Formulation and evaluation of sustained release tablets of ambroxol hcl using natural polymers

1. FORMULATION AND EVALUATION OF SUSTAINED
RELEASE TABLETS OF AMBROXOL HCl USING
NATURAL POLYMERS
Presented by
P.VENKATESH
M PHARMACY
DEPT.OF PHARMACEUTICS

2. Contents:
Introduction
Literature Review
Aim & Objective
Need of study
Plan Of Work
Materials & methods
Drug profile
Results & Discussion
Conclusion
Summary
References

3. What is Sustain Release Dosage Form?
“Drug Delivery system that are designed to achieve prolonged
therapeutic effect by continuously releasing medication over an
extended period of time after administration of single dose.”
The basic goal of therapy is to achieve steady state blood level that
is therapeutically effective and non toxic for an extended period of
time.
The design of proper dosage regimen is an important element in
accomplishing this goal.
INTRODUCTION

4. The difference between controlled release and sustained release,
Controlled drug delivery- which delivers the drug at a pre
determined rate for a specified period of time
Controlled release is perfectly zero order release that is the
drug release over time irrespective of concentration.
Sustain release dosage form- is defined as the type of dosage
form in which a portion i.e. (initial dose) of the drug is released
immediately, in order to achieve desired therapeutic response more
promptly, and the remaining(maintanance dose) is then released
slowly there by achieving a therapeutic level which is prolonged,
but not maintained constant.
Sustained release implies slow release of the drug over a time
period. It may or may not be controlled release.

5. Plasma drug concentration profile for conventional release, a sustained release and zero order controlled release
formulation.
Comparison of conventional and controlled release profiles.

6. Improved patient convenience and compliance due to less
frequent drug administration.
Reduction in fluctuation in steady-state level and therefore better
control of disease condition.
Increased safety margin of high potency drug due to better
control of plasma levels.
Maximum utilization of drug enabling reduction in total amount
of dose administered.
Reduction in health care cost through improved therapy, shorter
treatment period.
Merit
s.

7. Less frequency of dosing and reduction in personnel time to
dispense, administer monitor patients.
Better control of drug absorption can be obtained, since the high
blood level peaks that may be observed after administration of a
dose of high availability drug can be reduced.

8. Demerits..
Decreased systemic availability in comparison to immediate
release conventional dosage forms; this may be due to incomplete
release, increased first-pass metabolism, increased instability,
insufficient residence time for complete release, site specific
absorption, pH dependent solubility etc.,
Poor in-vivo, in-vitro correlation.
Possibility of dose dumping due to food, physiologic or
formulation variable or chewing or grinding of oral formulation by
the patient and thus increased risk of toxicity.

9. Retrieval of drug is difficult in case of toxicity, poisoning or
hypersensitivity reaction.
The physician has less flexibility in adjusting dosage regimens.
This is fixed by the dosage form design.
Sustained release forms are designed for the normal population
i.e. on the basis of average drug biologic half-life’s. Consequently
disease states that alter drug disposition, significant patient variation
and so forth are not accommodated.
Economics factors must also be assessed, since more costly
processes and equipment are involved in manufacturing many
sustained release forms.

10. Factors effecting the oral sustain release
dosage forms
A) Pharmacokinetics and pharmacodynamics factor:
1. Biological half-life
Drug with biological half-life of 2-8 hours are considered suitable candidate for
sustain release dosage form, since this can reduce dosing frequency. However this
is limited in that drugs with very short biological half lives may require excessive
large amounts of drug in each dosage unit to maintain sustained effects, forcing
the dosage form itself to become limitingly large.
2. Absorption
Rate of absorption of a sustained formulating depends upon release rate constant
of the drug from the dosage form, and for the drugs that are absorbed by active
transport the absorption is limited to intestine.

11. 3. Distribution
The distribution of drugs into tissues can be important factor in the
overall drug elimination kinetics. Since it not only lowers the
concentration of circulating drug but it also can be rate limiting in its
equilibrium with blood and extra vascular tissue, consequently
apparent volume of distribution assumes different values depending n
the time course of drug disposition. Thus for design of sustain release
products, one must have information of disposition of drug.
4. Metabolism
The metabolic conversion to a drug is to be considered before
converting into another form. Since as long as the location, rate, and
extent of metabolism are known a successful sustain release product
can be developed.

