FORMULATION DEVELOPMENT AND IN VITRO EVALUATION OF EXTENDED RELEASE MEBEVERINE HCL PELLETS

FORMULATION DEVELOPMENT AND IN VITRO EVALUATION OF

EXTENDED RELEASE MEBEVERINE HCL PELLETS

Amtun Noor1*, P.R.Sathesh Babu1, P. Aravind2

1

Department of Pharmaceutics, Gokaraju Rangaraju College of Pharmacy, Hyderabad, India.

2

Nosch labs private limited, Prashanthi Nagar, Kukatpally, Hyderabad.

ABSTRACT

The present study was aimed to formulate and evaluate extended

release mebeverine hydrochloride pellets using fluidized bed coater.

Mebeverine hydrochloride anti spasmodic drug being highly water

soluble drug with a half life of 2 h suitable to develop extended action

for treatment of irritable bowel syndrome. Nine formulations (M1-M9)

of mebeverine hydrochloride pellets were prepared using a

combination of two rate controlling polymers ethyl cellulose and

HPMCP HP 55 and other standard excipients. The prepared pellets

were subjected to micrometric properties and In vitro drug release

studies. The optimized formulation M9 showed 87.91% drug release

after 12 h. Scanning electron microscopy (SEM) studies revealed that

the prepared pellets for mebeverine hydrochloride are spherical in shape. The release profile

for optimized formulation M9 was comparable with that of marketed formulation (MEVA

SR) for mebeverine hydrochloride. The mathematical model was built on the hypotheses that

drug diffusion and drug dissolution in the release environment are the key phenomena

affecting drug release kinetics and it was found to be followed first order and diffusion

mechanism.

Keywords: Mebeverine hydrochloride; extended release; fluidized bed coater; irritable bowel syndrome.

INTRODUCTION

Pellets are agglomerates of fine powders or granules of bulk drugs and excipients. They

consist of small, free flowing spherical or semispherical solid units ranging from about 0.5-

1.5 mm. These are intended usually for oral administration. Pellets, give more stability from

compression and other stress conditions during formulation and storage conditions1,2.

Volume 3, Issue 3, 4783-4796. Research Article ISSN 2277 – 7105

Article Received on 12 March 2014,

Revised on 05 April 2014, Accepted on 28 April 2014

*Correspondence for Author

Amtun Noor

Moreover, pellets being multi-unit particulate dosage forms, can offer some additional

advantages such as easy dispersion in GI tract, increased drug absorption, and minimum

potential for local irritation of the drug3. The micropellets can be filled into hard gelatin

capsules or be compressed into tablets. The compression of multiparticulates into tablets is

becoming more popular, because of no problems of tampering4. The present study focused on

the development of extended release capsule containing mebeverine hydrochloride pellets.

Irritable bowel syndrome (IBS) is a disorder characterized most commonly by cramping,

abdominal pain, bloating, constipation, and diarrhoea5. IBS causes a great deal of discomfort

and distress, but it does not permanently harm the intestine and does not lead to a serious

disease, such as cancer. An anti spasmodic is usually prescribed which assists to control

colon muscle spasms and reduce abdominal pain. Oral ingestion is traditionally preferred

route of drug administration, providing a convenient method of effectively achieving both

local and systemic effects. Mebeverine hydrochloride is anti-spasmodic drug, chemically it is

(RS)-4-[ethyl (4-methoxy-α-methylphenyl) amino] butyl veratrate hydrochloride, is widely

used and having a direct non-specific relaxant effect on vascular, cardiac and other smooth

muscles5. Mebeverine HCl is a musculotropic antispasmodic drug without atropic side-effects

whose major therapeutic role is in the treatment of irritable bowel syndrome6. The short biological half life of 2 h with high solubility suggests its extended action in the treatment of

intestinal bowel syndrome.

