INTRODUCTION:

The goal of any drug delivery system is to provide a therapeutic amount of drug to the proper site in the body to promptly achieve and then maintain the desired drug concentration^1,2. The route of administration has a significant impact on the therapeutic outcome of a drug³. Most of these drug delivery systems are composed of polymer, which contain the drug in the form of a dispersion of the solid drug particles either in a solid or in liquid medium⁴.

For complete absorption and good bioavailability of orally administered drug, the drug must be dissolved in gastric fluids. Dissolution of drug is the rate-controlling step which determines the rate and degree of absorption. Drugs with slow dissolution rates generally show erratic and incomplete absorption leading to low bioavailability when administered orally⁵.

The extensive studies on release properties have revealed that the active ingredients in gel based formulations are better percutaneously absorbed than cream or ointment bases. Hence an attempt has made to prepare a formulation from naturally obtained drug which is not having any side effect.

MATERIAL AND METHOD:

Preparation of SCREX-6B gel:

Gels were prepared by using the following ingredients Drug2%, Carbopol 940 1.0%, Triethanol amine0.50%, Propylene glycol 10%, Methanol 2.5%, Water 100ml. Polymer and purified water I.P. were taken in a mortar and allow soaking for 24 hrs. And required amount of drug was dissolved in methanol and other additives were added. The titration was continued to get homogenous dispersion of drug in the gel.

Evaluation of gels:

Physical appearance and homogeneity: Gel formulation was visually inspected for clarity, color, homogeneity, presence of particles and fibers.

Determination of pH⁶: The pH of gels was checked by using a digital Elico pH meter at room temperature. Initially, the pH meter was calibrated using standard buffers of pH 4 and 9.2. Accurately 2.5 gm of gel was weighed and dispersed in 25 ml of purified water and then pH meter was dipped in the dispersion and the pH was noted.

Drug content analysis⁷: The drug content of the prepared gels was carried out by dissolving accurately weighed quantity ( 1.126gm) of gel equivalent to 25 mg of drug was dissolved in 25 ml of methanol, the volume was made up to 100 ml to give a concentration of 1 mg/ ml (1000 μg/ml) and 5 ml of the above solution was further diluted to 50 ml with methanol to produce the 50 μg/ml concentration and from the 50 μg/ml of the solution 6ml was taken and further diluted upto 10ml to give a concentration of 30 μg/ml.After suitable dilution absorbance of the solution was recorded by using Shimadzu UV/ visible spectrophotometer at 312 nm.

Viscosity and Rheological studies⁸: The viscosity of gels was determined by using Brookfield (DV-II+) viscometer. The gel was placed in the sample holder and the suitable spindle selected was lowered perpendicularly into the sample. The spindle was attached to viscometer and then it was allowed to rotate at a constant optimum speed at room temperature. The readings of viscosity of the formulation were measured after 2 minutes.

Gel Strength: The gel strength was measured by apparatus described by Chul Soon et al in which a fixed weight candle (30 g) was placed on the 15 ml gel in a 25 ml measuring cylinder and the time required to travel the candle down to 5 cm was noted.

Spreadability⁹: The spreadability of gel formulations was determined 48h after preparation, by measuring two 20X20 cm glass plates after 1 min. The mass of the upper plate was standardized at 125 g. The spreadability was calculated by using the formula S= m.l/t, where S is spreadability, m is the weight tied to the upper slide, l is the length of the glass slide, and t is the time taken.

Extrudability¹⁰: In the present study, the method adopted for evaluating gel formulation for extrudability was based upon the quantity in percentage of gel extruded from tube on application of certain load. More the quantity extruded better was extrudability. The formulation under study was filled in a clean, lacquered aluminum collapsible one ounce tube with a nasal tip of 5 mm opening. It was then placed in between two glass slides and was clamped. Extrudability was determined by weighing the amount of gels extruded through the tip when a constant load of 1 Kg was placed on the slides and gels extruded was collected and weighed. The percentage of gel extruded was calculated and grades were allotted (++ good; + fair).

