FORMULATION DEVELOPMENT AND EVALUATION … INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES FORMULATION DEVELOPMENT AND EVALUATION OF ORAL IN-SITU ... Gels …

Vol - 4, Issue - 3, Supl - 1 Apr-Jul 2013 ISSN: 0976-7908 Parekh et al

www.pharmasm.com IC Value – 4.01 228

PHARMA SCIENCE MONITOR

AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES

FORMULATION DEVELOPMENT AND EVALUATION OF ORAL IN-SITU

FLOATING GEL OF DOMPERIDONE

K. S. Parekh* and K. V. Shah

School of Pharmacy, RK University, Kasturbadham, Rajkot, Gujarat, India.

ABSTRACT Oral tablet administration to patients is a significant problem and has become the object of public attention. The demand for liquid dosage forms that can be easily ingested is particularly strong in the pediatrics and geriatric markets. Domperidone is a weakly basic drug used for treatment of upper gastrointestinal motility disorders such as nausea and vomiting. It is a weak base, which when exposed to environments of increasing pH results in precipitation of poorly soluble free base within the formulation. To resolve this problem the oral in-situ floating gel of Domperidone was formulated. The formulations of sodium alginate (F1-F6), poloxamer 407 (F7-F13) and combination of both the gelling polymers (F13-F16) along with HPMC K100 M as release retardant, were prepared and evaluated. CaCO3 is added which provided Ca2+ ion for gelation and CO2 which gets entrapped in gel matrix and induced floating of gel. The In-vitro drug release profile of all formulations was determined. Formulations F13-F16 provided sustained release for more than 9 hours. F14 showed 89.69% drug release over the period of 11 hours. Viscosity of all formulations was in acceptable range. The use of Poloxamer 407 and HPMC K 100M along with sodium alginate prolonged the release of drug from gel matrix.

Keywords: Domperidone, Sodium alginate, Poloxamer 407, HPMC K100 M, Floating gel. INTRODUCTION

Many patients have difficulty in swallowing tablets and capsules and consequently do

not take medications as prescribed. It is estimated that 50% of the population is

affected by this problem, which results in a high incidence of noncompliance and

ineffective therapy. Because the changes in various physiological functions associated

with aging including difficulty in swallowing, current dosage forms, like tablets and

capsules, are impractical.[1] The demand for liquid dosage forms that can be easily

ingested is particularly strong in the pediatrics and geriatric markets, with further

application to other patients who prefer the convenience of a readily administered

dosage form. [1]

Oral sustained release dosage forms (SRDFs) have been developed for the past three

decades due to their considerable therapeutic advantages. However, this approach has not



been suitable for a variety of important drugs, characterized by a narrow absorption

window and degradation at alkaline pH in the upper part of the gastrointestinal tract

(GIT), i.e. stomach and small intestine due to the relatively short transit time of the

SRDFs in these anatomical segments. This results in a short absorption phase that is often

accompanied by lesser bioavailability. The development of in situ gel systems has

received considerable attention over the past few years. This interest has been sparked by

the advantages shown by in situ forming polymeric delivery systems such as ease of

administration and reduced frequency of administration, improved patient compliance

and comfort.[2]

In the past few years, increasing number of in situ gel forming systems have been

investigated. Various natural and synthetic polymers are used for formulation

development of in situ forming drug delivery systems. These polymers undergo sol-gel

transition, once administered. In situ gel formation occurs due to one or combination of

different stimuli like pH change, temperature modulation and solvent exchange.[2]

Domperidone is a synthetic benzimidazole compound that has potent antiemetic as well

as gastrointestinal stimulatory properties. Domperidone is a peripheral dopamine-blocker.

It is a weak base, which when formulated as an oral sustained release dosage form is

exposed to environments of increasing pH with subsequent precipitation of poorly

soluble free base within the formulation.[3] Hence formulating in-situ floating dosage

form will retains the drug in stomach and prevents it from degradation. The main

objective is to formulate oral in-situ floating gel by using two gelling polymer, sodium

alginate and poloxamer and a release retarding polymer HPMC K 100 M which can

provide prolonged floating time and sustained drug delivery of drug.

