Purpose: The chief purpose of the present work was to fiction of gastro recollective high denseness microcapsules with both man-made and natural polymers for the controlled release of Famotidine to handle stomachic ulcers. Methods: The microcapsules were prepared by the coacervation stage separation technique. Famotidine was checked for its compatibility with polymers used by Fourier Transform Infrared spectrometry. The surface morphology was studied by scanning negatron microscopic surveies. The per centum of output, surface associated drug content, drug entrapment efficiency and in vitro disintegration surveies were performed and the disintegration informations was treated with mathematical kinetic theoretical accounts. Accelerated stableness surveies were besides carried out to the optimized preparation ( F-6 ) . Consequences: The FTIR spectrum of pure drug and drug-polymer blend showed the stable character of Famotidine in the micro capsules. The microcapsules were found to be spherical. The microcapsules had good entrapment efficiency and per centum output. The release of drug from the microcapsules extended up to 12 h. The release dynamicss informations and word picture surveies indicate that drug release from microcapsules was diffusion controlled and that the microcapsules were stable. Decision: The survey revealed that Gellan gum and Karaya gum in combinations found to be effectual combination for microcapsules.

Cardinal words: Famotidine, Microcapsules, Gellan gum, Karaya gum, Titanium dioxide.

1. Introduction

Microcapsules drug bringing systems made from the natural, biodegradable polymers have been attracted by several research workers for last decennary in prolonging the drug bringing [ 1 ] . Microcapsules have varied applications and are prepared utilizing assorted polymers. However, the success of microcapsules is limited due to their short abode clip at the site of absorption/action [ 2 ] . High denseness micro capsules provide an addition abode clip by doing them to drop in stomachic fluid. This can be achieved by matching high denseness stuffs which has higher denseness so stomachic fluid [ 3 ] . High denseness systems have advantages like increased stomachic abode clip and specific targeting of drugs in the soaking up site, efficient soaking up and enhanced bioavailability [ 4, 5 ] . Titanium dioxide was selected as high denseness stuff in explicating micro capsules [ 6 ] . Gellan gum was obtained from Pseudomonas Elodea, which is chemically D-glucose, D-glucuronic acid and rhamnose in & A ; szlig ; -1, 4 linkage whereas Karaya gum was obtained from the works Sterculia urens, which is chemically Mixture of D-galactose, L- rhamnose and D-galacturonic acid [ 7 ] .

Famotidine is a histamine H2-receptor adversary. It is widely prescribed in active duodenal ulcers, stomachic ulcers, Zollinger-Ellison syndrome, gastro esophageal reflux disease and erosive esophagitis. The recommended grownup unwritten dose of Famotidine is 150 mg twice daily or 300 milligrams one time daily. The effectual intervention of erosive esophagitis requires disposal of 150 milligram of Famotidine 4 times a twenty-four hours. A conventional dosage of 150 milligrams can suppress stomachic acid secernment up to 5 Hs but non up to 10 h. An alternate dosage of 300 milligrams leads to plasma fluctuations ; therefore a controlled release dose signifier of Famotidine is desirable. The short biological half life of drug ( ~2.5-3 H ) besides favors development of a controlled release preparation [ 8 ] . In competition of the above rule, a strong demand was recognized for the development of a dose signifier to present sustained release gastro recollective bringing system of Famotidine.

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2. Materials and methods

2.1. Materials

Famotidine was obtained as a gift sample from Waksman Selman Pharmaceuticals, Anantapur, India ( Batch # R 005288 ) , Gellan gum, Karaya gum ; Formaldehyde and Titanium oxide were procured from SD Fine Chemicals, Mumbai, India. Sunflower oil was procured from MORE ace market, Anantapur, India. All the trustees were of analytical reagent class and dual distilled H2O was used throughout the experiment.

2.2. Preformulation Surveies

2.2.1. Solubility analysis

Preformulation solubility analysis was done to choose a suited dissolver system to fade out the drug and besides to prove its solubility in the disintegration medium which was to be used.

2.2.2. Melting Point finding

Melting point finding of the obtained sample was done because it is a good first indicant of pureness of the sample since the presence of comparatively little sum of dross can be detected by a lowering every bit good as broadening in the thaw point scope.

