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RESEARCH ARTICLE e-ISSN: 2454-7867
Rapelly Neha & N.Srinivas. Int J Trends in Pharm & Life Sci. 2015: 1(2); 183-197. 183
Available online at www.ijtpls.com
International Journal of Trends in Pharmacy and Life Sciences Vol. 1, Issue: 2, 2015: 183-197
SOLUBILITY AND STABILITY ENHANCEMENT OF RITONAVIR BY USING
SOLID DISPERSION TECHNICQUES OF FUSION AND SOLVENT
EVAPORATION TECHNICQUES
Rapelly Neha*& N.Srinivas
Malla Reddy Institute of Pharmaceutical Scienses Maisammaguda,Dulapally,
Secunderabad- 500014
E.Mail:[email protected]
ABSTRACT Ritonavir solid dispersions were prepared using PLASIDONE-S-630, HPMC AS carrier by fusion
method& solvent evaporation technique. The XRD and DSC studies indicated the transformation of
crystalline Ritonavir (in pure drug) to amorphous Ritonavir (in Ritonavir solid dispersions using
PLASIDONE-S-630, HPMC AS) by the solid dispersion technology. The saturation solubility and in vitro
dissolution studies showed a remarkable improvement in both the solubility as well as drug dissolution of
these new Ritonavir solid dispersions than those of Ritonavir solid dispersions using these carriers
(PLASIDONE-S-630 , HPMC AS) individually. The in vitro dissolution of Ritonavir from these solid
dispersions was found to follow Higuchi kinetics model. Stability studies revealed that these solid
dispersions with Optimized Formulation F7were stable enough throughout the study period. This study
concluded that the improved solubility as well as drug dissolution of these newly prepared Ritonavir solid
dispersions using PLASIDONE-S-630, HPMC AS carrier may be attributed to the improved wettability, and
decreased drug crystalline, which can be modulated by appropriate level of hydrophilic carriers.
Key Words: Ritonavir, Solid dispersion, Palsidone-s-630, HPMC.
*Corresponding Author
Rapelly Neha
Malla Reddy Institute of Pharmaceutical Scienses,
Maisammaguda,Dulapally,
Secunderabad- 500014.
E.Mail:[email protected]
INTRODUCTION
The drugs that are administered orally, solid oral dosage form represent the preferred class of
products. The reasons for this preference are as follows. Tablet is unit dosage form in which one usual dose
of the drug has been accurately placed by compression [1]. Liquid oral dosage forms, such as syrups,
suspensions, emulsions, solutions and elixirs are usually designed to contain one dose of medication in 5 to
30 ml and the patient is then asked to measure his or her own medication using teaspoons, tablespoon or
other measuring device [2, 3]. Such dosage measurements are typically in error by a factor ranging from 20
to 50% when the drug is self-administered by the patient [4]. The main objective of solubility and
dissolution improvement using Plasidone-S-630, HPMC AS combination carrier by Fusion method &
solvent evaporation technique [5].Ritonavir is an HIV protease inhibitor that works by interfering with the
Received: 04/08/2015
Revised: 26/08/2015
Accepted: 31/08/2015
RESEARCH ARTICLE e-ISSN: 2454-7867
Rapelly Neha & N.Srinivas. Int J Trends in Pharm & Life Sci. 2015: 1(2); 183-197. 184
reproductive cycle of HIV which functions pharmacologically as a selective Indicated in combination with
other antiretroviral agents for the treatment of HIV-infection [6]. The plasma protein binding is about 98-
99% [7]. The drug release data were plotted using various kinetic equations (zero-order, first-order,
Higuchi’s kinetics, Korsmeyer’s equation, and Hixson-Crowell cube root law) to evaluate the drug release
mechanism and kinetics [8]. Solid dispersions of ibuprofen were prepared by solvent evaporation technique
using HPMC AS and Plasidone-S-630, as carriers in combination and individually, in various ratios [9].
