notes on formulation & evaluation of floating microspheres of an antibiotic drug

PREPARED BY:

Keyur Vasava…

1

“Formulation & Evaluation of floating microspheres of an antibiotic drug”

“Formulation & Evaluation of floating microspheres of an antibiotic drug”

Aim of present workObjectivesRationaleIntroductionMethodReview of literatureDrug profilePolymer profileExperimental workEvaluationconclusionReferences

2

Contents

3

AIM OF PRESENT WORK

Prevent degradation in alkaline pHTo maintain constant level of drug in the blood

plasma and minimize fluctuationremain buoyant to improve bioavailability.Prolonging gastric residence of a dosage form to

improve therapeutic value

4

Objectives Of Present Work

oral route: Ease of administrationMicrospheres(multiparticulate system):uniform

dosage formGRDDS: minimize fluctuationCephalexin ,BCS class ΙΙΙdrug has short half life

(80min) and low bioavailability hence it is suitable for gastroretentive system.

Method (W/O/W emulsion solvent evaporation method):simple ,economic & short processing time

Optimization: good % yield and good % drug release

5

Rationale

6

DrugCephalexin:

Antibiotic, BCS classш drug ,short half life,Low bioavailability

Gastro retentive Floating drug

delivery system

Floating Microspheres

spherical

Size range-10μm to 1000 μm

Introduction

The urinary tract is the body's filtering system for removal of liquid wastes.

Because have a shorter urinary tract, women are especially susceptible to bacteria that may invade the urinary tract and multiply -- resulting in infection known as a urinary tract infection, or UTI.

Fortunately, these infections are easily treated with antibiotics.

7

What is UTI???

8 Deshpandey.A A,Shah,Pharm res.1997 Atyabi,F.,Sharma H L,J control.Rel 1996

Approches toGRDDS

9 gaba Poonam,Floating microspheres a: Review,Volume 6 ,2008

Types of Gastroretentive drug Delivery system

10

Improves patient compliance Bioavailability enhancesGastric retention time is increased Drug releases in controlled manner for prolonged period. Superior to single unit floating dosage forms Avoidance of gastric irritationBetter therapeutic effect of short half-life drugs can be achieved.

Nayak Amit Kumar, Gastroretentive drug delivery systems: a review,

January-March 2010

Advantages of floating Microspheres

When Drugs are absorbed from specific site like from stomoch or upper GIT.

When such drugs are incorporated in SR system.

Only few drugs dissolve at absorption region and all other drug is going waste.

11

Need for gastric Retention

12

Limitation of Floating Drug Delivery system

Criteria for selection of Drug

Criteria for selection of Drug

14

Step 1 Preparation of aqueous phase

↓ Step 2 organic solvent (DCM:Acetone+ Polymer)W/O emulsion

↓ Step 3 primary emulsion poured to aq phase containing PVA(0.5%)

↓ Step 4 The resultant emulsion ( w/o/w type) was continually stirred ( 550 to 950 rpm)

↓ Step 5 fitration ,collection,washing and vaccum drying

Dr.Jose GR, Omidian H, Shah K. Pharm Tech 2003

Method of preparation of floating microspheres

15

DRUG WORK DONE AUTHOR YEAR

Verapamil hydrochloride

preparation and evaluation of floating microspheres of verapamil hydrochloride for improving the drug bioavailability by prolongation of gastric residence time.

Tanwar Yuveraj Singh 2007

Glipizide Microspheres can be successfully designed for sustained delivery of Glipizide and to improve dosage form characteristics for easy formulation.

Phutane P 2010

Ketoprofen Microspheres developed for prolongation of gastric residence time.

GargRajeev et

2010

List of Review of related litereture

16

Drug Work done Auther year

Piroxicame Microspheres with improvedmicromeritics property

RD Kale et al 2007

Famotidine Microsphreresto achieve an extended retention in the upper gastrointestinal tract, which may result in enhanced absorption and thereby improved bioavailability

Jain Abhishek Kumar

2009

Cimetidine Microspheres for prolongation of gastric residence time by the solvent evaporation method using polymers hydroxypropyl -methyl cellulose and ethyl cellulose.

