Sustained Release Matrix Tablets Of Aceclofenac Biology Essay

Published:

This essay has been submitted by a student. This is not an example of the work written by our professional essay writers.

The present research work was aimed to develop matrix tablets of Aceclofenac with Aloe barbadensis miller leaves mucilage and Poly Vinyl Pyrrolidone and to study its functionality as a better matrix forming combination for sustained release tablet formulations. Mucilage from Aloe barbadensis miller leaves was extracted, purified and characterized for its physicochemical characteristics. The powdered blend was evaluated for flow properties. Various formulations of Aceclofenac with Aloe barbadensis miller leave mucilage and Poly Vinyl Pyrrolidone were prepared by direct compression technique. The formulated tablets were found to have better flow properties with low standard deviation values. The formulated tablets were further studied for physical tests, swelling behavior and in vitro release rate characteristics. The in vitro dissolution study proved that the dried Aloe barbadensis miller mucilage in combination with Poly Vinyl Pyrrolidone may be good combination for making sustained release matrix tablets.

Key words: Aceclofenac, Aloe barbadensis miller, Poly Vinyl Pyrrolidone, matrix tablets, sustained release.

1. Introduction

Aceclofenac (2-[(2, 6-dichlorophenyl) amine] phenyl acetoxyacetic acid) is a newer non-steroidal anti-inflammatory drug (NSAID) [1]. Aceclofenac is a phenyl acetic acid derivative which is a commonly prescribed drug for the treatment of patients suffering with pain, rheumatoid arthritis, osteoarthritis and ankylosing spondylitis [2, 3]. It is a weak acid (pKa = 4.7) practically insoluble in water and acidic environment but highly permeable (class 2) according to the Biopharmaceutical classification System (BCS) [4]. The oral absorption is uniform, rapid and complete with a bioavailability of nearly 100% with an elimination half-life of 3-4 hours [5] requiring it to be administered in 100mg twice daily [6]. Hence we have selected Aceclofenac for the development of once daily sustained release matrix tablets. Poly Vinyl Pyrrolidone is already proved as release retardant in matrix tablets [7]. The mucilage of Aloe barbadensis miller leaves were clinically and experimentally proved analgesic and anti-inflammatory activity [8] and release retardant activity in the present study. The objective of present investigation is to design and evaluate sustained release tablets of Aceclofenac using Aloe barbadensis miller leaves mucilage and Poly Vinyl Pyrrolidone combination as release retardant for making sustained release matrix tablets.

2. Materials and Methods

Aceclofenac was obtained as a gift sample from Waksman and Selman Pharmaceuticals, Anantapur, Andhra Pradesh, India. Aloe barbadensis miller leaves were collected from plants growing in local areas of Anantapur, India. The plant was authenticated at the Botany Department of Sri Krishnadevaraya University, Anantapur, India. Poly Vinyl Pyrrolidone, Micro crystalline cellulose and Magnesium stearate were procured from SD Fine chemicals (Mumbai, India). All other chemicals used were of analytical reagent grade and double distilled water was used throughout the experiments.

2.1. Extraction of mucilage

The fresh Aloe barbadensis miller leaves were collected and washed with water. Incisions were made on the leaves and left over night. The leaves were crushed and soaked in water for 5-6 hours, boiled for 30 minutes and left to stand for 1 hour to allow complete release of the mucilage into the water. The mucilage was extracted using a multi-layer muslin cloth bag to remove the marc from the solution. Acetone (three times the volume of filtrate) was added to precipitate the mucilage. The mucilage was separated, dried in an oven at 40°C, collected, grounded, passed through a # 80 sieve and stored in desiccator at 30°C & 45% relative humidity till use [9]. Before tablet compression the formulated tablet blend was evaluated physical and flow properties.

2.2. Preparation of matrix tablets

Sustained release matrix tablets of Aceclofenac with Aloe barbadensis miller leaf mucilage and Poly Vinyl Pyrrolidone were prepared by using different drug: mucilage ratios as shown in Table 1. Aloe barbadensis miller leaves mucilage and Poly Vinyl Pyrrolidone were used as matrix forming materials while microcrystalline cellulose as a diluent and magnesium stearate as a lubricant. All ingredients used were passed through a # 100 sieve, weighed and blended. The granules were prepared by wet granulation technique and compressed by using 10 mm flat faced punches.

TABLE 1: Formulae of matrix tablets

Ingredients (mg)

Formulations

F-1

F-2

F-3

F-4

F-5

Aceclofenac

100

100

100

100

100

Aloe barbadensis miller leaves

mucilage (dried)

2.5

5

7.5

10

12.5

Poly Vinyl Pyrrolidone

2.5

5

7.5

10

12.5

Micro crystalline cellulose (Avicel)

90

85

80

75

70

Magnesium stearate

5

5

5

5

5

Total weight of tablet

200

200

200

200

200

2.3. Swelling behavior of matrix tablets

The extent of swelling was measured in terms of % weight gain by the tablet. The swelling behavior of formulations F-1, F-2, F-3, F-4 andF-5 was studied. One tablet from each batch was kept in a petri dish containing phosphate buffer (pH 7.4). At the end of 2 hours, the tablet was withdrawn, kept on tissue paper and weighed, repeated for every 2 hours till the end of 12 hours [10]. The percent weight gain by the matric tablet was calculated by eq.1.

