Formulation and Evaluation of Nizatidine Microspheres

 

S. Ramya Sri*

*Department of Pharmaceutics, University of Technology, Osmania University, Hyderabad, Telangana

*Corresponding Author E-mail:  

 

Abstract:

Emulsion cross linking method can be successfully employed to fabricate Nizatidine microspheres than Ionotropic gelation method. The technique provides characteristic advantage over conventional microsphere method, which involves an “all-aqueous” system, avoids residual solvents in microspheres. Other methods utilize larger volume of polymer, uneasy in dropping through syringe, air pollution, toxicity and difficult to remove traces during filtration. FT-IR spectra of the physical mixture revealed that the drug is compatible with the polymers and copolymer used. Micromeritic studies revealed that the mean particle size of the prepared microspheres was in the size range 540µm to 644µm.Increase in the polymer concentration led to increase in % Yield, % Drug entrapment efficiency, Particle size, % swelling and % Mucoadhesion. The in-vitro mucoadhesive study demonstrated that microspheres of Nizatidine using chitosan as polymer and glutaraldehyde as cross linking agent adhered to the mucus to a greater extent than sodium alginate along with Carbopol934.The invitro drug release decreased with increase in the polymer and copolymer concentration.

 

KEY WORDS: Nizatidine, Mucoadhesion, Ionotropic gelation method.

 

 


INTRODUCTION:

The oral route for drug delivery is the most popular, desirable, and most preferred method for administrating therapeutically agents for systemic effects because it is a natural, convenient, and cost effective to manufacturing process. Oral route is the most commonly used route for drug administration. Although different route of administration are used for the delivery of drugs, oral route remain the preferred mode. Even for sustained release systems the oral route of administration has been investigated the most because of flexibility in designing dosage forms.

 

INTRODUCTION TO ORAL CONTROLLED RELEASE DOSAGE FORM1:

The treatment of acute diseases or chronic illnesses has been achieved by delivery of drugs to the patients for many years. These drug delivery systems include tablets, indictables, suspensions, creams, ointments, liquids and aerosols. Today these conventional drug delivery systems are widely used. The term drug delivery can be defind as techniques that are used to get the therapeutic agents inside the human body. Conventional drug therapy require periodic doses of therapeutic agents. These agents are formulated to produce maximum stability, activity and bioavailability.

 

For most drugs, conventional methods of drug administration are effective, but some drugs are unstable or toxic and have narrow therapeutic ranges. Some drugs also possess solubility problems.

 

 

 

 

Figure1: Shows In such cases, a method of continuous administration of therapeutic agent is desirable to maintain fixed plasma levels

 

ADVANTAGES OF CONTROLLED DRUG DELIVERY SYSTEM:

1.    Improved patient convenience and compliance due to less frequent drug administration.

2.    Reduction in fluctuation in study-state levels and therefore better control of disease condition and reduced intensity of local or systemic side effects.

3.    Increased safety margin of high potency drugs due to better control of plasma levels.

4.    Maximum utilization drug enabling reduction in total amount of dose administered.

5.    Reduction in health care costs through improved therapy, shorter treatment period, less frequency of dosing and reduction personal time to dispense, administer and monitor patients.

 

DISADVANTAGES OF CONTROLLED DRUG DELIVERY SYSTEM:

1.    Decreased systemic availability in comparison to immediate release conventio-nal dosage forms; this may be due to incomplete release, increased first- pass metabolism, increased in stability, in sufficient residence time for complete release, site specific absorption, pH dependent solubility etc.

2.    Poor in vitro- in vivo correlation.

3.    Possibility of dose dumping due to food, physiologic or formulation variables or chewing or grinding of oral formulations by the patients and thus, increased risk of toxicity.

