DEVELOPMENT AND IN-VITRO EVALUATION OF PULSATILE … · 2017-04-29 · 1,2Marri Laxman Reddy...

www.wjpr.net Vol 6, Issue 5, 2017. 951

Jyosthna et al. World Journal of Pharmaceutical Research

DEVELOPMENT AND IN-VITRO EVALUATION OF PULSATILE

CORE IN CUP TABLET OF TORSEMIDE

Jyosthna Polishetti*1, Jyothsna Savula

2, Praveen Gogu

3 and Swetha G.

4

1,2

Marri Laxman Reddy Institute of Pharmacy, Dundigal, Qutbullapur, Hyderabad, 500043.

3Scientist at Dr. Reddy’s, FR&D, IPDO Global Oncology, Bhachupally, Hyderabad.

4Anwar-Ul-Uloom College of Pharmacy, Mallepally, Hyderabad.

ABSTRACT

Pulsatile systems are gaining a lot of interest as they deliver the drug at

the right site of action at the right time and in the right amount, thus

providing spatial and temporal delivery and increasing patient

compliance. Torsemide is used to reduce extra fluid in the body

(edema) caused by conditions such as heart failure, liver disease, and

kidney disease. The aim of the present work is to prepare and evaluate

pulsatile drug delivery system to increase the therapeutic efficacy of

torsemide. The drug torsemide is with short half life i.e.3.5 hrs and

when it is developed into core in cup type of tablet its half life is

extended to 12 hr and when compared to the other drugs like

furosemide which is modified to form torsemide is taken 200mg but torsemide is taken as

only 25mg with high solubility than furosemide. Core in cup tablet shows zero order kinetics

which is an advantage to this type of tablet. The concentration of soluble hydrophilic layer is

selected using 32 factorial designs. A typical pulsatile release is obtained from all the

formulation with no drug release in the lag time and the concentration of polymer on top

layer is a critical factor influencing the release pattern. The core-in-cup tablets were

compared with core only tablets and immediate release capsules.

KEYWORDS: Toresemide, pulsatile, core in cup, zero order kinetics, polymer, half life.

INTRODUCTION

Pulsatile systems are gaining a lot of interest as they deliver the drug at the right site of action

at the right time and in the right amount, thus providing spatial and temporal delivery and

increasing patient compliance. These systems are designed according to the circadian rhythm

World Journal of Pharmaceutical Research SJIF Impact Factor 7.523

Volume 6, Issue 5, 951-968. Research Article ISSN 2277– 7105

*Corresponding Author

Jyosthna Polishetti

Marri Laxman Reddy

Institute of Pharmacy,

Dundigal, Qutbullapur,

Hyderabad, 500043.

Article Received on

06 March 2017,

Revised on 26 March 2017,

Accepted on 16 April 2017

DOI: 10.20959/wjpr20175-8387



of the body. The principle rationale for the use of pulsatile release is for the drugs where a

constant drug release, i.e., a zero-order release is not desired. The release of the drug as a

pulse after a lag time has to be designed in such a way that a complete and rapid drug release

follows the lag time. Torsemide is used to reduce extra fluid in the body (edema) caused by

conditions such as heart failure, liver disease, and kidney disease. This can lessen symptoms

such as shortness of breath and swelling in your arms, legs and abdomen. The drug is also

used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart

attacks, kidney problem. Torsemide is “water pill” (diuretic) that causes you to make more

urine. This helps your body get rid of extra water and salt.

DESCRIPTION

Torsemide is a diuretic of the pyridine-sulfonylurea class. Its chemical name is 1-isopropyl-3-

[(4-m-toluidino-3-pyridyl) sulfonyl] urea and its structural formula is:

Torsemide was procured from Gland Pharma.

EXCIPIENTS

Microcrystalline Cellulose : Accent Microcel Industries, Paldi Kankaj.

Hydroxy propyl methyl cellulose : Corel Pharma Chem.

