Gellan gum (gm)	HPMC (gm)	Citric Acid (gm)	Calcium chloride (gm)	Distilled Water(ml)
B1	0.5	1	0.25	2.5	1.25	Upto100
B2	0.5	1	0.5	2.5	1.25	Upto100
B3	0.5	1	0.75	2.5	1.25	Upto100
B4	0.5	1.5	0.25	2.5	1.25	Upto100
B5	0.5	1.5	0.5	2.5	1.25	Upto100
B6	0.5	1.5	0.75	2.5	1.25	Upto100
B7	0.5	2	0.25	2.5	1.25	Upto100
B8	0.5	2	0.5	2.5	1.25	Upto100
B9	0.5	2	0.75	2.5	1.25	Upto100

Evaluation of in situ Raft:

pH:

The pH of the gel was determined at 27°C by diluting 5 gm of the formulation with 45 ml of water using the digital pH meter. The readings were taken in triplicates.

Gelling Capacity:

The gelling capacity of the formed gel was determined using visual inspection. The gel integrity, weight and rate of formation of gel were observed with respect to time.

Density of Raft:

The gel density of the following raft formulations was evaluated by weighing 5 ml of the raft gel. The prerequisite of density for the raft gel is less than 1.004 gm/ml so as to float on gastric contents. All readings were taken in triplicates.

Viscosity:

The Viscosity measurement of the formed raft gels were carried out on Brookfield Viscometer (Model No. CAT 200+) using Spindle no. 62. Viscosity of in situ gelling solutions was measured at different angular velocities at a temperature of 37±1°C. A run comprised changing of the angular velocity from 0.5 to 100 rpm with a run time of 30 sec. After completing the cycle with a similar wait at each speed the hierarchy of angular velocity was reversed (100 rpm to 0.5 rpm) with a similar wait of 30 sec. The absolute viscosity of formulations was reported at a fixed torque value of 60%. The averages of three readings were used to calculate the viscosity. The rheological behavior was explained by plotting viscosity against angular velocity.^{18, 19}

In Vitro Buoyancy Study:

In Vitro Buoyancy is characterized by floating lag time and total floating duration. In vitro buoyancy study of the sol was carried out in a 100 ml beaker containing 60 ml of 0.1N HCl. 5 ml of the formulation was added to the beaker. The time required for gelled mass to rise to the surface of the medium (Floating Lag-time) and the duration for which the gel constantly floated on the medium (Floating duration) was noted for each formulation.

Gel Strength:

Gel strength is expected to affect the drug dissolution characteristics from the formulations. A lab fabricated apparatus was used for the determination of gel strength. The apparatus consists of a syringe with sealed opening and the piston with arrangements to keep varying weights to apply pressure on the contents of the syringe from above. Pressure results in the penetration of piston into the contents of the syringe. A sample of 1gm of gel was placed in the syringe. The gel strength, which means the viscosity of the gels at physiological temperature, was determined in terms of the duration, required for penetration of 5 cm down through the prepared gel.

In Vitro Drug Release Study:

In vitro dissolution study was carried out using USP dissolution apparatus Type II. The medium used was 900 ml of 0.1N Hydrochloric acid. The testing was carried out at 50 rpm at 37 ± 0.5^oC. 5ml of the in situ gelling solution was added to dissolution medium. Aliquots of 5ml were withdrawn at hourly interval for duration of 8 hours maintaining sink condition. The analysis was done by UV spectrophotometer at 243 nm.

RESULTS AND DISCUSSIONS:

Yield of Fruit Extract:

The yield of the ethanolic extract of Ficus racemosa was found to be 9.58 grams by Soxhlet extraction process consisting of greenish white powder.

Calibration Curve of Fruit Extract:

^{The calibration curve was obtained at a wavelength (λ}max^{) of 243 nm.}A straight linewas observed at the concentration range of 10-50 μg/ml showing good linearity with coefficient of correlation equal to 0.993. The line equation is y=0.0149x +0.0059.

General Tests for Presence of Tannins in Fruit Extract:

The results obtained by the identification tests of the drug extract confirm presence of tannins.

Gelling Capacity:

The gelling capacity of the formed gel was determined visually and the different grades were allotted as per the gel integrity, weight and rate of formation of gel with respect to time. (Table 3) It was found that the in situ gels prepared were observed to have good to excellent nature and good consistency.

Gel Strength:

It can be observed that the gel strength (Table 3) is dependent on both the factors. Both Gellan gum and HPMC positively influence the gel strength. Increase in the gum as well as HPMC concentrations increases the gel strength. This might be due to better availability of cross- linked network due to the interaction between both the polymers used to formulate the gel.

Buoyancy study:

The results of buoyancy sty are tabulated in table 3. It can be observed that all the formulations show a rapid floating with a lag time ranging from 30 seconds to 121 seconds. The difference in the lag time might be due to the differences in the viscosity of the gel creating a barrier for gas formation. Faster penetration of water in the polymeric matrix results in rapid gas formation and floating. Similarly, all the formulations how floating duration greater than 8 hours.