MATERIALS AND METHODS

Bulk drug (mebeverine hydrochloride) and all other excipients (sucrose spheres, PVPK30,

maize starch, ethyl cellulose, HPMCP HP55, cetyl alcohol, sodium lauryl sulfate,

microcrystalline cellulose, mannitol, ethyl alcohol, isopropyl alcohol, acetone) were obtained

as gift samples from Nosch labs private limited, Hyderabad.

Drug – Excipient compatability studies

FT – IR studies: In this study, potassium bromide disc method was employed. IR studies of pure drug and physical mixtures of drug and excipients were done7. The powdered sample

was intimately mixed with dry powdered potassium bromide. The mixture was then

compressed into transparent disc under high pressure using special dies. The disc was placed

in IR spectrophotometer (Schimadzu FT – IR 8700) using sample holder and spectrum was

Stability studies: The drug and excipient compatibility study was done at accelerated conditions for short period of time (40 ± 2 ˚C / 75 ± 5 % RH) and long-term conditions (25 ±

2 ˚C /60 ± 5% RH) with periodic observation and physical evaluation. Samples of

mebeverine and individual excipients were intimately mixed in equal parts (1:1) ratio by

weight and filled in glass vials. Samples were physically observed at the end of 1st week, 2nd

week and 4th week.

Preparation of Mebeverine hydrochloride Pellets Preparation of drug loaded pellets

Mebeverine Hydrochloride was pulverized into a fine powder and kept aside. Load the

material (Mannitol, MCC) in a clean dry pulverizer/mill fitted with # 0.5 mm mesh. Pass the

API and above milled material through a clean sifter with # 20 sieve. Blend the above

materials along with SLS up to 45 min. Ethyl alcohol was taken in clean stainless steel vessel

which is kept under stirring, add PVP-K30 until to get clean solution. Pass above solution

through # 100 silk cloth filters, collect filtered solution in a clean stainless steel kettle. Charge

sucrose spheres (#30/40) into clean dry coating pan, coat the above sucrose spheres with

PVP-K30 solution till sucrose spheres are wetted. Continue process of wetting of spheres with

PVP-K30 solution and feeding of mixed API-Excipient blend till complete consumption of

blended powder is done. Pelletization time should be around 2 to 3 h. After completion of

coating, the coated pellets are dried in coating pan by maintaining inlet temperature at 50 ± 2

ºC for 3 h.

Coating-I of Mebeverine hydrochloride pellets (Sub coating)

A laboratory scale Umang Fluid bed multiple processor (Umang Pharma Tech Pvt Ltd) was

used for coating of pellets. Charge the ethyl alcohol in a clean stainless steel vessel kept

under homogenizer. Add ethyl cellulose under stirring; continue stirring until to get

homogenous solution (keep vessel under closed conditions). Coat drug pellets with ethyl

cellulose coating solution. Drug loaded pellets were transferred into the FBC and coated with

the above prepared coating solution. The air pressure was maintained at 3 - 3.5 kg/cm2, and

bed temperature was maintained at 40 ± 2 ºC. The bed temperatures are noted at every 1 h. In

order to dry ethyl cellulose coated pellets, temperature is maintained at 50 ± 2 ºC for 3h. The

conditions used in the coating are spray rate was 10-70 g/min, atomizing air pressure was 1-3

bar, fluidization air volume was 70-150 m3/h and inlet air temperature were adjusted in such a

Coating II of Mebeverine hydrochloride pellets (Enteric coating): Isopropyl alcohol and acetone were taken in clean stainless steel vessel and kept under homogenizer. Added cetyl

alcohol, hypromellose phthalate under stirring to get homogenous solution. Enteric coating

solution was sprayed into fluidized bed coater while maintaining air pressure at 3.5-5 kg/cm2

and bed temperature at 40 ± 2 ºC. Then the enteric coated pellets were dried at 50 ± 2 ºC for

30 min and allowed to cool. The coated pellets were transferred into the FBC and coated with

the above prepared coating solution. The coating process variables are same as above. The

dried pellets are sized on a sifter to remove agglomerates, broken pellets and fine powder and

these pellets are ready for filling into capsules.

