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FORMULATION AND EVALUATION OF
MICROBEADS
PROJECT SUBMITTED TO UTTRAKHAND TECHNICAL UNIVERSITY
In partial fulfillment of the requirement for the award of the degree of
BACHELOR IN PHARMACY
2012-2016
Submitted By
Gurleen kaur
Roll No. 120260300018
B.Pharm 8th Semester
Under the guidance of
DR.Ashutosh Badola
Department of Pharmaceutical Sciences
Shri Guru Ram Rai Institute of Technology & Science
Patel Nagar, Dehradun (Uttarakhand)
CONTENT
 Introduction
 Literature review
 Aim & objective
 Drug & polymer profile
 Result & discussion
 conclusion
INTRODUCTION
In recent years a wide variety of newer
drug delivery systems like oral
sustained/controlled release dosage forms
are designed and evaluated in order to
overcome the limitations of conventional
therapy. The non steroidal anti
inflammatory drug Ibuprofen is a good
candidate for the development of oral
controlled release formulation. It is used
for long term treatment of inflammation &
pain, with dosage 400-600mg (5-
10mg/kg)TDS as conventional
Adverse gastric discomfort have been observed, and its short biological half
life 2hr. Microencapsulation has been employed to sustain the drug release,
reduce or eliminate drug related adverse effects, dose intake and improve
the bioavailability inspite drug undergo extensive first pass metabolism
ultimately improve the compliance in pharmacotherapy of inflammation and
pain.
Microencapsulation by ionotropic gelation technique is one of the widely
used method for preparation of calcium alginate beads which has ability to
form gels reaction with calcium salts .
Recently the use calcium alginate gel beads as a vehicle for controlled drug
delivery system . However major disadvantage of alginate beads are their
fast disintegration in simulated intestinal fluid and high porosity, which
results in rapid drug release.
These consideration led to the objective of this
study, which was to prepare and evaluate oral
sustained release product namely microbeads for
ibuprofen by ionotropic gelation method using
sodium alginate alone to overcome the fast
disintegration of alginate beads in simulated
intestine.
Advantages:
 Decreasing dosing frequency
 Improve patient compliance
 Reducing side effects
 They are also attractive because it can be
fabricated into various shapes.
Disadvantages:
 Some synthetic polymers are not biocompatible
Literature review
 Thulasi v. menon , CI Sajeeth(2103), The main aim of the study is to formulate
Carvedilol loaded microbeads of sodium alginate using gelatine and pectin as
release modifiers by ionotropic gelation method. The microbeads were prepared by
varying the concentration of sodium alginate, gelatin and pectin. The drug-polymer
compatibility was studied by FTIR studies. The prepared microbeads were
evaluated for swelling ratio, particle size, drug entrapment, Scanning electron
microscopy (SEM), bio adhesion study and invitro release study. Particle size
distribution of both placebo and drug loaded formulations were measured by an
optical microscope and particle size of optimized beads was determined by SEM. No
significant drug-polymer interactions were observed in FT-IR studies. In-vitro drug
release profile of Carvedilol micro beads was examined in pH 1.2 N Hydrochloric
acid for first 2 hours followed by phosphate buffer pH 7.4 for remaining time. The in
vitro wash-off test indicated that the sodium alginate micro beads had good
mucoadhesive properties. The formulated beads had shown higher entrapment
efficiency, drug loading, low particle size and moisture content. The formulation F3
released Carvedilol for longer duration (24 hours) and showed better mucoadhesion.
 Nayak A,K, Khatuas (2011), researched on Diclofenac sodium is a non-steroidal
anti-inflammatory agent with a short biological half-life (1-2 hr) and requires multiple
dosing. This research was carried out to develop and optimize diclofenac sodium
loaded alginate-PVP K 30 microbeads to eliminate the need for multiple dosing and
adverse effects. Methods: Diclofenac sodium loaded alginate-PVP K 30 microbeads
AIM & OBJECTIVE
 To prepare microbeads of ibuprofen by using sodiun
alginate.
