INTRODUCTION:

Additives play an important role in pharmaceutical preparations like tablet, lotions, suspensions, syrups and ointments. Recent trends towards the use of the vegetable and nontoxic products demand the replacement of synthetic excipients with natural ones. Vegetable gums provide appropriate solution to the current problem. There are several reports about the successful use of hydrophilic polymers derived from plant, like guar, carrageenan, karaya, locust bean gum in pharmaceutical preparations¹. Gum karaya has been used as carrier for the dissolution enhancement of a poorly water soluble drug nimodipine². Abelmoschus esculentus gum has been used as mini matrix for furosemide and diclofenac sodium tablets³. Cashew-tree exudates have been used as a novel bioligand tool⁴. Seed gum of Cassia tora has been evaluated as a binder in tablets⁵. Plantago ovata and Trigonella foenum graecum mucilages have been evaluated for its binding properties⁶. Guar gum has been investigated for its application in colon specific dosage forms⁷.

Gum of the tree Moringa oleifera been reported to have gel forming potential for topical application⁸.When the gum mucilage is mixed with water, a protective soothing preparation results, which when applied externally will protect lesion or ulcer, from environmental contamination, infection, and sepsis⁹.

Diclofenac sodium (DS) is a substituted phenyl-acetic acid derivative; widely used in the management of many inflammatory conditions like arthritis and gout^10-11.It also has analgesic and antipyretic actions¹². But it is having short biological half-life and hazards of adverse gastrointestinal (GI) reactions¹³.

In view of the easy availability of the plant, the exudate from the stem of the tree Cissus refescence was investigated for its application as a gelling agent in gel formulation. Diclofenac sodium was used as a model drug. Cissus refescence is a small genus of quick growing tree distributed in India.

EXPERIMENTAL:

Materials:

The gum was collected locally from the trees. Diclofenac was obtained as gift sample from (Dr. Reddy’s laboratories, Hyderabad). All other excipients, solvents and reagents were of analytical/Pharmacopoeial grade.

Methods:

Isolation and purification of gum

The gum was collected from trees (injured site). It was dried, ground, and passed through sieve no 80. Dried gum (20 g) was stirred in distilled water (300 ml) for 6-8 h at room temperature. The supernatant was obtained by centrifugation. The residue was washed with water and the washings were added to separate supernatant. The procedure was repeated four more times. Finally the supernatant was made up to 500 ml and treated with twice the volume of acetone by continuous stirring. The precipitated material was washed with distilled water and dried at 50-60° under vacuum.

Evaluation of Toxicity

Toxicity studies were carried out according to the method of Knudsen and Curtis¹⁴. The animals used in the toxicity studies were sanctioned by the Institute Animal Ethical Committee. The male albino rats of Wistar strain weighing 160-200 gm were divided into different groups comprising of six animals each. The control group received normal 0.5%CMC solution (20ml/kg i.p). The other groups received 500, 1000, 2000, 3000, 4000 and 5000 mg/kg of gum suspension in normal saline orally. The animals were observed continuously for the behavioral changes for the first 4 hours and then observed for mortality if any for 72 hours. Since no mortality, no toxic manifestations were observed and behavioural pattern was unaffected. In chronic toxicity studies, 22 animals were used, divided in to two groups, 6 as control and 16 as test animals. In the test group a dose of 500 mg/kg was administered daily for a period of 30 d. body weights were recorded for both the groups at an interval of 10d. And at the end of 30 days, hematological and biochemical parameters were studied in both the groups and after 30 days of chronic toxicity study the animals were scarified and subjected to histopathological studies.

Physicochemical characterization of gum^15-20

The physicochemical properties such as solubility, ash values, pre-compression parameters, microbial load, swelling index, loss on drying were determined according to Indian Pharmacopoeial Procedures. The pH of the gum was determined using a digital pH meter (Elico, Hyderabad).