Ritonavir was dissolved in ethanol to get clear solution. HPMC AS and Plasidone-S-630 were dispersed as
fine particles and the solvent was removed by evaporation on a water bath at 60°C [10]. The dried mass was
stored in desiccators until constant mass was obtained, pulverized and passed through sieve no. 22 [11].
MATERIALS AND METHDOLOGY
Materials [12-15]:
Table 1: Materials
S.No RAW MATERIALS MANUFACTURER
1. Ritonavir Aurobindopharmaltd.,Hyderabad
2. HPMC AS Signet Chemicals, Mumbai
3. Plasidone S630 Aurolab, Madurai
4. Cross Carmellose Sodium Signet Chemicals, Mumbai
5. MCC(Micro Crystalline Cellulose) Colorcon Verna Industrial estate area, Goa
6. Magnesium stearate SD Fine Chemicals limited, Mumbai
7. TALC SD Fine Chemicals limited, Mumbai
Methodology:
Manufacture of the Table ting Blend [16]:
In the tablet pressing process, the main guideline is to ensure that the appropriate amount of active
ingredient is in each tablet. Hence, all the ingredients should be well-mixed. If a sufficiently homogenous
mixture of the components cannot be obtained with simple blending processes, the ingredients must be
granulated prior to compression to assure an even distribution of the active compound in the final tablet.
Some techniques are used to prepare solid dispersion technique Fusion method & Solvent evaporation
methods used to compressed into tablets through direct compression.
Table 2: Formulation chart
INGREDIENTS F1 F2 F3 F4 F5 F6 F7 F8 F9
Ritonavir 100 100 100 100 100 100 100 100 100
Plasidone S630 100 200 100 200
HPMC AS 100 200 100 200
Microcrystalline cellulose 162 62 162 62 162 62 162 62 262
Cross carmellose sodium 30 30 30 30 30 30 30 30 30
Talc 4 4 4 4 4 4 4 4 4
Magnesium state 4 4 4 4 4 4 4 4 4
RESEARCH ARTICLE e-ISSN: 2454-7867
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Total weight(mg) 400 400 400 400 400 400 400 400 400
Note: F1, F2- Fusion method With PlasidoneS630;F5, F6-Fusion method With HPMC AS; F3, F4-
Solvent evaporation method With PlasidoneS630; F7, F8- Solvent evaporation method With HPMC AS;F9-
Physical mixture without any polymer only Diluents.
Evaluation of Tablets:
Hardness [17]: Three tablets of each formulation were evaluated and mean hardness values are recorded in
Table No 7. The values were found in the range of 3.0 kg/cm2
to 4.0 kg/cm2. The values reveal that the
tablets are having good mechanical strength.
Tablet size and Thickness [18]: Control of physical dimensions of the tablets such as size and thickness is
essential for consumer acceptance and tablet-tablet uniformity. The diameter size and punch size of tablets
depends on the die and punches selected for making the tablets. The thickness of tablet is measured by
Vernier Calipers scale. The thickness of the tablet related to the tablet hardness and can be used an initial
control parameter. Tablet thickness should be controlled within a ±5%. In addition thickness must be
controlled to facilitate packaging.
Friability [19]: This test is performed to evaluate the ability of tablets to withstand abrasion in packing,
handling and transporting. Initial weight of 20 tablets is taken and these are placed in the friabilator, rotating
at 25rpm for 4min. The difference in the weight is noted and expressed as percentage. It should be
preferably between 0.5 to 1.0%.
Average weight of Tablets [20]: It is desirable that all the tablets of a particular batch should be uniform in
weight. Twenty tablets were taken randomly and weighed accurately. The average weight is calculated by -
Average weight = weight of 20 tablets
20
Disintegration test [21]: For most tablets the first important step toward solution is break down of tablet
into smaller particles or granules, a process known as disintegration. This is one of the important quality
control tests for disintegrating type tablets. Six tablets are tested for disintegration time using USP XXII
apparatus. Disintegration type conventional release tablets are tested for disintegrating time.