S.I = {(Mt-M0) / M0} X 100 ------ (1)

Where, S.I = Swelling Index, Mt = Weight of tablet at time 't' and

M0 = Weight of tablet at time 0.

3. Evaluation

3.1. Compatibilities study

The compatibility of drug and polymers under experimental conditions was conducted using Fourier Transform Infrared (FTIR) studies (KBr pellet method was employed).

3.2. Pre compression parameters

The powdered blend was evaluated for flow properties viz., angle of repose, loose bulk density (LBD), tapped bulk density (TBD) and Carr's compressibility index.

3.3. Post compression parameters

The formulated tablets were evaluated for various parameters viz., thickness, hardness and friability and uniformity of drug content [11].

3.4. In vitro drug release studies

Release of Aceclofenac from the matrix tablets was studied in phosphate buffer of pH 7.4 (900 ml) using United States Pharmacopoeia (USP) 8-station Dissolution Rate Test Apparatus (Model Electro lab, TDT- 06T, Mumbai, India) with a rotating paddle stirrer at 75 rpm and 37± 0.5°C. A sample of Aceclofenac matrix tablets equivalent to 100 mg of Aceclofenac was used in each test. Samples of dissolution fluid were withdrawn through a filter (0.45 μm) at different time intervals and were assayed at 223 nm for Aceclofenac content using a UV/ visible double-beam spectrophotometer (Elico SL 210, Mumbai, India). The drug release experiments were conducted in triplicate (n=3). The in- vitro release data was further treated for kinetic modeling.

3.5. Accelerated Stability studies

The promising formulation (F-5) was tested stability for a period of 3 months at accelerated storage conditions of a temperature 40±2oC and a relative humidity of 75±5% RH, for their drug content [12].

4. Results and Discussion

The compatibility of Aceclofenac with the polymer used (Aloe barbadensis miller and Poly Vinyl Pyrrolidone) were studied by FTIR spectrums (Figure 1, 2 and 3). The characteristic peaks in FTIR spectrums of Aceclofenac were also seen in the FTIR spectrum of formulated blend.

FIGURE 1: Infrared Spectrum of Aceclofenac Pure drug

FIGURE 2: Infrared Spectrum of Aloe barbadensis miller leaves mucilage and Poly Vinyl Pyrrolidone

FIGURE 3: Infrared Spectrum of formulation

Aloe barbadensis miller gave 23 ±2.173% of mucilage (yield). The collected mucilage was in brownish yellow in colour with characteristic odour and has a neutral pH, which was soluble and forms colloidal solution, in Luke warm water, practically insoluble in ethanol, acetone, ether and chloroform. The average particles in mucilage was found to be 165.15±10.265 µm, the weight loss on drying was minimum (4.20±2.573%) and acid insoluble ash was found to be 1.29±0.019%. The mucilage showed good swelling index (45±3.841%). The mucilage was charred and decomposed at and above 125oC. A 0.5% w/v of the mucilage showed a density of 1.451±0.045. The mucilage has negligible bio burden (Bacteria: 5 CFU; Fungi: 2 CFU). The Angle of repose of Aloe barbadensis millers leave mucilage was found to be 27.96±1.684, indicating excellent flow properties (25-30o) and the Carr's Index was found to be 26.41±1.54 indicating passable compression properties.

The formulation blend was also tested for flow properties. The Angle of repose of formulation blend was ranged from 26.65±0.02 to 29.73o±0.16, indicating excellent flow properties (25-30o). The loose bulk density and tapped bulk density values were considered in calculating compressibility index and the Carr's Index was ranged from 12.12±0.09 to 16.18±0.15% (12-16%), indicating good compression properties. The values of flow properties of formulation blend was showed in Table 2.

TABLE 2: Flow properties of formulation blend

Formulation

Angle of Repose (q)

Loose Bulk Density (g/cm3)

Tapped Bulk Density (g/cm3)

Compressibility

(%)

