This document presents the development of nizatidine mucoadhesive microballoons for the treatment of peptic ulcers. Peptic ulcers occur in the stomach and duodenum due to an imbalance between aggressive and defensive factors. Nizatidine is an H2 receptor antagonist used to treat peptic ulcers. The objective is to develop microballoons to increase gastric residence time and bioavailability of nizatidine. Preformulation studies including solubility, compatibility and analytical method development were conducted. Microballoons will be formulated using different polymer combinations and evaluated for properties like mucoadhesion, drug release and stability. The formulation aims to localize delivery and prolong drug release for better management of

1. FORMULATION AND EVALUATION OF GASTRO-
RETENTIVE MUCOADHESIVE MICROBALLONS OF
NIZATIDINE FOR MANAGEMENT OF PEPTIC
ULCER
Presented By
PARMANAND DHAKAD
Enroll. no. 0148PY16MP09
Supervised by
Dr. Sarang Jain
Principal
Co-GUIDE
Ms. Swati Saxena
Associate Professor
RAJEEV GANDHI COLLEGE OF PHARMACY, BHOPAL
SESSION 2020-2021

2. INTRODUCTION
PEPTIC ULCER
Peptic ulcer occurs in that part of the gastrointestinal tract (g.i.t.) which is exposed to
gastric acid and pepsin, i.e. the stomach and duodenum. The etiology of peptic ulcer is not
clearly known. It results probably due to an imbalance between the aggressive (acid,
pepsin, bile and H. pylori) and the defensive (gastric mucus and bicarbonate secretion,
prostaglandins, nitric oxide, high mucosal blood flow, innate resistance of the mucosal cells)
factors.
Symptoms of Peptic Ulcer
A patient with Peptic Ulcer would have some of the next symptoms
 Bloating of the abdomen
 Waterbrash – this is the rush of saliva in the mouth after an incident of regurgitation in
order to dilute the acid in the esophagus
 Abdominal pain – duodenal ulcers are characteristically relieved by food while gastric
ulcers are exacerbated by it
 Nausea and a lot of vomiting
 Loss of appetite
 Weight loss
 Hematemesis – vomiting of blood due to gastric ulcer or injure to esophagus from
frequent vomiting

3. CAUSES OF PEPTIC ULCER
 Bacteria: As much as 60% of gastric and up to 90% of duodenal ulcers are linked with Helicobacter
pylori, a spiral-shaped bacterium that lives in the acidic surroundings of the stomach.
 Reaction to medications: drugs such as aspirin and other non-steroidal anti-inflammatory drugs
 Tobacco: Smoking leads to atherosclerosis and vascular spasms.
 Heredity:
 Zollinger Ellison syndrome: Gastrinomas, rare gastrin-secreting tumors cause multiple ulcers which
are hard to heal.
Treatment of Peptic Ulcer
• Antacids: Bismuth compounds may in fact reduce or even clear organisms and no further treatment
is required.
• Antibiotics: When Helicobacter pylori infection is there, the most effective treatments are mixtures of
any two antibiotics like Clarithromycin, Amoxicillin, Tetracycline or Metronidazole along with a proton
pump inhibitor (PPI) and a bismuth compound.
• Surgery

4. Bioadhesive drug delivery systems
Bioadhesive drug delivery systems (BDDS) are used to localize a delivery device within the
lumen to enhance the drug absorption in a site-specific manner. This approach involves the
use of bioadhesive polymers which can adhere to the epithelial surface in the stomach.
Mucoadhesive Microballons
Microballons are small spherical particles, with diameters in the micrometer range (typically
1µm to 1000µm or 1mm). Microballons are defined as “the monolithic spheres or therapeutic
agents distributed throughout the matrix either as a molecular dispersion of particles”.
Microballons are small spherical particles with diameter in the micrometer range and
sometimes referred as microparticles. When adhesion is restricted to the mucous
layer lining of the mucosal surface it is termed as mucoadhesion. Mucoadhesion offers
prolonged residence time at the site of absorption, localization of the drug delivery
system at a given target site, increase in drug concentration gradient due to the
intestine contact of the particle with the mucosal surface.
Three regions within a mucoadhesive joint