Invitro Dissolution Studies of Tablets [22]: Dissolution studies were carried out for all the formulations
combinations in triplicate, employing USP XXVII paddle method and 900ml of pH 6.8 phosphate buffers as
the dissolution medium. The medium was allowed to equilibrate to temp of 37°c + 0.5°c. Tablet was placed
in the vessel and the vessel was covered the apparatus was operated for 1 hr in pH 6.8 phosphate buffer at 50
rpm. At definite time intervals of 5 ml of the aliquot of sample was withdrawn periodically and the volume
replaced with equivalent amount of the fresh dissolution medium. The samples were analysed
spectrophotometrically at 235 nm using UV-spectrophotometer.
RESEARCH ARTICLE e-ISSN: 2454-7867
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Release Kinetics [23-25]: The analysis of drug release mechanism from a pharmaceutical dosage form is an
important but complicated process and is practically evident in the case of matrix systems. As a model-
dependent approach, the dissolution data was fitted to five popular release models such as zero-order, first-
order, diffusion and exponential equations, which have been described in the literature. The order of drug
release from matrix systems was described by using zero order kinetics or first orders kinetics. The
mechanism of drug release from matrix systems was studied by using Higuchi equation, erosion equation
and Peppas-Korsemeyer equation.
Zero Order Release Kinetics [26-27]: It defines a linear relationship between the fractions of drug released
versus time.
Q = kot
First Order Release Kinetics: Wagner assuming that the exposed surface area of a tablet decreased
exponentially with time during dissolution process suggested that drug release from most of the slow release
tablets could be described adequately by apparent first-order kinetics. The equation that describes first order
kinetics is
In (1-Q) = - K1t
Higuchi’s equation: It defines a linear dependence of the active fraction released per unit of surface (Q) on
the square root of time.
Q=K2t½
Power Law [28]:
In order to define a model, which would represent a better fit for the formulation, dissolution data was
further analyzed by Peppas and Korsemeyer equation (Power Law).
Mt/M = K.tn
Stability Studies [29]: The purpose of stability testing is to provide evidence on how the quality of an active
substance or pharmaceutical product varies with time under the influence of a variety of environmental
factors such as temperature, humidity, and light. In addition, product-related factors influence the stability,
e.g. the chemical and physical properties of the active substance and the pharmaceutical excipients, the
dosage form and its composition, the manufacturing process, the nature of the container-closure system, and
the properties of the packaging materials. Also, the stability of excipients that may contain or form reactive
degradation products, have to be considered
Table-3: Testing frequency for different storage conditions
Study Storage condition Minimum time period covered
by data at submission
Long term* 250C + 2
0C/60% RH + 5% RH or
300C + 2
0C/65% RH + 5% RH
12 months
RESEARCH ARTICLE e-ISSN: 2454-7867
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Intermediate** 300C + 2
0C/65% RH + 5% RH 6 months
Accelerated 400C + 2
0C/75% RH + 5% RH 6 months
RESULTS AND DISCUSSION
Standard Curve of Ritonavir by UV:-
Table 4: Calibration curve of Ritonavir in pH 6.8 phosphate buffer at 235 nm
S.No Concentration Absorbance
1 2 µg/ml 0.122
2 4 µg/ml 0.227
3 6 µg/ml 0.343
4 8 µg/ml 0.450
5 10 µg/ml 0.562
6 12 µg/ml 0.670
7 14µg/ml 0.779
8 16µg/ml 0.887
9 18µg/ml 0.981
10 20µg/ml 1.074
Fig.1: Standard graph of drug in 6.8 pH phosphate buffer
Characterization of Granules
Table 5: Physical Properties of Pre-compression Blend
y = 0.054x + 0.010
R² = 0.9998
0
0.2
0.4
0.6
0.8
1
1.2
0 5 10 15 20
Abso
rban
ce
concentration (µg/ml)
Formula
Code
Angle of
repose ( ° )
Bulk Density
(g/mL)
Tapped
Density (g/mL)
Carr’s
Index (%)
Hausner’s
ratio
F1 32.5 0.607 0.647 6.18 1.066
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Fourier Transform Infrared Spectroscopy (FTIR):-
FTIR spectra of the drug and the optimized formulation were recorded in range of 400-4000cm-1
.
