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Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

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Open Access Full Text Article  Research Article

Formulation and Evaluation of Solid Dispersion Tablets of Aceclofenac

Baishali Ghosh, Sudipta Das*, Surita Basu, Sankar Narayan Bhunia, Udita Biswas, Abhishek Mandal

Department of Pharmaceutics, Netaji Subhas Chandra Bose institute of Pharmacy, Chakdaha, Nadia, West Bengal, India

 

 

INTRODUCTION:

Among the many alternatives available for the delivery of different pharmaceuticals, the oral route is the most commonly utilized due to its affordability, ease of use, patient friendliness, and simplicity of administration. This kind of distribution method serves as an illustration of a traditional drug delivery system, and these Conventional dosage forms can help the medication release instantly¹. This means that the drug is absorbed more quickly when using these formulations. Combining medications, however, raises the possibility of toxicity and leads to patients who are noncompliant. There are numerous ways to get around the disadvantages of standard dose formulations of this kind. The idea of a cutting-edge medication delivery system among them turns out to be the best method for creating matrix tablets. One important strategy for the development of improved medication delivery is the use of matrix tablets systems. The term "matrix tablets" refers to oral dosage forms where the active component is evenly distributed across hydrophilic or hydrophobic matrices².

A popular prescription for treating osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis is aceclofenac, a strong non-steroidal anti-inflammatory medicine. Aceclofenac is a chemical that has Analgesic action is shown by [2-(2, 6-dichlorophenyl) amino] phenylacetyl oxyacetic acid. Low gastrointestinal side effects are associated with this derivative of diclofenac. The material is crystalline and white in color. It dissolves easily in ethanol and acetone but not in water. It is highly bioavailable (nearly 90–95%) and well absorbed when taken orally. About 70–80% of the medication is eliminated by the renal route, and aceclofenac has a half-life of 4-6 hours³.

Aceclofenac, a medication belonging to BCS class II, has limited bioavailability and poor drug dissolution due to its high permeability and low water solubility. Therefore, increasing solubility and dissolving rate seems to be a challenging step. Thus, several strategies have been employed to improve the solubility and rate of dissolution of poorly soluble drugs, including as micronization, polymorphism, and solid dispersion techniques. One of the most practical and effective methods for improving the drug release profile of poorly soluble medications is solid dispersion⁴. Sekiguchi and Obi presented the solid dispersion theory for the first time in 1961. A solid dispersion is defined as "A group of solid items, especially pharmaceuticals that are hydrophobic, consist of a hydrophilic matrix containing two or more different moieties⁵.

An assortment of solid materials made up of two or more separate components, namely a hydrophobic drug and a hydrophilic matrix, with the drug evenly dispersed in either crystalline or amorphous particles, is called a solid dispersion⁶.In order to increase the bioavailability and solubility of drugs that are poorly soluble, the solid dispersion method is often used. The current work formulates and evaluates matrix tablets using a solid dispersion technique in an effort to increase the solubility and rate of dissolution through the use of various polymers⁷.

A lower frequency of dosage leads to a longer duration of drug release, reduction of drug buildup, enhancement patient adherence, reduction of medical expenses are the advantages of solid dispersion⁸. 

MATERIALS AND METHODS:

MATERIALS:

Aceclofenac was purchased from Yarrow chem product, Mumbai. Urea, mannitol, lactose monohydrate, HPMC E 15 LV, magnesium stearate, and talc were purchased by Loba Chemie Pvt. Ltd. (Mumbai). Micro Crystalline Cellulose was purchased from Merck speciality Pvt. Ltd. 

METHODS:

Preparation of solid dispersion by solution method:

In solution method, hydrophilic matrix (urea, Mannitol, Lactose Monohydrate) is first dissolved in adequate amount of water and melted in water bath with gradual increase in temperature until it completely melts. Now, drug is added in the melted urea or mannitol or lactose monohydrate with constant stirring and leaves this mixture to cool at room temperature. The ratio of drug and hydrophilic matrix taken is 1:1. The mixture was dried, crushed, pulverized and passed through sieve number #60 and stored in desiccators⁹.

Preparation of Tablets:

The solid dispersion of Aceclofenac tablets were prepared by direct compression method. Required quantity of solid dispersion of Aceclofenac, HPMC and MCC are weighted and mixed uniformly using pestle mortar. Then talc and magnesium Stearate are added with it. 