2.3. Compatibility Surveies

2.3.1. Fourier Transform Infrared Spectroscopy

Fourier Transformed Infrared ( FTIR ) spectrums of Famotidine with gums used were obtained separately and in combinations on a Fourier Transform Infrared ( FTIR ) spectrophotometer ( Perkin Elmer, spectrum-100, Japan ) utilizing the KBr disc method ( 5.2510 milligram sample in 300.2502 milligrams KBr ) . The scanning scope was 500 to 4000 cm-1 and the declaration was 1 cm-1. This spectral analysis was employed to look into the compatibility of drugs with the polymers used.

2.4. Preparation of microcapsules [ 9, 10 ]

Gellan gum, Karaya gum and Titanium dioxide mixture incorporating Famotidine Micro domains were prepared by coacervation stage separation technique utilizing temperature opportunity. Gellan gum, Karaya gum and Titanium dioxide were dissolved in 10ml of H2O which was antecedently heated to 50Es C, to this Famotidine was added and stirred at 300 r/ min with the aid of magnetic scaremonger for 15 min to acquire a stable scattering. The scattering was poured bead wise into the 10ml of sunflower oil which was besides antecedently heated to 500 C on a H2O bath. The mixture was stirred with a aid of magnetic scaremonger for 2 H at 300r/ min at room temperature. At the terminal of 2 H crosslinking agent formaldehyde 0.5ml was added to the scattering medium and stirring was continued for following 30 min. Finally it was kept in icebox for 24 H to guarantee the rigidity of Micro domains. This Procedure was followed to fix 6 batches of Famotidine Micro spheres with different ratios of Gellan gum and Karaya gum mixtures. The nucleus: coat ratio, sum of drug and polymers used were given in Table 1.

2.5. Flow Properties [ 11 ]

2.5.1. Angle of rest

This was determined by utilizing funnel method. Powder was poured from a funnel that can be raised vertically until a maximal cone tallness ( H ) , was obtained. Diameter of pile, ( D ) , was measured. The angle of rest ( O? ) was calculated by the eq.1 and 2.

tan O? = H / R ( 1 )

O? = tan-1 ( h / R ) ( 2 )

Where, O? = Angle of rest, H = tallness of the heap ( centimeter ) and R = radius of the heap.

2.5.2. Loose Bulk denseness

The sample under trial was screened through sieve no. 18, the sample equivalent to 25 g was accurately weighed and filled in a 100 milliliter graduated cylinder, the pulverization was leveled, and the unsettled volume, V0 was noted. The majority denseness was calculated in g/cm3 by the eq.3.

Db = M / V0 ( 3 )

Where, M= Mass of pulverization, V0= Bulk volume of the pulverization

2.5.3. Tapped Bulk Density

The sample under trial was screened through sieve # 18 and the weight of sample equivalent to 25 g was filled in 100 milliliter graduated cylinder. The mechanical tapping of the cylinder was carried out utilizing tapped denseness examiner at a nominal rate of 300 beads per min for 500 times ab initio and the tapped volume V0 was noted. Taping was continuing farther for an extra tapping 750 times and tapped volume Vb was noted. The difference between two tapping volume was less than 2 % , so Vb was considered as a tapped volume Vf. The tapped denseness was calculated in g/ cm3 by the combining weight. 4.

Dt = M / Vt ( 4 )

Where, M = Mass of pulverization, Vt = Tapped volume of the pulverization.

2.5.4. Compressibility Index

The majority denseness and tapped denseness was measured and squeezability index was calculated by the combining weight. 5.

IC = Dt – Db / Dt ( 5 )

Where, Dt = Tapped denseness of the pulverization, Db = Bulk denseness of the pulverization

2.5.5. Hausner ratio

The ratio of Tapped denseness and bulk denseness gives the Hausner ratio and it was calculated utilizing the combining weight. 6.

HR= Dt / Db ( 6 )

Where, Dt = Tapped denseness of the pulverization, Db = Bulk denseness of the pulverization

2.6. Particle Size Analysis

Particle size distribution was analyzed by puting 5 gram of the formulated microspheres in a set of standard trial screens and shaken for a peculiar clip interval utilizing Indian Standard Sieves # 16, # 20, # 30, # 40, # 60 and # 80. The atoms collected in each screen were weighed and the per centum atoms retained was calculated [ 12 ] .

2.7. Percentage output

The per centum output [ 12 ] of each batch of preparation was calculated utilizing the combining weight. 7.

