International Journal of Novel Drug Delivery Technology

Original Research

Influence of Co-Excipients on Release Rate of Aceclofenac from Carbopol Controlled Release Matrix Tablets
Riyaz Shaikh*, Gaffar Sayyad, Yogesh Bafana and Harish Lukkad Department of Pharmaceutics, Shri Amolak Jain Vidya Prasrak Mandal's Pharmacy College, Maharashtra,India
ABSTRACT
Objective: To develop matrix tablets for controlled release of aceclofenac and to study the effect of various co-exipients on release of drug. Methods: Matrix tablets of aceclofenac were prepared by using polymer like carbopol 974P and different co-excipients with varying proportions, by direct compression method. The enfluence of different proportion of microcrystalline cellulose (MCC), lactose and dibasic calcium phosphate (DCP) on the release rate of aceclofenac from matrix tablet was studied. The tablets were subjected to physicochemical studies, in vitro drug release carried out in phosphate buffer at pH 7.4. The drug release kinetics from the tablet was studied using PCP-Disso software. Results:Microcrystalline cellulose formulation with T 90 of 5.70 hrs,5.62 hrs and 7.20 hrs from formulation F1,F2,and F3 respectively showed increased the release rate of drug followed by lactose formulation with dissolution T 90 of 6.40 hrs,7.56 hrs and 6.77 hrs from F4,F5,and F6 respectively. And with DCP formulation showed much slower in rate release of drug from carbopol matrix tablet with dissolutionT 90 of 7.90 hrs, 7.82 hrs and 7.65 hrs from F7, F8 and F9 respectively. Conclusion: The results of the study revealed that release rate of drug were increased by MCC and lactose while decreased by DCP. Keywords: Aceclofenac, Carbopol 974P, Matrix tablets, Co-excipients.

INTRODUCTION ustained release dosage forms deliver the drug at a slow release rate over an extended period of time and achieve this objective. The development of controlled release dosage form by the oral route is natural, uncomplicated, convenient, patient compliance and safer route. Matrix tablets composed of drug and release retarding material (e.g. polymers) offer the simplest approach in designing a sustained release system. The present study aims to develop sustained release matrix tablets using hydrophilic matrix materials, such as Carbopol 974P along with drug in varying proportions by dry granulation method. They are synthetic high molecular weight crosslinked polymers of acrylic acid. It is highly hydrophilic in nature and absorbs the water with good degree of swelling [1,2]. Aceclofenac is a newer derivative of the diclofenac group of non-steroidal anti inflammatory drug (NSAID) (BCS Class II drug) that exhibits analgesic and antiinflammatory activities. It directly blocks the prostaglandin synthesis. It has less gastrointestinal complications. It is practically insoluble in water. Chemically it is [[[2-[(2, 6Dichlorophenyl) amino] phenyl] acetyl] oxy] acetic acid. It is use in various pain conditions like rheumatoid arthritis, osteoarthritis and ankylosing spondylitis. The successful treatment of arthritis depends on the maintenance of effective drug concentration level in the body for which a

constant and uniform supply of drug is desired1, [1,3]. Controlled release dosage forms deliver the drug at a slow release rate over an extended period of time. Controlled release formulations contains various expients and coexcipients which may significantly affect the release of drug from the formulation. The aim of this work was to prepare the aceclofenac controlled release tablets with carbopol 974P matrix tablet and to study the influence of co-excipients on release rate of aceclofenac. Co-excipients like microcrystalline cellulose (MCC), lactose, dibasic calcium phosphate (DCP) were [4,5] used for the study. MATERIALS AND METHODS Materials Aceclofenac was obtained as a gift sample from Shreya life sciences pvt. Ltd. Aurangabad. Carbopol 974P, MCC, DCP and Lactose were obtained as a gift sample from Wockhardt Ltd., Aurangabad. All other chemicals and reagents used were of analytical grade. Methods Preparation of Aceclofenac tablets Matrix drug tablets were prepared by using polymer carbopol 743P by direct compression method. MCC, Lactose and DCP were used as co-excipients. Magnesium stearate and talc was added as lubricant and gliadant prior to compression. Co-excipients were added with different