MATERIALS AND METHOD

Domperidone was obtained as a gift sample from Santech Pharmaceuticals ltd. Mumbai.

Poloxamer 407 (Sigma chemicals ltd.-USA), sodium alginate (Astron), sodium citrate

(Astron), CaCO3 (Astron) and HPMC K100 M (Astron) were used in the formulation.

Deionised water is used for the preparation of the formulation.



Method of preparation:

In-situ floating solutions using sodium alginate as polymer:

Specified quantity of Domperidone, HPMC K100M, calcium carbonate, sodium citrate

and sodium alginate was weighed according to formula. (Table -1)

The sodium alginate solutions of different concentration (F1 - F6) were prepared in

deionised water containing sodium citrate. HPMC K100M was added to it. The solution

was then heated to 70oC with stirring. After cooling to below 40oC, different

concentrations of calcium carbonate and the drug was added and dispersed well with

continuous stirring.[4]

In-situ gelling solutions using poloxamer 407 as polymer:

For preparation of pluronic solutions (F7 - F12), the required amount of polymers

(poloxamer and HPMC K 100M), sodium citrate and CaCO3 were dispersed in distilled,

deionized water with continuous stirring for 1 h at room temperature. The partially

dissolved pluronic solutions were stored in the refrigerator (at 4ºC) until the entire

polymer was completely dissolved (approximately for 24 h).[5]

In-situ gelling solutions using sodium alginate and poloxamer as gel forming

polymers:

The solutions (F13 - F16) were prepared in deionised water containing sodium citrate by

heating different concentration of polymers (Sodium alginate and HPMC) to 600C under

continuous stirring. After cooling below 400C, CaCO3 and the drug was dispersed under

continuous stirring. Then these solutions were cooled below 50C and a different

concentration of poloxamer was added with continuous stirring for 1 hour. The solutions

were refrigerated to ensure complete dispersion of poloxamer.

TABLE 1: FORMULATIONS OF DOMPERIDONE IN-SITU FLOATING GEL

Formulation Sodium

alginate (g) HPMC K 100M (g)

Poloxamer 407 (g)

Sodium Citrate (g)

CaCO3 (g)

F1 0.5 0.4 - 0.25 2 F2 1.5 0.4 - 0.25 2 F3 2.5 0.4 - 0.25 2 F4 0.5 0.6 - 0.25 2 F5 1.5 0.6 - 0.25 2 F6 2.5 0.6 - 0.25 2 F7 - 0.4 16 0.25 2



F8 - 0.4 18 0.25 2 F9 - 0.4 20 0.25 2 F10 - 0.6 16 0.25 2 F11 - 0.6 18 0.25 2 F12 - 0.6 20 0.25 2 F13 1.5 0.6 18 0.25 2 F14 1.5 0.6 20 0.25 2 F15 2.5 0.4 18 0.25 2 F16 2.5 0.4 20 0.25 2

*All formulations were made upto volume 100ml with deionised water.

Evaluation parameters:

1. Compatibility study by IR Spectroscopy

Fourier-transform infrared (FT-IR) spectra were obtained using an FT-IR spectrometer

(Shimadzu 8400S, Japan) at Parul Institute of pharmacy, Baroda. FT-IR spectroscopy

was carried out to check the compatibility between drug and polymer.[6]

2. General Appearance

The general appearance which Included colour, texture and consistency was visually

determined.[7]

3. pH Measurement

The pH of the prepared solution was measured by pH meter after its calibration at pH 4

and pH 9.[7]

4. In-Vitro Gelling Time

It was measured by adding one ml gelling solution in 0.1N HCl (pH 1.2) in a 250 ml

beaker maintained at 37±1ºC temperature. The gelling time of solution was evaluated on

the basis of time required for gelation. The in-vitro gelling capacity was graded in three

categories as below, on the basis of gelation time.

