EFFICIENT FORMULATION AND CHARACTERIZATION OF FLURBIPROFEN TRANSDERMAL GEL USING WATER SOLUBLE POLYACRYLAMIDE POLYMER

EFFICIENT FORMULATION AND CHARACTERIZATION OF FLURBIPROFEN TRANSDERMAL GEL USING WATER SOLUBLE POLYACRYLAMIDE POLYMER

Jeevaprakash Ganapathi*¹ and Dheivanai Jeevaprakash ²

Department of Pharmacy Practice, S. Chaavan College of Pharmacy ¹, Nellore- 524 346, Andhra Pradesh, India

Department of Pharmaceutics, Jagan’s College of Pharmacy ², Nellore- 524 346, Andhra Pradesh, India

ABSTRACT

High molecular weights water soluble homopolymer type of acrylamide was  reported to obtain very high viscosity in low concentration, transparency, film forming properties and useful in formation of transdermal gel. The flurbiprofen gels were prepared by using different concentration of polyacrylamide for topical drug delivery with an aim to gradually increase transparency and spreadability. These preparations were further compared with marketed known flurbiprofen gel. Spreadability and consistency of polyacrylamide gel containing flurbiprofen gel (S9) were 6.5g.cm/sec and 5mm as compared to 5.5g.cm/sec and 10mm respectively of known marketed gel, indicating good spreadability nature and consistency of the prepared gel (S9). The transparency nature of prepared batch (S9) was good as compared to the known marketed gel. The percent drug release was 97.85 and 98.84 from S9 and known marketed gel respectively. No irritation was felt in the skin irritation test. Stability studies conducted under accelerated condition was shown satisfactory results. It can be concluded that polyacrylamide gel containing flurbiprofen gel showed good consistency, spreadability, homogeneity and stability and had wider prospect for topical preparations.

Polyacrylamide

INTRODUCTION:Transdermal gel preparations are intended for superficial skin application or to some mucosal surfacesfor local action or skin penetration of medicament or for their soothing or protective action ¹.

Gels are typically formed from a liquid phase that has been thickened with other ingredients. The continuous liquid phase allows free diffusion of molecules through the polymers scaffold and hence release might be equivalent to that from a simple solution ².

NSAID’s nonsteroidal anti-inflammatory drugs are having excellent anti-inflammatory and analgesic activity but NSAID produces GIT ulceration, liver and kidney trouble  produced in case of oral administration. In view to reduce adverse drug reaction associated with oral formulations, we have prepared as transdermal gel.

MATERIAL AND METHODS: Flurbiprofen was purchased from Indian Drug House (Hyderabad, India).Polyacrylamide homopolymer were purchased by Suyog Chemicals Ltd (Nagpur, India). Sodium metabisulphite AR grade was procured by Sigma Pvt. Ltd. (Mumbai, India). All other ingredients were of analytical grade. Brufengel was purchased from market.

Procedure of Gel Preparation: About 5g of flurbiprofen was weighed and dissolved in 5g of isopropyl alcohol, to this solution, specified quantity of glycerin or propylene glycol or cocodiethanolamide was added and dissolved (solution A). Weighed quantity of polyacrylamide was added to the 75g of distilled water containing 0.1g of sodium metabisulfide  used as antioxidant and continuously stirred to dissolve the same (solution B). Solution A and B were mixed thoroughly and the final weight was made upto 100g (Table 1).

TABLE 1: COMPOSITION AND CONCENTRATION OF FLURBIPROFEN GEL

Precipitation or turbidity occurs in some of the batches (S1, S2, S3, S4, S5 and S6) of polyacrylamide gel containing flurbiprofen which  has been due to the incompatibility in the system due to presence of glycerin or propylene glycol. Hence, these batches were discarded finally and remaining batches (S7, S8 and S9) were considered for further study.

Effective evaluation of Polyacrylamide Gel containing Flurbiprofen  and Marketed Gel: The above prepared polyacrylamide gel containing flurbiprofen and marketed gel were subjected to evaluation for the following parameters:

1. pH: The pH of the various gel preparations was determined by using digital pH meter. (Table2)
2. Spreadability: It was estimted by wooden block and glass slide apparatus. Weights about 20g were added to the sterile pan and the time was accurately noted for upper slide (movable) to separate completely from the fixed slides ⁸ (Table 2).

