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Research Article

Vol: 2; Issue: 2

FORMULATION AND EVALUATION OF SOLID

DISPERSION OF GLIPIZIDE FOR SOLUBILITY AND

DISSOLUTION RATE ENHANCEMENT

Ankit Gupta1*, Mahesh Kumar Kataria

2, Ajay Bilandi

3

1M.Pharm. SEM IVth (Pharmaceutics), 2Assistant Professor and Head Department of Pharmaceutics,

3Lecturer, Department of Pharmaceutics, Seth G.L. Bihani S.D. College of Technical Education,

Sri Ganganagar, Rajasthan, India

Date Received:

28TH Jan 2014

Date of Accepted:

4th Feb 2014

Date Published:

11th Feb 2014

74

Abstract: The poor solubility of drug substances in water and their low dissolution rate in aqueous G.I.T fluid often leads to

insufficient bioavailability. Glipizide is a class-II antidiabetic drug which is purely insoluble in water. Since only

dissolved drug can pass the gastro intestinal membrane, proper solubility of the drug is ultimately desired. Solubility of

the poorly soluble drug, glipizide, is enhanced by formulating solid dispersion using melting fusion and solvent

evaporation method. Drug and carriers like Eudragit E-100, Croscarmellose and Sodium Starch Glycolate in different

ratios like 1: 1, 1: 2, 1: 3 and 1:4 were used for formulating solid dispersions. The FTIR spectra of the glipizide and

polymers alone and in combination show the compatibility of the drug and excipients. The solid dispersions were

evaluated for practical yield and in vitro dissolution. It was concluded that 1:4 ratio of drug: SSG shows better in vitro

dissolution rate compared to the pure drug and marketed preparation. Further the solid dispersion with highest release rate

was formulated in tablet dosage form. The angle of repose, bulk density, tapped density, carr’s index and hausner ratio

were calculated for the micromeritic characterization of the powder blend. The tablets were further studied for different

pharmacopoeial and non pharmacopoeial evaluation test. Similarity factor F2 was 52 and difference factor F1 was 14 for

glipizide was found to be within the standards. The in vitro release from the formulation was observed three times

increased from the glipizide API.

Keywords: Poor solubility, Eudragit E100, Croscarmellose sodium (CCS), Glipizide, Sodium Starch Glycollate

(SSG), Solid dispersion, Solvent evaporation method.

Introduction

Oral drug delivery is the simplest and easiest way of

administering drugs, because of the greater stability,

smaller bulk, accurate dosage and easy production.

Among the oral dosage form solid dosage forms have

many advantages over other types of oral dosage

forms. Therefore, most of the new chemical entities

under development these days are intended to be used

as a solid dosage form which produces an effective

reproducible in vivo plasma concentration after oral

administration. In fact, most new chemical entities are

poorly soluble drugs, not well-absorbed after oral

administration, which can distract from the drug’s

inherent efficacy. Drug absorption from the

gastrointestinal tract can be limited by a number of

factors; most significant contributors are poor aqueous

solubility & poor membrane permeability of the drug

molecule.

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Ankit Gupta et al; Vol: 2 Issue:2 Page:74-87

75

When delivering an active agent orally, it must first

dissolve in gastric and/or intestinal fluids before it can

permeate the membranes of the GI tract to reach systemic

circulation. Hence two areas of pharmaceutical research

that focus on improving the oral bioavailability of active

agents include enhancing solubility and dissolution rate

of poorly water soluble drugs & enhancing permeability

of poorly water-soluble drugs.

One of the major current challenges of the pharmaceutical

industry is related to strategies that improve the water

solubility of drug. Drug release is a crucial and limiting

step for oral drug bioavailability, particularly for drug

with low gastrointestinal solubility and high permeability.

By improving the drug release profile of these drugs, it is

possible to enhance their bioavailability and reduce side

effects. Solid dispersions are one the most successful

strategic approach to improve drug release of poorly

soluble drugs. Solid dispersion can be defined as a

molecular mixture of poorly water soluble drugs in

hydrophilic carriers, which present the drug release

profile that is driven by the polymer properties[1]

.