5. Structure of drug Nizatidine
Molecular formula: C12H21N5O2S2
Molecular weight : 331.5
Physical characteristics: A white to off–white crystalline solid.
Melting range: 130-132ºC
Mechanism of action: Nizatidine is a competitive, reversible inhibitor of histamine at
the histamine H2 receptors, particularly those in the gastric parietal cells.
Plasma half life: 1.5 hrs
Dose: Orally the usual daily dose is 150 to 600 mg. The total intravenous daily dose
should not exceed 480 mg.
DRUG PROFILE: NIZATIDINE

6. Rahamathulla et al., 2019 was develop valsartan floating tablets (VFT) via non-effervescent technique
using low density polypropylene foam powder, carbopol, and xanthan gum by direct compression.
Jain 2018, developed a simple Gastroretentive Mucoadhesive tablets of Riboflavin. Mucoadhesion is
one of the approach to prolong gastric retention
Wagh et al., 2018 Gastroretentive drug delivery system (GRDDS) is one of the novel approaches in the
area of oral sustained release dosage forms
El Nabarawi et al., 2017 developed a controlled-release floating matrix tablet and floating raft system of
Mebeverine HCl and evaluate different excipients for their floating behavior and in vitro controlled-
release profiles
Kumari et al, 2016 developed sustained release formulation of Verapamil Hydrochloride to maintain
constant therapeutic levels of the drug for over 12 hrs.
Dawang et al., 2015 developed a prolonged release gastro retentive (GT) formulation of Verapamil
hydrochloride. Drug was evaluated by UV and DSC.
Bharat et al, 2014, optimized bilayer gastric floating drug delivery system of Verapamil hydrochloride to
study the effect of formulation variables especially, combination of polymers on drug release showing
prolonged gastric residence time and optimized by using mathematical and statistical techniques.
LITERATURE REVIEW

7. Vidyadhara et al., 2014, developed osmotic controlled extended release formulations of
verapamil hydrochloride an angiotensin II receptor antagonist with anti-hypertensive
activity
Tola and Li 2014 developed a hydrophobic polymer to overcome the issue of pH-
dependent release of weakly basic model drug verapamil hydrochloride from matrix
tablets without the use of organic buffers in the matrix formulations.
Syeda et al., 2013 formulated Gastro retentive controlled release drug delivery system of
Verapamil HCl to increase the gastric retention time of the dosage form with controlling
the drug release pattern.
Sahi al., 2013, developed the Verapamil hydrochloride sustained-release floating matrix
tablets using gas-generation approach to prolong the gastric residence time
Ray and Gupta, 2013 formulated Matrix tablets of Verapamil Hydrochloride as sustained
release tablet employing sodium alginate, hydroxyl propyl methyl cellulose polymer, Ethyl
cellulose and the sustainedrelease tablets was investigated
LITERATURE REVIEW

8. The objective of the present investigation was to develop a formulation
gastroretentive nizatidine mucoadhesive microballons for treatment of peptic ulcer mainly
at gastric part of GIT, to improve gastric residence time and increase bioavailability.
HYPOTHESIS:
A major problem for gastric delivery is the attainment of an optimal concentration
at site of action with maximum bioavailability of drugs. The problem is associated with the
conventional dosage form for peptic ulcer diseases is frequent dosing due to the low half
life. The bioavailability of an instilled compound is generally low from 1.5 – 3.0 h and low
solubility, with only a small fraction reaching the target site.
In the present study an attempt was made to develop a mucoadhesive
Microballons of Nizatidine with variation in polysaccharide polymeric combination with
different ratios to increase mucoadhesion at gastric mucosa, which increase the gastric
residence time, thus increase the bioavailability.
PLAN OF WORK & HYPOTHESIS

9.  Preformulation Study
 Exhaustive literature survey
 Analytical methods: The drug samples (Nizatidine) was studied for determination of absorption
maxima (λmax) in solvents i.e. gastric pH 0.1 N HCl. The analytical method was validated in terms of
preparation of calibration curve, specificity, repeatability precision, intermediate precision and
accuracy.
 Preformulation studies of drug sample: The drug samples were studied for organoleptic properties,
microscopic examination by using phase contrast microscope. The physical characteristics of drug
samples i.e. density, particle size, flow properties, compatibility, solubility in various dissolution
medias, partition coefficient and drug-excipients compatibility study were characterized.
 Formulation and characterization of mucoadhesive Microballons: These prepared systems were
evaluated with various parameters such as the physical properties i.e., Flow properties
determination, particle size measurement, shape and surface morphology, mucoadhesive
properties, swelling study, percentage yield, drug entrapment efficiency, in-vitro drug release
studies and Stability Studies etc.
 Result and discussion
 Summary and conclusion
PLAN OF PRESENT WORK