Formulation trials: Formulation of mebeverine hydrochloride extended release pellets are based on preformulation data of various excipients and their compilation is shown in the

Table.1

Evaluation of pellets

Moisture content: It is determined with Karl-Fischer method. About 30 to 40 ml of methanol is taken into titration vessel and the solvent is neutralized with standard K.F.

reagent, then 0.3 g of the powdered pellet sample was accurately weighed and transferred into

titration vessel. The contents are titrated with Karl Fischer reagent to end point and

determined the moisture content.

Infrared spectroscopy analysis of drug and excipients: FT-IR spectra7 were obtained using FT-IR spectrometer (Model Schimadzu 8700) by the conventional KBr pellet method. The

samples were grounded gently with anhydrous KBr and compressed to form pellet and

recorded the spectrum. Scanning range was 400-4000 cm-1.

Flow properties: Bulk and tapped density of pellets was determined using USP bulk density apparatus. The bulk density, tapped densities were determined initially from which Hausners

ratio was calculated. The angle of repose was determined using fixed funnel method.

Sieve analysis: A series of sieves were arranged in the order of their decreasing pore diameter (increasing sieve number) (sieve # 10, 12, 14 and 18). Twenty grams of mebeverine

hydrochloride pellets was weighed accurately and transferred to sieve # 10 which was kept on

top. The sieves were shaken for about 10 min. Then the pellets retained on each sieve were

Abrasion resistance: A pre-weighed sample (approximately 10 g) was placed in an abrasion drum that was configured to raise and drop the pellets from 200 mm. The stress levels on

pellets were enhanced by adding 1 mm glass beads. After 100 revolutions at 25 rpm, the mass

retained on the sieve (1190 µm) was weighed and the abrasion resistance was calculated as

the percentage loss of mass between initial and final weights of each pellet batch. Each batch

is analyzed in triplicate.

Uniformity of weight (weight variation test): Ten capsules were randomly selected from each batch and individually weighed8. The average weight and standard deviation of ten

capsules were calculated. The batch passes the test for weight variation if the % deviation

is within the permissible limits (+ 5%).

.

Pellet shape analysis: To understand changes in the surface morphology, the topography of pellets was analyzed with help of scanning electron microscopy. A small amount of pellets

was spread on glass stub. Afterwards, the stub containing the sample was placed in the

scanning electron microscope chamber. The scanning electron photomicrograph was taken at

the acceleration voltage of 4 kV, chamber pressure of 19.7 mm Hg at different magnification

levels.

Estimation of drug content for mebeverine hydrochloride pellets

Five gms of pellets are grinded in a motor to a fine powder; equivalent to 200 mg of drug

accurately weighed which is dissolved with few drops of distilled water and made up to the

mark in 100 ml volumetric flask. The solution is kept for sonication followed by cyclomixing

and absorbance is measured at λmax of 263 nm.

In vitro release studies for mebeverine hydrochloride pellets

In vitro drug release was determined using USP Type-I dissolution testing apparatus (basket

method). Weigh accurately, about 290 mg of mebeverine hydrochloride pellets filled into

each capsule and placed in each of the dissolution flasks, containing 750 ml of 0.1 N HCl

previously which has been equilibrated to the temperature of 37 ºC ± 0.5 ºC. Start the

apparatus and run for 2 h. Withdraw 5 ml aliquot and replace with 5 ml of fresh 0.1 N HCl.

Take above 5 ml aliquot in 25 ml volumetric flask and make up to the volume with 0.1 N HCl

phosphate so that the pH gets adjusted to 6.8. Continued the dissolution apparatus and collect

the sample and repeat the same for every 3, 4, 6, 7, 9, 10, 11 and 12 h. The sample solutions

were diluted and spectrophotometry was carried out at a wavelength of 263 nm. Dissolution

studies were performed in triplicate.