Srivastava Anand kumar 2005

Ketorolac trometamol

Developed microspheres which can be prepared to improve the absorptionand bioavailability of ketorolac trometamol by retaining the system in to the stomach for prolonged period of time.

Barhate Shashikant

2009

DRUG WORK DONE AUTHER YEAR

Cefpodoxime proxatile

Developed microsphere in order to achieve an extended retention in the upper GIT, which may result in enhanced absorption and thereby improved bioavailability.

M.K.Deepa 2009

metformin Developed Microspheres may be used in clinic for prolonged drug release in stomach for at least 8 hrs, thereby improving the bioavailability and patient compliance.

Patel Asha et al 2006

diltiazem hydrochloride

microspheres developed ,The data obtained in this study thus suggest that a micro particulate floating dosage form of diltiazem hydrochloride can be successfully designed to give controlled delivery and improved oral bioavailability.

Gattani Yogesh S 2008

silymarin Microspheres developed for for prolonged gastric residence time and increased drug bioavailability.

Rajeev Garg 2010

18

Name of Drug Cephalexin

Drug Category Anti-Bacterial Agents

Chemical Formula C16H17N3O4S

Chemical IUPAC Name (6R,7R)-7-[[(2R)-2-amino-2-phenylacetyl]amino]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.

Chemical structure:

BCS class Class ш

Introduction to Cephalexin

19

Cephalexin Dose for Bacterial Infections 65mg

Administration Orally

Half Life : 1 hour

Protein Binding 14%

Mechanism of Action : Cephalexin, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis.

Absorption : Well absorbed from the gastrointestinal tract.

Metabolism: 80% excreted unchanged in urine within 6 hours of administration

Excreation: Renal

Toxicity: diarrhea, nausea, upper abdominal pain, and vomiting.

Clinical use to treat urinary tract infections, respiratory tract infections, and skin and soft tissue infections. It is also sometimes used to treat acne.

Side-effects diarrhea, dizziness, headache, indigestion, joint pain, stomach pain and tiredness.

20

Ethyl Cellulose:Functional Category Coating agent; flavoring agent; tablet

binder; tablet filler; viscosity increasing agent. Description Ethyl cellulose is a tasteless, free-flowing, white to

light tan-colored powder. Density (bulk): 0.4 g/cm3 Glass transition temperature: 129–133˚C Solubility Ethyl cellulose is freely soluble in chloroform, ethanol

( 95%), ethyl acetate, methanol, and toluene,acetone.Specific gravity: 1.12–1.15 g/cm3.

21

1.Materials and Equipments2.Priliminary study2.1Spectrophotometric analysis of cephalexin2.2Drug–Excipients COMPABILITY Study2.3IN Process Optimization 3.Application of Full factorial design layout4.Characterization of Micromeritics property 5.Other evaluation parameters6.Formulation and evaluation of check point batch S107.Fiting to kinetic model8.Stability Study

22

23

MATERIALS sources

Cephalexin Innova captab Ltd(chandigadh)

Ethyl cellulose(EC)

(18-24cps)

Qualikems Finechem

pvt.ltd,Nandesari,vadodara

Acetone Aatur Instra chem,Vadodara

Dichloromethane Suvidhinath laboratories,vadodara

Polyvinyl alcohol

(25-32cp)

Qualikems Finechem

pvt.ltd,Nandesari,vadodara

Hydrochloric acid IP Finar chemicals Ltd

24

Equipments Sources

Digital electronic balance Scaletec mechatronics pvt.Ltd

Propeller stirrer Remimotor Ltd

Optical microscope USICO, india

Tap density Tester Electrolab , USP ETD: 1020

UV spectrophotometer Shimadzu , UV-1700, Pharmaspec

Dissolution Test apparatus Electrolab,TDT-08L

2.1Spectrophotometric analysis of cephalexin2.2Drug–Excipients COMPABILITY Study2.3IN Process Optimization

Determination of absorption maxima (λmax) of Cephalexin

λmax for cephalexin is 257 nm.