Need of Solubility Enhancement

Drug absorption from the gastrointestinal tract can be

limited by a variety of factors, most significant

contributors being poor aqueous solubility and poor

membrane permeability of the drug molecule. When

delivering an active agent orally it must first dissolve in

gastric and/or intestinal fluids before it can permeate the

membranes of the GI tract to reach systemic circulation.

Hence, two areas of pharmaceutical research that focus

on improving the oral bioavailability of active agents

include; enhancing solubility and dissolution rate of

poorly water-soluble drugs and enhancing permeability of

poorly water soluble drugs. The BCS is a scientific

framework for classifying a drug substance based on its

aqueous solubility and intestinal permeability.

Glipizide is an oral rapid- and short-acting anti-diabetic

drug from the sulfonylurea class. It is classified as a

second generation sulfonylurea, which means that it

undergoes enterohepatic circulation. Second-generation

sulfonylureas are both more potent and have shorter half-

lives than the first-generation sulfonylureas. It helps to

control blood sugar levels. This medication helps your

pancreas produce insulin. Glipizide is used together with

diet and exercise to treat type II diabetes[2],[3]

. It is 100

times more potent than Tolbutamide.

As per BP, It

Glipizide is practically insoluble in water; because of its

poor aqueous solubility (classified as BCS class II drug),

conventional Glipizide dosage form show absorption

problem, and its dissolutions are considered to be a rate

determining step in its absorption from gastrointestinal

tract. During high blood glucose level conditions, an

antidiabetic drug should show quick and high oral

bioavailability, which can be achieved by high aqueous

solubility. Many hydrophilic excipients like sodium

starch glycolate, eudragit E-100, croscarmellose,

PEG4000, PEG 6000, urea, Mannitol, PVP and

poloxamers can be used to enhance the dissolution of

drugs. So the rationale is to enhance the solubility rate of

Glipizide with the use of combination of polymers like

sodium starch glycollate (SSG), eudragit E-100 and

croscarmellose (CCS)[4],[5]

.

Several approaches has been used to enhance the

dissolution of glipizide by solid dispersion with

polyethylene glycol, mannitol and PVP K 30[6]

,

Polyethylene glycol (PEG 4000 and 6000)[7]

, PVP K30

and PEG 6000 and with Skimmed Milk (SM)[8]

, PVP

K30[9]

, PEG (Polyethylene glycol) 4000[10]

, Poloxamer

(PXM) 188 and Poloxamer (PXM) 407[11]

, liquisolid

approaches by Avicel PH-102 and Aerosil 200[12]

, bio

nano composites (BNCs) by microwave-induced

diffusion (MIND)[13]

, microemulsion (ME) using

Capmul® MCM-based ME formulation with Cremophor

EL and Transcutol[14]

, nanoparticles by HPMC-E15[15]

.

EXPERIMENTAL

MATERIALS:

Glipizide was obtained as a gift sample from Morepen

Laboratories Ltd, Baddi, Himachal Pradesh.

Croscarmellose sodium and Sodium starch glycolate was

obtained from Maple Biotech Pvt Ltd., Pune. Eudragit e

100 was obtained from Evonik Degussa India Pvt. Ltd.,

Mumbai. All other reagents and solvents used were of

analytical grade.

METHODS

Preformulation studies:

Preformulation studies focus on those physiochemical

properties of the drug that could affect performance and

development of an efficacious dosage form. It is

necessary to determine purity of API before formulation

any dosage form. Preformulation studies are useful in

determining the formulation components and

physiochemical properties of new drug substance.

Description of drug

The sample of drug was observed for colour, state and

odour.

Infra red spectrophotometry:

Before formulating a dosage form it is very necessary to

confirm that drug is not interacting with the polymer

under certain experimental studies. Interacting among

drug and polymer may affect the efficacy of final dosage

form. Drug and different excipients were taken in 1:1



76

ratio. The excipients used cros carmellose, sodium starch

glycolate and eudragit E- 100. These studies performed

from faculty of pharmaceutical sciences Jodhpur National

University.