% output = ( weight of microspheres ) /weight of solid get downing stuff -100 ( 7 )

2.8. Surface associated drug content

The Famotidine encapsulated microcapsules prepared were evaluated for surface associated drug content on the surface of microcapsules. From each batch, 100 milligram of microcapsule was shaken in 20 milliliter of 0.1N HCl for 5 min and so filtered through what adult male filter paper 41. The sum of drug nowadays in filtrate was determined spectroscopically and calculated as a per centum of entire drug content. All the experiments were conducted in triplicate ( n=3 ) .

2.9. Appraisal of drug loading/incorporation efficiency

Drug loaded microcapsules tantamount to 40 milligrams were powdered and suspended in H2O and so sonicated ( Power sonic 505, Hwashin engineering carbon monoxide, Korea ) for approximately 20 min. It was shaken for another ( Orbitex, Scigenics biotech, India ) 20 min for the complete extraction of drug from the microcapsules. The mixture was filtered through a 0.45 ?m membrane filter ( Millipore, Bangalore, India ) . Drug content was determined by UV- seeable dual beam spectrophotometer ( Ellico SL210, India ) at 313 nanometer. The per centum entrapment was calculated utilizing the combining weight. 8 [ 12 ] .

Entire incorporation efficiency =surface associated drug + entrapped drug ( 8 )

2.10. Determination of wall thickness

Wall thickness of microcapsules was determined by the combining weight. 9 [ 12 ] . All the experiments units were studied in triplicate ( n=3 ) .

H = [ R ( 1-P ) d1/3 { Pd2+ ( 1-P ) d1 } ] – 100 ( 9 )

Where, h= wall thickness, R = arithmetic mean radius of microcapsules,

d1 and d2 = densenesss of nucleus and coat stuff severally,

P = proportion of medicine in microcapsules.

2.11. Appraisal of Famotidine

The content of Famotidine in the microcapsules was estimated by a dual beam UV spectrophotometer based on the measuring of optical density at 313 nanometers in phosphate buffer ( pH 7.4 ) . The method obeyed Beer ‘s jurisprudence ( at 1 to 10 mg/ml ) . The average mistake and preciseness were found to be 0.9 % and 1.0 % severally. These experiments were conducted for six times.

2.12. In vitro drug release survey

In vitro drug disintegration surveies were performed utilizing USP type I dissolution apparatus ( DR-3, Campbell Electronics, Mumbai, India ) at 75 r/ min. The micro capsules were weighed and filled in the empty capsule shells and placed in the basket. The disintegration medium ( 900ml ) consisted of 0.1M HCl for first 2 H and so changed to phosphate buffer pH 7.4 from 3rd to 12th H ; Temperature was maintained at 37 ± 0.50C. A 5 milliliter sample was withdrawn at specific clip intervals and replaced with an tantamount volume of disintegration fluid. Drug content was determined by UV – seeable dual beam spectrophotometer at 313 nanometer. The release surveies were conducted in triplicate.

2.13. In vitro drug release kinetic surveies

Kinetic theoretical account had described drug disintegration from solid dose signifier where the dissolved sum of drug is a map of trial clip. The exact mechanism of Famotidine release from the microsphere was farther studied by kinetic theoretical accounts. The drug release informations was analyzed by nothing order, first order, Higuchi [ 13 ] , Korsmeyer Peppas [ 14 ] and Hixson Crowell theoretical accounts [ 15 ] . The standard for choosing the most appropriate theoretical account were chosen on the footing of goodness of fit trial.

2.14. Scaning Electron Microscopy surveies

The surface morphology of selected micro capsules ( F6 ) was studied by scanning negatron microscopy ( SEM ) ( FE-SEM, Carl Zeiss, Germany ) . The samples were coated to 200A0 thickness with gilded Pd utilizing anterior to microscopy. The SEM exposure were shown in Fig. 8.

2.16. Accelerated Stability surveies

The promising preparation ( F-6 ) was tested for a period of 3 months at different temperature of 400C with 75 % RH, for their drug content [ 16 ] .