RESULTS AND DISCUSSION

Extended release pellets were developed for an anti spasmodic drug with a view to deliver the

drug in a controlled manner using fluidized bed processor technique. The details of results

and discussion were given in the following sections.

Estimation of mebeverine hydrochloride

The drug estimation was made in 0.1 N HCl and phosphate buffer pH 6.8 at λmax of 263 nm

using UV spectrophotometer (Schimadzu UV – 1700). Calibration curve obeyed Beer –

Lambert’s law in the concentration range of 5 – 30 µg/mL with R2

= 0.9969 for 0.1 N HCl

and concentration range of 5 – 35 µg/mL with R2 = 0.9982 using phosphate buffer pH 6.8.

Drug-excipient compatability studies for mebeverine hydrochloride pellets FT-IR studies for mebeverine hydrochloride

The FT-IR scans for mebeverine hydrochloride drug and for mixtures of mebeverine with

different excipients, and mebeverine hydrochloride pellets are taken and reproduced in

Figure 1 (a), (b) and (c). The data obtained from the FT-IR spectrum are reported in Table 2.

The results shown in the Table 2 indicated that the characteristic bands obtained for the pure

drug are retained in the formulation mixture as well as in the prepared pellets. These studies

indicated a prima – facie evidence of compatability of drug and excipients used in the

formulation.

Characterization of mebeverine hydrochloride pellets

Flow properties of mebeverine hydrochloride pellets: All the nine different formulations of mebeverine hydrochloride pellets (M1 to M9) are subjected for evaluating the flow

properties. The different tests carried out on these pellets are given in the Table 3.

A perusal to the Table 3 shown were well within the specification limits for bulk density and

tapped density indicated that the flow properties for all the mebeverine hydrochloride pellets

Particle size distribution for mebeverine hydrochloride pellets

The various formulations of mebeverine hydrochloride pellets (M1 to M9) are subjected for

particle size distribution by sieve analysis. The percentage of pellets retained on different

sieves after shaking the sieve shaker for the specified period for all nine formulations are

obtained. From the obtained results, the particle size distribution revealed that, all the

formulations passed the test.

Physicochemical characterization of mebeverine hydrochloride pellets

The prepared pellets (M1 to M9) were subjected to physicochemical characterization. The

results obtained from these studies are recorded in the Table 4. A perusal to the Table 4,

weight variation of pellets is in range from 253 to 322 mg and observed within specifications.

Abrasion resistance was found to be less than 1% for all formulations. The percentage

moisture content ranges from 1 to 1.75 % for different formulation (M1 to M9). Assay results

were found to be well within the specifications for all nine formulations (93.37 to 99.99%).

In vitro dissolution studies

The prepared pellets (M1 –M9) are subjected to in vitro release studies in 0.1 N HCl for 2 h

and followed by phosphate buffer pH 6.8 for another 10 h as dissolution media using USP

Type I dissolution apparatus. The data obtained from the study was shown in the Table 5 and

recorded in Figure 2 from various formulations (M1-M9). A perusal to the Figure 2 and Table

5, it is evident that the drug release was found to be in range of 59.67 to 87.91% for the

formulations M1-M9 in 12 h. Thus the studies indicated that drug release was consistent for

all formulations. The effect of polymers HPMCP HP 55 and ethyl cellulose was clearly

indicated in the release studies. From these studies, the formulations M9 is optimized as the

drug release is more consistent and found to be highest in 12 h. Further, the optimized

formulation M9 was used to compare with marketed formulation MEVA SR as shown in

Figure 3, which indicated that the release for M9 is comparable as that of marketed

formulation.