(+) Gels immediately, dispersed rapidly

(++) Immediate gelation, no dispersion

(+++) Gelation after few minutes.[8]

5. In-Vitro Buoyancy Studies

The in-vitro floating study was carried out using 900 mL of 0.1N HCl, (pH 1.2) at 37oC.

Ten millilitre formulations were introduced into the dissolution vessel containing

medium. The time the formulation took to emerge on the medium surface (floating lag



time) and the time the formulation constantly floated on surface of the dissolution

medium (duration of floating) was noted.[9]

6. Viscosity Measurement of The In-Situ Gelling Solution

Viscosity of the sols and the Gel Formulation was determined by using a Brookfeild

digital viscometer (DV-E Viscometer) at 30 RPM at 27 ±1 ºC for 30 sec.[10]

7. Measurement of Water Uptake By The Gel

Here in-situ gel formed in 0.1 N HCl (pH 1.2) was used. From each formulation the gel

portion from the 0.1 N HCl was separated and the excess HCl solution was blotted out

with a tissue paper. The initial weight of the gel taken was weighed and to this gel 10 mL

of distilled water was added at the interval of 1 hour. After every 60 minutes of the

interval water was decanted and the weight of the gel was recorded for the periods of 6

hrs and the difference in the weight was calculated and reported.[11] % weight gain can be

calculated by following equation;

% water gain = W3*100/ W1

Where, W3 = Weight gain by the gel = Final weight W2 – Initial weight W1

8. Measurement of Gelling Temperature (GT) of Poloxamer

Ten ml of the sample solution and a magnetic bar were put into a transparent vial that

was placed in a low temperature water bath. A thermometer was immersed in the sample

solution. The solution was then heated. The temperature was determined as GT, at which

the magnetic bar stopped moving due to gelation. Gelling temperature of solutions

containing only poloxamer as gelling polymer were evaluated.[5]

9. In-Vitro Drug Release Study

The release rate of Domperidone from in-situ gel was determined using USP dissolution

testing apparatus I at 50 RPM. This speed was slow enough to avoid the breaking of

gelled formulation and it maintained the mild agitation conditions which were believed to

exist in vivo. Ten mL of gelling solution was added into the 900 mL of 0.1 N HCl

dissolution medium, and temperature was maintained at 37 0C. From this dissolution

medium, 1 mL of the sample solution was withdrawn at different time intervals. The

samples were filtered through Whatsman filter paper and contents of it was determined

spectrophotometrically at 284 nm using double beam UV-Visible spectrophotometer.[11]



10. Determination of Drug Content

Accurately, 10 mL of in-situ gel from all the batches was taken and to this 50-70 mL of

0.1 N HCl was added and sonicated for 30 min and volume was adjusted to 100 mL.

Complete dispersion of contents was ensured and the contents were filtered using

Whatman filter paper. From this solution, 1 mL of sample was withdrawn and diluted

suitably with 0.1 N HCl and determined spectrophotometerically at 284 nm using double

beam UV-Visible spectrophotometer.[12]

RESULT AND DISCUSSION

1. FT-IR Spectroscopic Study

Figure 1: FT-IR Spectrum of Domperidone

Figure 2: FT-IR Spectrum of Mixture of Domperidone, Sodium Alginate,

Poloxamer, HPMC K100 M, Sodium Citrate and CaCO3



IR spectrum indicated that there is no interaction between Domperidone and polymers

when compared with infrared spectrum of pure drug as all functional group frequencies

were present.

2. General Appearance

The results of visual examination are indicated in table-2. The solutions were free

running solutions and did not show any gelation at room temperature. The grittiness that

was observed due to undissolved cluster of poloxamer in the solutions containing

poloxamer, was found to disappear and the clarity was regained after overnight

refrigeration of those solutions.

3. pH measurement

The pH of the formulations is indicated in table-2. It was found to be in the range of 8.50

to 8.95. The formulations were liquid at room temperature and at basic pH. Refrigeration

of the poloxamer containing solutions had no effect on the pH.

4. In-Vitro Gelling Studies

Table-2 shows the gelling capacity of formulations from F1 to F16.