Standard calibration curve:

A stock solution of glipizide (100 µg/ml) was prepared by

disolving 10 mg of glipizide in small volume of

methanol, in volumetric flask and the volume was

adjusted to 100 ml with 7.4 pH

phosphate buffers.

Spectral absorbance measurement was made on

Shimadzu-1700 UV-visible spectrophotometer.

Preparation of solid dispersion:

The melting or fusion method:

Four different formulation of glipizide solid dispersion

prepared with polymer Eudragit E 100 in 4 different

ratios 1:1, 1:2, 1:3, 1:4 by using melting fusion method.

The preparation of physical mixture involves of a drug

and a water-soluble carrier and heating it directly until it

melted. The melted mixture is then solidified rapidly in

an ice-bath under vigorous stirring. The final solid mass

is crushed, pulverized and sieved.

Solvent Evaporation Method: Eight different formulation of glipizide solid dispersion

prepared with 2 different polymers cros carmellose, and

sodium starch glycolate in 4 different ratios 1:1, 1:2, 1:3,

1:4 by using solvent evaporation method. The required

amount of Glipizide and the carrier were dissolved in

sufficient volume of methanol with continuous stirring.

The solvent was then completely evaporated at 45º C with

continuous stirring to obtain dry mass. The dried mass

was pulverized passed through 44 mesh sieve and stored

in dessicator until used for further studies. Formulation

batches are prepared with different ratio of polymer and

drug as shown in table no. 2.

Final batch was evaluated for angle of repose, bulk and

true density, compressibility index, hausner ratio.

Evaluation of solid dispersion:

Percentage yield:

Thoroughly dried solid dispersion were collected and

weighed accurately. The percentage yield was then

calculated using formulae given below,

Percentage Yield = ��

�� × 100

Estimation of drug content: An accurately weighed quantity of solid dispersion

equivalent to 50 mg of drug was taken into a 100 ml

volumetric flask and dissolved in minimum amount of

methanol and the volume was made up to the mark with

phosphate buffer pH 7.4, and measure at 274 nm using

UV double beam spectrophotometer[16]

.

In Vitro Dissolution: The dissolution study was carried out using USP

apparatus type-II. The dissolution medium was 900 ml

7.4 pH phosphate buffer kept at 37±1ºC. The basket was

rotated at 50 rpm. Samples of 5 ml were withdrawn at

specified time intervals and analyzed

spectrophotometrically at 275 nm using Shimadzu-1700

UV-visible spectrophotometer. The samples withdrawn

were replaced by fresh buffer solutions. The dissolution

study was continued for next 2 h.

Tablet preparation for optimized formulation:

1. Powder blend evaluation:

Bulk density

The bulk density of the formulated granules was

evaluated using a bulk density apparatus. It is expressed

in gm/ml and is given by

Bulk Density (ρb) = �� !�"# $ (�)

'�()* �� +)(, !�"# $ ('-)

Tapped density

It is the ratio of total mass of powder to the tapped

volume of powder. The tapped volume was measured by

tapping the powder to constant volume. It is expressed in

gram/ml and is given by[17]

Tapped Density (ρt) = �� !�"# $ (�)

.�!! # '�()* �� !�"# $ ('/)

Compressibility Index and Hausner Ratio

The Compressibility index and Hausner’s ratio are

measures of the propensity of a powder to be compressed

and the flow ability of granule. Carr’s index and

Hausner’s ratio were calculated using following formula

Carr’s Index (I) = ρ/0ρ-

ρ/

× 100

Hausner’s ratio = ρ/

ρ-

Where, ρt – Tapped density of the powder, ρb – Bulk

density of the powder

Angle of repose

Angle of repose was determined by Neumann’s method

and calculated using the formula, for unlubricated as well

as lubricated granules.

tanθ = h/r

θ = tan-1

(h/r) Where, h = height of pile, r = radius of the pile base

[18].

Ankit Gupta et al

2. Tablet preparation:

Direct compression method was used for tablets

preparation because it is a simple method of tableting that

can only be utilized when the powder mixture possesses

adequate flowing properties and compressibility.

3. Tablet evaluation:

Shape of Tablets

Compressed tablets were examined under the magnifying

lens for the shape of the tablets.