F-1

29.32±0.10

0.57±0.04

0.68±0.01

16.18±0.15

F-2

29.73±0.16

0.59±0.02

0.69±0.05

14.52±0.08

F-3

28.20±0.05

0.57±0.02

0.65±0.06

12.31±0.11

F-4

29.30±0.04

0.58±0.05

0.66±0.02

12.12±0.09

F-5

26.65±0.02

0.62±0.06

0.72±0.01

13.89±0.02

All values were expressed as mean ±S.D; Number of trials (n)=5

The thickness of the tablets was ranged from 2.85±0.035 to 3.48±0.074 mm, indicating uniformity in thickness. The average percentage deviation of 20 tablets of each formula was less than ±7.5%. The weights of matrix tablets were within the limits as prescribed in Pharmacopoeia. i.e., for the tablets of more than 80 mg and less than 250 mg is ±7.5%. The mean percentage deviation of all tablets was found to be within this limit and hence all batches passed uniformity of weight test as per India Pharmacopoeia. Drug content was found to be uniform among different formulations and ranged from 99.5±2.56 to 101.2±5.25. Good uniformity in drug content was found among different batches of the tablets and the percentage of drug content was more than 99%. The hardness of formulated tablets was ranged from 6.50±1.45 to 8.10±1.40kg/cm2, which was more than 5 kg/cm2 indicating good mechanical strength. Another measure of a tablet's strength is friability. Conventional compressed tablets that lose less than 1% of their weight are generally considered acceptable. In the present study, the percentage friability for all the formulations was below 1% (0.44±0.03 to 0.85±0.05), indicating that the friability is within the prescribed limits. All these values were represented in Table 3.

TABLE 3: Physical properties of formulated matrix tablets

Formulation

Thickness

(mm)

Hardness

(kg/cm2)

Friability

(%)

Drug content

(%)

F-1

3.16±0.065

7.50±1.25

0.50±0.02

100.2±3.95

F-2

2.88±0.103

8.10±1.40

0.85±0.05

101.2±5.25

F-3

3.05±0.050

6.80±1.35

0.44±0.03

99.5±2.56

F-4

3.48±0.074

6.50±1.45

0.62±0.06

99.9±2.16

F-5

2.85±0.035

7.40±1.30

0.73±0.07

100.5±3.67

All values were expressed as mean ±S.D; Number of trials (n)=5

The formulated tablets showed good swelling behavior, which was shown in Figure 4.

FIGURE 4: Swelling Index of formulated tablets

The rate of drug release was faster in F-1 and slower in F-5. To know the mechanism of drug release from these formulations, the dissolution data was treated using zero order, first order, Higuchi plot, Korsmeyer Peppas plot and Hixson-Crowell Models. Drug release from all the formulations was perfectly fitting to Higuchi's model. The kinetic models on drug release from dosage form were represented in Figures 5, 6, 7, 8 and 9.

FIGURE 5: Zero order release Plots

FIGURE 6: First order release Plots

FIGURE 7: Higuchi Plots

FIGURE 8: Korsmeyer Peppas Plots

FIGURE 9: Hixson-Crowell's Plots

The accelerated stability studies revealed that the formulation (F-5) was stable even after accelerated storage conditions and were tabulated in Table 4.

TABLE 4: Observed values of optimized formulation (F-5) parameters before and after accelerated stability studies

Parameter

Observation

Before stability studies

After stability studies

Angle of Repose (q)

26.65±0.02

26.44±0.01

Loose Bulk Density (g/cm3)

0.62±0.06

0.65±0.05

Tapped Bulk Density (g/cm3)

0.72±0.01

0.69±0.03

Compressibility (%)

13.89±0.02

14.16±0.06

Hardness (kg/cm2)

7.40±1.30

7.30±1.55

Friability (%)

0.73±0.07

0.79±0.05

Drug content (%)

100.5±3.67

100.3±4.29

All values were expressed as mean ±S.D; Number of trials (n)=5

5. Conclusion

The present study revealed that Aloe barbadensis miller leaves mucilage and Poly Vinyl Pyrrolidone combination appears to be suitable for use as a release retardant in the manufacture of sustained release matrix tablets because of its good swelling, good flow and suitability for matrix formulations. From the dissolution study, it was concluded that dried Aloe barbadensis miller leaves mucilage in combination with Poly Vinyl Pyrrolidone forms a good matrix for sustained release of drug from the tablets.

Writing Services

Essay Writing
Service

Find out how the very best essay writing service can help you accomplish more and achieve higher marks today.

Assignment Writing Service

From complicated assignments to tricky tasks, our experts can tackle virtually any question thrown at them.

Dissertation Writing Service

A dissertation (also known as a thesis or research project) is probably the most important piece of work for any student! From full dissertations to individual chapters, we’re on hand to support you.

Coursework Writing Service

Our expert qualified writers can help you get your coursework right first time, every time.

Dissertation Proposal Service

The first step to completing a dissertation is to create a proposal that talks about what you wish to do. Our experts can design suitable methodologies - perfect to help you get started with a dissertation.

Report Writing
Service

Reports for any audience. Perfectly structured, professionally written, and tailored to suit your exact requirements.

Essay Skeleton Answer Service

If you’re just looking for some help to get started on an essay, our outline service provides you with a perfect essay plan.

Marking & Proofreading Service

Not sure if your work is hitting the mark? Struggling to get feedback from your lecturer? Our premium marking service was created just for you - get the feedback you deserve now.

Exam Revision
Service

Exams can be one of the most stressful experiences you’ll ever have! Revision is key, and we’re here to help. With custom created revision notes and exam answers, you’ll never feel underprepared again.