All the formulations except F7 and F10 showed instantaneous gelation when contacted

with 0.1 N HCl (1.2 pH).

5. In-vitro buoyancy studies:

All the formulations were buoyant within few minutes and the formulations containing

higher amount of sodium alginate had shown the floating time for more than 18 hours

and the solutions containing only poloxamer were found to float for the duration of less

than 14 hours. Moreover the formulation F13 to F16 showed an increased floating time

upto 24 hours.

6. Viscosity measurement:

Table-2 shows the viscosity (cp) of formulations from F1 to F16 at 30 rpm. The viscosity

of all the formulations was found satisfactory and the solutions were free running at room

temperature.

It was also observed that the viscosity of gels of formulations F13, F14, F15, and F16

were higher which indicated stable gel formation. Hence, these formulations were found

appropriate for the selection of the optimized batch.



TABLE 2: GENERAL EVALUATION PARAMETERS OF ORAL IN-SITU

FLOATING GEL F

orm

ula

tion

C

ode

Col

our

Ave

rage

p

H

Gel

lin

g C

apac

ity

Flo

atin

g L

ag

Tim

e (s

ec)

Du

rati

on o

f

floa

tin

g (h

ours

)

Vis

cosi

ty o

f ge

llin

g so

luti

on

(cp

)

Vis

cosi

ty o

f ge

l (c

p)

F1 Off

White 8.96±0.01 ++ 63.33 19.67 209.66 1223.00

F2 Off

White 8.97±0.02 +++ 61.67 20.67 275.00 1538.33

F3 Off

White 8.91±0.02 +++ 56.67 21.67 347.00 1679.67

F4 Off

White 8.9±0.02 ++ 58.33 21.67 218.33 1365.67

F5 Off

White 8.76±0.02 +++ 63.33 23.50 291.66 1983.33

F6 Off

White 8.62±0.03 ++ 61.67 17.50 362.00 1730.67

F7 White 8.54±0.02 + 60.00 - 105.33 1034.33

F8 White 8.67±0.03 ++ 44.00 11 117.66 1379.33

F9 White 8.89±0.03 ++ 47.33 12 128.00 1673.67

F10 White 8.76±0.05 + 50.00 - 106.33 1193.00

F11 White 8.86±0.02 ++ 56.00 12 128.00 1528.67

F12 White 8.87±0.03 +++ 58.67 12 149.00 1869.00

F13 Off

White 8.52±0.02 +++ 61.00 23 294.33 1992.00

F14 Off

White 8.53±0.01 +++ 60.67 24 290.33 2166.67

F15 Off

White 8.55±0.02 +++ 62.00 24 432.33 2406.67

F16 Off

White 8.61±0.01 +++ 64.00 24 464.66 2504.00

*Values in parenthesis are standard deviation (n=3)



7. Measurement of Water Uptake by The Gel

The highest water uptake was found for formulation F16 which contained 1.5 % sodium

alginate and the maximum amount of poloxamer and HPMC K 100 M.

Figure 3: Measurement of Water Uptake By Oral In-Situ Floating Gel

8. Measurement of Gelling Temperature of Poloxamer Solutions

The Gelling Temprature (GT) of the Poloxamer Solutions were determined and is listed

in the below table.

TABLE 3: GELLING TEMPERATURE (GT) OF THE POLOXAMER

SOLUTIONS

Formulation code

F7 F8 F9 F10 F11 F12

Gelling temperature (0C)

- 30 30 - 31 30

The solutions containing only 16% poloxamer (F7 and F10) as gelling polymer failed to

gel.

9. In-Vitro Drug Release Study

The % cumulative drug release of F1-F16, are tabulated in Table -4, 5 and 6.