10. Determination of absorption maxima (λmax)
The absorption maxima of drug (Nizatidine HCl) were determined by scanning drug solution in ultraviolet
spectrophotometer between 200 to 400 nm wavelengths.
50 mg of drug was dissolved in 50 ml of dissolution medium (0.1 N HCl) in 50 ml volumetric flask with the
help of sonication in bath sonicator for 20 min to obtain 1000 μg/ml solution. The resulting solution was
labeled as Stock-I. 1 ml of this solution was diluted up to 100 ml with same solvent separately with
sonication for 20 min to obtain 10 μg / ml solution.
Absorption maxima (λ-max) of Nizatidine HCl in 0.1N HCl solution (10 μg/ml)
Analytical and Validation studies

11. 50 mg of drug was dissolved in 50 ml of dissolution medium (0.1 N HCl) in 50 ml volumetric flask with
the help of sonication in bath sonicator for 20 min to obtain 1000 μg/ml solution (Stock Solution-I)
From the above stock solution 10 ml was diluted with 100 ml of dissolution medium to obtain 100 μg /
ml solution (Standard Stock Solution-II) and 1 ml, 2.0 ml, 3.0 ml upto 5.0 ml aliquots were withdrawn
and diluted up to 10 ml with respective solvent in 10 ml volumetric flasks to get concentration of 10 μg
/ ml, 20 μg / ml, 30 μg / ml, upto 50 μg / ml respectively. The absorbance of each solution was
measured separately at 228 nm for 0.1 N HCl.
Preparation of calibration curve of Nizatidine HCl in 0.1N HCl
y = 0.0087x - 0.0008
R2
= 0.9951
0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
0.16
0.18
0.20
0 2 4 6 8 10 12 14 16 18 20
Concentration (µg/ml)
Absorbance
Standard curve of Nizatidine HCl in 0.1N HCl solution (228 nm)

12. Organoleptic properties: The organoleptic characteristics of drug molecule were determined
by various sensory organs of body.
Properties Nizatidine HCl
Color Whitish yellow
Odor Slightly pungent
Taste Slightly sweet
Organoleptic characteristics of Nizatidine HCl
PREFORMULATION STUDIES
Microscopic examination: Microscopic examination of the Nizatidine HCl sample was
done to study the nature / texture of the powder. A pinch of drug powder was spread on a
glass slide and observed under phase contrast microscope. The particles shows that
Nizatidine HCl were crystalline in nature.

13. Particle size: The average particle size (davg) of drug was determined by using a microscope
(66172/Olympus, 100 X, Olympus (India) Pvt. Ltd., New Delhi) fitted with ocular micrometer and stage
micrometer. The particle size of unmilled Nizatidine HCl powder was 78 μm.
Physical Characteristics:
Density:
The drug powder was exactly weighed (M) and poured gently through a glass
funnel into graduated cylinder and the volume was noted and bulk density was
determined. The tapped density was determined using tapped density apparatus. A bulk
and tapped density of Nizatidine HCl is to be 0.312 gm / cm3 to 0.316 gm / cm3,
respectively.

14. Drug Type of powder Carr’s index (%)a Hausner’s
ratio a
Angle of
repose θ a
Nizatidine HCl Unmilled 12.28±0.011 1.13±0.011 26.6±0.101
Milled 9.86±0.012 1.11±0.013 19.3±0.043
FLOW PROPERTIES OF DRUG
The Nizatidine HCl unmilled powder exhibited good flow characteristics, whereas
after milling the material showed excellent flow properties.
The flow properties of Nizatidine HCl powder were characterized in terms of carr’s index, hausner’s
ratio and angle of repose. The Carr’s index ((IC)) and Hausner’s ratio (HR) of drug powders were
calculating according to following equation:
Carr’s Index (IC) = ρTapped - ρBulk / ρTapped
Hausner’s ratio (HR) = ρTapped / ρBulk
The angle of repose (θ) was measured by fixed height method. This was calculated by following
equation:
Angle of repose (θ) = tan-1 2 H / D
Where H is the surface area of the free standing height of the powder heap and D is diameter of
heap that formed after powder flow from the glass funnel.