TABLE 2: EACH VALUES OF EVALUATION PARAMETERS OF DEVELOPED GEL AND MARKETED GEL

Spreadability was calculated by 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

3. Consistency: The estimation of consistency of the prepared gels was done by dropping a cone attached to a holding rod from a fixed distance of 10cm in other way that it should fall down  on the centre of the glass cup was filled with the gel. The penetration by the cone was accurately measured from the surface of the gel to the tip of the cone inside of the gel. The distance traveled by cone in the period was noted down after 10sec. ⁹ (Table 2).
4. Homogeneity: All developed gels were properly tested for homogeneity by visual inspection after gels has been set in the container. These were tested for their appearance and presence of any aggregates (Table 2).
5. Skin Irritation Test: Test for irritation was carefully performed as per guidelines after getting informed consent on human volunteers. For each gel, five volunteers were selected and 1.0g of formulated gel was applied on an area of 2 square inch to the back side of hand. The volunteers were examined for lesions or irritation (Table 2).
6. Drug Content: A specified quantity (100mg) of developed gel and marketed gel were taken and dissolved in 100ml of phosphate buffer of pH 6.8. The volumetric flask containing gel solution was shaken for the period  2hr on mechanical shaker in order to get absolute solubility of drug. This solution was filtered and estimated spectrophotometrically at 276.0nm using phosphate buffer (pH 6.8) as blank ¹⁰ (Table 2).
7. Accelerated Stability Studies: All the selected formulations were subjected to a stability testing for the period of three months as perICH norms at a temperature of 40±2^oC. All selected formulations were analyzed for the changes in appearance, pH or drug content by procedure stated earlier ¹¹ (Table 3).

TABLE 3: STABILITY STUDY OF VARIOUS KIND PREPARED GEL AND MARKETED GEL.

8. Permeability Studies ¹²: Phosphate buffer of pH 6.8 was used for in vitro release as  receptor medium. The pretreated skin of albino mice was used in fraz diffusion cell. The gel sample was applied on the skin of animal and then fixed in between donor and receptor compartment of quality diffusion cell. The receptor compartment contained phosphate buffer (100ml) of pH 6.8. The temperature of diffusion medium was thermostatically controlled at 37±1^oC by surrounding water in jacket and the medium was continuously stirred by magnetic stirrer at  speed of 500rpm. The sample at predetermined intervals were withdrawn and replaced by equal volume of freshly prepared fluid. The samples withdrawn were spectrophotometrically measured at 276nm against their blank (Table 4 and Figure 1).

TABLE 4: PERMEABILITY STUDIES OF S9 AND MARKETED GEL

FIG. 1: DRUG PERMEABILITY RELEASE PROFILE OF FLURBIPROFEN GEL FORMULATION S7, S8, S9

RESULTS AND DISCUSSION: The pH values of all formulated (S6, S7, S8 and S9) and marketed gel was 6.8.The values of measured spreadability indicate that the gel is easily spreadable by small amount of shear. Spreadability of marketed gel was 5.5g.cm/sec while S9 was 6.5g.cm/sec, indicating spreadability of polyacrylamide containing flurbiprofen gel was good as compared to the marketed gel.

The consistency reflects the capacity of the gel, this has been  get ejected in uniform and desired quantity when the tube is squeezed. Consistency in shake  of distance traveled  by cone was 5mm of all developed batches when compared to 10mm of marketed gel. Consistency is inversely proportional to the distance traveled by falling cone.

Though, the consistencies of polyacrylamide gel containing flurbiprofen were better as compared with marketed gel. All formulated and marketed gel showed good homogeneity with absence of lumps. The formulated  preparations shown  much clear and transparent when compared to marketed gel. The skin irritation studies of prepared transdermal  gel were carried out on human volunteers and that confirmed the absence of any irritation on the applied surface. During the stability studies the visible appearance was clear and no significant variation in pH which was observed.

Considering the accelerated stability studies and physiochemical parameters, batch S9 was selected for in vitro permeability release studies as well as compared with the marketed gel. In vitro Permeability study shown  that permeation studies of F9 and marketed gel were comparable. It was concluded that polyacrylamide gel containing flurbiprofen (batch S9) produced better spreadability nature  and consistency when compared to marketed flurbiprofen gel. The prepared S9 gel showed good homogeneity, no skin irritation, good stability and in vitro permeability was comparable with known marketed gel. The polyacrylamide forms completely  water washable gel due to its water solubility and has wider prospects to be used as a transdermal drug delivery system.

CONCLUSION: The prepared polymer being macromolecules of very high molecular weight remain unabsorbed on the skin and from our studies it can be concluded that polyacrylamide can be used for various topical dosage form for external application. It has been proved that optimized batch produces the gel with good consistency, homogeneity, spreadabiltity and stability. Hence, the polymer is water soluble; consequently, it forms water washable gel and has been wider prospects to be used as a transdermal drug delivery dosage form.

ACKNOWLEDGEMENT: Authors are thankful to Management  of  both S.Chaavan college of pharmacy and Jagan’s college of pharmacy (Nellore, Andhrapradesh, India) for providing necessary facilities to carry out this research work.

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