Formulation and Evaluation of Sustained Release Matrix Tablets of Aceclofenac

This study aimed to improve the dissolution rate of aceclofenac and release the drug in a controlled manner over a period of 24 hours. Matrix tablets were prepared by direct compression method, using hydrophilic polymers (HPMC/guar gum). Matrix tablets were prepared by wet granulation method using different hydrophilic polymers (HPMC/guar gum). Tablets were evaluated for in vitro drug release profile in phosphate buffer with pH 6.8 (without enzymes). The thickness and hardness of prepared tablets were 3.23 ± 0.035 to 3.28 ± 0.008 mm and 3.26 ± 0.115 to 3.60 ± 0.200 kg/cm2, respectively. The friability was within the acceptable limits of pharmacopoeial specifications (0.31 to 0.71%), which indicates the good mechanical strength of the tablets. Drug release was retarded with an increase in polymer concentration due to the gelling property of polymers. The in vitro drug release from the proposed system was best explained by Higuchi’s model, indicating that drug release from tablets displayed a diffusion-controlled mechanism. The results clearly indicate that guar gum could be a potential hydrophilic carrier in developing oral controlled drug delivery systems. Based on the study results, formulations F8 was selected as the best formulation.


INTRODUCTION
Controlled drug delivery systems have been developed to control the rate of drug delivery, sustaining the duration of therapeutic activity and targeting the delivery of drugs to tissues 5 . Controlled drug delivery or modified drug delivery systems are conveniently divided into four categories: delayed release, sustained release, site-specific targeting, and receptor targeting 6 .
A controlled drug delivery system is usually designed to deliver the drug at a particular rate. Safe and adequate blood levels are maintained for a period as long as the system continues to deliver the drug 7  Matrix systems are widely used for sustained release. It is the release system that prolongs and controls the release of the dissolved or dispersed drugs 12  Aceclofenac is a potent inhibitor of the enzyme cyclooxygenase, which is involved in the production of

Methods
The study was divided into three stages: preformulation, granule preparation-evaluation, and tablet formulationevaluation. Each stage consists of several tests and evaluations. The method flow chart is presented in

Physical appearance
Aceclofenac powder was poured on light and dark backgrounds, and its physical appearance was observed.
The results were compared with standard references 22 .

Determination of melting point
The melting point of the aceclofenac was determined by the capillary fusion method. A one-sided closed capillary was filled with drug and placed into the Remi's melting point apparatus. The temperature at which solid drug converted into liquid was recorded and compared with standard references 22 .

Solubility studies
The solubility of Aceclofenac was tested in different

Compatibility study of drug and polymer (FTIR)
The sample was mixed with a suitable amount of KBr and converted into pellets using KBr press at 15 tons hydraulic pressure. The IR scanning of samples was done in between 4000 and 400 cm -1 and spectrum observed for any occurrence and disappearance of characteristic drug peak and compared with the standard references 23 .

Tablet preparation
The tablet formulation was carried out by varying the matrix formers: HPMC and Guar gum. In total, there were nine formulas for tablets, as shown in Table I

Determination of bulk density
Bulk density was defined as the mass of the powder divided by the bulk volume and expressed as g/cm 3 . It depends upon particle size distribution, particle shape, and particle adhere. Apparent bulk density was determined by pouring the blend into a 10 mL graduated cylinder and calculated based on the equation as reported by Yasmin et al 24 .

Determination of tapped density
The measuring cylinder containing a known mass of powder blend was tapped 100 times using density apparatus. The minimum volume occupied by the powder in the cylinder was measured. The tapped density was calculated based on the equation as reported by Yasmin et al 24 .

Determination of angle of repose
The angle of repose (θ) was determined using the funnel method. Briefly, the powder blend was poured through a funnel that can be raised vertically until a maximum cone height was obtained. The radius of the heap was

Examination of tablet appearance
Twenty tablets of each formulation were randomly taken and examined to check any physical or surface roughness in the tablets.