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proportion for different tablet formulation . All the powders were passed through 60 mesh sieve separately. The compositions of the tablet formulations are given in Table 1. Weighed amounts of aceclofenac and all the excipients (MCC, lactose, DCP) except lubricant and gliadant and mixed thoroughly with mortar and pestle for 5 min. Then finally add the magnesium stearate and talc and mixed properly. Tablets were compressed on multistation punching machine (Karnavati eight stations) fitted with 7.0mm concave round surface punches. [2] Evaluation of matrix tablets The tablets were evaluated for thickness and diameter of the tablets was determined using digital vernier calipers. The hardness of randomly selected tablets was determined by using hardness tester (Monsanto hardnes tester). 7, 8 The friability of the tablets was determined using Roche Friabilator Weight variation test and uniformity contents of 7 the tablets were carried out as per the official method . (Table 2) In vitro release rate study In vitro dissolution study was carried out using USP Type II dissolution apparatus with paddle stirrer at 100 rpm

[6]

.The in-vitro test serve as a guide in estimating the amount of drug released with respect to time.900 ml phosphatebuffer solution (pH 7.5) was used as dissolution medium. Temperature was maintained 370.50C. Firstly half hour then after every hour, 5.0 ml of sample solution was withdrawn from vessel and was replaced by same quantity of fresh dissolution medium. The sample solutions withdrawn from each vessel were diluted and analyzed UV spectrophotometrically at 275 nm for drug release. Percentage drug release in each formulation was calculated using standard calibration curve of drug in same dissolution medium.

RESULTS AND DISCUSSION

In studies, controlled released tablets were prepared by using the polymer corbopol 974P with different proportion of co-excipients like MCC, lactose, DCP and investigate the effect of these co-excipients on the release rate of acelcofenac from matrix tablets. The prepared matrix tablets were evaluated for various physical properties, as indicated in Table 2. All the batches were produced under similar conditions to avoid processing variables. Tablets were evaluated for hardness, friability, content uniformity, weight variation, and in vitro drug release studies. The 2 hardness of the tablets was 4.5 to 5.5 kg/ cm . Average

Table-1: Drug formulation for the preparation of matrix tablets of Aceclofenac (for one tablet in mg)

Formulation Drug Code F0 F1 F2 F3 F4 F5 F6 F7 F8 F9 100 100 100 100 100 100 100 100 100 100

Carbopol MCC Lactose DCP 974P 40 40 40 40 40 40 40 40 40 40 --120 100 80 --------------------120 100 80 --------------------120 100 80

Magnesium Talc Stearate 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2

Weight of Each Tablet 144 264 244 224 264 244 224 264 244 224

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Table-2: Evaluation of tablets.

Thickness Formulation Code Weight variation(mg) (mm) F0 F1 F2 F3 F4 F5 F6 F7 F8 F9 143 0.0252 265 0.0126 245 0.0113 224 0.0141 264 0.0123 245 0.0103 226 0.0114 265 0.0103 245 0.0123 225 0.0105 2.9 0.2 3.1 0.4 3.0 0.3 3.1 0.4 2.9 0.2 3.0 0.3 3.2 0.3 3.5 0.2 3.1 0.4 3.2 0.2

Hardness (kg/ Cm 2) 3.0-4 4.5-6 4.5-5 4.5-5 5.5-6 4-5.5 4-5.5 5.5-6 5.0-6 4.5-5

Friability (%) 0.021 0.092 0.072 0.072 0.063 0.072 0.091 0.071 0.043 0.052

Table-3: Dissolution T 50 and T 90 values of various Aceclofenac matrix tablet

Formulation code F0 F1 F2 F3 F4 F5 F6 F7 F8 F9

T 50

T 90

4.09 hrs 6.80 hrs 3.19 hrs 5.70 hrs 3.98 hrs 5.62 hrs 4.17 hrs 7.20 hrs 3.88 hrs 6.40 hrs 5.08 hrs 7.56 hrs 3.34 hrs 6.77 hrs 3.80 hrs 7.90 hrs 3.80 hrs 7.82 hrs 3.20 hrs 7.65 hrs

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Table-4: Regression analysis data of Aceclofenac matrix tablets

Formulation Code

Zero Order First Order Higuchi Model Korsmeyer -Peppas model Hix.Crow. r 0.9890 r 0.9399 0.9871 0.9914 0.9898 0.9851 0.9767 0.9727 0.9850 0.9787 0.9814 0.8892 0.8705 0.8558 0.7846 0.8318 0.8142 0.9162 0.9004 0.8810 r 0.9467 0.9332 0.9379 0.9269 0.8984 0.9270 0.9209 0.9479 0.9332 0.9294 r 0.9811 0.9745 0.9809 0.9792 0.9787 0.9297 0.9159 0.9321 0.9049 0.9224 r 0.9766 0.9546 0.9456 0.9333 0.9039 0.9110 0.9017 0.9616 0.9501 0.9392

F0 F1 F2 F3 F4 F5 F6 F7 F8 F9

time in hours

Formulations

Figure-1: Dissolution comparison graph and T 50 and T 90 values.