Differential Scanning Calorimetry (DSC) Analyses

Thermal properties of Cissus refescence gum (CrG) powder were characterized using a Shimadzu DSC-60, Shimadzu Limited Japan. Nitrogen, at the rate of 20 ml/min, was used as purge gas; 2 mg of powdered material were sealed in aluminium pan and heated from 30°C up to 400°C at the rate of 10°C/min, followed by a cooling cycle back to 30°C at the same rate.

Fourier Transform Infra Red (FT-IR)

The FT-IR spectrum of the sample was recorded in an IR spectrometer (FT-IR: 8101 M,Shimadzu), using potassium bromide (KBr) discs prepared from powdered samples mixed with dry KBr in the ratio 1: 200.

Drug-excipient compatibility studies

This study has been done to check whether there is any compatibility related problems are associated with drug and the excipients used for the formulation of gels. The drug and excipients must be compatible with one another to produce a product that is stable, efficacious, attractive, and easy to administer and safe. Thermal analysis, H.P.T.L.C, FTIR, can be used to investigate and predict any physicochemical interactions between components in a formulation and can therefore be applied to the selection of suitable chemically compatible excipients.

IR Spectroscopy

The IR spectral analysis of a drug and other excipients were taken using Press pellet technique (using KBr). The IR spectra’s were determined by using 1601 PC Shimadzu UV Spectrophotometer.

DSC Studies

Differential Scanning Calorimetry was performed on a Shimadzu DSC-60, Shimadzu Limited Japan. A 1:1 ratio of drug and excipient was weighed into aluminum crucible. And sample was analyzed by heating at a scanning rate of 20⁰C over a temperature range 20⁰-300^0.

Preparation of gels

Gels were prepared by using different concentrations of gum, drug, methyl paraben (preservative) and glycerin (plasticizer), as shown in Table-1 and stored in cool place until further use.

Evaluation of prepared gels

The prepared gels were evaluated for various evaluation parameters which includes;

In vitro diffusion profile

Release of diclofenac from various gel formulations (F5, F6, F7 and the commercial preparation Volini®) were studied employing the permeation apparatus. A glass cylinder with both ends open, 10 cm height and 3.7 cm outer diameter was used as a permeation cell. A cellophane membrane (0.8 µm pore size, cut to suitable size, boiled in distilled water for 1 h and soaked in phosphate buffer of pH 7.4) was fixed to one end of the cylinder by adhesive tape. One gram of the prepared gel was taken in the cell (donor compartment) and the cell was immersed in a beaker containing 100 ml of phosphate buffer of pH 7.4 (receptor compartment). The cell was immersed in to a depth of 1 cm below the surface of buffer, which was agitated by a magnetic stirrer and the temperature was maintained at 37°±1° throughout the experiment. Aliquots were withdrawn from the receptor compartment periodically (0.5, 1,1.5 and 2 h). After each withdrawal, the volume of liquid in the receptor compartment was replaced by phosphate buffer of pH 7.4.The drug concentration was determined spectrophotometrically (UV-1700, Shimadzu, Japan) at 276 nm.

Skin irritation study

Guinea pigs (400-500 g) of either sex were used for testing of skin irritation. The animals were maintained on standard animal feed and had free access to water. The animals were kept under standard conditions. Hair was shaved from back of guinea pigs and area of 4 cm² was marked on both the sides, one side served as control while the other side was test. Gel was applied (500 mg/guinea pig) twice a day for 7 d and the site was observed for any sensitivity and the reaction if any, was graded as 0, 1, 2, 3 for no reaction, slight patchy erythema, slight but cofluent or moderate but patchy erythema and severe erythema with or without edema, respectively.

Consistency

The measurement of consistency of the prepared gels was done by dropping a cone attached to a holding rod from a fix distance of 10cm in such way that it should fall on the centre of the glass cup filled with the gel. The penetration by the cone was measured from the surface of the gel to the tip of the cone inside the gel. The distance traveled by cone was noted down after 10sec²¹.

Homogeneity

All developed gels were tested for homogeneity by visual inspection after the gels have been set in the container. They were tested for their appearance and presence of any aggregates.