12. B) Drug properties relevant to sustain release formulation:
1. Dose size
A dose size of 500-1000mg is considered maximal for a conventional
dosage form. This also holds true for sustain release dosage forms.
Since dose size consideration serves to be a parameter for the safety
involved in administration of large amounts with narrow therapeutic
range.
2. Ionization, pka and aqueous solubility
Most drugs are weak acids or bases and in order for a drug to get
absorbed, it must dissolve in the aqueous phase surrounding the site of
administration and then partition into the absorbing membrane.

13. 3. Partition coefficient
Bioavailability of a drug is largely influenced by the partition
coefficient, as the biological membrane lipophilic in nature transport
of drug across the membrane largely depends upon the partition
coefficient of the drug. Drugs having low partition coefficient are
considered as poor candidate for the sustain release formulation as it
will be localized in the aqueous phase eg: Barbituric acid and vice a
versa.
4. Drug stability
When drugs are orally administered, they come across acid-base
hydrolysis and enzymatic degradation. In this case, if the drug is
unstable in stomach, drug release system which provides medication
over extended period of time is preferred, whereas in contrast the drug
unstable in intestine will face problem of less bioavailability

14. Parameters for drug to be formulated in
sustained release dosage form
Physicochemical parameters for drug selection:
1. Molecular weight/size < 1000 Daltons.
2. Solubility > 0.1 mg/ml for pH 1 to pH 7.8.
3. Apparent partition coefficient High.
4. Absorption mechanism Diffusion.
5. General absorbability from all GI segments.
6. Release should not be influenced by pH and enzymes.

15. Pharmacokinetic parameters for drug selection:
1. Elimination half-life preferably between 2 to 8 hrs
2. Total clearance should not be dose dependent
3. Elimination rate constant required for design
4. Apparent volume of distribution (Vd) The larger Vd and MEC, the
larger will be the required dose size
5. Absolute bioavailability should be 75% or more
6. Intrinsic absorption rate must be greater than release rate

16. Formulation methods used to obtain the desired drug
availability rate from sustained action dosage form include…….
• Increasing the particle size of the drug.
• Embedding the drug in matrix.
• Coating the drug or dosage form containing
drug(microencapsulation).
• Forming complexes of the drug with material such as ion
exchange resins.
DESIGN OF ORAL SUSTAINED ACTION PRODUCTS

17. 1) Increasing the particle size of the drug:-
The purpose of increasing particle size is to decrease the
surface to volume ratio slow the rate of drug availability. This
method is a single means for obtaining the desired drug availability
rate is limited to poorly soluble drug.

18. 2) Embedding the drug in matrix:-
Matrix may be defined as uniform dispersion of drug in
solid which is less soluble than a drug in the dispersion fluid, &
which for the continuous external phase of the dispersion effectively
impeder the passage of the drug from the matrix to the dispersion
fluid.
One of the least complicated approaches to the
manufacture of sustained release dosage form involves the direct
compression of drug, materials & additives to form a tablet in
which drug is embedded in a matrix core of the retardant.

19. Polymers:-
• Insoluble, inert - polyethylene, polyvinyl chloride, methyl acrilate,
ethylcellulose.
•Insoluble, erodible – carnauba wax, stearyl alcohol, castor wax.
•Hydrophilic – methyl cellulose, hydroxyl ethyl cellulose, sodium
carboxymethyl cellulose, sodium alginate.
In a matrix system the drug is dispersed as solid particle within
a porous matrix formed of a water insoluble polymer, such as poly-
vinyl chloride.

20. Initially, drug particle located at the surface of the release unit
will be dissolved and the drug released rapidly. Thereafter, drug
partical at successively increasing distance from the surface of the
release unit will be dissolved and release by diffusion in the pores to
the exterior of the release unit.
The main formulation factor by which the release rate from
matrix system can be controlled are; the amount of the drug in the
matrix, the porosity of the release unit & the solubility of the drug.