 Preformulation studies
o Melting point
o Solubility
o U.V specroscopy
 Evaluation studies
o Drug interaction studies
o Particle size distribution
o Surface and drug entrapment
o Bulk and tapped density
DRUG & POLYMER
PROFILEDRUG PROFILE: IBUPROFEN
FORMULA: C13H18O2
IUPAC: 2-(p-isobutyl phenyl)propionic acid
PHARMACOKINETIC:
 Onset of action- 30min
 Plasma protein binding- 90-95%
 Biological halflife- 2hrs
 Excretion- urine(95%)
 Absorbtion sites-
 Bioavailability- 87-100%
SOLUBILITY:
SOLVENT SOLUBILITY
Methanol Soluble
Water Insoluble
Ethanol Soluble
Chloroform Soluble
Acetone Soluble
USES:
 Used primarily for fever, pain,
inflammatory diseases such as
rheumatoid arthritis
 Ibuprofen is a NSAID
 It is used in the treatment of other
painful conditions such as toothache,
pain after operations, period pain and
headache.
ADVERSE EFFECTS:
 Gastric discomfort
 Nausea and vomiting
 Dizziness and blurring of vision
POLYMER PROFILE:
SODIUM ALGINATE
 Definition – Sodium salt of alginic acid
 Chemical name - Sodium alginate: D-Galacturonic
acid sodium salt
 Chemical formula - C6H9NaO7
 Description – White to yellowish brown, filamentous,
grainy, granular or powdered forms.
 Functional uses – Stabilizer, thickner, gelling agent,
emulsifier.
 Solubility – Dissolves slowly in water, forming a
viscous solution, insoluble in ethanol and ether.
METHOD OF PREPARATION
By ionotropic gelation method.
RESULT & DISCUSSION
CALIBERATION CURVE: the observed
data ibuprofenS.NO CONCENTRATION ABSORBANCE
1 2 0.1602
2 4 0.3187
3 6 0.5383
4 8 0.7853
5 10 0.9816
6 12 1.197
y = 0.106x - 0.0785
R² = 0.9974
0
0.2
0.4
0.6
0.8
1
1.2
1.4
0 2 4 6 8 10 12 14
abs.
conc.
Chart Title
DISCUSSION - The standard curve plot between
conc. and absorbance. The value of R2 was found to
be 0.997 . So, the equation can be used for the further
calculations.
2. PERCENTAGE YIELD:FORM
ULATI
ON
THEORETIC
AL
YIELD
PRACTICLE
YIELD
PERCENTAG
E
YIELD
F1 1.5gm 1.06gm 70.6%
F2 2gm 1.14gm 57%
F3 2.5gm 1.81gm 72.4%
F4 3gm 2.42gm 80.6%
0.00%
10.00%
20.00%
30.00%
40.00%
50.00%
60.00%
70.00%
80.00%
90.00%
F1 F2 F3 F4
percentageyield
formulations
DISCUSSION – The formulation F4 was found to be the
best among all the other formulation.
3. DRUG CONTENT:
DISCUSSION – As the percentage of ibuprofen drug
increases the percentage of drug content also increases.
Formulation Drug content%
F1 78
F2 81
F3 85
F4 87
4. SURFACE AND DRUG ENTRAPMENT:
DISCUSSION - From the result we can
conclude that as the amount of polymer in
the formulation increases, the surface
entrapment decreases as a result of increase
in drug entrapment.