The pH of the various gel formulations was determined by using digital pH meter (Elico, Hyderabad).

Spreadability

It was determined by wooden block and glass slide apparatus. Weights about 20g were added to the pan and the time were noted for upper slide (movable) to separate completely from the fixed slides²².

Spreadability was then calculated by using the formula:

S = M.L/ T

Where; S = Spreadability; M = Weight tide to upper slide; L = Length of glass slide; T = Time taken to separate the slide completely from each other.

Drug content

A specific quantity (100mg) of developed gel and marketed gel were taken and dissolved in 100ml of phosphate buffer of pH 7.4. The volumetric flask containing gel solution was shaken for 2hr on mechanical shaker in order to get complete solubility of drug.

This solution was filtered and estimated spectrophotometrically (UV-1700, Shimadzu, Japan) at 274 nm Using phosphate buffer (pH 7.4) as blank²³.

Viscosity

Viscosity was determined using Brookfield synchronic viscometer with helipath stand at room temperature with a shear rate of 5 rpm for 5 min.

Accelerated stability studies²⁴

All the selected formulations were subjected to a stability testing for three months as per ICH norms at a temperature of 40º ± 2ºC in stability chambers (Lab-Care, India). All selected formulations were analyzed for the change in appearance, pH or drug content and also physical stability and synersis (spontaneous contraction of gel exuding some of the fluid medium).

In vitro anti-inflammatory activity

The in vitro anti-inflammatory activity of the gel formulation was performed using carrageenan induced rat hind paw edema model. The Wistar albino male rats weighing 150 - 210 g were fasted overnight, but water was allowed ad libitum. The animals were divided into three groups of six animals each. Group I (control) received placebo gel, group II received 1.2 mg/mL of diclofenac suspension in water and the group III received 1.2 mg/kg equivalent to diclofenac in gel formulation. Immediately after drug administration 0.05 mL of 1% w/w solution of carrageenan was injected into the planter surface of the hind paw. The hind paw volume was measured at different time intervals for 6 h after carrageenan treatment using a plethysmograph. The percent inhibition in hind paw edema volume was calculated using the following formula and compared with those recorded for control group.

Anti-inflammatory activity (%) = (1-A/B) × 100

Where A is the change in paw volume in the treated group and B is the change in paw volume in the control group.

RESULTS AND DISCUSSION

Plant products serve as an alternative to synthetic products because of local accessibility, environment friendly nature and lower prices compared to imported synthetic products. Herbs are non-polluting renewable resources for sustainable supplies of cheaper pharmaceutical products. Today, we have a number of plant-based pharmaceutical excipients. In view of the easy availability of the plant, the exudate from the stem of the tree Cissus refescence was investigated for its application as a gelling agent in diclofenac gel formulation.

Physicochemical characterization of CrG

The percentage yield of the gum was 35% w/w. The gum obtained was an off white to cream color powder, and the viscosity of its 1% aqueous dispersion was 600cP.The powder was slightly soluble in water and practically insoluble in ether, acetone, chloroform, methanol and ethanol. The binder gum is natural and has a pH of 6.5.The swelling characteristic of CrG been studied in different media; 0.1N hydrochloric acid, phosphate buffer (pH 7.4) and water. The swelling was highest in water (25) followed by 0.1N HCl pH (15) and least in phosphate buffer (5). Generally, the results show that CrG has high swelling index suggesting that the gum may perform well as binder/disintegrant/matrixing agent. The gum is a pH responsive polymer, it is therefore a “smart polymer,” and may find application in controlled release dosage formulations. The moisture content of CrG was low (1%), suggesting its suitability in formulations containing moisture sensitive drugs. The total ash, water soluble ash and acid insoluble ash value of CrG was found to be 0.75, 0.25 and 0.11%w/w respectively. Ash values reflect the level of adulteration or handling of the drug. The bulk and tapped densities give an insight on the packing and arrangement of the particles and the compaction profile of a material. The compressibility index, Hausner ratio and angle of repose of CrG were 16.20%, 0.15 and 20.25° respectively, implying that the CrG has a good flow with moderate compressibility. The loss on drying, ash value and microbial count were well within official limits. The result of physicochemical characterization of CrG is reported in table 2.