Pellet shape analysis for mebeverine pellets by scanning electron microscopy

Scanning electron photomicrographs of optimized formulation of mebeverine hydrochloride

pellets M9 were taken. Acceptable shape was obtained indicating perfect sphericity of pellets

Kinetics of drug release from optimized formulation for mebeverine hydrochloride pellets

The in vitro drug release studies obtained for optimized formulation, M9, was subjected for

kinetics of drug release. The regression value for M9 is higher with first order than zero order

and therefore the release kinetics followed first order. Hixson-Crowell cube root law and

Higuchi’s models were applied to test the release mechanism. The R2

values are higher for

Higuchi law of diffusion in comparison to Hixson Crowell cube root law and hence release

followed diffusion rate controlled mechanism.

Table no. 1: Formulae used for mebeverine hydrochloride pellets.

Ingredients (mg or ml)

# Formulation code

M1 M2 M3 M4 M5 M6 M7 M8 M9

Powder blend Mebeverine

HCl 200 200 200 200 200 200 200 200 200 MCC 11.4 11.4 11.4 11.4 11.4 11.4 11.4 11.4 11.4 Mannitol 28.0 24.0 22.0 20.0 20.0 18.0 18.0 16.0 20.0 SLS 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0

Coating of blended powder Sucrose

spheres (30#40)

34.0 34.0 34.0 34.0 34.0 34.0 34.0 34.0 34.0

Drug layering

PVP-K 30 6.0 6.0 6.0 6.0 6.0 6.0 6.0 6.0 6.0

Ethanol-syrup preparation

q.s q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s.

Sub coating Ethyl

cellulose 4.0 6.0 6.0 4.0 12.0 12.0 6.0 10.0 8.0 Ethyl

alcohol q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. Enteric coating

HPMCP

HP 55 4.0 6.0 8.0 12.0 4.0 6.0 12.0 10.0 8.0 Cetyl

alcohol 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 Isopropyl

alcohol q.s q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. Acetone. q.s q.s q.s q.s q.s q.s q.s q.s q.s # Weight of each unit = 290 mg.

Table no. 2: Characteristic bands for mebeverine hydrochloride, formulation mixture and mebeverine hydrochloride pellets obtained in FT-IR spectrum.

Functional group

Bands in pure drug (cm-1)

Bands in formulation mixture (cm-1)

Bands in mebeverine pellets (cm-1) O-H stretching 2998.3 2980.02 2991.59 C=O(saturated

acyclic compounds)

1717.6 1718.58 1716.65

C-H stretching 2839.73 2881.56 2310.72 N=O stretching 1291.6 1280.73 1267.23 C=O (presence of

ketone group) 1678.2 1718.58 1601.77 C-H deformation

(presence of methyl group)

961.9 881.47 960.55

-OH stretching (Intra molecular hydrogen bond)

3420.8 3288.6 2883.58

Table no. 3: Flow properties of mebeverine hydrochloride pellets.

Formulation code

*Bulk density (g/ml)

*Tapped density (g/ml)

Hausners ratio M1 0.441 ± 0.003 0.524 ± 0.004 1.18

M2 0.587 ± 0.008 0.651 ± 0.004 1.10

M3 0.698 ± 0.004 0.742 ± 0.003 1.06

M4 0.559 ± 0.003 0.658 ± 0.005 1.12

M5 0.532 ± 0.005 0.605 ± 0.003 1.13

M6 0.543 ± 0.005 0.623 ± 0.005 1.14

M7 0.554 ± 0.003 0.632 ± 0.003 1.14

M8 0.541 ± 0.007 0.622 ± 0.001 1.14

M9 0.589 ± 0.002 0.630 ± 0.003 1.06

Table no. 4: Physicochemical characterization of mebeverine hydrochloride pellets.