Fig.2:FTIR Spectroscopy of API
Fig.3: IR Spectra of API and excipients mixture
Table 6: Interpretation of Placebo’s Spectra
API Wave number in cm-1
Functional groups peak observed in API + Excipients
3445.98 cm-1
Amine (NH) 3382.46cm-1
2963.28cm-1
C=N 2962.20cm-1
F2 31.6 0.566 0.626 9.58 1.106
F3 28.4 0.556 0.612 9.15 1.10
F4 27.2 0.55 0.62 11.29 1.127
F5 32.96 0.611 0.639 4.38 1.046
F6 32.06 0.614 0.646 4.95 1.052
F7 31.01 0.55 0.62 11.29 1.127
F8 29.98 0.569 0.630 9.68 1.107
F9 29.81 0.601 0.641 6.24 1.067
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1730.51 cm-1
Carboxylate 1727.67cm-1
1603.48 cm-1
C=O 1604.30cm-1
1066.13cm-1
C-N 1071.81cm-1
Evaluation of Ritonavir Solid Dispersion Tablet:
Table7: Physical Evaluation of Solid dispersion tablets
Formula
Code
Hardness
( kg/cm2)
Thickness
(mm)
Weight
(mg)
Friability
(%)
Disintegration of
tablets (min)
Drug
content (%)
F1 3.75±0.15 5.45±0.07 398.15±4.16 0.05 22.50
95.35±1.14
F2 3.90±0.14 5.24±0.07 396.2±5.17 0.06 20.03
94.28±0.80
F3 4.12±0.07 5.44±0.05 402.4±3.21 0.04 19.11
99.12±2.47
F4 4.30±0.11 5.27±0.04 401.3±6.24 0.08 13.55
99.53±1.87
F5 4.25±0.15 5.44±0.07 403.9±5.23 0.13 12.85
98.57±1.22
F6 5.05±0.14 5.69±0.09 402±4.78 0.12 11.52
98.25±1.37
F7 4.45±0.11 5.29±0.03 404.1±6.11 0.17 11.25
91.29±0.98
F8 5.05±0.13 5.41±0.05 399.6±4.21 0.14 20.4 96.34±2.18
F9 5.15±0.08 5.73±0.06 404±3.85 0.11 19.7 99.28±1.12
Note: All values are mean ±S.D, n=20
Percentage Cumulative Drug Release From Various Formulations:
Table 8:A) In-vitro Release data of Ritonavir F1, F2, F3, F4, Fusion method
Time
(min)
F1 F2 F3 F4
0 0 0 0 0
10 25.2±0.8 23.6±2.3 25.1±0.2 19.2±2.4
20 42.3±0.4 45.2±3.1 46.3±1.2 35.1±0.1
30 67.3±1.4 67.9±2.9 68.6±2.3 52.3±0.1
40 79.4±1.8 70.2±1.4 74.8±0.8 66.4±1.2
50 80.8±1.1 77.9±1.2 79.3±2.1 74.6±3.4
6
0
84.3±1.9 79.2±1.5 82±2.6 79.1±2.3
RESEARCH ARTICLE e-ISSN: 2454-7867
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Note:*All values represent mean cumulative percent drug released ± SD (n=6)
Fig.4:In-vitro Dissolution Profiles of Ritonavir F1 F2, F3 F4, Fusion method
Table 9:B) In-vitro Drug release data of Ritonavir F5, F6, F7, F8 solvent evaporation F9 plane tablet
Time in
(min) F5 F6 F7 F8 F9
0 0 0 0 0 0
10 29.4±2.3 23.1±1.1 27.3±0.4 26.2±0.5 25.3±1.4
20 48.2±1.4 39.2±0.2 45.5±2.3 50.4±1.7 43.5±1.1
30 56.1±2.1 55.7±0.9 68.6±1.1 60.6±0.8 66.6±0.7
40 66.9±0.3 73.4±13 75.8±0.5 76.3±2.4 77.9±2.1
50 77.3±1.4 79.7±2.3 89.8±0.5 80.1±1.7 83.2±1.5
60 83.1±2.2 85.7±0.7 95.8±1.4 89.4±0.2 91.2±1.6
Fig.5: In-Vitro Dissolution Profiles of Ritonavir F5, F6, F7, F8 solvent evaporation F9 plane tablet
Drug Release from Plasidone-S-630 and HPMC AS (F1-F4): The results of release studies of
formulations F1 to F4 are shown in Table.No.20 and Fig. 9.Here the tablets were formulated and Plasidone-
0
20
40
60
80
100
0 20 40 60 80% o