26

Calibration curve

No of sample

Concentration(μg/ml)

Abs

1 10 0.109

2 20 0.25

3 30 0.357

4 40 0.465

5 50 0.567

6 60 0.668

7 70 0.791

8 80 0.901

27

Conc (μg/ml) vs Abs

FT-IR spectra of drug

28

Functional group

O-H Β-Lactom Amide -COOH -COOH

Standard Cephalexin

3148.13 1758.31 1689.43 1595.00 1399.94

FT-IR Spectra of Drug+polymer(E.C+PVA)

29

Functional group

O-H Β-Lactom

Amide -COOH -COOH

CFL+EC+PVA 3168.49 1758.36 1689.36 1595.90 1399.01

There is no chemical interaction between Cephalexin and other excipients.

A. Volume of aqueous phase for primary emulsion

B. Volume of organic phase

C. Acetone : Dichloromethane

D. Stirring rate

E. Polymer:Drug

30

31

A. VOLUME OF AQUEOUS PHASE FOR PRIMARY EMULSION

Volume of the organic phase 10 ml

Acetone: DCM ratio 1:1

Stirring rate 550 rpm

Concentration of PVA 0.5% w/v

Batch No. Volume of the aqueous

Phase

characteristic

A1 5 ml Thick emulsion(Not

easily pourable)

A2 10 ml Proper amount to

form emulsion

A3 15 ml Break down of

emulsion

Optimization of volume of aqueous phase for primary emulsion

Volume of the aqueous phase 10 ml

Acetone:DCM ratio 1:1


Concentration of PVA 0.5 % w/v

32

B.VOLUME OF ORGANIC PHASE

Optimization of volume of the organic phase

Batch No. Volume of the organic

Phase

Product characteristic

B1 10 ml Aggregated lump

B2 20 ml Spherical microspheres

B3 30 ml Coarse, not complete

spherical




Concentration of PVA 0. 5 % W/V

33

C.ACETONE:DICHLOROMETHANE

Optimization of Acetone:Dichloromethane ratio

Batch No. ACT:DCM ratio Product characteristic Aggregation

C1 3:1 Spherical microspheres ++

C2 2:1 Spherical microspheres +

C3 1:1 Irregular microspheres ++

C4 1:2 Spherical microspheres +++

C5 1:3 Spherical microspheres +++



Acetone: DCM ratio 2:1

Concentration of PVA 0.5 % W/V

34

Batch No. Stirring rate Product characteristic Aggregation

D1 350 rpm Very large size particles +++

D2 550 rpm Larger size,Nearly

spherical

++

D3 750 rpm Small size, spherical ++

D4 950 rpm Small size microparticles +

D5 1150rpm very small,breakdown of

microparticles

++

Optimization of stirring rate

Batch No. Polymer:

drug ratio

Product

characteristic

Aggregation % yield

P1 6:1 Spherical + 78.93%



P4 3:1 spherical + 59.41%


P6 1:1 Spherical ++ 53.89%

P7 1:1.5 Spherical ++ 49.45%

P8 1:2 Irregular +++ -----

35+++:high aggregation

Parameter Selected batch Specification

Volume of aqueous phase A2 10 ml of aqueous phase

Volume of organic phase B3 20 ml of organic phase

Acetone : DCM ratio C2 2:1 ratio of ACT:DCM

Stirring rate D3 550rpm

750rpm

950 rpm36

OPTIMIZED BATCH

32 FACTORIAL DESIGNIndependent variables X1:Polymer concentration

X2: Stirring speed

Dependable variablesY1:particle size(μm)

Y2:% Drug encapsulation efficiency

Y3:t80%(min)

37

3. APPLICATION OF FULL FACTORIAL DESIGN

level INDEPENDENT VARIABLES

X1(polymer concentration)(%)

X2(stirring speed)(rpm)

Low 8.33 550

Medium 10.43 750

high 12.50 950

38

Batch code X1 (%) X2(rpm)

S1

8.33 550

S2

10.43 550

S3

12.50 550

S4

8.33 750

S5

10.43 750

S6

12.50 750

S7

8.33 950

S8

10.43 950

S9

12.50 95039

32 DESIGN LAYOUT

Micromeritics propertyScanning Electron Microscopy% buyovancyEvaluation of dependent variables

i. Particle size

ii.% drug Encapsulation efficiency

iii.t80%

TAPPED DENSITYBULK DENSITYCOMPRESSIBILITY INDEXANGLE OF REPOSE

41

4.MICROMERITICS PROPERTY

42

Characterization of microspheres

FORMULATION CODE

BULK DENSITY(gm/cm)