4.    Retrieval of drug is difficult in case of toxicity, poisoning or hypersensitivity reactions.

5.    Reduced potential for dosage adjustment of drugs normally administered in varying strengths.

6.    Higher cost of formulation.

 

MICROSPHERES:

For many decades, medication of an acute disease or a chronic disease has been accomplished by delivering drugs to the patients via various pharmaceutical dosage forms like tablets, capsules, pills, creams, ointments, liquids, aerosols, injectables and suppositories as carriers. To achieve and then to maintain the concentration of drug administered within the therapeutically effective range needed for medication, it is often necessary to take this type of drug delivery systems several times in a day. This results in a fluctuated drug level and consequently undesirable toxicity and poor efficiency. This factor as well as other factors such as repetitive dosing and unpredictable absorption leads to the concept of controlled drug delivery systems3. The word new or novel in the relation to drug delivery system is a search for something out of necessity. An appropriately designed sustained or controlled release drug delivery system can be major advance toward solving the problem associated with the existing drug delivery system.

 

MATERIALS USED:

Nizatidine was a gift sample Provided by Watson Pharma Private Limited. Sodium alginate, Carbopol-934, carbopol 971, HPMC K4M were obtained from S.D Fine chemicals., Mumbai.

 

METHODOLOGY:

PREPARATION OF 0.1N HCl (pH 1.2):

Take 8ml of HCl in a 1000ml volumetric flask and make up the volume with distilled water.

 

 

DETERMINATION OF λMAX:

Stock solution (1000µg/ml) of Nizatidine was prepared in methanol. This solution was appropriately diluted with 0.1N HCl (pH 1.2) to obtain a concentration of 10µg/ ml. The resultant solution was scanned in the range of 200nm to 400nm on UV-Visible spectrophotometer. The drug exhibited a λmax at 315nm.

 

PREPARATION OF STANDARD CALIBRATION CURVE OF NIZATIDINE:

·        10 mg of Famotidine was accurately weighed and dissolved in 10ml of methanol (Stock Solution – I) to get a concentration of 1000 μg/ml.

·        From the stock solution- I,1ml of aliquots was taken and suitably diluted with 0.1N HCl (Stock Solution-II) to get concentrations of 100μg/ml.

·        From the stock solution- II,aliquots were taken and suitably diluted with 0.1N HCl (pH 1.2) to get concentrations in the range of 2 to 10μg/ml.The absorbance of these samples were analyzed by using UV-Visible Spectrophotometer at 314nm against reference solution 0.1N HCl (pH 1.2).

 

The Linear Regression Analysis:

The linear regression analysis was done on Absorance points. The standard calibration curve obtained had a Correlation Coefficient of 0.998 with of slope of 0.0290 and intercept of 0.0028.

 

COMPATIBILITY STUDIES:

A proper design and formulation of a dosage form requires considerations of the physical, chemical and biological characteristics of both drug and excipients used in fabrication of the product. Compatibility must be established between the active ingre-dient and other excipients to produce a stable, efficacious, attractive and safe product. If the excipient(s) are new and if no previous literature regarding the use of that particular excipient with an active ingredient is available, then compatibility studies are of paramount importance. Hence, before producing the actual formulation, compa-tibility of Nizatidine with different polymers and other excipients was tested using the Fourier Transform Infrared Spectroscopy (FT-IR) technique.

 

FOURIER TRANSFORM INFRARED SPECTROSCOPY (FT-IR):

In order to check the integrity (Compatibility) of drug in the formulation,FT-IR spectra of the formulations along with the drug and other excipients were obtained and compared using Shimadzu FT-IR 8400 spectrophotometer. In the present study, Potassium bromide(KBr) pellet method was employed. The samples were thoroughly blended with dry powdered potassium bromide crystals. The mixture was compressed to form a disc. The disc was placed in the spectrophotometer and the spectrum was recorded.The FT-IR spectra of the formulations were compared with the FT-IR spectra of the pure drug and the polymers.