Tablet Dimensions:

Thickness and diameter of tablets were measured using

Vernier Calipers. It was determined by checking ten

tablets from final formulation. It is expressed in mm.

Hardness

Hardness indicates the ability of a tablet to withstand

mechanical shocks while handling. The hardness of the

tablets was determined using Pfizer hardness tester. It

was expressed in kg/cm2.

Friability

It is performed as per I.P. specification. Maximum loss

of weight (from a single test or from the mean of the three

tests) not greater than 1.0 per cent is acceptable for most

tablets[19]

.

Uniformity of Weight of Single-Dose Preparations

It is performed as per I.P. specification. 20 tablets

selected for the test.

Disintegration Test

Disintegration is defined as that state in which

of the unit under test remains on the screen of the

apparatus or, if a residue remains, it consists of fragments

of disintegrated parts of tablets component parts such as

insoluble coating of the tablets or of capsule shells, or of

any melted fatty substance from the pessary or

suppository or is a soft mass with no palpable core.

performed as per I.P. specification.

In Vitro Dissolution:

The dissolution study of final optimized formulation was

carried out using USP apparatus type-II. Th

study was continued for next 2 h.

Dissolution Profile Comparison:

Similarity and Difference Factors:

The in vitro dissolution of glipizide solid dispersion

tablets were prepared and matched with innovator

product by calculating the similarity and difference



Direct compression method was used for tablets

preparation because it is a simple method of tableting that

can only be utilized when the powder mixture possesses

properties and compressibility.

Compressed tablets were examined under the magnifying

Thickness and diameter of tablets were measured using

Vernier Calipers. It was determined by checking ten

formulation. It is expressed in mm.[17]

.

Hardness indicates the ability of a tablet to withstand

handling. The hardness of the

tablets was determined using Pfizer hardness tester. It

It is performed as per I.P. specification. Maximum loss

of weight (from a single test or from the mean of the three

eater than 1.0 per cent is acceptable for most

Dose Preparations

It is performed as per I.P. specification. 20 tablets

Disintegration is defined as that state in which no residue

of the unit under test remains on the screen of the

apparatus or, if a residue remains, it consists of fragments

of disintegrated parts of tablets component parts such as

insoluble coating of the tablets or of capsule shells, or of

atty substance from the pessary or

suppository or is a soft mass with no palpable core. It is

The dissolution study of final optimized formulation was

The dissolution

The in vitro dissolution of glipizide solid dispersion

tablets were prepared and matched with innovator

product by calculating the similarity and difference

factors. A model independent approach

estimate the dissimilarity factor (f

(f2) to compare the dissolution profile of optimized

formulation (F12) with innovator’s preparation. The

following equations were used for calculating f

The similarity factor (f2) is given by the following

equation:

Where n = no of time points, Rt = dissolution value of the

reference batch at time t,

Tt=dissolution value of the test batch at same time point.

Number of time points, n = 8

where both products ≥ 85%

Number of points in Rt and Tt must be the same and must

be the similar to n[20]

.

RESULT & DISCUSSION

Description of drug

Various properties of drug related with physical

appearance, state, solubility given in table

Table – 1 Description of Drug

S.No. Properties

1. Colour White Coloured

2. State Amorphous

3. solubility Practically insoluble in water,

sparingly soluble in acetone

and soluble in methylene

chloride (Dichloromethane),

chloroform and

formamide.

Drug excipients compatibility study

The possible interaction between drug and excipients

were studied by IR spectroscopy. Below spectra shows

the peaks of pure drug sample and polymers as compared

to standard drug sample that is i.e

occurs between polymers and drug samples as shown in

figure 1 – 6.

77

factors. A model independent approach was used to

estimate the dissimilarity factor (f1) and similarity factor

) to compare the dissolution profile of optimized

) with innovator’s preparation. The

following equations were used for calculating f1 and f2.

The similarity factor (f2) is given by the following

= dissolution value of the

=dissolution value of the test batch at same time point.

number of points

must be the same and must

Various properties of drug related with physical

appearance, state, solubility given in table no. 1.