TAPPED DENSITY(gm/cm)

COMPRESSIBILITY INDEX

ANGLE OF REPOSE

S1 0.350±0.013 0.394±0.006 11.16±0.231 19.29±0.22

S2 0.375±0.009 0.434±0.009 13.59±0.942 21.00±0.34

S3 0.400±0.110 0.450±0.003 11.11±0.620 22.19±0.29

S4 0.412±0.050 0.471±0.005 12.61±0.742 18.67±0.18

S5 0.437±0.060 0.507±0.010 13.80±0.426 22.58±0.65

S6 0.462±0.007 0.521±0.007 11.32±0.378 24.95±0.22

S7 0.487±0.060 0.557±0.015 12.59±0.672 19.29±0.65

S8 0.525±0.090 0.583±0.009 10.17±0.722 25.17±0.54

S9 0.562±0.030 0.633±0.016 11.21±0.465 27.11±0.27

Micromeritics property shows good flowability and packagability

Mean ± S.D., n=3

Spherical and uniform in shape,porous in nature and rough surface,shows good floating characteristics and flowability to the dosage form.

43

Scanning electron Microscopy

Buoyancy (% ) = ( Qf * 100 ) / ( Qf + Qs )

Formulation code % buoyancy(%)

S1 97±1.71

S2 88±1.81

S3 84±3.07

S4 91±2.65

S5 85±1.85

S6 81±2.85

S7 83±5.43

S8 81±4.41

S9 80±2.91

44

Good %buoyancy shows good floating ability for prolong period of time.

Mean ± S.D., n=3

Formulation code

Particle size (µm)

%encapsulation efficiency(%)

t80% (min)

S1 475±1.32 67.95±3.75 657±7.02

S2 481±1.53 74.28±4.00 660±3.05

S3 491±0.95 81.93±4.39 695±6.00

S4 375±0.99 64.74±3.51 573±6.43

S5 385±1.17 72.33±2.63 586±5.03

S6 390±1.11 77.45±4.32 600±2.31

S7 239±1.56 59.52±3.21 521±2.30

S8 250±0.99 70.47±2.75 527±2.00

S9 275+1.56 74.16±2.42 566±3.50

45

6.EVALUATION OF DEPENDABLE VARIABLES

Mean ± S.D., n=3

Batch code

Particle size(µm)

S1 475±1.32

S2 481±1.53

S3 491±0.95

S4 375±0.99

S5 385±1.17

S6 390±1.11

S7 239±1.56

S8 250±0.99

S9 275+1.56

46

EFFECT OF X1 AND X2 ON PARTICLE SIZE

Mean ± S.D., n=3

Contour plot Response Surface plot

47

Graphical representation of Effect of FactorX1 & X2 On particle size

Conclusion: As Polymer concentration increases particle size increases,and with incresing stirring speed it will decreases.

By Design expert version 8.0.5.2

Design-Expert® SoftwareFactor Coding: Actualparticle size

Design Points491

239

X1 = A: polymer concentrationX2 = B: stirring speed

8.33 9.02 9.72 10.41 11.11 11.81 12.50

550.00

630.00

710.00

790.00

870.00

950.00particle size

X1: A: polymer concentrationX2: B: stirring speed

300

350

400

450

Design-Expert® SoftwareFactor Coding: Actualparticle size

Design points above predicted valueDesign points below predicted value491

239


550.00

630.00

710.00

790.00

870.00

950.00

8.33

9.02

9.72

10.41

11.11

11.81

12.50

200

250

300

350

400

450

500

par

ticle

siz

e

A: polymer concentration

B: stirring speed

Table – Out put of regression analysis for Effect of X1 and X2 on PARTICLE SIZE

Regression statistics

R Square 0.9922

Adjusted R Square 0.9896

Standard error 3.99

Coefficients

Coefficient coefficient Value P-value

Intercept 373.44 < 0.0001

X1 11.17 0.0360

X2 -113.83 < 0.0001

Equation: Y1==+381.89+11.17X1-113.83X2+5.00 X1X2+2.17X12-14.83X2

2

SUMMURY OUT PUT OF REGRESSION ANALYASIS

P value <0.05 indicats model is significant and +sign of coefficient of X1—if polymer concentration increases,particle size increases- Sign of coefficient of X2 shows if stirring speed decreases,particle size increases