21. Types of matrix systems
Two types of matrix systems
1. Slowly eroding matrix
2. Inert plastic matrix
1.Slowly eroding matrix
Consists of using materials or polymers which erode over a period
of time such as waxes, glycerides, stearic acid, cellulosic materials
etc.
Principle:
• Portion of drug intended to have sustained action is combined with
lipid or cellulosic material and then granulated.
• Untreated drug granulated
• Both mixed

22. Principle:
Drug granulated with an inert, insoluble matrix such as
polyethylene, polyvinyl acetate, polystyrene, polyamide or
polymethacrylate.
Granulation is compressed results in MATRIX
Drug is slowly released from the inert plastic matrix by leaching
of body fluids
Release of drug is by diffusion.
2. Embedding drug in Inert plastic matrix

23. Preparation of matrix tablets:
Solidify
Grind
Suspension of
drug in wax
Powder
Granulate
Drug
Granulate
Tablets
Methods of preparation

24. 3) Coating the drug or a dosage form containing the
drug (microencapsulation)
The method for retarding drug release
from the dosage form is to coat its
surface with a material(polymers) that
retards penetration by the dispersion
fluid. Drug release depends upon the
physiochemical nature of coating
material.
Microencapsulation is rapidly
expanding technique as a process; it is a
means of applying relatively thin coating
to small particles of solid or droplets of
liquids and dispersion.

25. The application of microencapsulation might will include,
sustained release or prolonged action medication, taste masked,
chewable tablet, powder and suspension, single layer tablets.
Containing chemically incompatible ingredient & new formulation
concepts for creams, ointments, aerosols, dressing, plasters,
suppositories & injectables.
Polymers: - polyvinyl alcohol, polyacrylic acid, ethyl
cellulose, polyethylene, polymethacrlate, poly (ethylene-vinyl
acetate), cellulose nitrite, silicones, poly (lactide-co-glcolide)

26. Mechanism of Drug Release from Matrix Tablets:
• In erodible matrices, polymer erosion from the surface of the matrix determines the drug
release; whilst in hydrophilic matrices, formation of the gel layer and its dynamics as a
function of time determines the drug release. Gel layer thickness, which determines the
diffusion path length of the drug, corresponds to the distance between the diffusion and
erosion fronts. As the swelling process proceeds, the gel layer gradually becomes thicker,
resulting in progressively slower drug-release rates; however, due to continuous hydration,
polymer disentanglement occurs from the surface of the matrix, resulting in a gradually
decreasing depletion zone and an increased dissolution rate.

27. Tablet Manufacturing Methods:
• A) Direct compression:
• Manufacturing steps for direct compression
• Direct compression involves comparatively few steps:
• Milling of drug and excipients
• Mixing of drug and excipients
• Tablet compression
• B) Granulation:
• Granulation may be defined as a size enlargement process which converts
small particles into physically stronger and larger agglomerates.
• Granulation method can be broadly classified into two types: Wet
granulation and Dry granulation.

28. Literature Review:
• JM. Packiaraj et.,al 2013(11) Clarithromycin ER (extended-release) tablets
containing 500 mg of Clarithromycin is available in the market under the brand
name BIAXIN® XL Film tab® manufactured by AbbVie LTD. The objective of
the research work is to make a formulation equivalent which will exhibit
comparative in-vitro and in-vivo drug release profile. The objective was
accomplished using a combination of Hypromellose 5 cps and Hypromellose 15
cps as drug release rate controlling polymers with Purified Water as a granulating
fluid in a Fluid Bed Top Spray Granulation Process. The prepared ER core
tablets were film coated up to 3% w/w coating build up using 20% w/w
dispersion of Opadry II White 85F18422. Final tablets showed comparative in
vitro and in vivo drug release profile against BIAXIN®XL Film tab®. The
physico-chemical properties of the finalized ER tablets of Clarithromycin was
found to be stable at accelerated temperature and humidity conditions of 40°C /
75% RH for 3 months.

29. • Heras J et al., 2009(12) found that functional dyspepsia as a highly common disorder.
The physiopathological mechanisms of this entity are not yet completely known and
prokinetic drugs seem to be useful. The aim of this study was to evaluate the
prokinetic effect of cinitapride in patients with dysmotility-like dyspepsia and
delayed gastric emptying.
• Portincasa P et al., 2009 (13) evaluated the prokinetic effect of cinitapride in patients
with dysmotility-like dyspepsia and delayed gastric emptying. Oral cinitapride is safe
and effective in improving gastric emptying and symptoms in patients with
dysmotility-like dyspepsia and mild-to-moderate delayed gastric emptying.