Formulation code

Parameter * Uniformity of

weight (mg)

Abrasion

resistance (%) Assay (%)

Moisture content (%) M1 275.4 ± 0.850 0.56 ± 0.01 93.37 ± 0.09 1

M2 288.5 ± 0.503 0.55 ± 0.04 95.32 ± 0.10 1.46

M3 322.0 ± 0.152 0.54 ± 0.04 98.34 ± 0.22 1.11

M4 253.6 ± 0.776 0.71 ± 0.04 96.98 ± 0.03 1.10

M5 261.4 ± 0.556 0.57 ± 0.07 99.98 ± 0.01 1.75

M6 291.9 ± 0.450 0.63 ± 0.07 99.99 ± 0.01 1.43

M7 298.9 ± 0.808 0.72 ± 0.02 99.98 ± 0.80 1.41

M8 297.7 ± 0.702 0.65 ± 0.02 99.99 ± 0.05 1.75

M9 300.8 ± 0.208 0.57 ± 0.03 99.01 ± 0.10 1.16

Table no. 5: Dissolution profile for mebeverine hydrochloride pellets (M1 to M9) and marketed capsule

Medium TIME

(h)

% Cumulative drug release*(A.M±S.D)

M1 M2 M3 M4 M5 M6 M7 M8 M9 Marketed capsule

0.1 N HCl

0 0.00 ± 0.00 0.00± 0.00 0.00± 0.00 0.00± 0.000 0.00± 0.00 0.00± 0.00 0.00± 0.00 0.00± 0.00 0.00± 0.00 0.00 ± 0.00

0.5 16.99± 0.258 10.72± 0.477 13.46± 0.117 15.58± 0.116 17.73± 0.112 21.84± 0.344 22.91± 0.136 24.56± 0.07 27.76±

0.121 24.76 ± 0.121

1 21.57± 0.46 18.33± 0.488 15.55± 0.095 18.78± 0.135 22.62± 0.346 23.49± 0.504 25.73± 0.171 29.57± 0.051 29.71±

0.06 29.37 ± 0.045

1.5 28.99± 0.242 21.89± 0.563 19.53± 0.377 23.51± 0.169 25.87± 0.267 28.09± 0.178 29.66± 0.101 34.48± 0.031 35.61±

0.02 34.58 ± 0.076

2 31.76± 0.435 26.16± 0.191 25.61± 0.269 29.31± 0.287 29.9 ± 0.477 32.56± 0.305 37.07± 0.571 39.39± 0.051 41.86±

0.096 40.86 ± 0.096

Phosphate buffer pH6.8

2.5 34.98± 0.256 32.28± 0.308 29.4 ± 0.225 32.49± 0.205 33.69± 0.231 35.24± 0.295 39.74± 0.411 42.37± 0.107 43.8 ±

0.071 42.81 ± 0.076

3 36.45 ±0.202 34.86± 0.605 33.35± 0.35 36.31± 0.35 37.77± 0.355 37.42± 0.431 41.63± 0.056 45.82± 0.204 49.73±

0.046 50.73 ± 0.046

4 42.4 ± 0.528 40.49± 0.231 41.23± 0.535 39.35± 0.106 42.48± 0.221 41.66± 0.215 45.08± 0.422 49.66± 0.092 54.65±

0.065 55.65 ± 0.06

6 45.32± 0.651 42.69± 0.36 46.17± 0.197 43.97± 0.25 47.63± 0.092 44.76± 0.086 49.46± 0.098 54.76± 0.11 61.57±

0.045 59.54 ± 0.098

7 48.31± 0.047 44.29± 0.286 48.82± 0.444 48.45± 0.701 50.09± 0.129 49.42± 0.208 54.74± 0.167 56.81± 0.951 65.99±

0.379 64.32 ± 0.201

9 51.03± 0.35 47.45± 0.815 52.7 ± 0.259 53.17± 0.536 53.64± 0.315 55.01± 0.594 59.63± 0.072 62.08± 0.508 70.01±

0.174 67.78 ± 0.32

10 54.36± 0.744 51.23± 0.325 54.35± 0.14 57.02± 0.404 58.01± 0.295 57.7 ± 0.462 63.67± 0.11 67.86± 0.079 75.44±