Batch code Y2 (%encapsulationefficiency)

S1 67.95±3.75

S2 74.28±4.00

S3 81.93±4.39

S4 64.74±3.51

S5 72.33±2.63

S6 77.45±4.32

S7 59.52±3.21

S8 70.47±2.75

S9 74.16±2.42

49

EFFECT OF X1 AND X2 ON ENCAPSULATION EFFICIENCY(Y2)

Contour plot Response surface plot

Conclusion :As Polymer concentration increases % encapsulation efficiency increases,and with incresing stirring speed %encapsulation efficiency decreases.

50

EFFECT OF X1 AND X2 ON %Encapsulation efficiency (Y2)


Design-Expert® SoftwareFactor Coding: Actual%encapsulation efficiency

Design Points81.93

59.52


8.33 9.02 9.72 10.41 11.11 11.81 12.50

550.00

630.00

710.00

790.00

870.00

950.00%encapsulation efficiency


65

70 75

80

Design-Expert® SoftwareFactor Coding: Actual%encapsulation efficiency

Design points above predicted valueDesign points below predicted value81.93

59.52


550.00

630.00

710.00

790.00

870.00

950.00

8.33

9.02

9.72

10.41

11.11

11.81

12.50

55

60

65

70

75

80

85

%en

caps

ulat

ion

effic

ienc

y

A: polymer concentration B: stirring speed

Table – Out put of regression analysis for Effect of X1 and X2 on % ENCAPSULATION EFFICIENCY.


R Square 0.9694


Standard error 0.45

Coefficients


Intercept 71.43 < 0.0090

X1 6.89 < 0.0001

X2 -3.34 0.0010

Equation: Y1=72.44+6.89 X1-3.34X2+0.17X1X2-1.40X12-0.12 X2

2

SUMMURY OUT PUT OF REGRESSION ANALYSIS

P value <0.05 indicats model is significant and

+sign of coefficient of X1—if polymer concentration increases,% encapsulation efficiency increases

- Sign of coefficient of X2 shows if stirring speed decreases,%encapsulation efficiency increases

Batch code t80% (min)

S1 657±7.02

S2 660±3.05

S3 695±6.00

S4 573±6.43

S5 586±5.03

S6 600±2.31

S7 521±2.30

S8 527±2.00

S9 566±3.50

52

EFFECT OF X1 AND X2 ON t80%(Y3)

Contour plot Response surface plot

Conclusion :As Polymer conc increases ,t80% increases & t80% decreases with increasing stirring speed. 53

EFFECT OF X1 AND X2 ON t80%(Y3)


Design-Expert® SoftwareFactor Coding: Actualt80%

Design Points725.62

586.22


8.33 9.02 9.72 10.41 11.11 11.81 12.50

550.00

630.00

710.00

790.00

870.00

950.00t80%


600

620

640

660

680

700

720

Design-Expert® SoftwareFactor Coding: Actualt80%

Design points above predicted valueDesign points below predicted value725.62

586.22


550.00

630.00

710.00

790.00

870.00

950.00

8.33

9.02

9.72

10.41

11.11

11.81

12.50

580

600

620

640

660

680

700

720

740

t80

%

A: polymer concentration

B: stirring speed

Table – Out put of regression analysis for Effect of X1 and X2 on t80%


R Square 0.9633


Standard error 4.48

Coefficients


Intercept 598.33 < 0.0031

X1 18.33 0.0005

X2 -66.33 < 0.007

Equation: Y1==+644.42+13.69X1-57.98X2-3.23X1X2+2.76X12+5.93X2

2

SUMMURY OUT PUT OF REGRESSION ANALYSIS

P value <0.05 indicats model is significant and +sign of coefficient of X1—if polymer concentration increases,t80% increases- Sign of coefficient of X2 shows if stirring speed decreases,t80% increases

55

The overlay plot of the responses generates an optimized area, as per the desired criteria. The polymer concentration value was targeted 12.44 and Stirring speed was set to 950.15