30. • Golor G. et al., 2007(14) designed to evaluate the possible pharmacokinetic and
electrocardiographic interactions of the gastro enteric prokinetic drug cinitapride
with ketoconazole. The safety and tolerability of the study treatments were also
evaluated. The study showed that cinitapride, either given alone or after
• Co-administration with ketoconazole 200 mg bid. Had no effect on cardiac
repolarization as measured by changes in the heart rate-corrected QT interval on
the surface electrocardiogram.
• Georg Golor et al., 2007(15) evaluated the possible pharmacokinetic and
electrocardiographic interactions of the gastroenteric prokinetic drug cinitapride
with ketoconazole. The safety and tolerability of the study treatments were also
evaluated. The study showed that cinitapride, either given alone or after
coadministration with ketoconazole 200 mg b.i.d., had no effect on cardiac
repolarization as measured by changes in the heart rate-corrected QT interval on
the surface electrocardiogram.

31. • M.A.Blanco López et al., 1998(16) developed a method for the determination
of cinitapride by differential pulse polarography and adsorptive stripping
voltammetry (ASV) in Britton–Robinson buffer, with 3s detection limits of
1.3×10−8 and 8.4×10−10 M, respectively. ASV was applied for the
determination of cinitapride in urine samples with an accumulation time of 65
s. A method is also proposed for the polarographic determination of cisapride
in which the electro active product is obtained by nitration with potassium
nitrate in sulphuric acid. The 3s detection limit is 1.8×10−7 M and the relative
standard deviation 1%.
• Motilva V et al., 1998 (17) examined the effects of cinitapride, a novel
prokinetic benzamide-stimulating gastrointestinal motility agent, on gastric
secretion and ulceration in rats and elucidate some possible vascular and anti-
oxidant mechanisms of such protection.

32. • To prepare and evaluate sustained release tablets of Ambroxol HCL by
using natural polymers

33. Objectives of drug delivery
• To formulate sustained release tablets of Ambroxol HCL
• Improve its oral bioavailability
• Reduce its dosing frequency.
• To optimize optimum concentration of various sustained
release polymers.
• To perform various quality control evaluation parameters
for the prepared tablets.
4 March 2015 33

34. Need Of Study
• Ambroxol Hydrochloride is an active N-desmethyl metabolite of the mucolytic
bromohexine . It is chemically described as trans-4-[(2-Amino-3,5- dibromobenzyl)
amino]-cyclohexanol. It is widely used as a mucolytic agent prescribed in respiratory
infections like bronchitis and bronchial asthma . It was postulated that Ambroxol HCl
decreased airway hyper-reactivity by either increasing lysophosphatidyl choline
turnover and/or modifying epithelial secretion where successful treatment needs a
constant and uniform supply of drug. Ambroxol HCl is sparingly water solubility.
Hence it presents significant formulation challenges.
• Ambroxol HCl has a half-life of 4 hours and the usual oral dosage regimen is 75 mg
. Therefore, it is an ideal candidate to be designed as a sustained release(SR) dosage
form, which would result in prolonged clinical efficacy, reduced frequency of dosage
and lesser side-effects
4 March 2015 34

35. Drug Profile:
Name: Ambroxol HCL
Proprietary Name: Ambroxol
Chemical structure:
• Chemical Name: trans-4-(2-Amino-3,5-dibrombenzylamino)-
cyclohexanol.
• Molecular Formula: C13H18Br2N2O•HCl.
• Molecular weight: 414.6.

36. • Category: An expectorant antioxidant and anti inflammatory agent.
• Appearance: White crystalline powder.
• Solubility: Soluble in methanol, water (~5 mg/ml), ethanol (~5 mg/ml), and Insoluble in ether .
• Melting point: 233-234 °C.
• pKb: 8.69.
• Absorption: Good absorbed by digestive tract
• Bioavailability: 79%
• Half life: 10-12hrs
• Protein binding: 90%
• Metabolism: oxidative biotransformation to dibromoanthranilic acid and glucronides through
cytochrome P450 3A4.
• Excretion: kidney, approximately 5-6% of a dose is excreted.
• Mechanism of action: It stimulates synthesis and release of surfactant by type II pneumocytes.
Surfactant acts as an anti-glue factor by reducing the adhesion of mucus to the bronchial wall,
in improving its transport and in providing protection against infection and irritating agents.
• Side/adverse effect: Mild gastrointestinal effects, runny nose and allergic reactions.

