Introduction                                 

Diclofenac sodium is a non- steroidal anti inflammatory agent¹, which is widely used in the long term therapy for rheumatoid arthritis. The biological half life of diclofenac sodium is about 1-2h, therefore, it requires multiple dosing to maintain therapeutic drug blood level. The most frequent adverse side effect of Diclofenac sodium on long term administration are GI disturbences⁸,peptic ulceration & gastro intestinal bleeding .Diclofenac sodium is poorly soluble in water & acidic pH (1-3) but rapidly soluble in alkaline pH(5-8)hence an attempt was made to formulate a delayed release² tablet  i.e. enteric coating³ of Diclofenac sodium which will released in alkaline pH(5-8) which eliminates GI disturbances ⁴& provides better patient compliance.

Materials and Methods

Diclofenac sodium delayed release tablets (F1-F4)  were prepared by wet granulation method by using Lactose monohydrate⁷, Maize starch, Povidone, Micro crystalline cellulose, Colloidal silicone dioxide, Magnesium stearate¹¹, PEG 400, HPMC E5 EP  with various  ratios of CAP,HPMC,& EUDRAGIT L30D55. Preformulation studies of pure drug and mixed blend were carried out for organoleptic properties, Angle of repose ,Bulk density, Tapped density, Carr’s index   & Hausner’s ratio. After compression, the tablets were evaluated for Weight variation, Thickness, Hardness, Friability, drug content uniformity & invitro dissolution studies as per standards.

Preparation of Core Tablets (F1-F4)

Core tablets were prepared by wet granulation method⁹ by using PVPK 30 binder solution¹⁰.Which is mixed with diclofenac sodium, lactose monohydrate, corn starch were shifted through sieve no 40 and mixed for 10 min. Granules were dried and achieved LOD < 2.0%. Dried granules were passed through sieve no 18 .Micro crystalline cellulose PH102 & corn starch 400L which is passed through sieve no 40 should be added to above mixture.  Megnesium sterate which is passed through sieve no 60 was to added to above mixture and compression was carried out by using 7mm punches. Results are shown in table 1

Preparation of Seal Coated Tablets F5

HPMC E5 was weighed & added water slowly under stirring. For this PEG 400L was added under stirring till clear solution obtained.  Among F1-F4  core  tablets one batch is optimized and taken for seal coating at suitable temperature &rpm.

Preparation of Enteric Coated Tablets

Seal coated tablets were taken and coated with different enteric coated solutions using HPMC,CAP&EUDRAGIT.table1.

Table1.Formulation  of enteric coated tablets

Table 2 :physical parameters of blend.    

Charcterization of Blends

Prior to compression blends were evaluated for their characteristic parameters.

The results were shown in table. 3

Table 3

Characterization of tablets

The  properties of coated tablets, such as thickness, weight variation, hardness, friability, disintegration time was determined using standard procedures .Briefly hardness was determined by using  Monsanto hardness tester, friability was determined using Roche friabilator apparatus. The drug content was determined as described for blend. The results were shown in following table.

Evaluation of tablets ¹²

Physical parameters of formulated tablets like Weight variation, Hardness, Thickness, Frianility.& % of coating are shown in tables 4 &5.

Table 4: evaluation of core tablets and seal coated tablets.

Table 5: Evaluation of Enteric coated tablets.

Invitro Dissolution Studies^13-14

The invitro dissolution studies were performed using USP II dissolution apparatus¹⁵ paddle type at 50 rpm. The  dissolution studies were carried out for 2hrs in 0.1 N Hcl and the subsequently with Phosphate buffer  pH 6.8 for next 1  hr at 37°c. the release studies were conducted in triplicate . Aliquots of sample (5ml) were with drawn at specific time intervals and drug content was determined  at spectrophotometrically at 278 nm .the invitro release studies data obtained was treated to zero order equation,first order equation.Higuchi equation(Q=Kt_1/2) and Korseymer peppas to know  the  drug release mechanism from enteric coated  tablet.showin in figures 3,4.5&6

Results and Discusssion

The blend for tablets were prepared and characterized  with respect to angle of repose ,bulk density,tapped density,carr’s index.the other parameters for blend were also determined and found to be in acceptable range.

The tablets of different formulations(F1-F10) were subjected to various evaluation tests  such as weight variation ,friability,hardness& content uniformity according to procedure specified in IP.the weight variation and friability was less than 200.1mg & 0.29% for F1-F4,204.4 mg &0.32% for F5,222.7mg&0.35% for F6-F11.drug content uniformity was more than 955 in all batches in vitro release profile different concentrations of HPMC(8%&11%)F6 &F7,CAP(8%&11%)F8&F9 &EUDRAGIT(8%&11%)F10& F11.the tablets with the tablets with 8% optimum concentration shows  significant release at 2 hr to 3hr. The  EUDRAGIT polymer showed much better release than the other two polymers used for thw same purpose where as with the same weight given as that of HPMC,CAP& EUDRAGIT coated tablets showed release in 0.1 N Hcl. The % of coating is increase upto 11% in CAP & HPMC.there is no release in 0.1 N Hcl. Among the enteric coated tablets F 10 was the best.

Figure 1: Comparitive  of Dissolution profile for F6, F8, F10.   Click here to View figure

Figure 2:  comparative dissolution profile of F7, F9, F11.   Click here to View figure

Figure 3   Click here to View figure

Figure 4   Click here to View figure

Figure 5   Click here to View figure

Figure 6   Click here to View figure

Conclusion

Result of present study demonstrated that pH resistant polymers could be employed for successfully for formulated enteric coated tablets of Diclofenac sodium.. The investigated delayed release tablet was capble of release drug in alkaline pH but in acid pH. This can be expected to avoid the GI disturbance and reduces dose of administration.

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