Differential Scanning Calorimetry

Differential scanning calorimetry (DSC) was used to measure the occurrence of exothermal or endothermal changes with increase in temperature. DSC, because of its sensitivity and accuracy, has been extensively used to study the phase transitions of polymers. The thermogram for CrG is shown in Figure 1.It shows that the gum has both amorphous and crystalline portions. Glass transition (Tg) temperature occurred at 235°C while a melting peak was observed at about 273°C.

Fourier Transform Infra Red (FT-IR)

The IR spectrum of CrG is shown in Figure 2. The finger print region of the spectrum consists of two characteristic peaks between 700 and 1316 per cm, attributed to the C-O bond stretching. The band at 1604 per cm was assigned to the O-H bending of water. There are absorptions (weak) in the 1730 per cm area that indicate carbonyls. The absence of significant aromatic stretches in the 1660-1690 per cm region and the weakness of the stretches, imply that there is a modest amount of peptidic cross linking by amide bond formation. The sharp band at 2939 per cm is characteristic of methyl C-H stretching associated with aromatic rings. The broad band at 3286 cm-1 is due to the hydrogen-bonding that contributes to the complex vibrational stretches associated with free inter and intra-molecular bound hydroxyl groups which make up the gross structure of carbohydrates.

Table 2: Results of Physicochemical Characterization of Cissus refescence gum

Parameters	Result
State	Amorphous powder
Odor	No characteristic odor
Taste	Tasteless
Color	Off white- cream yellow color
Identification	-
a. Mounted in 96% ethanol	Transparent angular masses
b. Mounted in Ruthenium red	Particles stained red
c. Mounted in iodine solution	Particles stained blue
pH (1%w/v)	6.2
Moisture content (%)	1.0
Ash value (%)	0.75
Water-soluble ash (%)	0.25
Acid insoluble ash (%)	0.11
Swelling index	-
In distil water	25
In 0.1 N HCl	15
In Phosphate Buffer pH 7.4	5
Test for carbohydrate (Mollish’s test)	+
Test for tannins (Ferric chloride test)	-
Test for chloride (silver nitrate test)	-
Test for sulphate (Barium chloride test)	-
Total bacterial count
E.coli	Absent
Salmonella typhi	Absent
S.aureus	Absent
Solubility	Slightly soluble in cold water, practically insoluble in ether, acetone, chloroform, methanol, ethanol.
Angle of repose	20.25⁰
Bulk density	0.53
Tapped density	0.62
Compressibility Index (%)	16.20
True density	1.6g/dl
Yield (%)	35
Viscosity (1%)	600 cP
Hausner ratio	0.15

Table 3: Results of biochemical parameters in rats treated with Cissus refescence gum powder

Treatment

ALP (U/L)

ACP (U/L)

AST (U/L)

ALT (U/L)

Urea (U/L)

Creatinine (U/L)

Control (0.5%CMC)***

65±4.58*

39±2.42

70±3.86

55±2.56

45±1.73

0.6±0.15

Treatment (CrG)****

500 mg/kg)

69±4.25**

41±3.12

68±3.41

59±2.36

41±2.04

0.5±0.17

*Data represents as the mean ±SD of 6 animals; **Data represents as the mean ±SD of 16 animals

***CMC; Carboxy methyl cellulose; CrG**** Cissus refescence gum powder

Table 4: Results of Hematological changes observed in rats during and after treatment of CrG for 30 days

Treatment	RBC (10⁶/mm³)	WBC (10³/mm³)	Hb (g/dl)	N	L	E
Control (0.5% CMC)	4.3±0.05*	6945±0.15	13±0.25	11±0.19	91± 0.12	0±0.00
Test(CrG) 500 mg/kg)	4.1±0.07**	7200±0.14	14.25± 0.12	12±0.15	87± 0.18	1± 0.32