Table 1: Various composition of Aceclofenac SD Tablets

Ingredients	F1	F2	F3
Aceclofenac (SD)	100mg	100mg	100mg
Urea	100mg	---	---
Mannitol	---	---	100mg
Lactose Monohydrate	---	100mg	---
HPMC E 15 LV	100mg	100mg	100mg
Micro Crystalline Cellulose	15mg	15mg	15mg
Magnesium Stearate	5mg	5mg	5mg
Talc	5mg	5mg	5mg

All ingredients are mixed uniformly. After that, the powders are punched in a tablet compression machine and get tablets⁹.The various composition of Aceclofenac SD tablet shown on the table 1.

Characterization of granules flow characteristics:

Bulk Density: 

A precise amount (m) of granules was carefully added to the measuring cylinder. The granules were read to the closest graded unit to determine the unsettled apparent volume (V) after being leveled without compacting if required. The bulk density was determined using the formula m/V and represented as grams per ml¹⁰.

Tapped Density:

A predetermined amount of granules was placed in a measuring cylinder and tapped for five minutes using a mechanical tapping device¹⁰. Both the first and last volumes were mentioned.

 

Angle of Repose:

The angle of repose measures the frictional forces in loose powder or granules. The angle between the surface of a pile of granules or powder and the horizontal plane is as large as it can be. The funnel method is used for this¹¹. The following formula is used to determine the angle of repose value:

 

Where, 

Ɵ =Angle of repose, h =Height of the pile, r =Radius of the pile

Compressibility Index and Hausner ratio:

A powder's tendency to consolidate is measured by its compressibility index (CI), which is a measure of the relative significance of interparticulate interactions.

A measure of a material's flowability that accounts for the resistance a bed of particles encounters as a result of their interactions is called the Hausner ratio (HR)¹¹. Compressibility index and hausner ratio were calculated by using the following formula:

 

 

The results of bulk density, tapped density, angle of repose, compressibility index and hausner’s ratio are noted on table 2.

Evaluation of Tablets:

Hardness Test: A tablet's hardness is an indicator of its strength and capacity to withstand mechanical shocks during processing and handling. Using a Monsanto hardness tester, the tablets' hardness was assessed for each formulation. kg/cm-2 is the unit of measurement¹². 

Friability Test: Friability tests are used to evaluate the impact of shocks and friction, which frequently result in tablets breaking, chipping, or capping. Roche Friabilator was employed to assess the tablets' friability¹². 

Drug Content: Ten tablets were chosen at random from each batch for this test, and they were ground up in a mortar. The powder was dissolved in 10 ml phosphate buffer pH 7.4 by sonication for 15 min and filtered through Whatman filter paper. Suitable dilutions were made, and the drug content was analysed spectrophotometrically at 276 nm using a UV-VIS spectrophotometer (model Jasco V730)^13,14.

Dissolution Test: In vitro dissolution study of tablets were conducted using USP dissolution apparatus II at 50 rpm, using phosphate buffer pH 7.4 as a dissolution media maintaining at 37 ± 0.5° C¹⁵.

The results of hardness, friability, drug content are shown in table 3.

Drug Release Kinetic:The following formulas were used to assess the data from the in vitro release study using the linear regression method:

i) Zero Order:

 

Where, Q= Amount of drug release in time t

K0 = Zero order rate constant expressed in unit of concentration/ time

t = Release time 

ii) First Order:

 

Where, Q0 = The initial concentration of drug

K= The first order rate constant

t = Release time

iii) Higuchi Model:

Q= Kt_1/2

Where, K= Release rate constant

T= Release time 

iv) Hixon- Crowell model:

W₀^1/3 -W_t^1/3 = kt

Where, W0 = Initial amount of drug in the pharmaceutical dosage form

W_t = Remaining amount of drug in the pharmaceutical dosage form at time t

K = Rate Constant incorporating the surface volume relation 

V) Kormeseyer- Peppas model:

 

Where, Mt = Amount of drug release at time t

M∞ = Amount of drug released after infinite time

Mt/M∞ = Fraction solute release

t= Release time 

K= Kinetic constant incorporating structural and geometric characteristics of the polymer system

n= Diffusion exponent that characterizes the mechanism of the release of traces ^16,17

The results are shown in table 5 and figs 2-6.