0.115 72.91 ± 0.542

11 57.04± 0.447 54.29± 0.352 59.02± 0.528 61.57± 0.911 62.1 ± 0.15 64.83± 0.335 67.93± 0.035 71.78± 0.105 83.5 ±

0.457 79.48 ± 0.63

12 59.67± 0.974 59.84± 0.061 62.19± 0.136 64.97± 0.505 65.12± 0.363 67.34± 0.095 70.17± 0.201 79.87± 0.085 87.91±

0.040 87.04 ± 0.242

500 750 1000 1250 1500 1750 2000 2500 3000 3500 4000 1/cm 80 82.5 85 87.5 90 92.5 95 97.5 100 %T 29 97 .3 8 29 81 .9 5 25 57 .6 1 24 59 .2 4 24 39 .9 524 05 .2

3 2384

.0 2 23 51 .2 3 23 16 .5 1 17 16 .6 5 16 04 .7 7 15 12 .1 9 14 85 .1 9 14 56 .2 6 13 94 .5 3 13 40 .5 3 13 13 .5 2 12 90 .3 8 12 67 .2 3 12 49 .8 7 12 17 .0 8 11 74 .6 5 11 30 .2 9 10 26 .1

3 960.

55 87 3. 75 83 1. 32 81 7. 82 76 3. 81 mebev erine (a) 500 750 1000 1250 1500 1750 2000 2500 3000 3500 4000 1/cm 94.5 95.25 96 96.75 97.5 98.25 99 99.75 %T 32 21 .1 2 29 80 .0 2 28 81 .6 5 28 19 .9 3 24 65 .0 3 23 03 .0 1 17 18 .5 8 15 10 .2 6 14 81 .3 3 14 21 .5 4 13 98 .3 9 13 38 .6 0 13 07 .7 4 12 80 .7 3 12 51 .8 0 12 17 .0 8 10 80 .1 4 10 18 .4 1 92 9. 69 88 1. 47 63 2. 65 58 4. 43 41 8. 55 mebev erine-excipients (b) 500 750 1000 1250 1500 1750 2000 2500 3000 3500 4000 1/cm 90 91.5 93 94.5 96 97.5 99 %T 29 91 .5 9 28 83 .5 8 25 59 .5 4 24 59 .2 4 23 49 .3 0 23 10 .7 2 20 38 .7 6 18 94 .1 0 17 16 .6 5 16 04 .7 7 15 14 .1 2 14 81 .3

31452

.4 0 13 96 .4 6 13 40 .5 3 13 09 .6 7 12 92 .3 1 12 67 .2

3 1249

.8 7 12 19 .0 1 11 76 .5 8 11 30 .2 9 10 26 .1 3 96 0. 55 87 3. 75 81 7. 82 76 1. 88

mebev erine pellets

(c)

0 20 40 60 80 100

0 2 4 6 8 10 12

Time (h)

M1

M2

M3

M4

M5

M6

M7

M8

Fig. 2: In vitro dissolution profile for the mebeverine HCl pellets from formulations M1 to M9.

Fig. 3: In vitro dissolution profile obtained for the optimized formulation of mebeverine hydrochloride M9 and marketed capsule ‘Meva SR’.

(a) (b) (c)

CONCLUSION

Oral multiparticulate drug delivery systems of extended release mebeverine hydrochloride in

the form of pellets were successfully developed. The developed formulations were found to

have positive impact on in vitro dissolution behavior. The optimized formulations showed

gradual release and the release is comparable with marketed formulation. Thus, the fluidized

bed coating technique delayed the drug release for mebeverine hydrochloride pellets to the

desired extent.

ACKNOWLEDGEMENTS

The authors are thankful to Gokaraju Rangaraju College of Pharmacy and Nosch labs Pvt

Ltd, Hyderabad, (Andhra Pradesh, India) for providing all the chemicals and equipments and

other facilities required to carry out the present research project.

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