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weight variation, thickness, was found to be within the prescribed official limits for each tablet. The percentage friability of all formulations was between 0.21 and 0.31 %. From release profiles of the matrix tablets, it was found that formulation of aceclofenac containing only polymer 9 that is F0 released 95.88% in 8 hours. In formulation F1, F2, and F3 prepared with different proportion of MCC as co-excipient with polymer. This formulation release of 98.27%, 99.08% and 98.74% in 8 hours of aceclofenac. It is found that release rate of drug is faster than the F0 in which only carbopol is present.[10, 11] In formulation F4, F5, and F6 in which lactose is present, show the release of 99.42%, 95.12% and 96.54% in 8 hours. It is found that slightly high rate release as compared to F0 without lactose. Formulation F7, F8 and F9 in which DCP is presented, show rate release of 91.18%, 92.04% and 92.83% in 8 hours. From this observe that, rate release of drug is decreased as compared to F0 without co-excipients. All formulation with co-excipients like MCC, lactose and DCP with polymer Carbopol 973P were compared with each other. The effect of these co-excipients on release rate of aceclofenac from carbopol matrix tablet show in T50 and T90 dissolution values. It was observed that formulation containing MCC as co- excipients show decreased dissolution time as compared to lactose and DCP. And DCP show the higher dissolution time as compared to other formulation. This is because of insolubility of DCP in dissolution medium. For finding out the mechanism of drug release from tablets, the dissolution data obtained from the above experiments were treated with the different release kinetic equations. The in vitro drug release was subjected to regression analysis according to zero order, first order kinetic equations, Higuchi's equation as percent cumulative drug release versus square root of time and log cumulative percent drug release versus log time as per korsmeryer's equation in order to determine the mechanism of drug [12] release . The result of linear regression analysis data of aceclofenac is given in table-2 Regression coefficient values of zero order and first order plots were compared,and observed that the 'r' values of zero order plots were in the range of 0.97 to 0.99 indicating drug release from most of the carbapol formulations was found to follow zero order kinetics. CONCLUSION From above results, it can conclude that the rate release of drug form matrix tablet is depending upon the polymer. If the polymer's amount increased then rate release of drug decreased. And also observed that co-excipients microcrystalline cellulose, lactose, dibasic calcium

phosphate influenced on the released rate of drug from matrix tablet. From the three co-excipients studies, Microcrystalline cellulose formulation with T 90 of 5.70 hrs,5.62 hrs and 7.20 hrs from formulation F1,F2,and F3 respectively showed increased the release rate of drug followed by lactose formulation with dissolution T 90 of 6.40 hrs,7.56 hrs and 6.77 hrs from F4,F5,and F6 respectively. And with DCP formulation showed much slower in rate release of drug from carbopol matrix tablet with dissolution T 90 of 7.90 hrs, 7.82 hrs and 7.65 hrs from F7, F8 and F9 respectively. ACKNOWLEDGEMENT Authors thank Shreya life sciences Pvt. Ltd. Aurangabad for providing the gift sample of aceclofenac, Wockhardt Pvt. Ltd., Aurangabad for the providing the gift sample of Carbopol 974P and MCC, DCP, Lactose and Y.B.Chavan college of Pharmacy, Aurangabad for providing necessary facilities to carry out the work.

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9. Cheong LWS, Hang PWS, Wong LF: Relationship between polymer viscosity and drug release from a matrix system. Pharma. Res; 1992, 9(11): 1510- 1514. 10. Korner A, Larsson A, Piculell L: Turning the polymer release from hydrophilic matrix tablets by mixing short and long matrix polymers. J. Pharm. Sci. 2005, 94(4): 759-769.

11. Cobby J, Mayersohn M, Walker GC. Influence of shape factors on kinetics of drug release from matrix tablets. J. Pharm. Sci. 1974, 63: 725-731. 12. Higuchi T, Mechanism of sustained-action medication.Therotical analysis of rate of release of solid drugs dispersed in solid matrices.J. Pharm. Sci. 1963, 51: 1145-1149.

Received :10 Jul 2011 Accepted :20 Sep 2011 Published:21 Dec 2011 Correspondence to : Riyaz Shaikh E-mail:[email protected]

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