 

METHOD OF PREPARATION:

IONOTROPIC GELATION METHOD:

Batches of microspheres were prepared by ionotropic gelation method which involved reaction between sodium alginate and polycationic ions like calcium to produce a hydrogel network of calcium alginate. Sodium alginate and the mucoadhesive polymer were dispersed in purified water (10 ml) to form a homogeneous polymer mixture. The API, Famotidine (100 mg) were added to the polymer premix and mixed thoroughly with a stirrer to form a viscous dispersion. The resulting dispersion was then added through a 22G needle into calcium chloride (4% w/v) solution. The addition was done with continuous stirring at 200rpm. The added droplets were retained in the calcium chloride solution for 30 minutes to complete the curing reaction and to produce rigid spherical microspheres. The microspheres were collected by decantation, and the product thus separated was washed repeatedly with purified water to remove excess calcium impurity deposited on the surface of microspheres and then air-dried. 

 

 

Figure 2: Photograph of prepared microspheres

 

Table 1: Prepared formulation of Bioadhesive Microspheres

S. No.

Formulation Code

Drug: Polymer

Ratio

1

F1

1:1

Sod.alginate:carbopol 934(3:1)

2

F2

1:2

Sod.alginate:carbopol 934(3:1)

3

F3

1:3

Sod.alginate:carbopol 934(3:1)

4

F4

1:1

Sod.alginate:carbopol 971(3:1)

5

F5

1:2

Sod.alginate:carbopol 971(3:1)

6

F6

1:3

Sod.alginate:carbopol 971(3:1)

7

F7

1:1

Sod.alginate:HPMC K4M(3:1)

8

F8

1:2

Sod.alginate:HPMC K4M (3:1)

9

F9

1:3

Sod.alginate:HPMC K4M(3:1)

 

CHARACTERIZATION OF MICROSPHERES:

PERCENTAGE YIELD:

The percentage of production yield was calculated from the weight of dried microsphe-res recovered from each batch and the sum of the initial weight of starting materials. The percentage yield was calculated using the following formula:

                     Practical mass (Microspheres)

% Yield= -----------------------------------------------x100

                   Theoretical mass (Polymer + Drug)

 

Drug entrapment efficiency:

Microspheres equivalent to 15 mg of the drug Nizatidine were taken for evaluation. The amount of drug entrapped was estimated by crushing the microspheres. The powder was transferred to a 100 ml volumetric flask and dissolved in 10ml of methanol and the volume was made up using simulated gastric fluid pH 1.2. After 24 hours the solution was filtered through Whatmann filter paper and the absorbance was measured after suitable dilution spectrophotometrically at 315 nm. The amount of drug entrapped in the microspheres was calculated by the following formula,

                                                               Experimental Drug Content

% Drug Entrapment Efficiency =        - - - - - - - - - - - - - - - - - - - - - - - × 100

                                                                Theoretical Drug Content

 

Particle size analysis:

Samples of the microparticles were analyzed for particle size by optical microscope. The instrument was calibrated and found that 1unit of eyepiece micrometer was equal to 12.5μm. Nearly about 100 Microparticles sizes were calculated under 45x magnification.

 

The average particle size was determined by using the Edmondson’s equation:

              nd

Dmean=------

              n

Where,

n – Number of microspheres observed

d – Mean size range

 

Swelling study:

Swelling ratio of different dried microspheres were determined gravimetrically in simulated gastric fluid pH 1.2.The microspheres were removed periodically from the solution, blotted to remove excess surface liquid and weighed on balance. Swelling ratio (% w/v) was determined from the following relationship:

   

                          (Wt – W0)

Swelling ratio = - - - - - - - - - - - × 100

                              (W0)

 

Where W0 & Wt are initial weight and Final weight of microspheres respectively.

