Gliclazide Azadirachta Indica Fruit Mucilage Povidone Biology Essay

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The purpose of the present investigation was to design matrix type oral tablets of Gliclazide with Azadirachta indica fruit mucilage and Povidone. The polymers were studied for its functionality as a matrix forming property to sustain the Gliclazide release from formulated matrix tablets. Physicochemical properties of dried powdered mucilage of Azadirachta indica fruit mucilage and Povidone blend were studied. Various formulations of Gliclazide Azadirachta indica fruit mucilage and Povidone were prepared. The designed tablets were found to have better pharmacopoeial parameters with low standard deviation values. The swelling behavior and release rate characteristics were studied. The in-vitro dissolution study proved that the dried Azadirachta indica fruit mucilage and Povidone combination can be used as a matrix forming polymers for making sustained release matrix tablets.

Key words: Gliclazide, Azadirachta indica, Povidone, matrix tablets, sustained release.

INTRODUCTION:

The mucilage of Azadirachta indica fruits clinically and experimentally proved anti-diabetic activity1and release retardant property in the present investigation.

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Gliclazide is an oral hypoglycemic agent, which is a commonly prescribed drug for the treatment of patients with type II diabetes mellitus. It belongs to sulfonyl ureas drug class. Gliclazide is a weak acid with PKa of 5.98. Gliclazide is practically insoluble in water and acidic environment but highly permeable (class 2) according to the Biopharmaceutical classification System (BCS) 2. The oral absorption is uniform, rapid and complete with nearly 100% bioavailability. The usual dose of Gliclazide is 80-320 mg daily3. The pharmacokinetics and dosage schedule supports once daily sustained release formulations for Gliclazide for better control of blood glucose levels to prevent hypoglycemia, enhance clinical efficacy and patient compliance4. The objective of present investigation is to design and evaluate sustained release tablets of Gliclazide using Azadirachta indica fruits mucilage and Povidone combination as release retardant for making sustained release matrix tablets.

MATERIALS AND METHODS:

Gliclazide was obtained as a gift sample from Dr. Reddy's Laboratories, Hyderabad, India. Azadirachta indica fruits 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. Povidone, Micro crystalline cellulose (Avicel) 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.

Extraction of mucilage

The fresh Azadirachta indica fruits were collected and washed with water. The outer shells were removed and the seeds with mucilage were placed 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 (in the quantities of three times the volume of filtrate) was added to precipitate the mucilage. The mucilage was separated, dried in an oven at 40°C, collected, powdered, passed through a # 80 sieve and stored in desiccator at 30°C & 45% relative humidity till use5. The collected mucilage was tested for flow properties which were shown in Table 1. All values were found to be satisfactory.

Drug-Excipient compatibility studies

Differential Scanning Calorimetry (DSC)

DSC analysis was performed using Shimadzu DSC-60, Shimadzu Limited Japan. A 1:1 ratio of drug and excipient was weighed into aluminum crucible. The sample was analyzed by heating at a scanning rate of 200C over a temperature range 200-3000 under nitrogen environment.

Fourier Transform Infrared (FTIR) Spectroscopy

FTIR spectra were recorded on samples prepared in potassium bromide (KBr) disks using a Shimadzu Corporation, (Tokyo, Japan) Model-1601 PC. Samples were prepared in KBr disks by means of a hydrostatic press at 6-8 tons pressure. The scanning range was 500 to 4000 cm-1.

Preparation of matrix tablets

Sustained release matrix tablets of Gliclazide with Azadirachta indica fruit mucilage and Povidone were prepared by using different drug: mucilage ratios as shown in Table 2, Azadirachta indica fruits mucilage and Povidone were used as matrix forming materials while microcrystalline cellulose as a diluent and Magnesium stearate as a lubricant6. 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. The compositions of formulations were showed in Table 2. These matrix tablets were evaluated for their physical properties as per I.P methods 7, 8 which were shown in Table 3.

Swelling behavior of matrix tablets

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The extent of swelling was measured in terms of % weight gain by the tablet. The swelling behavior of formulation GPA-1, GPA-2, GPA-3, GPA-4 and GPA-5 were studied. One tablet from each formulation was kept in a Petri dish containing phosphate 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. The % weight gain by the tablet was calculated by formula9.

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

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

Mo = Weight of tablet at time 0. Swelling behavior of Sustained release matrix tablets were represented in Fig. 7.

Estimation of Gliclazide

An ultraviolet spectrophotometric method based on measurement of absorbance at 229 nm in Phosphate buffer of pH 7.4. The method obeyed Beer-Lambert's law in the concentration range of 1-20 µg/ml. No interference was observed from the excipients used.