*Data represents as the mean ±SD of 6 animals; **Data represents as the mean ±SD of 16 animals

Table5: Results of evaluation parameters of developed gel and marketed gel

Batch No	pH	Spreadibility (g.cm/sec)	Consistency (60 sec)	Homogeneity	Skin irritation test	Drug content (%)	Physical Appearance
F5	6.5	5.5	5.5	Homogeneous	Nil	98.50	Opaque
F6	6.7	7.0	6.0	Homogeneous	Nil	99.65	White
F7	7.0	6.5	6.5	Homogeneous	Nil	97.21	White
Marketed gel	6.7	6.0	8.0	Homogeneous	Nil	98.87	Opaque

Table 6: Stability study of various formulated gel and marketed gel.

Batches	Months	pH	Appearance	Drug content	Consistency	Spreadibility	Viscosity
F5	0	6.5	Opaque	98.50	NC*	NC*	NC*
	1	6.6	Opaque	98.00	NC	NC	NC*
	2	6.56	Opaque	97.50	NSC	NSC	NC*
	3	6.5	Opaque	97.00	NSC	NSC	NSC*
F6	0	6.7	white	99.65	NC	NC	NC*
	1	6.9	white	99.00	NC	NC	NC*
	2	6.85	white	98.50	NC	NC	NSC*
	3	6.8	white	98.00	NSC**	NSC**	NC*
F7	0	7.0	white	97.21	NSC	NSC	NC*
	1	7.1	white	97.00	NSC	NSC	NC*
	2	7.0	white	96.5	NSC	NSC	NC*
	3	7.0	white	96.00	NC	NC	NC*
Marketed gel	0	6.7	Opaque	98.87	NC	NC	NC*
	1	6.8	Opaque	98.00	NC	NC	NC*
	2	6.9	Opaque	98.00	NSC	NSC	NC*
	3	6.9	Opaque	97.40	NSC	NSC	NSC*

NC* = No change; NSC**= No significant change

Table 7: Results of Percent inhibitions of hind paw edema

Formulations	Percentage Inhibition (%)
Formulations	1h	2h	3h	4h	5h	6h
Control	-	-	-	-	-	-
Diclofenac oral	0.78	7.0	60.75	55.12	32.45	20.78
Diclofenac gel	0.65	5.13	50.78	45.65	30.41	10.32

Acute oral toxicity study

To determine the safety level of the extracted CrG, acute toxicity and chronic toxicity studies were carried out. In both toxicity study of the gum revealed no behavioral changes for first four hours and no mortality, no toxic syndromes were observed even at the dose level 4000mg/kg body weight after 24 hours, indicating the safety of the gum. To assess the suitability of gum for the oral delivery we have recorded the body weight profile for the animals during the chronic toxicities at regular intervals of 10 d. it was found that the body weight of both test and control and rate of increase were also comparable. Hence it is concluded that chronic administration of the gum might not influence either the food intake or growth. Hematological and biochemical parameters that were determined at the end of 30 d of continuous administration were also found to be comparable to that of control rat. The effect of CrG on hematological and biochemical parameters is summarized in table3 and 4 respectively.

Characterization of Drug and excipients

Differential Scanning Calorimetry (DSC)

The DSC thermogram (Figure 3) of pure diclofenac sodium showed 2 endothermic peaks. The first small endothermic peak at 63⁰C was due to water loss. The second sharp endothermic peak at 288⁰C and an exothermic peak at 296⁰C indicated the fusion of the solvated crystals and the oxidation reaction between diclofenac sodium and oxygen in air environment fusion, respectively. The DSC analysis of physical mixture of drug and excipients revealed negligible change in the melting point of diclofenac sodium in the presence excipients, indicating no modification or interaction between the drug and excipients.