15. Media Solubility (mg / ml) Mean
Water 18.93 18.97
0.1 N HCl 22.33 22. 65
Phosphate buffer pH 4.5 14.91 14. 96
Phosphate buffer pH 6.8 13.01 13. 02
Phosphate buffer pH 7.4 17.94 17.93
The solubility of Nizatidine HCl at different pH medium (n=3)
The solubility of drug Nizatidine HCl was determined in various solvents (Water,
0.1 N HCl, phosphate buffer pH 4.5, phosphate buffer 6.8 and phosphate buffer 7.4).
Sodium thiosulphate was added to the medium, when phosphate buffer pH 6.8 and
phosphate buffer pH 7.4 were used to prevent oxidation. The excess amount of drug
Nizatidine HCl was added to 100 ml of medium and stirred continuously overnight at
37±0.5ºC. The solubility value of drug Nizatidine HCl in different medium was determined
by above UV-Visible spectrophotometric method.
SOLUBILITY DETERMINATION

16. The partition coefficient of drug (Nizatidine HCl) was determined in n-octanol: 0.1 N HCl
solution. An accurately weighed (100 mg) amount of drug was added into 25 ml each of an n-octanol
and buffer phase in a separating funnel. The mixture was shaken for 24 h until equilibrium reached.
Both phases were separated and collected separately, filtered. The amount of drug solubilized in
aqueous phase was diluted and determined by UV-Visible spectrophotometric method. The amount
of drug in organic phase was calculating by subtracting the amount of drug in aqueous phase from
the total drug taken. The partition coefficient of drug was calculated from the ratio between the
concentrations of drug in organic and aqueous phase using following equation.
Log P (n-oct / 0.1 N HCl) = Log (C n-Oct / C 0.1 N HCl) equilibrium
The partition coefficient of Nizatidine HCl was found to be (0.2442).
PARTITION COEFFICIENT

17. For compatibility studies drug / excipients ratio are choosen and investigated based on the
reasonable drug / excipient ratio in the final product.
Procedure of sample preparation for compatibility studies: Drug and other Excipients were weighed as
per pre-determined ratio and passed through sieve # 40, mixed well. The blend was filled in amber color
glass vials and closed with grey rubber stoppers followed by aluminium seal .The samples as per above
were loaded in chambers at conditions mentioned in the protocol. Samples were withdrawn for analysis as
per the protocol and observed for physical condition followed by content determination.
Batch no. Drug-excipient combinations
S1 Pure drug Nizatidine HCl
S2 Nizatidine HCl + all excipients
Drug-excipient combinations for compatibility study
Drug-excipients compatibility studies

18. Batch
No.
Initial
observation
40±2 ºC 25±2 ºC or Room temperature
I week II
week
III
week
IV
week
I week II week III
week
IV
week
S1 White yellow
Crystals
++ ++ ++ ++ ++ ++ ++ ++
S2 Pale Yellow
Crystals
++ ++ ++ ++ ++ ++ ++ ++
Results of physical observation
++ Indicated no color change and no lump formation
Results of content determination
Batch No. Initial
observation (%)
40±2 ºC 25±2 ºC or
Room temperature
I week (%) II week (%) I week (%) II week (%)
S1 99.99 98.81 96.87 99.34 97.17
S2 99.94 98.69 97.02 99.02 97.03
Drug-excipients compatibility studies

19. The I. R. Spectrum of sample of pure Nizatidine HCl (S1)

20. The I. R. Spectrum of sample of Nizatidine HCl and all excipients
(S2)

21. Buoyant mucoadhesive microballons loaded with Nizatidine HCl as core material were
prepared by a non-aqueous solvent evaporation method. The different polymer used for the
development of buoyant mucoadhesive Microballons were HPMC, Chitosan and Carbopol
934.
Drug and polymer in different proportion 1:1, 1:2 and 1:1:1 were dissolve in 1:1 mixture
of solvent system. This clear solution was poured slowly as a thin stream in aqueous phase
consisting of 150 ml of 0.1 M acidic solution containing polyvinyl alcohol. The solution was
stirred mechanically at 500 rpm at room temperature for 2 h to allow the solvent to evaporate
completely and the mucoadhesive Microballons were collected by decantation process. The
mucoadhesive Microballons were washed separately with water for three times. The
collected mucoadhesive Microballons were dried for 1 h at room temperature and
subsequently stored in dessicator over fused calcium chloride.
PREPARATION OF MUCOADHESIVE MICROBALLONS