Evaluation of mucoadhesive property:

The mucoadhesive property of microspheres was evaluated by an in vitro adhesion testing method known as wash-off method. Freshly excised pieces of goat stomach mucous were mounted on to glass slides with cotton thread. About 20 microspheres were spread on to each prepared glass slide and immediately thereafter the slides were hung to USP II tablet disintegration test, when the test apparatus was operated, the sample is subjected to slow up and down movement in simulated gastric fluid pH 1.2 at 37°C contained in a 1-litre vessel of the apparatus. At an interval of 1 hour up to 8 hours the machine is stopped and number of microspheres still adhering to mucosal surface was counted.

                               Number of microspheres adhered

% Mucoadhesion= ------------------------------------------ ×100

                               Number of microspheres applied

 

In vitro drug release study:

The dissolution studies were performed in a fully calibrated eight station dissolution test apparatus (37 ± 0.50C, 50 rpm) using the USP type – I rotating basket method in simulated gastric fluid pH 1.2 (900ml). A quantity of accurately weighed microspheres equivalent to 20mg Nizatidine each formulation was employed in all dissolution studies. Aliquots of sample were withdrawn at predetermined intervals of time and analyzed for drug release by measuring the absorbance at 314nm. At the same time the volume withdrawn at each time intervals were replenished immediately with the same volume of fresh pre-warmed simulated gastric fluid pH 1.2 maintaining sink conditions throughout the experiment.

 

IN-VITRO DRUG RELEASE KINETICS:

The release data obtained was fitted into various mathematical models.The parameters ‘n’ and time component ‘k’,the release rate constant and ‘R’,the regression coefficient were determined by Korsmeyer-Peppas equation to understand the release mechanism.

To examine the release mechanism of Nizatidine from the microspheres, the release data was fitted into Peppa’s equation,

Mt / M∞ = Ktn

 

RESULTS AND DISCUSSION:

Determination of λmax:

A solution of 10µg/ml of Nizatidine was scanned in the range of 200 to 400nm. The drug exhibited a λmax at 315nm in simulated gastric fluid pH 1.2 and had good reproducibility. Correlation between the concentration and absorbance was found to be near to 0.9999, with a slope of 0.0290and intercept of 0.00280.

 

 

Figure 3: UV Spectrum of Nizatidine in simulated gastric fluid (pH 1.2)

 

Calibration curve of Nizatidine in simulated gastric fluid pH 1.2:

Table shows the calibration curve data of Nizatidine in simulated gastric fluid pH 1.2 at 315nm. Fig. 5.2 shows the standard calibration curve with a regression value of 0.998, slope of 0.028 and intercept of 0.004 in simulated gastric fluid pH 1.2. The curve was found to be linear in the concentration range of 2-10µg/ml.

Table 2: Calibration curve data for Nizatidine in simulated gastric fluid pH 1.2

Concentration  (µg /ml)

Absorbance

0

0

5

0.143

10

0.288

15

0.429

20

0.574

25

0.718

30

0.876

 

 

Figure 4: Standard graph Of Nizatidine in simulated gastric fluid pH 1.2

 

COMPATIBILITY STUDIES:

Drug polymer compatibility studies were carried out using Fourier Transform Infra Red spectroscopy to establish any possible interaction of Nizatidine with the polymers used in the formulation. The FT-IR spectra of the formulations were compared with the FTIR spectra of the pure drug. The results indicated that the characteristic absorption peaks due to pure Nizatidine have appeared in the formulated microspheres, without any significant change in their position after successful encapsulation, indicating no chemical interaction between Nizatidine and Polymers.

 

 

Fig 5 : FTIR of Nizatidine pure drug

 

 

Fig 6: FTIR of Nizatidine optimized formulation

EVALUATION AND CHARACTERISATION OF MICROSPHERES:

PERCENTAGE YIELD:

It was observed that as the polymer ratio in the formulation increases, the product yield also increases. The low percentage yield in some formulations may be due to blocking of needle and wastage of the drug- polymer solution, adhesion of polymer solution to the magnetic bead and microspheres lost during the washing process. The percentage yield was found to be in the range of 80.3 to 83.4% for microspheres containing sodium alginate along with carbopol 934 as copolymer, 77.6 to 86.4% for microspheres containing sodium alginate along with carbopol 971 as copolymer and 80.2 to 83.7% for microspheres containing sodium alginate along with HPMC K 4 M as copolymer. The percentage yield of the prepared microspheres is recorded in Table 5.3 and displayed in Figures 5.7 to 5.9.