Formulation of Core and Cup Tablets

(i) Formulation of Core Tablets:

Core tablets were prepared by wet granulation method. Torsemide, HPMC K15, HPMC

K100, Lactose were dry mixed in a polybag for 5 min and then wet granulated with

magnesium stearate and talc as the binder in a hydro alcoholic granulating fluid of isopropyl

alcohol: water (9:1) to form granules. The granules were dried in a tray dryer at 60C for

sufficient time until the loss on drying (LOD) was not more than 3%. The dried granules

were passed through sieve no. 45 to form granules of uniform size. Finally colloidal silicon

dioxide was added and dry mixed and finally lubricated with magnesium stearate the loss on

drying was not more than 3%. The dried granules were first passed through mesh no. 45, to

obtain granules of uniform size. The granules were then lubricated with magnesium stearate.



iii) Compression of Core-in-Cup Tablets: and evaluated for various physical properties

such as angle of repose, bulk density, tapped density, Carr’s index and Hausner’s ratio. Then

Core tablets composed of the active ingredient were punched on compression machine using

6 mm round, flat punches to form disc shaped core tablets.

ii) Formulation of Blend for the Hydrophobic Cup

Weighed quantities of sodium CMC and xanthum gum as per the batch size were dry mixed

in a polybag for 5 min and then wet granulated with a hydroalcoholic solution (Isopropyl

alcohol: water 9:1) of talc to form granules. These granules were dried in a tray drier at 60C

for an hour so that.

The disc shaped tablets of the active core were manually placed in the centre of a10 mm

larger round flat faced punch in the die cavity of the tablet press, before the addition of the

cup material and the machine was run until the lower punch moved down slightly. Weighed

quantity of the blend for the cup was manually poured into the die cavity using a spatula and

the gap between core tablet and die was filled with other materials like polymers, finally

compressed to produce the desired core in cup tablet. The formulation for preparation of core

and cup are depicted

Table-1: Formulation of F1 –F6 Torsemide tablets

CORE

Batch No. F1 F2 F3 F4 F5 F6

Ingredient Qty

(mg/ Tab)

Qty

(mg/ Tab)

Qty

(mg/ Tab)

Qty

(mg/ Tab)

Qty

(mg/ Tab)

Qty

(mg/ Tab)

Torsemide 25 25 25 25 25 25

Lactose 60 50 40 60 50 40

HPMC-P 15 10 20 30 -- -- --

HPMC-P 100 -- -- -- 10 20 30

Magnesium Stearate 2 2 2 3 3 3

Talc 3 3 3 2 2 2

Total weight 100 100 100 100 100 100

CUP

Na CMC 100 100 100 100 100 100

Xanthum gum 5mg 5mg 5mg 5mg 5mg 5mg

Isopropyl alcohol Q.S Q.S Q.S Q.S Q.S Q.S

Magnesium stearate 1% 1% 1% 1% 1% 1%

Talc 1% 1% 1% 1% 1% 1%

Total tablet weight 250 mg 250 mg 250 mg 250 mg 250 mg 250 mg



Figure-1: Core in cup tablet

EVALUATION TESTS

PREFORMULATION EVALUATION TESTS

Determination of Bulk density and Tapped density

An accurately weighed quantity of the powder (W), was carefully poured into the graduated

cylinder and the volume (V0) was measured. Then the graduated cylinder was closed with lid,

set into the density determination apparatus. The density apparatus was set for 100 taps and

after that, the volume (Vf) was measured and operation was continued till the two consecutive

readings were equal. The bulk density and tapped density were calculated using the following

formulae

Bulk density = W / V0

Tapped density = W / Vf

Where, W = Weight of the powder

V0 = Initial volume

Vf = Final volume

Compressibility Index or Carr’s Index (CI)

It indicates the ease with which a material can be induced to flow. The Compressibility Index

(Carr’s Index) is a measure of the propensity of a powder to be compressed. It is determined

from the bulk and tapped densities. In theory, the less compressible a material, the more

flowable it is. As such, it is a measure of the relative importance of inter-particulate

interactions. In a free-flowing powder, such interactions are generally less significant and the

bulk, taped densities will be closer in value. For poorer flowing materials, there are

frequently greater inter-particle interactions and a greater difference between the bulk and



tapped densities will be observed. These differences are reflected in the Compressibility

Index which is calculated using the following formula:

Hausner’s Ratio

Hausner’s ratio was measured by the ratio of tapped density to bulk density.