In vitro drug release studies

Release of Gliclazide 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 50 rpm and 37° ± 0.5°C. A sample of Gliclazide matrix tablets equivalent to 100 mg of Gliclazide 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 229 nm for Gliclazide content10 using a UV/ visible single-beam spectrophotometer-117 (Systronics Corporation, Mumbai, India). The drug release experiments were conducted in triplicate (n = 3). The in vitro release rates were showed in Fig. 8.

RESULTS AND DISCUSSION:

The DSC of Gliclazide Pure drug, Azadirachta indica fruits mucilage with Povidone and physical mixture were shown in Fig 1, 2 and 3 respectively. Infrared Spectrum of Gliclazide Pure drug, Infrared Spectrum of Azadirachta indica fruits mucilage with Povidone, Infrared Spectrum of formulation was obtained. The FTIR spectrums revealed that the formulation spectrum retains the peaks of drug used and these spectrums were represented in Fig. 4, 5 and 6 respectively.

Matrix tablets, each containing 100 mg of Gliclazide, were prepared using dried fruit mucilage of Azadirachta indica in various drug: mucilage ratios. In-vitro drug release profile of Gliclazide from formulated matrix tablets were studied using zero order, first order, Higuchi, Korsmeyer Peppa's and Hixson-Crowell's Models which were shown in Fig. 8, 9, 10, 11 and 12 respectively. The rate of release was faster in GPA-1 and slower in GPA-5. The kinetic plots were perfectly fitting to the formulated Azadirachta indica fruits mucilage- Gliclazide matrix tablets. This result shown that as the proportion of Azadirachta indica fruits mucilage increased, the overall time of release of the drug from the matrix tablet was also increased. Drug releases from matrix tablets were by drug dissolution, drug diffusion or a combination of both.

CONCLUSION:

The present study revealed that Azadirachta indica fruits mucilage and Povidone 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 Azadirachta indica fruits mucilage can be used as an excipient for making sustained release matrix tablets.

ACKNOWLEDGEMENT:

The authors are thankful to Dr. Reddy's Laboratories, Hyderabad, India for providing the gift sample of Gliclazide.

Table 1: Flow properties of dried Azadirachta indica fruit mucilage

Parameters

Value

Loose Bulk Density (g/ml)

0.578±0.08

Tapped Bulk Density (g/ml)

0.788±0.03

Compressibility index (%)

26.59±0.21

Hausner's ratio

1.24±0.04

Angle of repose (0)

29.45±1.68

Number of experiments (n)= 3

Table 2: Formulae of matrix tablets

Ingredients (mg)

Formulations

GPA-1

GPA-2

GPA-3

GPA-4

GPA-5

Gliclazide

100

100

100

100

100

Azadirachta indica fruits

mucilage

2

4

6

8

10

Povidone

2

4

6

8

10

Micro crystalline cellulose (Avicel)

91

87

83

79

75

Magnesium stearate

5

5

5

5

5

Total weight of tablet

200

200

200

200

200

Table 3: Physical properties of Azadirachta indica fruit mucilage Gliclazide matrix tablets

Sl. No

Formulation

code

Thickness

(mm)

Hardness

(kg/cm2)

Friability

(%)

Drug content

(%)

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GPA-1

5.9±0.19

6.52±1.04

0.70±0.08

99.8±7.51

2

GPA-2

5.8±0.48

7.52±1.18

0.80±0.01

100.8±6.37

3

GPA-3

5.7±0.23

5.85±1.55

0.19±0.04

99.9±5.81

4

GPA-4

6.1±0.16

7.56±0.52

0.53±0.04

99.1±3.66

5

GPA-5

6.2±0.19

6.92±0.29

0.64±0.01

100.4±2.55

Number of trials (n) = 5

Fig.1: DSC Spectra of Gliclazide

Fig. 2: DSC Spectra of Azadirachta indica fruits mucilage Povidone

Fig. 3: DSC Spectra of Physical Mixture

Fig. 4: Infrared Spectrum of Gliclazide Pure drug

Fig. 5: Infrared Spectrum of Azadirachta indica fruits mucilage and Povidone

Fig. 6: Infrared Spectrum of the formulation blend

Fig. 7: Swelling Index of formulated matrix tablets

Fig. 8: Zero order release Plots

Fig. 9: First order release Plots

Fig. 10: Higuchi Plots

Fig. 11: Korsmeyer Peppa's Plots

Fig.12: Hixson-Crowell's Plots