37. Marketed Products
S. No Brand Name Combination Generics Manufacturers
1 Amrox - S Ambroxol,
Roxithromycin,Serratiopeptidase
Norwest
Pharmaceuticals Inc.
2 Amroxit Ambroxol, Roxithromycin Nicholas Piramal India
Ltd.
3 Aurox (50 mg) Ambroxol, Roxithromycin Aurobindo Pharma Ltd.
4 Cetzine -A Ambroxol, Cetirizine Glaxo Smithkline
Pharmaceuticals Ltd.
5 Finecef AM Ambroxol, Cefpodoxime Piramal Healthcare
6 Novamox -AX Ambroxol, Amoxycillin Cipla Limited

38. Plan Of Work:
To achieve the objectives of the work, the following work was planned
and undertaken:
Literature survey
Preformulation studies
 Determination of absorption maxima
 Preparation of reagents
 Drug excipient compatibility studies
 Pre formulation parameters
Selection of excipients

39. Formulation of SR tablets with different polymers like guar gum,
magnesium stearate, xanthan gum.
Evaluation of tablets
 Weight variation test
 Hardness test
 Thickness test
 Friability test
 In vitro drug release studies
Selection of best formulation based on in-vitro drug release testing
Optimization of the selected formula

40. Materials:
Drug:
Ambroxol HCL
Excipients:
Polymers: Xanthan gum, guar gum,
Micro crystalline cellulose
Pvp k-30
Magnesium stearate
Talc

41. Methods
• Analytical method development:
a) Determination OF UV Absorption maxima
b) Preparation of reagents
Preparation of 0.1 N HCl solution
Preparation of Phosphate buffer (pH 6.8)
Preparation of 0.02 M NaOH
Preparation of phosphate buffer solution
• Preparation of Standard Calibration Curve of AMBROXOL HCL with
0.1N HCl
• Preparation of Standard Calibration Curve of AMBROXOL HCL with
Phosphate buffer(6.8pH)

42. • Tablet formulation:
• Formulation of Ambroxol HCl sustained release Tablet by Direct-
Compression:
• Composition of preliminary trials for ambroxol HCl sustained release
Tablet by direct compression is shown in table. All the ingredients were
weighed. Required quantity of drug and excipient mixed thoroughly in a
polybag. The blend is compressed using rotary tablet machine-8 station with
9mm flat punch, B tooling. Each tablet contains 300mg of ambroxol HCl and
other pharmaceutical ingredients.

43. Table. Formulation of Ambroxol HCL sustained release tablets
INGREDIENTS F1 F2 F3 F4 F5 F6 F7 F8
Ambroxol HCL 75 75 75 75 75 75 75 75
Guar gum
30 60 90 120 - - - -
Xanthan gum
- - - - 30 60 90 120
Pvp k-30 15 15 15 15 15 15 15 15
Talc 3 3 3 3 3 3 3 3
Mg. Stearate 3 3 3 3 3 3 3 3
Mcc Ph102
Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S
TOTAL 300 300 300 300 300 300 300 300
All ingredients are expressed in mg only

44. Results & Discussion
Conc
[µg/l]
Abs
5 0.122
10 0.31
15 0.43
20 0.582
25 0.724
30 0.822
Observations for graph of Ambroxol HCL in
0.1N HCl (243nm)
Standard graph of Ambroxol HCl in 0.1N HCl
Analytical Method: Graphs of Ambroxol HCL were taken in Simulated Gastric
fluid (pH 1.2) and in p H 6.8 phosphate buffer at 243 nm and 244 nm respectively.

45. Conc
[µg/l]
Abs
5 0.107
10 0.207
15 0.302
20 0.388
25 0.499
30 0.58
Observations for graph of Ambroxol HCl
in pH 6.8 phosphate buffer (244nm)
Standard graph of Ambroxol HCl p H 6.8 phosphate
buffer (244nm)

46. • Fourier Transform-Infrared Spectroscopy:
FT-IR Spectrum of Ambroxol HCl pure drug.