1 Description of Drug

Inference

White Coloured

Amorphous

Practically insoluble in water,

sparingly soluble in acetone

and soluble in methylene

chloride (Dichloromethane),

chloroform and Dimethyl

formamide.

Drug excipients compatibility study

The possible interaction between drug and excipients

were studied by IR spectroscopy. Below spectra shows

the peaks of pure drug sample and polymers as compared

to standard drug sample that is i.e. no chemical reaction

occurs between polymers and drug samples as shown in

Ankit Gupta et al

Figure 1: FT IR spectra of drug and Eudragit E 100 mixture immediate

Figure 2: FT IR spectra of drug and Eudragit E 100 mixture after 15 Days



FT IR spectra of drug and Eudragit E 100 mixture immediate

FT IR spectra of drug and Eudragit E 100 mixture after 15 Days

78

FT IR spectra of drug and Eudragit E 100 mixture immediate

FT IR spectra of drug and Eudragit E 100 mixture after 15 Days

Ankit Gupta et al

Figure 3: FT IR spectra of drug and Croscarmellose Sodium mixture immediate

Figure 4: FT IR spectra of drug and Croscarmellose Sodium mixture after 15 days



FT IR spectra of drug and Croscarmellose Sodium mixture immediate

FT IR spectra of drug and Croscarmellose Sodium mixture after 15 days

79

FT IR spectra of drug and Croscarmellose Sodium mixture immediate

FT IR spectra of drug and Croscarmellose Sodium mixture after 15 days

Ankit Gupta et al

Figure 5: FT IR spectra of drug and Sodium Starch Glycolate mixture immediate

Figure 6: FT IR spectra of drug and Sodium Starch Glycolate mixture after 15 days

Analytical Method for glipizide using standard

calibration curve:

Analytical methods were developed for analysis of

glipizide in powder mixtures, formulations and in

solutions of different pH values using UV Spectroscopy.

The method obeyed Beer’s law and was found suitable

for the study. Standard calibration curve of glipizide in

different solvents of varying pH are shown in Figure 7.




IR spectra of drug and Sodium Starch Glycolate mixture after 15 days

Analytical Method for glipizide using standard

Analytical methods were developed for analysis of

glipizide in powder mixtures, formulations and in

different pH values using UV Spectroscopy.

The method obeyed Beer’s law and was found suitable

for the study. Standard calibration curve of glipizide in

different solvents of varying pH are shown in Figure 7.

FTIR Studies showed the follow

at 1646 cm-1

due to CONH stretc

SO2NH stretching, 1154 cm-

stretching and 1648 cm-1

due

obtained in the spectrum of pure d

given in standards.

80


IR spectra of drug and Sodium Starch Glycolate mixture after 15 days

ing characteristic peaks

ching, 1330 cm-1

due to -1

due to cyclohexyl

to C=O, urea. Peaks

durg were similar to that



81

Evaluation Tests:

Percentage yield: Percentage yield of different

formulation was determined by weighing the solid

dispersion after drying. The percentage yield of different

formulation was in range of 43.5 - 82.2% as shown in

Table 3. The maximum percentage yield was found in

F12.

Figure 7: Glipizide standard calibration curve and UV scan in phosphate buffer pH 7.4 at 275 nm λmax

Formulation Batches:

Table- 2: Formulation batches of glipizide solid dispersion

F1 – F4 batch were prepared with Melting Fusion and F5 – F12 Batches were prepared with solvent evaporation method.

S.NO. Formulation

code

Drug

(mg)

Eudragit E

100 (mg)

Croscarmellose

(mg)

Sodium Starch

Glycolate (mg)

1 F1 5 5 0 0

2 F2 5 10 0 0

3 F3 5 15 0 0

4 F4 5 20 0 0

5 F5 5 0 5 0

6 F6 5 0 10 0

7 F7 5 0 15 0

8 F8 5 0 20 0

9 F9 5 0 0 5

10 F10 5 0 0 10

11 F11 5 0 0 15

12 F12 5 0 0 20

y = 0.010x + 0.027

R² = 0.997

0

0.2

0.4

0.6

0.8

1

1.2

0 50 100 150

Ab

sorb

an

ce

Concentration (µg/ml)

Series1

Linear (Series1)



82

Table 3: Percentage yield of the Prepared Solid Dispersion.