Table 3: Evaluation of In situ Raft

Batch code.	Gel strength (gm)	Density (gm/ml)	Floating lagtime (sec)	Floating duration (hrs)	Gelling Capacity	Gelling pH
B1	35.32	0.721	30	>8	Good	6.32
B2	36.57	0.733	44	>8	Good	6.53
B3	38.98	0.803	50	>9	Good	6.36
B4	40.72	0.874	50	>9	VeryGood	6.45
B5	42.49	0.91	60	>9	Verygood	6.53
B6	43.81	0.861	68	>9	Excellent	6.11
B7	44.23	0.896	85	>9	Verygood	6.05
B8	45.01	0.91	106	>10	Excellent	6.56
B9	46.44	0.924	121	>10	Excellent	6.50

Table 4: Viscosity of Raft

RPM/ Batch	B1	B2	B3	B4	B5	B6	B7	B8	B9
0.5	2989	14888	121900	289600	24860	154100	12090	932200	153200
1	6220	16624	53545	20000	14587	22278	14587	30215	15921
1.5	18800	3890	48760	4523	10584	12786	14892	58202	15420
2	6547	2845	46000	2148	13587	43578	15487	47891	8998
2.5	4457	3550	5345	2547	2956	4954	17888	13548	9878
5.0	1090	1841	5478	2145	1872	6540	2787	8784	5547
10	1114	1200	11460	3587	988	5800	1548	7900	4510
20	555	387	5230	847	489	2210	1840	994	2118
50	122	830	1012	882	255	896	472	1870	1414
100	301	478	612	478	878	487	1470	221	289
50	647	1200	348	1347	807	1647	1247	1478	847
20	806	789	1348	1647	547	878	5478	4779	2012
10	578	847	8678	1834	958	2145	1800	3457	2840
5.0	878	2230	2547	1245	1114	4754	547	8052	3847
2.5	1120	1974	42134	1745	1841	5510	1423	19689	5080
2	1241	2265	3468	5478	1845	6450	780	23541	8041
1.5	1945	1560	1741	2300	1560	9000	1120	25000	11260
1	4140	2880	6450	1800	1154	15140	1900	40985	14100
0.5	4740	7600	3870	2450	6940	26200	1600	76600	9100

Table 5: Drug Release of Raft

Time(hr)	R1	R2	R3	R4	R5	R6	R7	R8	R9
0	0	0	0	0	0	0	0	0	0
1	75.23	64.11	52.56	87.25	54.72	65.27	72.11	79.02	71.21
2	62.88	86.04	63.89	85.21	73.82	68.02	71.99	83.25	74.87
3	72.65	95.74	75.25	91.02	85.07	70.23	82.23	92.54	83.12
4	54.21	85.41	76.12	92.85	90.05	79.45	89.63	100.55	92.44
5	89.72	64.25	88.56	97.33	96.45	90.08	95.44	103.23	104.58

Factorial Study:

The factorial study was done for dependent parameters viz. Gel strength and buoyancy behavior of the raft formulations. Fig. 2 and 3 represent the factorial study to investigate the influence of the selected independent variables over the selected dependent variables.

Fig2: Graphical Representation of Effect of Polymers on Floating Lag Time of Raft

Y=59.33 +31.33X1+12.33X2 +13.33X1X2

The mean value of Floating Lag Time found to be 59.33. It can be calculated from the equation that Gellan Gum and HPMC show positive effect on Floating Lag Time. But Gellan Gum has more prominent effect as evident from the coefficients. The combined effect of both polymers also favour the Floating Lag Time. The effect of both polymers also favor the Floating Lag Time.

Fig 3: Graphical Representation of Effect of Polymers on Gel Strength of Raft

Y=42.14+4.13X1 +1.39X2+(-1.05X1X2)

The mean value of Gel Strength found to be 42.14. It can be calculated from the equation that Gellan Gum and HPMC show positive effect on Gel Strength. But Gellan Gum has more prominent effect as evident from the coefficients. The combined effects of both polymers show the negative effect on Gel Strength. Thus effect of both polymers does not favour the Gel Strength some extent. Thus the use of Gellan Gum and HPMC can be recommended in such formulations.

CONCLUSION:

From the present study which was carried out on formulating a gastro-retentive raft of Ficus racemosa,using Gellan gum and HPMC with Calcium Carbonate, it can be concluded that a prolonged duration of floating in gastric pH could be achieved by varying the combing concentrations of gellan gum and HPMC, as these both polymers contribute the floating performance and also increase in durability of action. As these polymers are excellent ingredients for the formulation of these types of dosage forms and can be used for further development. The formulation represents a blend of the modern technology and the ancient knowledge of India.

ACKNOWLEDGEMENTS:

The Author would like to thank to Principal, D.S.T.S.Mandal’s College of Pharmacy, Solapur for their support, encouraging nature and help regarding the research and for their appreciation of the knowledge and benefits to be gained from this research work.

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Received on 08.06.2023 Modified on 22.07.2023

Research J. Pharm. and Tech 2023; 16(8):3951-3956.

DOI: 10.52711/0974-360X.2023.00650