Formulati
on
%surface entrapment %drug entrapment
F1 4.43 78.21
F2 4.21 80
F3 3.98 84.04
F4 3.86 88.72
5. BULK & TAPPED DENSITY:
DISCUSSION – From the formulations we
observed that BD and TD for all the
formulations were found in the range
between 0.13 to 0.41 g/cm3 and o.20 to 0.34
3
Formulatio
n
Bulk density(gm/ml) Tapped
density(gm/ml)
F1 0.13 0.20
F2 0.25 0.29
F3 0.30 0.33
F4 0.41 0.34
6. FTIR:
FTIR of ibuprofen
FTIR of ibuprofen & polymer
Drug_007
Name
Sample 002 By Administrator Date Tuesday, April 12 2016
Description
4000 4003500 3000 2500 2000 1500 1000 500
63
17
20
25
30
35
40
45
50
55
60
cm-1
%T
2955.60cm-1, 18.38%T
2922.26cm-1, 18.83%T
2868.89cm-1, 20.23%T
3452.54cm-1, 21.38%T 1721.20cm-1, 21.63%T
3044.80cm-1, 22.35%T
2729.78cm-1, 26.48%T
2632.73cm-1, 27.32%T
1231.00cm-1, 27.41%T
1420.07cm-1, 29.40%T
1183.74cm-1, 32.35%T
1321.17cm-1, 32.63%T
1461.91cm-1, 33.46%T
1268.31cm-1, 33.51%T
1507.76cm-1, 33.51%T
779.71cm-1, 34.63%T
1379.89cm-1, 35.42%T
936.11cm-1, 37.06%T
1365.00cm-1, 40.24%T
1067.23cm-1, 40.41%T
866.32cm-1, 40.43%T
1168.20cm-1, 41.42%T
1008.14cm-1, 41.45%T
668.57cm-1, 41.77%T
1123.08cm-1, 44.05%T
969.58cm-1, 44.36%T
1091.90cm-1, 44.65%T 588.68cm-1, 45.89%T
849.23cm-1, 47.18%T
521.92cm-1, 47.78%T
880.36cm-1, 48.58%T
636.63cm-1, 48.78%T
746.67cm-1, 50.38%T
691.00cm-1, 50.45%T
819.93cm-1, 52.91%T
421.01cm-1, 55.06%T
479.83cm-1, 57.20%T
Drug +poly
Name
Sample 009 By Administrator Date Tuesday, April 12 2016
Description
4000 4003500 3000 2500 2000 1500 1000 500
48
13
14
16
18
20
22
24
26
28
30
32
34
36
38
40
42
44
46
cm-1
%T
2955.56cm-1, 14.02%T
2922.17cm-1, 14.41%T
2868.80cm-1, 15.62%T 1721.25cm-1, 16.17%T
3019.76cm-1, 16.63%T
3451.37cm-1, 17.31%T
2731.88cm-1, 20.36%T
2632.84cm-1, 21.31%T
1230.97cm-1, 21.38%T
1420.01cm-1, 21.77%T
1183.71cm-1, 24.95%T
1321.09cm-1, 25.08%T
1461.88cm-1, 25.73%T
1507.63cm-1, 26.09%T
1268.28cm-1, 26.23%T
1379.91cm-1, 27.10%T
779.74cm-1, 28.59%T
936.09cm-1, 29.47%T
1067.25cm-1, 29.74%T
1365.05cm-1, 30.15%T
1008.22cm-1, 30.66%T
1123.11cm-1, 31.50%T
1091.89cm-1, 31.52%T
866.32cm-1, 33.27%T
668.50cm-1, 34.30%T
969.67cm-1, 34.59%T
588.78cm-1, 37.54%T
849.19cm-1, 38.10%T
880.47cm-1, 38.21%T
521.89cm-1, 38.61%T
636.66cm-1, 38.89%T
746.66cm-1, 39.84%T
690.98cm-1, 40.02%T
819.98cm-1, 40.16%T
420.84cm-1, 43.53%T
479.94cm-1, 44.37%T
7. PARTICLE SIZE:
F1 F2 F3
DISCUSSION: The particle size varies from
125 to 165µm
Formulation Particle size (µm)
F1 125
F2 132
F3 140
F4 165
CONCLUSION
It could be concluded that the sustained release alginate
beads of Ibuprofen evaluated by qualitative method gave
effective data’s. Microbeads are one of the microparticulate
systems and are prepared to obtain prolonged or controlled
drug delivery, to improve bioavailability or stability and to
target drug to specific sites. Microbeads can also offer
advantages like limiting fluctuation within therapeutic range,
reducing side effects, decreasing dosing frequency and
improving patient compliance. Microbeads of ibuprofen were
prepared according to the using modified ion gelation method
by selecting concentration of sodium alginate and calcium
chloride as independent variables. Increasing polymer
concentration led to more sustained release effect whereas
presence of sodium alginate improves the encapsulation
efficiency. Calcium chloride can be increased up to certain
limit above which encapsulation was decreased. Moreover,
the effect of each variable on release characteristic was found
to be significant as confirmed by data analysis. Respectively,
the mathematical model developed in the present study can
be used to design microbeads of desired release
characteristic.