S.NO. Formulation No. % yield

1. F1 43.5

2. F2 52.1

3. F3 60.9

4. F4 67.6

5. F5 47.3

6. F6 56.0

7. F7 60.5

8. F8 65.4

9. F9 51.8

10. F10 62.9

11. F11 71.6

12. F12 82.2

Table 4: Drug content of formulation batches

Formulation Batch Drug Content

F1 95.87%

F2 96.23%

F3 96.33%

F4 97.73%

F5 92.67%

F6 94.12%

F7 93.09%

F8 97.97%

F9 94.73%

F10 96.25%

F11 97.66%

F12 98.36%

2. Drug Content:

Only F12 formulation complied with the test of glipizide

content uniformity according to Indian Pharmacopoeia, as

beside these all formulations fall outside the limit of 98-

102 %. This is because of R value ( R=Q/q), ratio of

carrier (Q) to coating material (q) of 10 contained by

these formulations, which had sufficient concentration of

carrier (Eudragit E-100 & SSG) that might lead to

uniform distribution of drug by either adsorption onto, or

absorption into carrier, therefore having more

homogeneous distribution throughout the batch.

3. In-vitro dissolution Studies

Glipizide solid dispersions presented better dissolution

performance over corresponding the pure GZ. Glipizide

with Eudragit E 100 Solid Dispersion showed a marked

increase in the cumulative % drug release upto 61.90%.

Similarly Solid Dispersion of Glipizide with

Croscarmellose Na showed marked drug release upto

58.61% respectively as shown in table 5. Solid Dispersion

of Glipizide with Sodium Starch Glycolate showed

significantly increases the drug release upto 80.13%. The

enhanced dissolution was observed in case of Glipizide:

Sodium Starch Glycolate in 1:4 ratio solid dispersions.

Dissolution profile shown in the form of curve shape in

figure 8.

As per as the percentage yield, drug content and

dissolution studies are concerned, it indicated that f12

formulation gives best yield, having best drug content

and shows best dissolution release. By the result

observation, it can conclude that F12 formulation should

be a better candidate for solid dispersion with best

output.

Formula and evaluation test of final formulation:

1. Physical evaluation of solid dispersion powder: From the results obtained (Table 6), the angle of repose

was 26°65”, it indicates good flow property. Bulk density

was 0.37gm/ml and tapped density values ranged

between 0.42 g/ml and 0.44 g/ml indicates good flow

property. Hausner ratio was found to be 1.13. Carr’s

index was 11.8% and these indicate the prepared

granules exhibited good flow properties. Drug content

was found to be in the range of standard as per as the

Indian Pharmacopoeia is concerned (98 to 102%).



83

Table 5: In-vitro Dissolution Profile of Glipizide and Solid Dispersions of polymers in pH 7.4 Buffer.

S.No. Batches Cumulative % Release at Different Time Intervals in min

5 10 15 30 45 60 90 120

1 Glipizide 1.343 3.122 4.871 6.442 14.11 16.87 19.79 28.92

2 F1 7.45 12.83 16.51 22.76 25.56 29.92 34.77 39.61

3 F2 8.12 13.55 17.11 25.23 27.44 32.12 36.88 41.73

4 F3 8.23 14.21 19.10 27.98 30.55 33.64 40.11 47.16

5 F4 15.56 20.11 23.01 30.44 40.75 45.11 53.88 61.90

6 F5 5.66 8.93 13.67 16.44 20.51 25.64 29.49 35.54

7 F6 7.23 9.12 14.67 17.55 23.88 29.09 34.66 40.56

8 F7 10.32 14.65 17.50 21.65 25.76 30.77 39.67 47.87

9 F8 16.34 18.56 20.44 24.76 29.55 36.82 45.03 58.61

10 F9 8.33 14.22 21.45 30.57 41.52 43.87 46.99 49.52

11 F10 10.34 18.98 28.84 36.95 48.98 53.75 58.01 61.98

12 F11 14.65 22.89 34.95 43.16 56.27 60.12 65.12 70.21

13 F12 20.66 29.56 40.12 55.27 64.21 70.15 75.55 80.13

Figure 8: Scatter chart of dissolution profile of various solid dispersion of glipzide with different polymer