Angle of Repose (θ)

The frictional forces in a loose powder can be measured by angle of repose, θ. This is the

maximum angle possible between the surface of a pile of powder and the horizontal plane.

The powder mixture was allowed to flow through the funnel fixed to a stand at definite

height. The angle of repose was then calculated by measuring the height and radius of the

heap of the powder formed.

The fixed funnel method was employed to measure the angle of repose. A funnel was secured

with its tip at a given height (h), above a graph paper that is placed on a flat horizontal

surface. The blend was carefully poured through the funnel until the apex of the conical pile

just touches the tip of the funnel. The radius (r) of the base of the conical pile was measured.

The angle of repose (θ) was calculated using the following formula:

Tan θ = h/r

θ = tan-1

(h/r)

Where, θ = angle of repose, h = height of the pile in cms, r = radius of the pile

DRUG – EXCIPIENT INTERACTION STUDIES (FT-IR)

Infrared spectroscopy is one of the most powerful analytical techniques when it comes to the

determination of presence of various functional groups involved in making up the molecule.

It provides very well accountable spectral data regarding any change in the functional group

characteristics of a drug molecule occurring in the process of formulation. IR spectra of

Torsemide and its formulations were obtained by KBr pellet method using FT-IR Shimadzu

ST EQ-025 Spectrophotometer in order to rule out drug-carrier interaction occurring during

the formulation process.



DIFFERENTIAL SCANNING CALORIMETRY (DSC) STUDIES:

In order to investigate the possible interaction between Torsemide, HPMC K15, HPMC

K100, Lactose differential scanning calorimetry (DSC) analysis was carried out on pure

substances and their physical mixtures (PM) in equimolar ratios using the Perkin Elmer

Thermal Analyzer instrument equipped with a computerized data section. Samples (3-4 mg)

were placed in an aluminium pan and heated in an aluminium pan and heated at a rate of

10.00⁰c/min with indium in the reference pan in an atmosphere of nitrogen at a rate of 50.0

ml/min to a temperature of 200.00⁰c.

POST FORMULATION EVALUATION TEST OF THE TABLETS

Hardness

Hardness of the tablet is defined as the force applied across the diameter of the tablet in the

order to break the tablet. The resistance of the tablet to chipping, abrasion or breakage under

condition of storage transformation and handling before usage depends on its hardness. For

each formulation, the hardness of 6 tablets was determined using a Monsanto hardness tester.

It is expressed in Kg / cm2.

Friability (F)

It is a measure of mechanical strength of tablets. The friability of the tablet was determined

using Roche Friabilator. It is expressed in percentage (%).It should be preferably between o.5

to 1.0%. 10 tablets were initially weighed (Winitial) and transferred into the friabilator. The

friabilator was operated at 25 rpm for four mins. The tablets were weighed again (Wfinal). The

percentage friability was then calculated by:

Weight Variation

Twenty tablets were selected randomly from the lot and weighed individually to check the

weight variation. IP limit for weight variation in case of tablets weighing up to 80 mg is ±

10%.



Table-2: Pharmacopoeial specifications for tablet weight variation

Average weight of

Tablets (mg) (I.P)

Average weight of

Tablets (mg) (U.S.P)

Maximum percentage

difference allowed

Less than 80

80 – 250

More than 250

Less than 130

130 – 324

More than 324

10

7.5

5

Thickness

Tablet thickness is an important characteristic in reproducing appearance. Twenty tablets

were taken and their thickness was measured by Vernier callipers. It is expressed in mm.

Content Uniformity

For determination of drug content three tablets from each formulation were weighed

individually, crushed and diluted to 100ml with sufficient amount of purified water. Then

aliquot of the filtrate was diluted suitably and analyzed spectrophotometrically at 288 nm

against blank. The drug content of each formulation was evaluated as per the standard

protocol ranges between 99-101%w/v.