47. FT-IR Spectrum of Optimized Formulation

48. FT-IR Spectrum of Guar gum

49. FT-IR Spectrum of Xanthan Gum

50. FT-IR Spectrum of pvp k-30

51. FT-IR Spectrum of talc

52. FT-IR Spectrum of Mg. Stearate

53. FT-IR Spectrum of Mcc Ph102

54. Formulati
on Code
Angle of
Repose
Bulk
density
(gm/ml)
Tapped
density
(gm/ml)
Carr’s
index
(%)
Hausner’
s Ratio
F1 23.11 0.49 0.57 14.03 1.16
F2 26.76 0.45 0.52 13.46 1.15
F3 28.54 0.50 0.58 13.79 1.16
F4 22.38 0.41 0.49 16.32 1.19
F5 25.43 0.42 0.50 16.0 1.19
F6 24.22 0.44 0.52 15.38 1.18
F7 25.81 0.53 0.62 14.51 1.16
F8 24.22 0.58 0.67 13.4 1.15
F9 25.05 0.52 0.60 13.33 1.15
Preformulation parameters of powder blend:
Pre-formulation parameters of Core blend

55. Quality Control Parameters For tablets:
Formulation
codes
Weight
variation(mg)
Hardness(kg/cm2)
Friability
(%loss)
Thickness
(mm)
Drug
content
(%)
F1 312.5 4.5±0.026 0.55 2.8±0.026 96.76
F2 305.4 4.3±0.032 0.56 2.9±0.034 98.45
F3 298.6 4.4±0.023 0.58 3.4±0.027 95.34
F4 310.6 4.5±0.025 0.62 3.9±0.026 99.87
F5 309.4 4.0±0.039 0.56 3.7±0.015 101.14
F6 300.7 4.5±0.022 0.45 2.5±0.019 97.56
F7 302.3 4.1±0.026 0.51 3.4±0.036 100.42
F8 301.2 4.3±0.027 0.59 3.7±0.018 98.56
F9 298.3 4.2±0.035 0.54 3.6±0.026 95.21
Invitro quality control parameters for tablets

56. In-Vitro Drug Release Studies:
TIME
(hr)
CUMULATIVE
PERCENT DRUG
DISSOLVED (n=3+SD)
F1 F2 F3 F4
0 0 0 0 0
0.5 24.55 20.12 16.45 13.54
1 36.73 32.43 20.72 18.35
2 54.56 45.31 26.66 22.76
3 78.42 50.23 32.04 29.37
4 87.83 67.53 39.41 32.51
5 96.74 73.14 44.14 36.36
6 - 80.58 49.34 40.16
7 - 88.46 51.05 45.41
8 - 95.74 60.31 51.63
9 - - 69.56 58.42
10 - - 74.35 63.12
11 - - 83.86 67.37
12 - - 91.23 74.26
Dissolution Data of Ambroxol HCl Tablets Prepared
with Guar gum In Different Concentrations
Dissolution profile of Ambroxol HCL (F1, F2, F3, F4
formulations)

57. TIME
(hr)
CUMULATIVE PERCENT
DRUG DISSOLVED (n=3+SD)
F5 F6 F7 F8
0 0 0 0 0
0.5 17.25 14.42 10.62 7.84
1 28.26 23.73 19.68 14.32
2 34.16 30.63 24.35 20.83
3 52.01 38.04 29.45 25.23
4 68.26 44.25 33.80 30.37
5 77.10 50.33 40.25 37.23
6 83.56 66.41 48.24 41.16
7 93.85 74.84 53.73 49.78
8 - 87.80 61.34 54.03
9 - 95.12 67.52 59.62
10 - - 74.17 64.51
11 - - 85.10 70.27
12 - - 96.10 78.92
Dissolution Data of Ambroxol HCl Tablets Prepared
with Xanthan gum In Different Concentrations
Dissolution profile of Ambroxol HCL (F5, F6, F7, F8
formulations)