 

DRUG ENTRAPMENT EFFICIENCY:

Percentage Drug entrapment efficiency of Nizatidine ranged from 82.66 to 84.66% for microspheres containing sodium alginate along with carbopol 934 as copolymer, 76.42 to 89.05% for microspheres containing sodium alginate along with carbopol 971 as copolymer and 80.06 to 82.32% for microspheres containing sodium alginate along with HPMC K 4 M as copolymer. The drug entrapment efficiency of the prepared microspheres increased progressively with an increase in proportion of the respective polymers. Increase in the polymer concentration increases the viscosity of the dispersed phase. The particle size increases exponentially with viscosity. The higher viscosity of the polymer solution at the highest polymer concentration would be expected to decrease the diffusion of the drug into the external phase which would result in higher entrapment efficiency. The % drug entrapment efficiency of the prepared microspheres is displayed in Table 5.3, and displayed in Figure 5.7 to 5.9.

 

 

Table 3: Percentage yield and percentage drug entrapment efficiency of the prepared microspheres

S. No.

Formulation code

% Yield

% Drug Entrapment Efficiency

1

F1

80.3

82.66

2

F2

82.3

84.47

3

F3

83.4

84.66

4

F4

86.4

89.05

5

F5

77.6

76.42

6

F6

79.7

78.73

7

F7

83.7

 80.06

8

F8

80.2

82.32

9

F9

81.2

81.36

 

PARTICLE SIZE ANALYSIS:

The mean size increased with increasing polymer concentration which is due to a significant increase in the viscosity, thus leading to an increased droplet size and finally a higher microspheres size. Microspheres containing sodium alginate along with carbopol 934 as copolymer had a size range of 540µm to 644µm, microspheres containing sodium alginate along with carbopol 971 as copolymer exhibited a size range between 512µm to 624µm and microspheres containing sodium alginate along with HPMC K 4 M as copolymer had a size range of 588µm to 626µm. The particle size data is presented in Tables 5.4 to 5.15 and displayed in Figure 5.10 to 5.12. The effect of drug to polymer ratio on particle size is displayed in Figure 5.13. The particle size as well as % drug entrapment efficiency of the microspheres increased with increase in the polymer concentration.

 

 

Table 4: Average particle size of Nizatidine microspheres

S. No

Batches

Mean Particle Size (µm)

1

F1

540 µm

2

F2

602 µm

3

F3

644 µm

4

F4

512 µm

5

F5

528 µm

6

F6

624 µm

7

F7

588 µm

8

F8

598 µm

9

F9

626 µm

 

 

SWELLING STUDY:

The swelling ratio is expressed as the percentage of water in the hydrogel at any instant during swelling. Swellability is an important characteristic as it affects mucoadhesion as well as drug release profiles of polymeric drug delivery systems. Swellability is an indicative parameter for rapid availability of drug solution for diffusion with greater flux. Swellability data revealed that amount of polymer plays an important role in solvent transfer. It can be concluded from the data shown in Table 5.16 that with an increase in polymer concentration, the percentage of swelling also increases. Thus we can say that amount of polymer directly affects the swelling ratio. As the polymer to drug ratio increased, the percentage of swelling increased from 31 to 67% for microspheres containing sodium alginate along with carbopol 934 as copolymer, 46 to 85% for microspheres containing sodium alginate along with carbopol 971 as copolymer and 65 to 78 for microspheres containing sodium alginate along with HPMC K 4 M as copolymer. The percentage swelling of the prepared microspheres is displayed in Fig. 5.14 to 5.16. The effect of drug to polymer ratio on percentage swelling is displayed in Figure 5.17.