Fourier Transform Infrared (FTIR) Spectroscopy

The IR spectral analysis of diclofenac sodium and the physical mixture of diclofenac sodium and other excipients are presented in Figure 4. Pure diclofenac sodium spectra showed principal peaks at 1280 and 1303 cm⁻¹ resulted from C-N stretching and the peak at 1501 and 1571 cm⁻¹ resulted from C=C stretching and C=O stretching of carboxylate group, respectively. Confirming the purity of the drug as per established standards. All the above characteristic peaks appear in the spectra of physical mixture of diclofenac sodium and other excipients, indicating no modification or interaction between the drug and excipients.

Figure 1: Differential scanning calorimetry curve of Cissus refescence gum powder

Figure 2: FTIR spectrum of Cissus refescence gum powder

Figure 3: Differential scanning calorimetry thermograms of pure diclofenac and physical mixture of drug and excipients

Figure 4: Fourier transform infrared spectroscopy of (a) pure diclofenac (b) Physical mixture of drug and excipients

Fig 5: Drug permeability release profile of diclofenac gel formulation.

Fig6: Change in edema volume with Diclofenac oral, placebo gel and Diclofenac gel after carrageenan treatment.

Figure 7: Percent inhibitions of hind paw edema after oral administration of diclofenac and application of diclofenac gel.

Figure 8: Higuchi matrix release kinetics of optimized formulation (F6)

Figure 9: Korsmeyer and Peppas release kinetics of optimized formulation (F6)

Evaluation of diclofenac gel

The gelling concentration of the gum was found to lie between 6.0 and 8.0% w/v but better gel characteristics were observed at the concentration of 7.0%. The pH of the gum was below 7.0, which is ideal for topical application. Eight batches of gel were prepared corresponding to 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0 and 9.0 % w/w of CrG, 1% w/w of Diclofenac sodium, 0.2% w/w methyl paraben as preservative and 10% w/w glycerin as plasticizer. The pH values of those batches were determined. There was no significant difference in pH between pure gum solution and the different batches of gels formulated. Hence the gels were ideal for topical application. Among the prepared gels the batch containing 7% gum had opaque color without any characteristic odor and pH of 6.7. Therefore this was considered as ideal batch. The gels exhibited pseudoplastic flow (shear thinning) the viscosity was found to be ideal for topical application. The stability of the gel was determined 40º ± 2ºC. Precipitation or turbidity occurs in some of the batches (F1, F2, F3, F4 and F8) gel containing diclofenac sodium which could be due to the incompatibility in the system due to presence of glycerin or propylene glycol at accelerated temperature. Hence, these batches were discarded and remaining batches (F5,F6 and F7) were considered for further study. The study revealed that the gel formulations containing 5.0, 6.0, and 7.0% w/w of gum were physically stable and synerisis was not observed where as other formulations showed synerisis. Hence these three formulations were considered for in vitro diffusion study along with a marketed formulation. Skin irritation study revealed no sensitivity reaction in guinea pig.

The pH values of all developed (F5, F6 and F7) and marketed gel was 6.7. The values of spreadability indicate that the gel is easily spreadable by small amount of shear. Spreadibility of marketed gel was 7.0g.cm/sec while F6 was 6.0 g.cm/sec, indicating spreadability of gum (at a concentration of 7%) containing Diclofenac sodium gel was good as compared to the marketed gel. The consistency reflects the capacity of the gel, to get ejected in uniform and desired quantity when the tube is squeezed. Consistency in terms of distance travel by cone was 6mm of all developed batches as compared to 8mm of marketed gel. Consistency is inversely proportional to the distance traveled by falling cone. Hence, the consistencies of gum (at a concentration of 7%) containing Diclofenac sodium gel was better as compared with marketed gel. All developed and marketed gel showed good homogeneity with absence of lumps. The developed preparations were much clear and opaque as compared to marketed gel. The skin irritation studies of developed gel were carried out on guinea pig and that confirmed the absence of any irritation on the applied surface. During the stability studies the appearance was clear and no significant variation in pH was observed. The results are tabulated in table5 and 6.Considering the accelerated stability studies and physiochemical parameters, batch F6 was selected for in vitro permeability release studies as well as compared with the marketed gel. In vitro Permeability study showed that permeation studies of F6 and marketed gel were comparable. The results are shown in figure 5.