3. Consequences and treatment

The Famotidine sample was found to be freely soluble in H2O and in methyl alcohol, meagerly soluble in ethyl alcohol and really somewhat soluble in methylene chloride. The runing point of the obtained drug sample was found to be 1320C which is within the reported bound 133.50C. It complies with IP criterions therefore bespeaking the pureness of the drug sample. The FTIR spectrum of the pure drug was found to be similar to the standard spectrum of Famotidine. It was observed that all the characteristic extremums of Famotidine were present in the pure drug spectrum were present in combination spectra which indicates the compatibility of the drug with the polymers used. The FTIR spectrums were shown in Fig. 1 and 2. The angle of rest of formulated microcapsules was ranged from 22.26±0.18 to 28.12±0.250 which indicates the microcapsules have first-class flow belongingss. The Loose Bulk denseness of preparations was ranged from to 0.419±0.02 to 0.741±0.05 g/cm3 and the tapped Bulk denseness of preparations were ranged from 0.584±0.08 to 0.875±0.05 g/cm3. The Loose Bulk denseness and the tapped Bulk denseness values were utilized for finding the squeezability Index which was raged from 15.55±0.12 to 28.34±1.15 % and The Hausner ratio which was ranged from 0.010±0.001 to 1.176±0.001. These surveies revealed the granules have good flow belongingss. All these values were represented in table 2. The mean atom sizes of F-1 to F-6 preparations were Particle size ( ?m ) 615.00, 494.00, 362.00, 562.00, 704.00 and 630.00 ?m severally. The sieve analysis inside informations of Famotidine Microspheres were shown in Table 3. The per centum outputs of among formulated micro capsules, F-6 showed highest per centum output of 86.75±0.24 % . The surface associated drug content was least for F-6 ( 10.41±0.09 ) . High drug entrapment efficiency was observed to the preparation F-6 and it was 92.58±2.39 % . The wall thickness of formulated microcapsules was ranged from 15.54±0.02 to 24.16±0.54 ?m. The wall thickness of formulated micro capsules was found to be increased from F-1 to F-6. All these values were shown in Table 4. In vitro drug release dynamicss informations surveies indicate that the preparations either followed zero order release or the Higuchi release theoretical account. Famotidine release from microcapsules was diffusion controlled. The in vitro kinetic informations ( Zero order, First order, Higuchi, Korsmeyer Peppas and Hixson Crowell ) was tabulated in Table 5, 6 and represented in Fig. 3, 4, 5, 6 and 7. The accelerated stableness revealed that the formulated Famotidine microcapsules were stable even at accelerated environmental conditions. The SEM consequences shows that the microcapsules were spherical and with a smooth surface. The SEM exposure were shown in Fig. 8. The consequences indicate that F-6 preparation showed the slowest release rate while FTIR indicated that there was no drug polymer interaction. The consequences of accelerated stableness survey showed the stable nature of the drug. Good entrapment efficiency was observed with preparation F-6. SEM demonstrated the spherical nature of the microcapsules and the presence of drug atoms on their surface.

4. Decision

The Famotidine microcapsules prolonged drug release for 12 H or longer. The formulated Famotidine micro capsules cut down the frequence of disposal and the dose-dependent side effects associated with the perennial disposal of conventional Famotidine tablets. No drug polymer interaction was found and Famotidine was remained stable over a long period of clip.


The writers greatly acknowledged the Waksman Selman Pharmaceuticals, Anantapur, India, for the gift of Famotidine. The writers are thankful to Indian Institute of Science, Bangalore, India for aid in executing the word picture surveies.

Table 1: Composition of Famotidine Micro domains















Gellan gum ( g )





Karaya gum ( g )





Titanium dioxide ( g )







Table 2: Flow Properties of Famotidine Microspheres


Angle of

rest ( 0 )

Loose Bulk Density ( g/cm3 )

Tapped Bulk Density ( g/cm3 )

Carr ‘s Index ( IC )

Hausner ‘s ratio ( HR )

Pure drug










































Table 3: Atom size, Percentage of output, Surface associated drug content, Drug entrapment efficiency, Wall thickness of Famotidine Microspheres








Atom size ( ?m )







Output ( % )







Surface associated drug content ( % )







Drug entrapment efficiency ( % )







Wall thickness ( ?m )







Fig. 1: FTIR spectrum of Famotidine

Fig. 2: FTIR spectrum of F-6 blend

Fig. 3: Zero order secret plans

Fig. 4: First order secret plans

Fig. 5: Higuchi secret plans

Fig. 6: Korsmeyer- Peppas secret plans

Fig. 7: Hixson Crowell secret plans

Fig. 8: SEM exposure of microcapsules ( F-6 ) ; A ) whole micro capsules, B ) Cross subdivision of microcapsule


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