TABLE 4: % CUMULATIVE DRUG RELEASE OF F1-F6

Time (hr)

Cumulative % drug

release of F1

Cumulative % drug

release of F2

Cumulative % drug

release of F3

Cumulative % drug

release of F4

Cumulative % drug

release of F5

Cumulative % drug

release of F6

0 0 0 0 0 0 0

1 34.7 15.14 13.2 40.82 17.68 46.34

2 68.29 23.52 29.77 53.21 25.94 66.93

3 97.4 39.6 46.81 73.42 47.12 78.11

4 - 53.32 57.03 83.18 53.98 95.39

5 - 84.28 69.52 93.04 72.48 -

6 - 95.65 83.71 - 83.72 -

7 - - 96.55 - 93.57 -

TABLE 5: % CUMULATIVE DRUG RELEASE OF F8, F9, F11, F12

Time Cumulative % drug release of

F8

Cumulative % drug release of

F9


F11


F12 0 0 0 0 0 1 27.98 29.17 27.98 12.46 2 57.699 42.86 43.66 33.04 3 97.21 73.18 61.74 71.39 4 - 94.88 94.74 91.59

TABLE 6: % CUMULATIVE DRUG RELEASE OF F13-F16

Time Cumulative % drug release of

F13


F14


F15


F16 0 0 0 0 0

1 17.85 15.89 17.23 13.80

2 24.75 20.99 21.75 22.46

3 32.93 30.33 27.96 34.20

4 39.26 36.93 44.99 42.19

5 50.14 45.54 57.57 51.61

6 53.81 56.48 74.24 59.03

7 62.82 61.20 82.50 62.88

8 73.94 70.81 93.84 74.00

9 94.13 77.53 - 83.74

10 - 84.32 - 89.10

11 - 89.69 - 96.01



Figure 4: Cumulative % drug release (F1-F6)

Figure 5: Cumulative % drug release (F8, F9, F11, F12)

Figure 6: Cumulative % drug release (F13, F14, F15, F16)

In-vitro dissolution studies showed that formulation F14 showed 89.69% drug release

over the period of 11 hours. More over it was also depicted that increased concentration

Time



of HPMC K 100 M was useful for sustained drug delivery. Use of Poloxamer 407 also

added to decrease the drug release and prolonged the drug release.

The results obtained from in vitro release studies of the optimised batch (F14) was

attempted to fit into various mathematical models. The regression coefficient (r2) values

of zero order, first order, Higuchi matrix, Peppas and Hixson-Crowell are tabulated in

table-7 for optimised formulation. From the table, it is clear that the drug is released in a

controlled manner over a period of time and shows zero order drug release for all

formulations.

TABLE 7: IN-VITRO DRUG RELEASE PROFILE OF DOMPERIDONE

FORMULATION F14

Formulation R2 value

Best fit model Higuchi

Zero order

First order

Hixon-crowell

K Peppas

F14 0.967 0.996 0.962 0.982 0.969 Zero order

Figure 7: In-Vitro Drug release profile of Domperidone Formulation F14 (Zero

Order)



Figure 8: In-Vitro Drug release profile of Domperidone Formulation F14 (First

Order)

Figure 9: In-Vitro Drug release profile of Domperidone Formulation F14 (Higuchi

Matrix)

Figure 10: In-Vitro Drug release profile of Domperidone Formulation F14 (Hixon-

crowell)



Figure 11: In-Vitro Drug release profile of Domperidone Formulation F14 (K

Peppas Treatment)

10. Measurement of Drug Content

The absorbance of the suitably diluted solutions was measured. All the readings were

measured in triplicate and the average of the % Drug content is determined by using

standard calibration curve taken at 284 nm. (Table - 8)

TABLE 8: MEASUREMENT OF DRUG CONTENT OF IN-SITU GELLING

SOLUTIONS

Formulations Average% drug content

1 102.89

2 102.63

3 98.65

4 101.03

5 101.44

6 99.17

7 100.20

8 102.17

9 100.10

10 100.51

11 101.39

12 100.98

13 101.13

14 99.22

15 101.29

16 102.22



In the present study the content uniformity of all the batches are found to be in the range

of 98.65-102.89. Hence all the batches have passed the content uniformity test, because

all the batches lies within the acceptable limit.