formulation and evaluation of microbeads

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formulation and evaluation of microbeads

  • 1. FORMULATION AND EVALUATION OF MICROBEADS PROJECT SUBMITTED TO UTTRAKHAND TECHNICAL UNIVERSITY In partial fulfillment of the requirement for the award of the degree of BACHELOR IN PHARMACY 2012-2016 Submitted By Gurleen kaur Roll No. 120260300018 B.Pharm 8th Semester Under the guidance of DR.Ashutosh Badola Department of Pharmaceutical Sciences Shri Guru Ram Rai Institute of Technology & Science Patel Nagar, Dehradun (Uttarakhand)
  • 2. CONTENT  Introduction  Literature review  Aim & objective  Drug & polymer profile  Result & discussion  conclusion
  • 3. INTRODUCTION In recent years a wide variety of newer drug delivery systems like oral sustained/controlled release dosage forms are designed and evaluated in order to overcome the limitations of conventional therapy. The non steroidal anti inflammatory drug Ibuprofen is a good candidate for the development of oral controlled release formulation. It is used for long term treatment of inflammation & pain, with dosage 400-600mg (5- 10mg/kg)TDS as conventional
  • 4. Adverse gastric discomfort have been observed, and its short biological half life 2hr. Microencapsulation has been employed to sustain the drug release, reduce or eliminate drug related adverse effects, dose intake and improve the bioavailability inspite drug undergo extensive first pass metabolism ultimately improve the compliance in pharmacotherapy of inflammation and pain. Microencapsulation by ionotropic gelation technique is one of the widely used method for preparation of calcium alginate beads which has ability to form gels reaction with calcium salts . Recently the use calcium alginate gel beads as a vehicle for controlled drug delivery system . However major disadvantage of alginate beads are their fast disintegration in simulated intestinal fluid and high porosity, which results in rapid drug release.
  • 5. These consideration led to the objective of this study, which was to prepare and evaluate oral sustained release product namely microbeads for ibuprofen by ionotropic gelation method using sodium alginate alone to overcome the fast disintegration of alginate beads in simulated intestine. Advantages:  Decreasing dosing frequency  Improve patient compliance  Reducing side effects  They are also attractive because it can be fabricated into various shapes. Disadvantages:  Some synthetic polymers are not biocompatible
  • 6. Literature review  Thulasi v. menon , CI Sajeeth(2103), The main aim of the study is to formulate Carvedilol loaded microbeads of sodium alginate using gelatine and pectin as release modifiers by ionotropic gelation method. The microbeads were prepared by varying the concentration of sodium alginate, gelatin and pectin. The drug-polymer compatibility was studied by FTIR studies. The prepared microbeads were evaluated for swelling ratio, particle size, drug entrapment, Scanning electron microscopy (SEM), bio adhesion study and invitro release study. Particle size distribution of both placebo and drug loaded formulations were measured by an optical microscope and particle size of optimized beads was determined by SEM. No significant drug-polymer interactions were observed in FT-IR studies. In-vitro drug release profile of Carvedilol micro beads was examined in pH 1.2 N Hydrochloric acid for first 2 hours followed by phosphate buffer pH 7.4 for remaining time. The in vitro wash-off test indicated that the sodium alginate micro beads had good mucoadhesive properties. The formulated beads had shown higher entrapment efficiency, drug loading, low particle size and moisture content. The formulation F3 released Carvedilol for longer duration (24 hours) and showed better mucoadhesion.  