Skin irritation test: Gels should not produce skin irritation when applied topical drug delivery system. Hence, skin irritation study was performed. The skin irritation test was performed on healthy white rabbit of average weight 1.75 to 2.25 Kg. About 9 cm² area on the dorsal surface of the rabbits in each group was shaved and cleaned with spirit.

Rabbits were divided into three groups (n=3) as follows:

Group-I (control): There was no application on the surface of the rabbit skin.

Group-II (negative control): An aqueous solution of 1 ml containing 0.8% formalin soaked in 9 cm² cotton wool (standard irritant) was placed in the back of the rabbit as negative control. The cotton wool was secured firmly in the place with adhesive plaster.

Group-III (test): 1 ml of gel containing 20 mg of diclofenac gel was applied to 9 cm² area on the dorsal surface of the rabbit. The visual inspection was observed for 3 days to check any evidence of skin irritation (sign of edema and erythrema). The scoring system of Draize et al was followed in grading the severity of the effect.

Stability studies11: Formulated gel preparations were kept at different temperature condition like ambient temperature 5±3°C (refrigerator temperature), 45±2°C at 75±5°C (condition of accelerated stability testing) for span of three months. The following parameters of the gel such as color, pH, viscosity, spreadability, extrudability, and drug content and in-vitro drug release were studied.

IR Spectroscopy¹²: FT-IR spectra of gel, and pure drug were obtained by Perkin-Elmer FT-IR spectrophotometer using potassium bromide (KBr) pellets. KBr pellets were prepared by gently mixing the sample with KBr (1:100). The sample was scanned from 4,000 to 400 cm-1.

RESULTS AND DISCUSSION:

1- Standardization of SCREX-6B:

Description, Melting range, Loss on drying, Identification

Identification of IR:

The IR spectrum of the compound exhibited the presence of the number of O-H moieties in the molecule at 3430 cm^-1 suggesting that there must be number of OH groups present in the molecule. Hence sugar moieties are attached with flavone ring structure as expected. There is a strong cyclic C=O at 1692 cm^-1which fact that flavones structure present in the given molecule.

3-Standard Calibration Curve of ScREX-6B:

a) Standard Calibration Curve of SCREX-6B in methanol

Solvent, Methanol, Wave length 312nm, Unit for concentration mg/ml

Table -1:- Standard calibration data of SCREX-6B in methanol

Sl. No.	Concentration(mcg/ml)	Absorption (nm)
0	0	0.000
1	10	0.014
2	20	0.034
3	30	0.053
4	40	0.073
5	50	0.095

*Average of triplicates

Standard calibration curve of ScReX-6b in methanol:

CONCLUSION:

We concluded that ScReX-6b which was isolated from the roots of Syzygium cummini (L) skeel having analgesic activity when applied externally in the form of gel, however in the present work we have described the formulation and evaluation of prepared gel and screening for analgesic activity of this phytoconstituents responsible for the observed activity is currently under progress in our lab as further detailed studies are required to validate its use in traditional system of medicine.

ACKNOWLEDGEMENTS:

Authors are thankful to the Director and Head, Dept. of Pharmacology Dr. D. K. Suresh and management of LCP Gulbarga for providing necessary research facilities.

REFERENCES:

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Received on 14.12.2010 Accepted on 28.01.2011

Res. J. Topical and Cosmetic Sci. 2(1): Jan. –June 2011 page 30-32

Sl. No.	Formulation Code	Viscosity (cps)	Spreadability (gm-cm/sec)	Extrudability
1	Carbopol 940 gel	2450	13.60	++

Sl. No.	Formulation Code	Physical Appearance	Homogeneity	pH	% Drug content (mean ±SD)
1	Carbopol 940 gel	Light brown	++	9	98.64 ± 0.68