11. Stability Study

11.1 In-Vitro Drug Release Studies

Figure 12: Stability Study of Optimized Formulation at Room Temperature

Stability study was carried out for optimized formulation at room temperature for 1

month. The cumulative drug release of optimized formulation F14 showed that 89.69%

drug got released in 11 hours, while after one month the percent drug release was found

to be 92.96% in 11 hours. So, there was no major change during one month.

11.2 Measurement of viscosity, pH and % drug content

TABLE 9: MEASUREMENT OF GENERAL PARAMETERS OF OPTIMISED

FORMULATION AFTER 1 MONTH

Formulation F14 pH Viscosity of solution and gel (cp)

% drug content

Before one month 8.53 290.33 2166.67 99.22 After one month 8.46 309.6 2119.33 100.97 No significant difference in the pH, viscosity and % drug content was found during the

period of 1 month.



References

1. Chauhan B, Singh L, Chatterjee A, et al. An Approach Based on Advantages

over Conventional System. Journal of Biomedical and Pharmaceutical

Research. 2013; 2: 41-51.

2. Madan M, Bajaj A, Lewis S, Udupa, et al. In Situ Forming Polymeric Drug

Delivery Systems. Indian J PharmSci. 2009; 71(3):242-251.Shah S, Pandya S,

Waghulade M. Development and investigation of gastro retentive dosage form of

weakly basic drug. Asian journal of pharmaceutics. 2010; 4: 11-13.

3. Sarrof R, Shaikh A, Yogesh Y et al. Sodium Alginate Based Oral in Situ Floating

Gel of Metformin Hydrochloride. Research Journal of Pharmaceutical,

Biological and Chemical Sciences. 2012; 3: 890.

4. Varshosaz J, Tabbakhian M, Salmani Z. Designing of a Thermosensitive

Chitosan/Poloxamer in-Situ Gel for Ocular Delivery of Ciprofloxacin. The Open

Drug Delivery Journal. 2008; 2: 61-70.

5. Miyazaki S, Kawasaki N, Kubo W, et al. Comparison of in situ gelling

formulations for the oral delivery of Cimetidine International Journal of

Pharmaceutics. 2001; 1: 161–168.

6. Bhimani D, Patel J, Patel V, et al. Development and evalution of Floating in-situ

gelling system of Clarithromycin. International journal of pharmaceutical research

and development. 2011; 3; 32-40.

7. Panwar P, Chourasiya D, Jain G, et al. Formulation and evaluation of oral

floatable in-situ gel of Diltiazem HCL. International Journal of Novel Drug

Delivery Technology. 2012; 2: 264-270.

8. Rajalakshmi R, Sireesha A, Subhash KV, et al. Development and Evaluation of a

Novel Floating In-situ Gelling System of Levofloxacin Hemihydrate.

International Journal of Innovative Pharmaceutical Research 2011; 2: 102-108.

9. Gratieri T, Gelfuso M, Melani E, et al. A poloxamer/chitosan in situ forming gel

with prolonged retention time for ocular delivery. European Journal of

Pharmaceutics and Biopharmaceutics. 2010; 75: 186–193.

10. Patel D, Patel D, Patel C et al. Formulation and evaluation of floating oral in-situ

gelling system of Amoxicillin. ISRN Pharmaceutics. 2011; 1-8.



11. Gamal M. Maghraby E, Elzayat E, et al. Development of modified in situ gelling

oral liquid sustained release formulation of Dextromethorphan. Drug

Development and Industrial Pharmacy. 2012; 38: 971-978.

12. Liew C, Chan L, Ching A et al. Evaluation of sodium alginate as drug release

modifier in matrix tablets. International Journal of Pharmaceutics 2006; 309: 25–

3.

13. Paul J. Hesketh. Chemotherapy-Induced Nausea and Vomiting. The New England

journal of medicine. 2008; 358: 2482-94.

14. Tyagi R, Dhillon V. Enhancement of solubility and dissoultion rate of

Domperidone using cogrinding and kneading technique. Journal of Drug Delivery

& Therapeutics. 2012; 2: 152-158.