Nayak A,K, Khatuas (2011), researched on Diclofenac sodium is a non-steroidal anti-inflammatory agent with a short biological half-life (1-2 hr) and requires multiple dosing. This research was carried out to develop and optimize diclofenac sodium loaded alginate-PVP K 30 microbeads to eliminate the need for multiple dosing and adverse effects. Methods: Diclofenac sodium loaded alginate-PVP K 30 microbeads
  • 7. AIM & OBJECTIVE  To prepare microbeads of ibuprofen by using sodiun alginate.  Preformulation studies o Melting point o Solubility o U.V specroscopy  Evaluation studies o Drug interaction studies o Particle size distribution o Surface and drug entrapment o Bulk and tapped density
  • 8. DRUG & POLYMER PROFILEDRUG PROFILE: IBUPROFEN FORMULA: C13H18O2 IUPAC: 2-(p-isobutyl phenyl)propionic acid PHARMACOKINETIC:  Onset of action- 30min  Plasma protein binding- 90-95%  Biological halflife- 2hrs  Excretion- urine(95%)  Absorbtion sites-  Bioavailability- 87-100% SOLUBILITY: SOLVENT SOLUBILITY Methanol Soluble Water Insoluble Ethanol Soluble Chloroform Soluble Acetone Soluble
  • 9. USES:  Used primarily for fever, pain, inflammatory diseases such as rheumatoid arthritis  Ibuprofen is a NSAID  It is used in the treatment of other painful conditions such as toothache, pain after operations, period pain and headache. ADVERSE EFFECTS:  Gastric discomfort  Nausea and vomiting  Dizziness and blurring of vision
  • 10. POLYMER PROFILE: SODIUM ALGINATE  Definition – Sodium salt of alginic acid  Chemical name - Sodium alginate: D-Galacturonic acid sodium salt  Chemical formula - C6H9NaO7  Description – White to yellowish brown, filamentous, grainy, granular or powdered forms.  Functional uses – Stabilizer, thickner, gelling agent, emulsifier.  Solubility – Dissolves slowly in water, forming a viscous solution, insoluble in ethanol and ether.
  • 11. METHOD OF PREPARATION By ionotropic gelation method.
  • 12. RESULT & DISCUSSION CALIBERATION CURVE: the observed data ibuprofenS.NO CONCENTRATION ABSORBANCE 1 2 0.1602 2 4 0.3187 3 6 0.5383 4 8 0.7853 5 10 0.9816 6 12 1.197 y = 0.106x - 0.0785 R² = 0.9974 0 0.2 0.4 0.6 0.8 1 1.2 1.4 0 2 4 6 8 10 12 14 abs. conc. Chart Title
  • 13. DISCUSSION - The standard curve plot between conc. and absorbance. The value of R2 was found to be 0.997 . So, the equation can be used for the further calculations. 2. PERCENTAGE YIELD:FORM ULATI ON THEORETIC AL YIELD PRACTICLE YIELD PERCENTAG E YIELD F1 1.5gm 1.06gm 70.6% F2 2gm 1.14gm 57% F3 2.5gm 1.81gm 72.4% F4 3gm 2.42gm 80.6% 0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% 80.00% 90.00% F1 F2 F3 F4 percentageyield formulations
  • 14. DISCUSSION – The formulation F4 was found to be the best among all the other formulation. 3. DRUG CONTENT: DISCUSSION – As the percentage of ibuprofen drug increases the percentage of drug content also increases. Formulation Drug content% F1 78 F2 81 F3 85 F4 87
  • 15. 4. SURFACE AND DRUG ENTRAPMENT: DISCUSSION - From the result we can conclude that as the amount of polymer in the formulation increases, the surface entrapment decreases as a result of increase in drug entrapment. Formulati on %surface entrapment %drug entrapment F1 4.43 78.21 F2 4.21 80 F3 3.98 84.04 F4 3.86 88.72