F1-F4=glipizide with Eudragit E-100, F5-F8= glipizide with Cros Carmellose, F9-F12= glipizide with Sodium Starch

Glycollate

Table 6: Physical evaluation of solid dispersion containing glipizide and SSG

S.NO. EVALUATION GLIPIZIDE : SSG (1:4)

1. Bulk density 0.37

2. Tapped density 0.42

3. Compressibility 11.8±3.55

4. Hausner ratio 1.13±0.05

5. Angle of repose 26°65”±0.63

6. Drug content 98.10%±0.2602

0

10

20

30

40

50

60

70

80

90

5 10 15 30 45 60 90 120

Cu

mu

lati

ve

Per

cen

t R

elea

se

Time (Min.)

Glipizide (GZ)

F1

F2

F3

F4

F5

F6

F7

F8

F9

F10

F11

F12



84

2. Formulation of tablets of glipizide solid dispersion

with sodium starch glycolate (1:4):

Tablets of final formulation prepared with direct

compression method using the various ingredients listed

in table no. 7 in different quantity as needed.

3. Evaluation of final formulation tablets:

The tablets prepared were flat faced round with 8mm

diameter. Tablet thickness was almost uniform in all the

formulations and values for tablets ranged from 3.2 to 3.5

mm. The weight variation values of tablets ranged from

0.18 gm to 0.21 gm. All the tablets passed weight

variation test as the % weight variation was within the

Pharmacopoeias limits of ±7.5% of the weight as shown

in table no. 8.

Selected glipizide formulation meets the requirements of

friability test, hence they are expected to show durability

and withstand abrasion in handling, packaging and

shipment. All tablet formulations had acceptable hardness

(Table 8). The optimized hardness for each formulation

was such that the tablets would be sufficiently hard to

resist breaking during normal handling and yet soft

enough to disintegrate after swallowing.

The disintegration time test revealed that all the formulae

disintegrated in less than 5 minutes (Table 8). Hence we

say that microcrystalline cellulose, the disintegrants have

similar disintegration property, and therefore

microcrystalline cellulose can be a good candidate of

disintegrant.

In vitro dissolution study was carried out for pure drug,

Glynase (marketed) and solid dispersion in phosphate

buffer pH 7.4 (table 9). The dissolution curve of Glipizide

from F12 solid dispersion & Glynase presented in figure

9,10. The release rate profile were plotted as the

percentage glipizide dissolved from the solid dispersion,

from marketed and pure Glipizide verses time. In case of

pure drug only 28.92% was dissolved at the end of 2

hours in phosphate buffer pH 7.4, but the dissolution of

the drug was increased with increase in the carrier ratio in

the formulations. From the result obtained, it can be seen

that in phosphate buffer pH 7.4, Glynase marketed

product, the percent release was found 74.27% &

Glipizide: SSG solid dispersion (1:4 ratio), the percent

release was found 89.44% up to 2 hours. This result

demonstrates that glipizide dissolution rate is

significantly enhanced by solid dispersion using solvent

evaporation method. Solubility of solid dispersion is

increased because of reduce particle size of drug,

improved wettability & drug becomes in amorphous state.

4. Dissolution Profile Comparison:

Rt = Cumulative percentage dissolved of reference

product (marketed) at time t

Tt = Cumulative percentage dissolved of Test Product

(Solid dispersion) at time t

The data for calculation of f1 and f2 were shown in Table

10. The similarity and dissimilarity factor obtained for

glipizide was found to be within the standards. The

standards for similarity factor and dissimilarity factor are

50-100 and 0-15.