 

Table 5: Percentage swelling of the prepared microspheres

S. No.

Formulation Code

Initial (Wt)

Final (Wt)

Percentage Swelling

1

F1

10

13.1

31

2

F2

10

15.3

53

3

F3

10

16.7

67

4

F4

10

18.5

85

5

F5

10

12.4

24

6

F6

10

14.6

46

7

F7

10

16.5

65

8

F8

10

17.4

74

9

F9

10

58.5

78

 

IN VITRO MUCOADHESION TEST:

As the polymer to drug ratio increased, microspheres containing sodium alginate along with carbopol 934 as copolymer exhibited % mucoadhesion ranging from 60 to 70%, microspheres containing sodium alginate along with carbopol 971 as copolymer exhibited % mucoadhesion ranging from 60 to 75% and microspheres containing sodium alginate along with HPMC K 4 M as copolymer exhibited % mucoadhesion ranging from 65 to 80%.

 

Table 6: Percentage mucoadhesion of the prepared microspheres

S. No.

Formulation

Code

No. of microspheres

Percentage mucoadhesion

INITIAL

FINAL

1

F1

20

12

60

2

F2

20

13

65

3

F3

20

14

70

4

F4

20

15

75

5

F5

20

12

60

6

F6

20

14

70

7

F7

20

15

75

8

F8

20

16

80

9

F9

20

13

65

 

 

Figure 7: Comparison of percentage mucoadhesion of prepared microspheres

IN-VITRO DRUG RELEASE STUDIES:

Dissolution studies of all the formulations were carried out using dissolution apparatus USP type I. The dissolution studies were conducted by using dissolution media, pH 1.2. The results of the in-vitro dissolution studies of formulations F1 to F3, F4 to F6 and F7 to F9 are shown in table no.5.18 to 5.20. The plots of Cumulative percentage drug release Vs Time. Figure 5.22 shows the comparison of % CDR for formulations.

 

Table 7: In-Vitro drug release data of Nizatidine microspheres containing sodium alginate along with carbopol 934 as copolymer

TIME (h)

 

Cumulative Percent of Drug Released  

F1

F2

F3

0

 0

0

0

1

 24.88

21.11

18.66

2

31.55

31.55

28.11

3

42.44

39.77

37.44

4

53.55

47.77

44.66

5

60.21

56.66

54.67

6

68.54

65.44

63.33

7

77.55

75.55

73.11

8

86.33

83.33

78.11

9

92.66

84.66

82.33

10

 

91.06

86.66

11

 

 

92.66

12

 

 

93.55

 

 

Figure 8: Comparison of In-Vitro drug release profile of Nizatidine microspheres containing sodium alginate along with carbopol 934 as copolymer

 

Table 8: In-Vitro drug release data of Nizatidine microspheres containing sodium alginate along with carbopol 971 as copolymer

Time (h)

 

Cumulative percent of drug released

F4

F5

F6

0

0

0

0

1

16.88

27.77

22.44

2

25.22

36.44

32.22

3

35.66

43.77

40.88

4

39.33

54.66

48.66

5

52.55

64.01

57.55

6

55.77

75.77

63.55

7

61.77

84.65

70.44

8

69.55

90

76.55

9

77.55

92.22

85.55

10

85.55

 

91.33

11

90.66

 

 

12

95.66

 

 

 

 

Figure 9: Comparison of In-Vitro drug release profile of Nizatidine microspheres containing sodium alginate along with carbopol 971 as copolymer.