  • 16. 5. BULK & TAPPED DENSITY: DISCUSSION – From the formulations we observed that BD and TD for all the formulations were found in the range between 0.13 to 0.41 g/cm3 and o.20 to 0.34 3 Formulatio n Bulk density(gm/ml) Tapped density(gm/ml) F1 0.13 0.20 F2 0.25 0.29 F3 0.30 0.33 F4 0.41 0.34
  • 17. 6. FTIR: FTIR of ibuprofen FTIR of ibuprofen & polymer Drug_007 Name Sample 002 By Administrator Date Tuesday, April 12 2016 Description 4000 4003500 3000 2500 2000 1500 1000 500 63 17 20 25 30 35 40 45 50 55 60 cm-1 %T 2955.60cm-1, 18.38%T 2922.26cm-1, 18.83%T 2868.89cm-1, 20.23%T 3452.54cm-1, 21.38%T 1721.20cm-1, 21.63%T 3044.80cm-1, 22.35%T 2729.78cm-1, 26.48%T 2632.73cm-1, 27.32%T 1231.00cm-1, 27.41%T 1420.07cm-1, 29.40%T 1183.74cm-1, 32.35%T 1321.17cm-1, 32.63%T 1461.91cm-1, 33.46%T 1268.31cm-1, 33.51%T 1507.76cm-1, 33.51%T 779.71cm-1, 34.63%T 1379.89cm-1, 35.42%T 936.11cm-1, 37.06%T 1365.00cm-1, 40.24%T 1067.23cm-1, 40.41%T 866.32cm-1, 40.43%T 1168.20cm-1, 41.42%T 1008.14cm-1, 41.45%T 668.57cm-1, 41.77%T 1123.08cm-1, 44.05%T 969.58cm-1, 44.36%T 1091.90cm-1, 44.65%T 588.68cm-1, 45.89%T 849.23cm-1, 47.18%T 521.92cm-1, 47.78%T 880.36cm-1, 48.58%T 636.63cm-1, 48.78%T 746.67cm-1, 50.38%T 691.00cm-1, 50.45%T 819.93cm-1, 52.91%T 421.01cm-1, 55.06%T 479.83cm-1, 57.20%T Drug +poly Name Sample 009 By Administrator Date Tuesday, April 12 2016 Description 4000 4003500 3000 2500 2000 1500 1000 500 48 13 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 cm-1 %T 2955.56cm-1, 14.02%T 2922.17cm-1, 14.41%T 2868.80cm-1, 15.62%T 1721.25cm-1, 16.17%T 3019.76cm-1, 16.63%T 3451.37cm-1, 17.31%T 2731.88cm-1, 20.36%T 2632.84cm-1, 21.31%T 1230.97cm-1, 21.38%T 1420.01cm-1, 21.77%T 1183.71cm-1, 24.95%T 1321.09cm-1, 25.08%T 1461.88cm-1, 25.73%T 1507.63cm-1, 26.09%T 1268.28cm-1, 26.23%T 1379.91cm-1, 27.10%T 779.74cm-1, 28.59%T 936.09cm-1, 29.47%T 1067.25cm-1, 29.74%T 1365.05cm-1, 30.15%T 1008.22cm-1, 30.66%T 1123.11cm-1, 31.50%T 1091.89cm-1, 31.52%T 866.32cm-1, 33.27%T 668.50cm-1, 34.30%T 969.67cm-1, 34.59%T 588.78cm-1, 37.54%T 849.19cm-1, 38.10%T 880.47cm-1, 38.21%T 521.89cm-1, 38.61%T 636.66cm-1, 38.89%T 746.66cm-1, 39.84%T 690.98cm-1, 40.02%T 819.98cm-1, 40.16%T 420.84cm-1, 43.53%T 479.94cm-1, 44.37%T
  • 18. 7. PARTICLE SIZE: F1 F2 F3 DISCUSSION: The particle size varies from 125 to 165µm Formulation Particle size (µm) F1 125 F2 132 F3 140 F4 165
  • 19. CONCLUSION It could be concluded that the sustained release alginate beads of Ibuprofen evaluated by qualitative method gave effective data’s. Microbeads are one of the microparticulate systems and are prepared to obtain prolonged or controlled drug delivery, to improve bioavailability or stability and to target drug to specific sites. Microbeads can also offer advantages like limiting fluctuation within therapeutic range, reducing side effects, decreasing dosing frequency and improving patient compliance. Microbeads of ibuprofen were prepared according to the using modified ion gelation method by selecting concentration of sodium alginate and calcium chloride as independent variables. Increasing polymer concentration led to more sustained release effect whereas presence of sodium alginate improves the encapsulation efficiency. Calcium chloride can be increased up to certain limit above which encapsulation was decreased. Moreover, the effect of each variable on release characteristic was found to be significant as confirmed by data analysis. Respectively, the mathematical model developed in the present study can be used to design microbeads of desired release characteristic.