Determination of tablet thickness
Tablet thickness was an essential parameter in reproducing appearance and also in counting by suing filling equipment. Many tablet filling/packaging equipment utilizes the uniform thickness of the tablets as a counting mechanism 25 . In the present study, 10 tablets were randomly selected, and their thickness was recorded using a micrometer.

Determination of uniformity of weight
The weight variation test would be a satisfactory method of determining the drug content uniformity. USP procedure for uniformity of weight was followed. The allowed weight variation limits were 10%, 7.5%, and 5% for tablets having weight 130 mg or less, 130-324 mg, and >324 mg, respectively 26 . Briefly, 20 tablets were taken and weighed individually and collectively using a digital analytical balance. The average weight of one tablet was determined from the collective weight.

Determination of tablet hardness
The hardness of the tablet was defined as the force applied across the diameter of the tablet to break it. The resistance of a tablet to chipping, abrasion, or breakage under the condition of storage, transportation, and handling before use depends on its hardness or strength 27 . For the determination of tablet hardness, 10 tablets from each batch were randomly selected, and hardness was determined using Monsanto tablet hardness tester.

Determination of tablet friability
The friability of the prepared tablets was determined

Determination of in vitro dissolution profile
The in vitro dissolution studies were carried out in the USP tablet dissolution test apparatus, type 1 (basket). As much as 900 mL of phosphate buffer (without enzymes) was used as a dissolution medium. Dissolution studies were carried out for 24 hours. The temperature of the dissolution medium was maintained at 37±0.5°C. The paddle was rotated at 75 rpm. Sample (5 mL) was withdrawn data predetermined interval for 24 hours.
Complete sink condition was maintained by replacing the same volume of fresh dissolution medium after each sampling. The samples were diluted to a suitable volume with phosphate buffer, and the absorbance was recorded at 273.5 nm using a UV spectrophotometer 23 .

Physical appearance
Pure aceclofenac used in the form of a faded white crystalline powder as stated in the physical identification results of the drug sample was identical to the reference standard. These results confirm the identity of aceclofenac.

Determination of melting point
The melting point value observed was 149ºC. These values match the values mentioned in standard references (149-153ºC) 22 , confirming that the drugs used in this study were in their pure form.

Solubility studies
Aceclofenac has better solubility in phosphate buffer and does not have good solubility in distilled water and 0.1 N HCl, as presented in Table II.

Compatibility study of drug and polymer (FTIR)
The peaks at 3319 cm -1 and 3267 cm -1 in the FTIR spectrum of aceclofenac (Figure 2) are associated with OH hydrogen bonds. This peak at 2970 cm -1 was due to the aromatic stretching of NH. The stick peak character near 2937 cm -1 may be due to the stretching of the CH from the CH groups. The peak at 1750 cm -1 indicates the presence of carboxylic acids in the compound. The peaks at 1589 cm -1 , 1577 cm -1 , and 1508 cm -1 indicate a stretch of the C = C ring. The overall functional group analysis is presented in Table III.

Micromeritic properties
The flow property of granules was estimated based on different micromeritic properties. The bulk density and tapped density were determined using USP bulk density apparatus, and the results are represented in Table IV.
The bulk density and tapped density were found to be almost similar, indicating similar flow properties. The differences in bulk density and tapped density were minimal, indicating that the change volume is significantly less even after 100 tapping 30 , which confirms uniform particle size range and reproducibility in drug.
Hausner's ratio is related to inter-particle friction.
Hausner's ratio is indirect measures of bulk density, size, It is well known that particle size and shape influence flowability. The fine particles (<100 mm) tend to be more cohesive and therefore less free-flowing, whereas larger denser particles tend to be free-flowing. The rougher and more irregular the surface of the particles, the higher will be the angle of repose 32 . In the present study, the angle of repose increased from 26.78±0.600 to 30.60±0.566° as the particle size increased, indicating the decrease in flowability of granules 33 . This is also supported by the results of Hausner's ratio study.