 

Table 9: In-Vitro drug release data of Nizatidine microspheres containing sodium alginate along with HPMC K 4 M as copolymer

TIME (h)

CUMULATIVE PERCENT OF DRUG RELEASED

F7

F8

F9

0

0

0

0

1

18.44

17.11

13.88

2

29.33

26.44

23.22

3

39.55

37.55

33.66

4

45.55

46.88

33.33

5

56.33

55.77

51.55

6

61.33

63.55

52.77

7

69.55

71.33

60.77

8

75.56

75.77

67.55

9

81.55

79.77

73.55

10

86.33

82.44

79.55

11

86.5

86.88

83.66

12

86.8

93.66

92.66

 

 

Figure 10: Comparison of In-Vitro drug release profile of Nizatidine microspheres containing sodium alginate along with HPMC K 4 M as copolymer

 

IN-VITRO DRUG RELEASE KINETICS:

For understanding the mechanism of drug release and release rate kinetics of the drug from dosage form, the in-vitro drug dissolution data obtained was fitted to various mathematical models such as zero order, First order, Higuchi matrix, and Krosmeyer-Peppas model. The values are compiled in Table 5.21. The coefficient of determination (R2) was used as an indicator of the best fitting for each of the models considered. The kinetic data analysis of all the formulations reached higher coefficient of determination with the Zero order (R2 = 0.958) whereas release exponent. From the coefficient of determination and release exponent values, it can be suggested that the mechanism of drug release follows higuchis model along with erosion mechanism which leading to the conclusion that a release mechanism of drug followed combination of diffusion and spheres erosion.

Table 10: Release Kinetics Studies of The Optimized Formulation

 

ZERO

FIRST

HIGUCHI

PEPPAS

 

% CDR Vs T

Log % Remain Vs T

%CDR Vs √T

Log C Vs Log T

Slope

7.579725275

-0.1445403

29.0101023

1.195069374

Intercept

8.840879121

2.259122878

-10.9512781

0.789416458

R 2

0.985574735

0.697526127

0.967128051

0.714124414

 

 

Figure 11:Zero order kinetics graph for F4 formmulation

 

 

Figure 12:First order kinetics graph for F4 formulation

 

 

Figure 13:Higuchis model graph for F4 formulation

 

 

Figure 14:Peppas model graph for F4 formulation

 

CONCLUSION:

In the present work, bioadhesive microspheres of Nizatidine using Sodium alginate along with Carbopol 934, Carbopol 971, HPMC K4M as copolymers were formulated to deliver Nizatidine via oral route. Details regarding the preparation and evaluation of the formulations have been discussed in the previous chapter. From the study following conclusions could be drawn:-

Ÿ  The results of this investigation indicate that ionic cross linking technique Ionotropic gelation method can be successfully employed to fabricate Nizatidine microspheres. The technique provides characteristic advantage over conventional microsphere method, which involves an “all-aqueous” system, avoids residual solvents in microspheres. Other methods utilize larger volume of organic solvents, which are costly and hazardous because of the possible explosion, air pollution, toxicity and difficult to remove traces of organic solvent completely.

Ÿ  FT-IR spectra of the physical mixture revealed that the drug is compatible with the polymers and copolymers used.

Ÿ  Micromeritic studies revealed that the mean particle size of the prepared microspheres was in the size range of 512-644µm and are suitable for bioadhesive microspheres for oral administration.

Ÿ  Increase in the polymer concentration led to increase in % Yield, % Drug entrapment efficiency, Particle size, % swelling and % Mucoadhesion.

Ÿ  The in-vitro mucoadhesive study demonstrated that microspheres of Nizatidine using sodium alginate along with Carbopol 971 as copolymer adhered to the mucus to a greater extent than the microspheres of Nizatidine using sodium alginate along with Carbopol 934and HPMC K4M as copolymers.

Ÿ  The invitro drug release decreased with increase in the polymer and copolymer concentration.

Ÿ  Analysis of drug release mechanism showed that the drug release from the formulations followed higuchis model of drug release.

Ÿ  Based on the results of evaluation tests formulation coded F4 was concluded as best formulation.

 

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Received on 05.04.2018       Modified on 21.06.2018

Accepted on 10.08.2018      ©A&V Publications All right reserved

Research J. Science and Tech. 2019; 11(1):14-26.

DOI: 10.5958/2349-2988.2019.00003.2