Disintegration Time

The Invitro disintegration time was determined using disintegration test apparatus. A tablet

was placed in each of the six tubes of the apparatus and one disc was added to each tube. The

time in seconds or minutes taken for complete disintegration of the tablet in distilled water

with no palpable mass remaining in the apparatus was measured.

Dissolution Profile of the Tablets

Dissolution of Torsemide tablets was studied using USP type 2 paddle dissolution test

apparatus (Labindia) employing paddle stirrer. 900 ml of 0.1 N HCL (1.2 pH), 6.8 pH

phosphate buffer were used as dissolution medium. The stirrer was adjusted to rotate at 50

rpm and a temperature of 37±0.5⁰c in 6.8 pH phosphate buffer for 24h. The dissolution

samples of 10ml were withdrawn at sampling intervals 1, 2, 4, 6, 8, 10, 12 hours. The

dissolution media was replenished with 10ml of pH 6.8 phosphate buffer after each withdrawl

and analyzed for Torsemide by measuring the absorbance at 288 nm.

Table-3: Parameters for Invitro dissolution study

Invitrodissolution study was carried out in USP dissolution test apparatus type 2

(paddle)

Dissolution medium 6.8 pH phosphate buffer

Volume of dissolution medium 900 ml



Temperature 37 ± 0.5⁰c

Rotation speed 50 rpm

ƛmax 288 nm

RESULTS AND DISCUSSION

Six formulations of core in cup tablets of Torsemide were developed by preparing core

tablets using Lactose as diluent and xanthum gum as a binder and different grades of HPMC

polymer as a release retardant in different proportions in core formulation. The core tablets

and Cup material was prepared by wet granulation method.

IR spectra

The compatibility evaluations were performed by FTIR spectroscopy analysis. The study

implies that the drug and polymers are compatible with each other. There were no interaction

found between polymers and drug.

PRE FORMULATION STUDIES

Bulk density and tapped density for the formulations were in the range of 0.442- 0.485

gm/ml & 0.537 – 0.593 gm/ml. Compressibility index and Hauser’s ratios were in the range

of 16.8-18.7 % and 1.10-1.28. From results of the trial batches almost all Formulation trials

showed good flow properties. The results obtained confirm that all the batches which exhibit

good flow properties have good packing characteristics. Pre-formulation results are

mentioned in the table no:

POST COMPRESSION PARAMETERS

Thickness of tablets was found to be almost uniform in all the six formulations. They were

found to be in the ranges of 3.2 -3.3 mm. All the tablets passed weight variation test as the %

weight variation, which was within the pharmacopoeial limits of ± 5% of the weight. The

average weight of all tablet formulations was within the ranges of 245-251mg. The weights

of all the tablets were found to be almost uniform. The measured hardness of tablets of each

batch of all formulations was ranged between 5.0-6.0 Kg/cm2, which is falling within the

hardness specification as per I.P. The friability of tablets was found to be within the ranges

between 0.38 to 0.64%, which are generally considered and acceptable as per I.P. The data

indicates that the percentage friability was less than 1% in all the formulations ensuring no

physical damage will be take place during handling and shipping of tablets. The results

indicate that the percentage of drug content was within the ranges of 97.2 to 100.6% of

Torsemide which was within the acceptable limits as per the I.P. Trial (F2) is taken as



optimized formulation batch, since all the parameters are found to be within limits when

compared with all formulations.

In Vitro Dissolution Studies

Dissolution of Torsemide tablets was studied using USP type 2 paddle dissolution test

apparatus (Labindia) employing paddle stirrer. 900 ml of 0.1 N HCL (1.2 pH), 6.8 pH

phosphate buffer were used as dissolution medium. The stirrer was adjusted to rotate at 50

rpm and a temperature of 37±0.5⁰c in 6.8 pH phosphate buffer for 24h. The dissolution

samples of 10ml were withdrawn at sampling intervals 1, 2, 4, 6, 8, 10, 12 hours. The

dissolution media was replenished with 10ml of pH 6.8 phosphate buffer after each withdrawl

and analyzed for Torsemide by measuring the absorbance at 288 nm, after filtering the

solution through 0.45 μm millipore filters. Concentration was determined from the standard

plot of Torsemide and finally the results were plotted as cumulative % drug release versus

time graphs.