Overlay plot for Optimization


Design-Expert® SoftwareFactor Coding: ActualOverlay Plot

particle size%encapsulation efficiencyt80%

Design Points


8.33 9.02 9.72 10.41 11.11 11.81 12.50

550.00

630.00

710.00

790.00

870.00

950.00Overlay Plot


particle size: 299.191

particle size: 400.000

t80%: 605.140particle size 271.014%encapsula74.5152t80%: 605.153X1 12.44X2 950.00

FORMULATION INGREDIENT FORMULATION BATCH F10

Volume of aqueous phase 10 ml of aqueous phase

Volume of organic phase 20 ml of organic phase

Aceton:DCM 2:1 ratio of ACT:DCM

Stirring speed 605.15 rpm

Cephalexin 200mg

Polymer concentration 12.44%

PVA 0.5%

56

6.Formulation and evaluation of check point batch

TEST PARAMETERSBATCH S10 % Error

PREDICTED ACTUAL

Particle size 271μm 275μm 0.014%

% Encapsulation Efficiency

74.51% 73.21% 0.017%

t80% 605.15min 599.27min 0.0097%

TIME(hr) S1

S2

S3

S4 S5 S6 S7 S8 S9

0min 0 0 0 0 0 0 0 0 0

0.5min 1.97 0.987 0.074 3.94 2.96 1.97 6.9 4.93 2.96

1hr 8.92 6.92 4.93 6.99 7.93 4.93 10.94 8.92 7.93

2hr 16.02 12.99 9.86 11.09 11.09 10.01 18.08 14.07 13.42

3hr 23.27 18.21 13.2 20.2 18.98 18.89 27.34 24.26 23.18

4hr 30.67 26.49 16.13 29.51 24.32 22.26 36.8 33.65 31.57

5hr 38.22 32.96 23.38 37.04 34.7 32.6 44.48 42.25 39.14

6hr 46.91 38.58 29.79 45.71 42.34 41.18 53.3 52.01 47.85

7hr 53.79 46.28 36.33 54.54 51.11 48.94 60.31 58.02 54.76

8hr 60.81 53.15 42.02 61.57 59.07 57.85 67.71 64.13 63.77

9hr 67.95 61.93 58.75 69.73 68.42 64.95 76.7 74.3 71.96

10hr 72.26 68.27 64.86 77.04 77.04 73.16 81.18 81.74 79.32

11hr 78.61 74.57 71.08 83.5 82.15 79.55 89.8 88.28 86.8

12hr 84.1 84.1 79.38 89.5 86.74 84.1 98.17 96.91 93.22

57

58

%cumulative drug release of Batch S1 to S9

59

%cumulative drug release of Batch S10

TIME(hr) Batch S10

0min 0

0.5min 4.934

1hr 9.974

2hr 14.136

3hr 25.290

4hr 32.733

5hr 39.339

6hr 48.048

7hr 56.928

8hr 64.994

9hr 74.196

10hr 84.556

11hr 92.149

12hr 98.885

Results of Model Fitting of optimized Batch

Intercept Slope R2

Zero order plot 8.24 0.322 0.998

First order plot 0.0125 0.753 0.773

Higuchi 30.48 19.21 0.920

Korsmeyer peppas 1.17 0.749 0.828

60

7.Fitting to kinetic model

n > 0.749 > 1.0 indicates Drug release mechanism was non-fickian transport

Stability Study

Days Particle Size(µm) %drug Encapsulation efficiency(%)

t80%(min)

Before Storage

0 Days 275±0.23 73.21±1.23 599.27±3.65

After storage

7days 275±0.84 72.13±0.21 597.33±5.43

15days 273±0.43 71.09±1.23 595.45±3.25

30days 271±0.32 70.32±2.21 592.25±5.21

*Storage at 40 and 75%RH for 1month,mean±SD;n=3

61

8.Stability Study

Conclusion: Stability studies indicated that there was no significant difference observed between the release pattern of microspheres at 40ºC and 75% RH for one months

The results of a 32 full factorial design revealed that

the polymer ratio (X1) and stirring speed (X2)

significantly affected the dependent variablesThe microspheres of the check point batch (F10) exhibited

73.21% drug encapsulation efficiency, mean particle size of 275 µm and 599.27 min t80% which were nearer to predicted values obtained from overlay contour plot

of all the responses.These result shows a good relationship between the

experimental & predicted values,which confirms the practicability of the model.