CONCLUSION

Glipizide, an anti diabetic drug has poor water solubility

there by posing problems in their formulations in

absorption leads to poor bioavailability. As it is anti

diabetic drug it has to be absorbed rapidly. So

enhancement of the solubility of drug is important. Solid

dispersions of glipizide were prepared with polymers

(SSG, CCS) in different ratios by solvent evaporation

method. From the studies it is concluded that the

formulation with drug: polymer ratio 1:4 showed better

dissolution rate in comparison with glipizide API and

marketed drug. Solid dispersion of GZ: SSG showed

faster release than other dispersions in ratio of 1:4. It

was noticed from the study that increases in the polymer

concentration increases the drug release from solid

dispersions. The formulation was successful converted to

tablet dosage form. The micromeritic characterizations of

the powder blend were in favorable range. The tablets

formulated were in acceptable hardness, disintegration

time and in vitro release. The tablet of glipizide from

optimized formulation shows almost 30percent increase

in the dissolution from the marketed tablet. Thus this can

be concluded from the work that such combination can

further be used for the development of glipizide tablet for

enhanced dissolution.

ACKNOWLEDGMENT

The author is thankful for the cooperation and facilities

provided by the institute with kind permission of Prof.

Sanjeev Thacker, Director/Principal, Seth G.L. Bihani

S. D. College of Technical Education, Sri Ganganagar

(Raj). The author is also grateful to the Morepen

Laboratories, Chandigarh, Evonik Degussa India Pvt.

Ltd, Mumbai and Maple Biotech Pvt. Ltd., Pune for

exgratis samples of Glipizide, Eudragit E-100,

Croscarmellose Sodium and Sodium starch glycollate

respectively.



85

Table 7: Composition of the Glipizide 20mg tablet

S.no. Ingredients Percentage Quantity (mg) Use

1. Glipizide:SSG 50 100 Solid Dispersion

2. Microcrystalline cellulose 47.5 95 Disintegrating agent

3. Magnesium stearate 1 2 Lubricant

4. Talc 1.5 3 Lubricant

Table 8: Evaluation of prepared tablet

S. NO. EVALUATION Glipizide : SSG (1:4)

1. Thickness (cm.) 0.337±0.01

2. Hardness (kg.) 8.67±1.52

3. Friability (%) 0.45

4. Average weight (gm.) 0.198±0.0081

5. Disintegration time (min) 2.58±0.29

Table 9: Dissolution profiles of best formulation, pure drug and marketed formulation

S.No. Batches Cumulative % Release at Different Time Intervals in min

5 10 15 30 45 60 90 120

1 Glipizide 1.343 3.122 4.871 6.442 14.11 16.87 19.79 28.92

2 Glynase

(Marketed) 21.98 32.87 40.42 49.45 58.11 64.88 70.12 74.27

3 Glipizide SD 22.95 33.88 45.77 52.32 62.96 78.15 83.98 89.44

Figure 9: Scatter Chart of Comparisons of In-vitro

profiles of F12, Glynase (Marketed) and pure

glipizide

Figure 10: Bar chart of Comparisons of In-vitro

profiles of F12, Glynase (Marketed) and pure

glipizide

0

10

20

30

40

50

60

70

80

90

100

5

10

15

30

45

60

90

12

0Cu

mu

lati

ve

Per

cen

tage

Rel

ease

Time (Min)

Glipizide

(GZ)

Glynase

(Markete

d)

Glipizide

SD

0

10

20

30

40

50

60

70

80

90

100

5 10 15 30 45 60 90 120

Cu

mu

lati

ve

Per

cen

tage

Rel

ease

Time (Min)

Glipizide

(GZ)

Glynase

(Marketed

)Glipizide

SD



86

Table 10: Calculation of Difference factor f1 and Similarity factor f2

Time Rt Tt {Rt-Tt} (Rt-Tt)2

Similarity

factor (f2)

Difference

factor (f1)

5 21.98 22.95 0.97 0.9409 52 14

10 32.87 33.88 1.01 1.0201

15 40.42 45.77 5.35 28.6225

30 49.45 52.32 2.87 8.2369

45 58.11 62.96 4.85 23.5225

60 64.88 78.15 13.27 176.093

90 70.12 83.98 13.86 192.1

120 74.27 89.44 15.17 230.129

Sum 412.1 57.35 660.664

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