Among all the formulations, F2 shows 99.54% drug release in 12 Hrs. Optimized

formulations (F2) of Torsemide core in cup tablets was compared with Marketed product.

Kinetic data for optimized formulation

The kinetic treatment of the drug release data of the prepared formulations followed zero

order drug release; the prepared formulations followed Hixson crowell plot, as the plot

showed high linearity (R2 = 0.949) indicating errosion as one mechanism of drug release. F2

showed high linearity in Higuchi plot (R2 = 0.972) and the Korsmeyer -Peppas plot (R2

=0.994) and the slope value “n” was 0.024. The relative complexity of this formulation and

its components may indicate that the drug release is controlled by more than one process. The

result from the Peppas equation indicates that a combination of diffusion and erosion may be

the mechanism of release.

Stability Studies of Optimized formulations

Stability Studies of Optimized formulation from the results shown in graphs, it can be

inferred that the physical appearance of the tablets, remained unchanged at the end of 30, 60

& 90th day for at room temperature and at 400C±200C/75±5% RH for 90days. Results show

no change in physical appearance and invitro dissolution. Hence Optimized formulation was

found stable at tested temperature.



Calibration curve

Table-4 & Fig: 2: Determination of ƛmax of Torsemide in pH phosphate buffer

Wavelength Absorbance

220 0.223

240 0.247

245 0.252

260 0.278

288 0.295

300 0.212

Table -5 & Fig: 3: Standard calibration curve absorbance in 6.8 pH phosphate buffer

at 288nm

Concentration

(mcg) Absorbance (nm)

0 0

0.0112 0.277

0.0168 0.419

0.0224 0.553

0.0280 0.693

0.0336 0.830



RESULTS

Table-6: Evaluation of Pre-Formulation Parameters of Core in cup torsemide Tablet

Blend

Formulation

Code

Angle of

Repose ± S.D Bulk Density

Tapped

Density

% Carr’s

Index

Hausner’s

Ratio

F1 29.56 ± 0.46 0.485 0.593 18.2 1.10

F2 27.12 ± 0.13 0.460 0.556 17.2 1.21

F3 30.35 ± 0.35 0.478 0.575 16.8 1.24

F4 32.12 ± 0.84 0.450 0.554 18.7 1.28

F5 30.65 ± 0.35 0.442 0.537 17.6 1.27

F6 31.25±0.23 0.456 0.550 17.0 1.20

Figure-4: FT-IR of Pure Torsemide

Table-7: Evaluation of disintegration time of Torsemide formulation (F2):

S.no Disintegration

time (minutes)

1 55 ± 0.11

2 56 ± 0.15

3 58 ± 0.21

4 60 ± 0.18

5 60 ± 0.18

6 62 ± 0.17

Average

disintegration time 58.5 ± 0.29

Table-8: Evaluation of Post-Compression parameters of Torsemide tablets

Formulation

Code

Hardness

(kg/cm2)

Average

weight of 20

tablets (mg)

Friability

(%)

Thickness

(mm)

Drug Content

± S.D (%)

F1 5.5 245.5 ± 0.56 0.64 3.2 98.6 ± 0.61

F2 6.0 247.3 ± 0.64 0.54 3.2 99.9 ± 0.58

F3 5.0 246.6 ± 0.25 0.58 3.2 97.2 ± 0.28



F4 5.0 251.3 ± 0.35 0.45 3.2 99.9 ± 0.70

F5 5.5 247.8 ± 0.33 0.38 3.2 100.6 ± 0.74

F6 5.5 249.2± 0.42 0.62 3.3 99.8 ± 0.35

Table-9 & Fig: 5: Invitrodrug release from Torsemide formulations (F1-F3)

Time in

HR's F1 F2 F3

0 0.00 0.00 0.00

0.5 10.23 17.93 24.90

1 25.44 29.66 43.08

2 36.88 40.87 54.99

4 42.90 58.54 69.87

6 53.88 72.45 83.03

8 64.90 84.23 91.99

10 76.65 92.94 100.00

12 89.66 99.54 100.00

F1=……

F2=……

F3=……

Table 10 & Fig-6: Invitro drug release from Torsemide formulation (F4-F6)