15. Patel K, Jain K, Baghel R, et al. Preparation and in vitro evaluation of a

microballoon delivery system for domperidone . Scholars Research Library. 2011;

3: 131-141.

16. Trivedi P, Maheshwari D. Estimation of Esomeprazole and Domperidone by

absorption ratio method in Pharmaceutical Dosage Forms. International Journal of

ChemTech Research CODEN (USA). 2011; 2: 1598-1605.

17. Shah S, Pandya S, Waghulade M. Development and investigation of gastro

retentive dosage form of weakly basic drug. Asian journal of pharmaceutics.2010;

4: 11-13.

18. Tintinalli, Judith E. Emergency Medicine: A Comprehensive Study Guide

(Emergency Medicine (Tintinalli). New York: McGraw-Hill

Companies. 830. 2010.

19. Raymond C, Rowe Paul J, Sheskey Marian E. Handbook of Pharmaceutical

Excipients. Editors: American Pharmaceutical Association and The

Pharmaceutical Society of Great Britain. Washington, London: American 1986:

326-329.

20. Jayswal BD, Yadav VT, Patel KN, et al. Formulation and Evaluation of Floating

In Situ Gel Based Gastro Retentive Drug Delivery of Cimetidine. International

Journal for Pharmaceutical Research Scholars 2012; 1: 327-337.



21. Kakkar S, mahant S. In-situ gelling systems for ‘Smart’ drug delivery.

International journal of natural product science. 2012; spl issue: 1-86.

22. Kumar V, Krishnarajan D, Manivannan R et al. Formulation and evaluation of bi-

layer Domperidone floating tablets. International journal of pharmaceutical

science and research. 2011; 2: 2217-2225.

23. Deshmukh R. Pharmaceutical research on Controlled release in-situ forming

Moxifloxacin hydrogel for ophthalmic drug delivery. B.Pharm thesis Department

of Pharmaceutics, JN medical college, Belgaum, Karnataka, India 2010: 1-147.

24. Stockman A, Caron D, Gallant J, Boghaert A. Postoperative nausea and vomiting

treated with domperidone (r 33812) an open and a double-blind study.

Anesthetist. 1978; 27: 540-546.

25. Zegveld C, Knape H, Smits J, et al. Domperidone in the Treatment of

Postoperative Vomiting: A Double-Blind Multicenter Study. Ansth anlg. 1978; 7:

700-703.

26. Nappi C, Colace G, Renzo G.F, et al. Domperidone antagonizes

Bromoergocriptine -Induced nausea and vomiting without affecting its inhibition

of prolactin secretion in puerperal women. European Journal of Clinical

Pharmacology, 1987; 32: 457-460.

27. Shinde S, Pawar R, Joshi H. Domperidone Floating Microspheres: Formulation

And In Vitro Evaluation. Journal of Pharmacy Research. 2012; 5: 2235-2238.

28. Prajapati ST, Patel LD, Patel DM. Studies on formulation and In

vitro evaluation of floating matrix tablets of Domperidone. Iranian Journal of

Pharmaceutical Research. 2010; 10: 447-455.

29. Zhang C, Zhao B, Huang Y, et al. A Novel Domperidone Hydrogel:

Preparation, Characterization, Pharmacokinetic, and Pharmacodynamic

Properties. Journal of Drug Delivery. 2011; 201: 1-9.

30. Singh I, Kumar P, Singh H et al. Formulation and evaluation of Domperidone

loaded mineral oil entrapped emulsion gel (moeg) buoyant beads. Acta poloniae

pharmaceutica n drug research. 2011; 68: 121-126.



31. Khan A, Saeed M, Badshah A, et al. Design, formulation, optimization and

evaluation of sustained release tablets of Domperidone. African Journal of

Pharmacy and Pharmacology. 2011; 5: 1882-1887.

For Correspondence: K. S. Parekh Email: [email protected]

Documents

FORMULATION DEVELOPMENT AND EVALUATION … INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES FORMULATION DEVELOPMENT AND EVALUATION OF ORAL IN-SITU ... Gels …