62

conclusion

Gholap S. B. , Hollow Microsphere: A Review :volume 1, Issue 1, March –April 2010; Article 015 International Journal of Pharmaceutical Sciences Review and Research Page 74

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Bardonnet, P. L . Gastro retentive dosage form: Overview and special case of H.pylori. J. Control Release. 2006 , Vol.111 , pp. 1-18.

Poonam gaba,Floating microspheres a: Review,Volume 6 ,issue 5,2008 www.rjptonline.org AV Mayavanshi , SS Gajjar Floating drug delivery systems to increase

Gastric Retention Of drugs: A Review Research J. Pharm. and Tech. 1(4):oct.-Dec.2008.

Li Shum. Drug Dev. Ind.Pharm. 1989 , Vol. 15( 8 ), pp. 1137-1159. Dr.Jose GR, Omidian H, Shah K. Pharm Tech 2003;152-154. Streubel A, Siepmann I, Bodmeier R, Int J Pharm 2002;241(2):279-292. Swarbrick, J. Boylan, J.C. Encyclopedia of Pharmaceutical technology.1990,

Vol.3, pp.281, 286. , Vol.10, pp. 1-29. Abrahm, M.A., Shirwaiker, A. Indian J. Pharm.Sci. 1997 , Vol.

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RD Kale , PT Tayade A multiple unit floating drug delivery system of piroxicam using eudragit polymer Year : 2007 ,Volume : 69,Issue : 1,Page : 120-123

Abhishek Kumar Jain1, CP Jain1,YS Tanwar2, PS Naruka2,Formulation, characterization and in vitro evaluation of floating microspheres of famotidine as a gastro retentive dosage form,Year : 2009,Volume : 3,Issue : 3,Page : 222-226

Srivastava Anand kumar ,Devendra narayanrao ridhurkar , Floating microspheres of cimetidine: Formulation,characterization and in vitro Evaluation,Acta Pharm. 55 (2005) 277–285

Shashikant D. Barhate, Formulation and Evaluation of floating microsphreres of ketorolac troletamol, Publication Ref No.: IJPRD/2009/PUB/ARTI/VOV-1/ISSUE-9/NOV/005

M.K. Deepaa,*, M. Karthikeyanb,* Cefpodoxime Proxetil Floating Microspheres: Formulation and In Vitro Evaluation, Iranian Journal of Pharmaceutical Sciences Spring 2009: 5(2): 69-72

Patel Asha, Subhabrat Ray, Thakur Sharnagat Thakur, Invitro evaluation and optimization of controlled release floating drug delivery system of metformin hydrochloride. DARU Volume 14, No. 2, 2006,57

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Gattani Yogesh S, Durgacharan A Bhagwat, Akhil P Maske ,Formulation and evaluation of intragastric floating drug delivery system of diltiazem hydrochloride Year : 2008 ,Volume : 2 ,Issue : 4,Page : 228-231

Punitha.K*, Khadhir.S, Ravichandiran.V, Umadevi.S.K, Vijayanthi.V, Padmapriya.S, Suresh kumar.S Intragastric Floating drug delivery system of ranitidine hydrochloride : Formulation and evaluation International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 2, Issue 4, 2010,

Rajeev Garg and GD Gupta, Gastroretentive Floating Microspheres of Silymarin:Preparation and In Vitro Evaluation,Tropical Journal of Pharmaceutical Research, February 2010; 9 (1): 59-66

Yuveraj Singh Tanwar*, Pushpendra Singh Naruka, Garima Rani Ojha ,Development and evaluation of floating microspheres ofverapamil hydrochloride Brazilian Journal of Pharmaceutical Sciencesvol. 43, n. 4, out./dez., 2007

P Phutane1, S Shidhaye2, In vitro evaluation of novel sustained release microspheres of glipizide prepared by the emulsion solvent diffusion-evaporation method,year ;2010,volume:2,Issue:1,Page :35-41

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notes on formulation & evaluation of floating microspheres of an antibiotic drug

Documents

drug bioavailability

antibiotic drug

floating microspheres

gastroretentive system

sr system

bcs class drug

prolonged drug release

increased drug releases