Time in

HR's F4 F5 F6

0 0.00 0.00 0.00

0.5 11.98 24.87 29.76

1 21.76 39.76 43.98

2 32.09 51.89 58.54

4 43.90 65.43 70.75

6 54.54 76.98 81.53

8 65.95 91.87 94.89

10 79.07 100.00 100.00

12 93.98 100.00 100.00



F4=……

F5=……

F6=……

Table-11& Fig-7: Zero-order plot of Torsemide formulation (F2):

TIME F2

0 0.00

0.5 17.93

1 29.66

2 40.87

4 58.54

6 72.45

8 84.23

10 92.94

12 99.54

Table 12 & Fig-8: First-order plot of Torsemide formulation (F2)

TIME F2

0 0.0

0.5 0.3

1 0.8

2 1.2



4 1.4

6 1.5

8 1.8

10 1.9

12 2.0

Table-13 & Fig-9: Higuchi Plot of Torsemide formulation (F2)

Table-14 & Fig-10: Korsmeyer & Peppas plot of Torsemide formulation (F2)

log time F2

0.0 1.0

0.3 1.3

0.5 1.5

0.6 1.6

0.7 1.8

0.8 1.9

Root T F2

0.707107 6.850467

1 9.58181

1.414214 11.8651

2 15.0765

2.44949 17.379

2.828427 19.2152

3.162278 20.518

3.464102 21.5443



0.8 1.9

0.9 2.0

1.0 2.0

Table 15 & Fig-11: Hix crowell Plot of Torsemide (F2)

Table-16: Stability data of Torsemide Formulation (F2) at 40±2⁰C/75±5%RH

S. No. Time in

days

Physical

changes

% Drug Content ± SD

(40±2⁰C/75±5%RH)

1. 01 -- 98.64 ± 0.82

2. 30 No change 98.00 ± 0.30

3. 60 No change 97.35 ± 0.51

4. 90 No change 97.09 ± 0.40

TIME F2OR2

0.5 2.61734

1 3.095449

2 3.444569

4 3.882853

6 4.168817

8 4.383513

10 4.52968

12 4.641589



Table-17 & Fig-12 Comparative Dissolution Profiles of Optimized Batch (F-2) With

Innovator

Comparision of Marketed and optimized Formulation Dissolution Profiles

CONCLUSION

From the above experimental results it can be concluded that core in cup tablets of Torsemide

can be prepared by using different proportion & combination of excipients and selected F2 as

best formulation based on desired drug release profile. The core-in-cup technology is a

potential technology, which can control the release of highly water soluble drugs for Twice-a-

Time (hrs) Innovator F2

0 0 0

1 1.40 0

2 17.95 15.20

4 36.15 21.63

6 50.85 42.56

8 74.63 65.44

10 89.25 85.90

12 99.97 99.54



day administration with the use of a combination of hydrophilic and hydrophobic polymers.

This technology has already proved successful for sparingly soluble drugs and with this study

proves potential for developing a system capable of delivering highly water soluble drugs that

follow zero- order release kinetics.

REFERENCES

[1]

EfenkatisM, Koligliati S et al,” Design and evaluation of a dry coated drug delivery

system, an impermeable cup, swellable top layer and pulsatile release”, International

journal of Pharmaceutics, 311: pp-147-156, .14

[2] Roy P, Shahiwala A,” Multiparticulate formulation approach to pulsatile drug delivery

current perspective”, Journal of controlled release”, 2009; 134: 74-80.

[3] BussemerT, Bodmeier RA,” Drug delivery: Pulsatile encyclopedia of pharmaceutical

technology”, 2006; 1287-1297.

[4] Sharma S, Pawar A,” Low density multiparticulate system for pulsatile of Meloxicam”,

International journal of Pharmaceutics, 2006; 313: 150-158.

[5]

Karvasa E ,Georgarakis E et al,” Felodipinenanodispersion as active core for predictable

pulsatile chronotherapeutics using using PVP/HPMC blends as coating layer”,

International Journal of Pharmaceutics, 2006; 313: 189-197.