RESULTS:

The granules were assessed by using the following parameters: angle of repose which ranges from 25.80 ± 0.135 to 28.44 ± 0.198, bulk density ranges from 0.38 ± 0.005 to 0.45 ± 0.008 kg/ cm³, tapped density ranges from 0.42 ± 0.003 to 0.51 ± 0.006 kg/ cm³, Carr’s index ranges from 9.52 ± 0.004 to 16.32 ± 0.009 and hausner’s ratio 1.10 ± 0.02 to 1.19 ± 0.04.

 

 

Table 2: Precompression Evaluation [ Characterization of Granules]

Formulation	Angle of Repose	Bulk Density	Tapped Density	Carr’s Index	Hausner’s Ratio
F1	25.75±0.423	0.38±0.005	0.42±0.003	9.52 ± 0.004	1.10±0.02
F2	28.44±0.198	0.41±0.012	0.49±0.007	16.32±0.009	1.19±0.04
F3	26.80±0.135	0.45±0.008	0.51±0.006	11.76±0.007	1.13±0.06

*Mean± SD (n=3)

The hardness of the tablet’s ranging from 3.8 ± 0.03 to 5.4 ± 0.06 kg/ cm², friability ranges from 0.56 ± 0.03 to 0.71 ± 0.04 % and drug content ranges from 81.2 ± 0.032 to 83.38 ± 0.028 %. 

Table 3: Postcompression Evaluation

Formulation	Hardness (Kg/ cm2)	Friability (%)	Drug Content (%)
F1	5.4 ± 0.06	0.56±0.04	83.38±0.028
F2	4.9± 0.08	0.71±0.03	81.2±0.032
F3	3.8±0.03	0.67±0.02	82.09±0.025

*Mean± SD (n=3)

Table 4: Comparative release study of three formulations

Formulation	% of Drug Release
F1	94.616
F2	76.687
F3	57.694

 

Table 5 : Kinetic study of in-vitro release data of  Aceclofenac

Formulation Code	Zero Order	First Order	Higuchi Model	Hixon – Crowell Model	Korsmeyer Peppas Model
Correlation Coefficient
F1	0.954	0.711	0.997	0.994	0.952
F2	0.977	0.829	0.982	0.961	0.976
F3	0.979	0.743	0.989	0.9759	0.974

 

Figure 1 : Comparative Release Profile of various formulation

 

 

 

Figure 2: Zero order release plot for prepared solid dispersion tablets

 

Figure 3: First order release plot for prepared solid dispersion tablets

 

 

Figure 4: Higuchi release plot for prepared solid dispersion tablets

 

Figure 5: Hixon Crowell release plot for prepared solid dispersion tablets

Figure 6 : Korsmeyer Peppas release plot for prepared solid dispersion tablets

DISCUSSIONS:

 A variety of precompression experiments, including angle of repose, tapped density, bulk density, Carr's index, and Hausner's ratio, were conducted after the aceclofenac was produced in SD form utilizing a variety of matrix, including urea, mannitol, and lactose. Upon examining these outcomes, it was decided that the results are within standard limit and highly satisfactory.  After preparing the SD of aceclofenac tablets, it was found that the F1 batch had superior hardness and friability compared to the other two batches. The F1 batch had a drug content of 83.38 ± 0.028 percent, which is significantly higher than the other two formulations. After three hours, the dissolution study for formulations F1, F2, and F3 reveals that they release 94.616%, 76.687 %, and 57.694 % of the medication, respectively. Consequently, after the discussion, it has been determined that, out of the three formulations, F1 is the best batch. The release data was analyzed using various kinds of kinetic models, including zero order, first order, Higuchi model, Hixon-Crowell model and korsmeyer Peppas model as illustrated in figs 2-6. The value of R2 was reported in table 5. All of the above formulations fit the Higuchi model the best.

CONCLUSION:

Pure aceclofenac had an extremely sluggish rate of dissolution. The rate of dissolution was quite rapid when the aceclofenac was produced in SD form. Aceclofenac SD tablets were made, and a release study was performed. When compared to tablets made with mannitol and lactose, the release of aceclofenac SD tablets made with urea was superior. Aceclofenac SD tablets' bioavailability improved in conjunction with their rate of dissolution. For this formulation's future development, a long-term stability study is also necessary.

Conflict of Interest: The authors declare no potential conflict of interest with respect to the contents, authorship, and/or publication of this article. 

Author Contributions: All authors have equally contributed.

Source of Support: Nil 

Funding: The authors declared that this study has received no financial support. 

Informed Consent Statement: Not applicable. 

Data Availability Statement: The data presented in this study are available on request from the corresponding author. 

Ethics approval: Not applicable.

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