58. CUMULATIVE
(%) RELEASE
Q
TIME
(T)
ROOT
( T)
LOG( %)
RELEASE
LOG
( T )
LOG
(%)
REMAIN
RELEASE
RATE
(CUMULA
TIVE %
RELEASE /
t)
1/CUM
%
RELEA
SE
PEPPAS
log Q/100
% Drug
Remaining
Q01/3 Qt1/3
Q01/3-
Qt1/3
0 0 0 - 2.000 - - - 100 4.642 4.642 0.000
10.62 0.5
0.707 1.026 -0.301 1.951 21.240 0.0942 -0.974 89.38 4.642 4.471 0.170
19.68
1 1.000 1.294 0.000 1.905 19.680 0.0508 -0.706 80.32 4.642 4.315 0.327
24.35
2 1.414 1.386 0.301 1.879 12.175 0.0411 -0.614 75.65 4.642 4.229 0.412
29.45
3 1.732 1.469 0.477 1.848 9.817 0.0340 -0.531 70.55 4.642 4.132 0.510
33.8
4 2.000 1.529 0.602 1.821 8.450 0.0296 -0.471 66.2 4.642 4.045 0.596
40.25
5 2.236 1.605 0.699 1.776 8.050 0.0248 -0.395 59.75 4.642 3.909 0.732
48.24
6 2.449 1.683 0.778 1.714 8.040 0.0207 -0.317 51.76 4.642 3.727 0.915
53.73
7 2.646 1.730 0.845 1.665 7.676 0.0186 -0.270 46.27 4.642 3.590 1.052
61.34
8 2.828 1.788 0.903 1.587 7.668 0.0163 -0.212 38.66 4.642 3.381 1.260
67.52 9 3.000 1.829 0.954 1.512 7.502 0.0148 -0.171 32.48 4.642 3.191 1.451
74.17 10 3.162 1.870 1.000 1.412 7.417 0.0135 -0.130 25.83 4.642 2.956 1.686
85.1 11 3.317 1.930 1.041 1.173 7.736 0.0118 -0.070 14.9 4.642 2.461 2.181
96.1 12 3.464 1.983 1.000 0.591 8.008 0.0104 -0.017 3.9 4.642 1.574 3.068
Table: Release kinetics data for optimized formulation

59. Zero order release kinetics graph Higuchi release kinetics graph

60. Kars mayer peppas graph First order release kinetics graph

61. Conclusion:
In the present work, an attempt has been made to develop sustained release
tablets of ambroxol HCl by selecting different grades of xanthan gum and
Guar gum as retarding polymers. All the formulations were prepared by direct
compression method using 9mm punch on 8 station rotary tablet punching
machine. The blend of all the formulations showed god flow properties such
as angle of repose, bulk density, tapped density. The prepared tablets were
shown good post compression parameters and they passed all the quality
control evaluation parameters as per I.P limits. Among all the formulations F7
formulation showed maximum % drug release i.e., 96.10 % in 12 hours
hence it is considered as optimized formulation.

62. Summary:
• Graphs of Ambroxol HCl were taken in Simulated Gastric fluid (pH 1.2)
and in pH 6.8 phosphate buffer at 240 nm.
• Tablet powder blend was subjected to various pre-formulation parameters.
The angle of repose values indicates that the powder blend has good flow
properties.
• The bulk density of all the formulations was found to be in the range of
0.36 to 0.59 (gm/cm3) showing that the powder has good flow properties.
• The tapped density of all the formulations was found to be in the range of
0.49 to 0.67 showing the powder has good flow properties.

63. • The compressibility index of all the formulations was found to be ranging
Between 12 to 16 which shows that the powder has good flow properties.
• All the formulations has shown the hausner ratio ranging between 0 to 1.2
indicating the powder has good flow properties.
• All the parameters such as weight variation, friability, hardness and drug
content were found to be within limits.
• From the dissolution data it was evident that the formulations prepared with
Guar gum as polymer retard the drug release up to desired time period i.e.
12 hours and showed 91.23% in 12 hrs.
• Whereas the formulations prepared Xanthan gum retarded the drug release
in the concentration of 90 mg showed required release pattern i.e. retarded
the drug release up to 12 hrs. And showed maximum of 96.10% in 12 hrs.
With good retardation.

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