22. S. No. Code Ingredients
Drug :
Polyme
r
Qty (mg)
Organic Solvent
System
Stabilizing
agent (PVA) (%
w/v)
1 A1 Drug : HPMC 1:1 150:150
Dichloromethane:
ethanol
1
2 A2 Drug : HPMC 1:2 100:200
Dichloromethane:
ethanol
1
3 CH1 Drug : Chitosan 1:1 150:150
Dichloromethane:
ethanol
1
4 CH2 Drug : Chitosan 1:2 100:200
Dichloromethane:
ethanol
1
5 CA1 Drug : Carbopol 934 1:1 150:150
Dichloromethane:
ethanol
1
6 CA2 Drug : Carbopol 934 1:2 150:300
Dichloromethane:
ethanol
1
7 B1 Drug : HPMC:Chitosan 1:1:1 100:100:100
Dichloromethane:
ethanol
1
8 B2
Drug : HPMC:Carbopol
934
1:1:1 100:100:100
Dichloromethane:
ethanol 1
9 B3
Drug : Chitosan:Carbopol
934
1:1:1 100:100:100
Dichloromethane:
ethanol 1
PREPARATION OF OF MUCOADHESIVE MICROBALLONS OF
NIZATIDINE HCL (A1 – B3)

23. Percentage yield determination: The prepared mucoadhesive microballons were weighed after drying for
the determination of actual yielding after preparation process.
Percentage Yield = (Actual weight x 100)/ Theoretical Weight
EVALUATION OF MUCOADHESIVE MICROBALLONS
S.
No.
Code Ingredients Drug:Polymer
Theoratical yield
(gm)
practical
yield (gm)
percentage
yield (%)
1 A1 Drug : HPMC 1:1 3 2.646 88.2
2 A2 Drug : HPMC 1:2 3 2.748 91.6
3 CH1 Drug : Chitosan 1:1 3 2.769 92.3
4 CH2 Drug : Chitosan 1:2 3 2.649 88.3
5 CA1 Drug : Carbopol 934 1:1 3 2.672 89.1
6 CA2 Drug : Carbopol 934 1:2 3 2.736 91.2
7 B1 Drug : HPMC:Chitosan 1:1:1 3 2.796 93.2
8 B2 Drug : HPMC:Carbopol 934 1:1:1 3 2.895 96.5
9 B3 Drug : Chitosan:Carbopol 934 1:1:1 3 2.745 91.5
The prepared mucoadhesive Microballons were determine for percentage yield and the
range of percentage yield is 88.2 % - 96.5.

24. Shape and surface morphology: Scanning electron microscopy (SEM, JealJX 840-A,
Tokyo, Japan) was performed to characterize the surface of formed mucoadhesive
Microballons. Samples for SEM were prepared by lightly sprinkling the powder on a double
adhesive tape stuck to an aluminum stub. The stubs were then coated with gold film under
reduced pressure. This film acts as a conducting medium on which a stream of electron was
allowed to flow and then photograph was taken with scanning electron microscope (Figure
5.5 – 5.6).
Photograph of microspheres (100X) SEM photomicrograph of microspheres (650X)

25. Particle size analysis: Mucoadhesive microballons were studied microscopically
for their size and size distribution using calibrated ocular micrometer.
S. No. Code dmean (µm)
1 A1 361.45±0.540
2 A2 372.86±0.436
3 CH1 371.15±0.495
4 CH2 377.10±0.512
5 CA1 382.12±0.436
6 CA2 371.95±0.378
7 B1 381.17±0.435
8 B2 383.24±0435
9 B3 381.86±0.532

26. Drug Entrapment Efficiency: Mucoadhesive microballons were studied for determination drug
entrapment efficiency 500mg of microballons containing a drug were taken, crushed by trituration and
suspended in a minimal amount of dichloromethane (10ml) for dissolving the coat shell of the
Microballons. The suspension was suitably diluted with 0.1N HCl buffer (100mL) for 1hr and filtered to
separate the shell fragments. Then Drug entrapment efficiency was analyzed after suitable dilution by
spectrophotometrically with a UV-detector (Shimadzu, UV-1800) at 228 nm.
Drug entrapment efficiency = Calculated drug concentration ×100/Theoretical drug
content
S. No. Code
Dtug content (mg./gm.
Of microspheres)
Encapsulation efficiency
(%)
1 A1 428.1 85.62
2 A2 272.1 81.71
3 CH1 431.2 86.24
4 CH2 281.1 84.41
5 CA1 427.8 85.56
6 CA2 278.8 83.72
7 B1 301.2 90.45
8 B2 311.4 93.51
9 B3 303.8 91.23