Figure 6 represents the change in edema volume after carrageenan treatment with Diclofenac oral suspension, Diclofenac gel and control gel. As shown in table 7 and Figure 7, the maximum 60.75% inhibition of edema was observed with oral Diclofenac at 3 h after carrageenan treatment and maximum 50.78% inhibitions of edema was observed with Diclofenac gel formulation at 3 h after carrageenan treatment. It may be due to the initial slower release of drug from the gel formulation. The better antiinflammatory activity found with the Diclofenac gel treatment may be accelerated for controlled drug release and protection of drug from first-pass hepatic metabolism which is encountered in the oral route.

It was observed that gum (at a concentration of 7%) containing Diclofenac sodium (batch F6) produced better spreadability and consistency as compared to marketed Diclofenac sodium gel. The developed F6 gel showed good homogeneity, no skin irritation, good stability and in vitro permeability was comparable with marketed gel. The CrG forms water washable gel because of its water solubility and has wider prospects to be used as a topical drug delivery system.

Drug release kinetics

In order to investigate the release mechanism, the drug release data of diclofenac were fitted to Higuchi’s and Korsmeyer’s models. The data were processed for regression analysis using MS EXCEL statistical function. The results are shown in figure 8 and 9. From the graphs, it is concluded that the optimized gel (F6) followed Higuchi release kinetics (r² =0.9909). Further, to understand the drug release mechanism, the data were fitted to Peppas exponential equation Mt/M8 =Ktn, where Mt/M8 is the fractional drug release into the dissolution medium, K is a constant which incorporates the properties of the macromolecular polymeric system and drug and n is the diffusional exponent, which characterizes the drug transport mechanism. When n =0.5, it indicates quasi-Fickian diffusion mechanism. For n> 0.5, an anomalous non-Fickian diffusion. In the present study also it was observed (figure9) that the optimized gel formulation (F6) followed quasi-Fickian diffusion mechanism, which indicates the drug release through diffusion controlled mechanism.

CONCLUSION:

Diclofenac sodium gel was prepared successfully using CrG as gelling polymer to formulate the gel and to retard release and to achieve required dissolution profile. The formulation F6 consisting of 7% w/w CrG was found to be suitable for topical application based upon its physicochemical properties. Drug release kinetics of the optimized formulation (F6) correspond best to Higuchi’s model and drug release mechanism as per n value of Korsmeyer and Peppas model predicted clearly as it appears to be a complex mechanism of swelling, diffusion and erosion. The anti-inflammatory activity of this gel formulation in rat hind paw edema model reveals that Diclofenac was delivered to the inflammation site at a controlled level over a period of 3 h. These results suggest the feasibility of the topical gel formulation of Diclofenac. As primary ingredients are cheap, biocompatible, biodegradable and easy to manufacture. They can be used as gelling agents in place of currently marketed synthetic gelling agents.

ACKNOWLEDGEMENTS:

Authors thank Dr.Narayana Swamy V.B., Principal, Karavali College of Pharmacy, Mangalore for providing necessary facilities for conducting the present work. Authors also thank Dr. Reddy’s laboratories, Hyderabad, India for providing gift sample of Diclofenac sodium.

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Received on 16.01.2012 Modified on 25.02.2012

Research J. Pharm. and Tech. 5(3): Mar.2012; Page 415-423

Ingredients	F1	F2	F3	F4	F5	F6	F7	F8
CrG*(%)	2.0	3.0	4.0	5.0	6.0	7.0	8.0	9.0
Diclofenac (%)	1	1	1	1	1	1	1	1
Glycerin (%)	10	10	10	10	10	10	10	10
Methyl paraben (%)	0.02	0.02	0.02	0.02	0.02	0.02	0.02	0.02
Purified water q.s. to (g)	10	10	10	10	10	10	10	10