[6] Krogel I, Bodemeier R,” Floating or pulsatile drug delivery system based on coated

effervescent core”, International journal of Pharmaceutics, 1999; 187: 175-184.

[7]

Lin HL, Lin SY,” Release characteristics and invitro-invivo correlation of pulsatile

pattern for a pulsatile drug delivery system activated by membrane rupture via osmotic

pressure and swelling”, European journal of pharmaceutics and biopharmaceutics, 2008;

70: 289-301.

[8]

KarvasaE, Georgarakis E et al, “Application of pulsatile miscible blends with enhanced

mucoadhision properties for adjusting drug release in predictable pulsatile

chronotherapy”, European journal of pharmaceutics and biopharmaceutics, 2006; 64:

115-126.

[9]

Maroni A, ZemaL, “Oral pulsatile delivery: rational and

chronopharmaceuticalformulaion. International journal of Pharmaceutics”, 2006; 398:

1-8.

[10]

Roy P, “ShahiwalaA. Stastical optimization of ranitidine HCl floating pulsatile delivery

system for chronotherapy of nocturnal acid breakthrough,” European journal of

pharmaceutical sciences, 2009; 37: 363.

[11]

Bussemer T, Bodmeier R, “Formulation parameters affecting the performance of coated

gelatin capsules with pulsatle release profiles,” International journal of Pharmaceutics,

2003; 267: 59-68.

[12]

Fan TY, Wei SL et al, “An investigation of pulsatile release tablets with ethylcellulose

and eudragit L as film coating material and cross linked polyvinylpyrrolidone in the core

tablet,” Journal of controlled release, 1993; 77: 245-251.

[13]

CoughanDC, Quilty FP, “Effect of drug physicochemical properties on swelling kinetics

and pulsatile drug release from thermoresponsive poly(N-isopylaacrylamide) hydrogels.

Journal of controlled release”, 2004; 98: 97-114.

[14] Sungthongieen S, Puttipipakhachorn S et al,” Development of pulsatile release tablets



with swelling and rupturable layer’” Journal of controlled release, 2004; 147: 147-159.

[15]

McconvillJT, Rose Ac et al,” The effect of wet granulation on the erosion behavior of an

HPMC lactose table, used as a rate controlling component in pulsatile drug delivery

capsule formulation”, European journal of Pharmaceutics and biophrmaceutics, 2007;

57: 541-549.

[16]

Schellekens RCA, Stellard F et al.,” Pulsatile drug delivery to ileo-colonic segments by

structured incorporation of disintegrants in PH responsive polymer coating”, Journal of

controlled release, 2007; 932: 91-98.

[17]

BussemerT, Peppas NA et al, “Evaluation of the swelling hydration and rupturing

properties of the swelling layer of the rupturable pulsatile drug delivery system”,

European journal of pharmaceutics and biopharmaceutics, 2003; 56: 261-270.

[18]

Dashevsky A, Mohamad, “Development of pulsatile multiparticulate drug delivery

system coated with aqeous dispersion aqua coat ECD”, International journal of

Pharmaceutics, 2003; 318: 124-131.

[19] Bussemer T. Dashevsky A et al, “A pulsatile drug delivery system based on rupturable

coated heard gelatin capsules. Journal of controlled release”, 2003; 93: 313-339.

[20]

Mohamad A, Dashevsky, “PH independent pulsatile drug delivery system based on hard

gelatin capsules coated with aqeous dispersion aquacoatECD. European journal of

pharmaceutics and biopharmaceutics”, 2006; 64: 173-179.

[21] GiunchediP, magi L, “Ketoprofen pulsatile absorption from multiple unit hydrophilic

matrices”, International journal of pharmaceutics, 1991; 77: 177-81.

DEVELOPMENT AND IN-VITRO EVALUATION OF PULSATILE … · 2017-04-29 · 1,2Marri Laxman Reddy...

Documents

Transcript of DEVELOPMENT AND IN-VITRO EVALUATION OF PULSATILE … · 2017-04-29 · 1,2Marri Laxman Reddy...