27. Degree of Swelling of microballons: For estimating the degree of swelling 1gm of
microsphere were suspended in 5 mL of simulated gastric fluid USP (pH 1.2). The particle size
was monitored by microscopy technique every 1 hour using an optical microscope (Labomed
CX RIII). The increase in particle size of the Microballons was noted for up to 8 hours.
The formula used for calculation of degree of swelling is given below
= [g-0]/0
Where  = degree of swelling,
0 = initial weight of Microballons
g = final weight of Microballons

28. S. No. Code Swelling rate (%)
1 A1 42.5 ± 1.15
2 A2 44.6 ± 1.18
3 CH1 47.7 ± 0.88
4 CH2 49.2 ± 1.38
5 CA1 53.9 ± 2.48
6 CA2 55.9 ± 2.48
7 B1 58.9 ± 2.48
8 B2 61.5 ± 0.76
9 B3 59.9 ± 2.48
Degree of Swelling of microballons

29. In vitro Wash-off Test for microballons: The mucoadhesive properties of the Microballons
were evaluated by in vitro wash-off test. For this 1 cm piece of rat stomach mucosa was tied
onto a glass slide using thread. About 100 Microballons was spread onto the wet, rinsed,
tissue specimen, and the prepared slide was hung onto the groves of a USP tablet
disintegrating test apparatus and operated such that the tissue specimen was given regular
up and down movements in a beaker containing the simulated gastric fluid USP (pH 1.2). At
the end of 1 hr, 5 hr and 10 hr intervals and the number of Microballons still adhering onto
the tissue was measured.
S. No. Code Percent Mucoadhesion
1 A1 75.63 ± 0.018
2 A2 77.64 ± 0.077
3 CH1 81.22 ± 0.123
4 CH2 84.64 ± 0.198
5 CA1 85.57 ± 0.208
6 CA2 81.64 ± 0.110
7 B1 83.64 ± 0.111
8 B2 88.64 ± 0.198
9 B3 86.64 ± 0.198

30. In-vitro buoyancy percentage: Mucoadhesive microballons (0.3 g) were spread over the
surface of USP XXIV dissolution apparatus (type II) filled with 900 ml 0.1 N hydrochloric acid
containing 0.02 % Tween 80. The medium was agitated with paddle rotating at 100 rpm for
24 h. the floating and the setteled portion microballons were recovered separately. The
Microballons were dried and weighed. The buoyancy percentage was calculated as the ratio
of the mass of the Microballons, that remained floating and the total mass of Microballons.
S. No. Code
Buoyancy (%) DOF
(h)
4 h 8 h 12 h
1 A1 55.1 23.8 21.1 ˃ 7
2 A2 55.2 27.1 23.3 ˃ 7
3 CH1 62.4 31.9 20.4 ˃7
4 CH2 67.1 32.1 21.1 ˃ 8
5 CA1 66.1 33.3 23.1 ˃ 8
6 CA2 71.4 41.1 21.7 ˃ 12
7 B1 76.2 43.1 23.1 ˃ 12
8 B2 88.2 50.1 30.1 ˃ 12
9 B3 75.2 44.3 25.1 ˃ 12

31. In vitro drug release studies in simulated gastrointestinal fluids: The dissolution test of
Nizatidine Hcl mucoadhesive microballons was carried out by the paddle type-II
dissolution apparatus specified in USP XXIII. 500 mg of Nizatidine loaded microballons was
weighed accurately and gently spread over the surface of 900 mL of dissolution medium.
The content was rotated at 100 rpm and thermostatically controlled at 370.5°C. Perfect
sink condition was prevailed during the drug dissolution. The release was tested in
dissolution medium of SGF (pH 1.2). An aliquot of the release medium was withdrawn at
predetermined time intervals and an equivalent amount of fresh medium was added to
the release medium. The collected samples were filtered through 0.45µm-syringe filter
(Millipore millex HN) and analyzed spectrophotometricaly.

32. Time A1 A2 CH1 CH2 CA1 CA2 B1 B2 B3
0 0 0 0 0 0 0 0 0 0
2 4.71 3.01 1.54 0.781 4.68 3.23 0.571 0.322 1.23
4 13.21 8.23 5.43 3.45 10.12 9.23 1.76 2.45 3.39
6 18.68 10.34 9.23 7.46 18.34 15.67 5.67 4.67 3.39
8 35.67 19.87 19.87 13.23 27.45 26.78 12.34 16.46 14.5
10 45.27 31.23 31.25 26.56 38.54 33.24 25.67 26.56 21.34
12 53.25 41.34 44.78 38.34 47.65 44.28 36.45 38.78 37.56
14 66.34 53.37 52.34 48.34 59.67 53.68 46.78 49.87 58.45
16 76.54 65.78 64.21 58.34 75.6 69.76 59.04 59.03 74.23
18 88.74 77.45 74.34 69.87 84.34 79.32 69.34 71.23 86.46
20 95.37 87.32 82.1 81.26 91.23 89.65 79.67 81.23 93.6
22 98.12 97.51 92.1 91.36 96.99 94.78 90.23 91.13 98.01
24 99.99 99.24 99.68 99.21 99.98 99.78 99.01 98.13 99.34
Dissolution data of mucoadhesive microballons of Nizatidine HCl (A1 – B3)

33. 0
20
40
60
80
100
120
0 2 4 6 8 10 12 14 16 18 20 22 24
Cummulative
%
drug
released
Time (h)
Zero - order kinetic plot (in-vitro drug release study)
A1
A2
CH1
CH2
CA1
CA2
B1
B2
B3
Zero-order plots for mucoadhesive microballons of Nizatidine HCl (A1 – B3)

34. 0
0.5
1
1.5
2
2.5
0 2 4 6 8 10 12 14 16 18 20 22 24
Log
cummulative
%
drug
retained
Time (h)
First - order kinetic plot (in-vitro drug release study)
A1
A2
CH1
CH2
CA1
CA2
B1
B2
B3
First-order plots for for mucoadhesive microballons of Nizatidine HCl (A1 – B3)

35. SUMMARY AND CONCLUSION
 The absorption maxima (λ-max) of Nizatidine HCl (10 μg / ml) in 0.1 N HCl solution were found to be
at 228 nm. The calibration curves show excellent linearity of data as evidenced by the values of
correlation coefficients that were found to be greater than 0.99.
 Nizatidine HCl is Whitish yellow, slightly pungent odor, slightly sweet taste and crystalline powder
in nature .
 The bulk and tapped density are 0.312 gm / cm3 to 0.316 gm / cm3, respectively. The average particle
size (davg) of unmilled powder was 78 μm. Drug powder exhibited good flow characteristics
 The result indicated that the drug have maximum solubility water, and also soluble in 0.1 N HCl. The
partition coefficient of Nizatidine HCl was found to be (0.2442).
 The characteristic peaks of Nizatidine HCl were observed at 3280, 3210, 3107, 3094, 2945, 2860, 2829,
2784, 1622, 1587, 1470, 1458, 1435, 1422, 1377 and 1359 cm-1.
 The prepared mucoadhesive microballons were determine for percentage yield and the range of
percentage yield is 88.2 % - 96.5 % .
 The Shape and surface morphology of prepared mucoadhesive microballons was studied by scanning
electron microscope

36.  The prepared mucoadhesive microballons were determine for percentage yield and the range of
percentage yield is 88.2 % - 96.5 % .
 The particle size of prepared mucoadhesive microballons were studied microscopically . All the
formulations were shown in good flow ability and the particle size in the range of davg is 361.45 µm –
383.24 µm. The drug entrapment efficiency was in the range of 81.71 % - 93.51 %
 The Swelling rate and percent mucoadhesion of mucoadhesive microballons of Nizatidine HCl was in
the range of 75.63 % - 88.64 %.
 The in-vitro buoyancy percentage of mucoadhesive microballons for determination of floating ability
of all formulations. All the prepared formulations was floated more than 7 h - 12 h
 Floating mucoadhesive microballons B2 is the best formulations containing naturally occurring
polysaccharide polymeric blend as Drug : HPMC: Carbopol 934 (1:1:1) that release more than 98.13 %
of the drug in gastric environment in controlled and sustained manner upto 24 h.
 Regression analysis was performed and the r2 values suggested that the curves were fairly linear and
slope values were computed from the graph. For all of the batches the value of release exponent “n”
was > 0.89 indicating Super-case II transport mechanism.
SUMMARY AND CONCLUSION

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