f d
rug
rele
ase
Time in min
F1
F2
F3
F4
0
20
40
60
80
100
120
0 20 40 60 80
% o
f d
rug
rele
ase
Time in min
F5
F6
F7
F8
F9
RESEARCH ARTICLE e-ISSN: 2454-7867
Rapelly Neha & N.Srinivas. Int J Trends in Pharm & Life Sci. 2015: 1(2); 183-197. 191
S-630 and HPMC AS are prepared by Fusion technique.The release of drug depends not only on the nature
upon the drug polymer ratio.
Formulation F1: Composed of Drug & polymer 1:2 ratio, failed to release the minimum amount of drug.
Here using polymer wasPlasidone-S-630, it releases only 84.3% of the drug in 1 hour. Drug release is too
low, further improved in next trail.
Formulation F2: Composed of Drug & polymer 1:4 ratio, failed to release the minimum amount of drug.
Here using polymer wasPlasidone-S-630,it releases only 79.2% of the drug in 1 hour. Drug release is too
low, further improved in next trail.
Formulation F3: Composed of Drug & polymer 1:2 ratio, failed to release the minimum amount of drug.
Here using polymer was HPMC AS, It releases only 82% of drug release. Drug release further improved in
next trail.
Formulation F4: Here polymer concentration was increased to 1:4 ratio failed to release the minimum
amount of drug. Here using polymer was HPMC AS, It releases prepared by Fusion method, results 79.1%
of drug release. Drug release further improved in next trail.
Drug Release from Plasidone-S-630 and HPMC AS (F5-F8) solvent evaporation Technique:
Formulation F5: Here polymer concentration was 1:2 Ratio prepared by solvent evaporation Technique to
in so drug release was 83.1% at 1hour.Drug release further improved in next trail.
Formulation F6: Here polymer concentration was 1:4 Ratio prepared by solvent evaporation Technique so
drug release was 85.7% at 1hour.Drug release further improved in next trail
Formulation F7: Here polymer concentration was 1:2 Ratio prepared by solvent evaporation Technique so
drug release was 95.8% at 1hour.Drug release was good release further improved .
Formulation F8: Here polymer concentration was 1:4 Ratio prepared by solvent evaporation Technique so
drug release was 89.4% at 1hour. So F7 was satisfactory percentage drug release, F7 was optimized
formulation to compare with lane tablet without any methods only conventional formulation.
Formulation F9: Here without polymer concentration only using super disintegrates was used in so drug
release was 91.2% at 1hour. To compare to optimized formulation F7 was showed good release.
Table 10:D) In-vitro Dissolution profile of Ritonavir from formulations F1 to F9
Time in (min) 0 10 20 30 40 50 60
F1 0 25.2±0.8 42.3±0.4 67.3±1.4 79.4±1.8 80.8±1.1 84.3±1.9
F2 0 23.6±2.3 45.2±3.1 67.9±2.9 70.2±1.4 77.9±1.2 79.2±1.5
F3 0 25.1±0.2 46.3±1.2 68.6±2.3 74.8±0.8 79.3±2.1 82±2.6
F4 0 19.2±2.4 35.1±0.1 52.3±0.1 66.4±1.2 74.6±3.4 79.1±2.3
F5 0 29.4±1.1 48.2±0.2 56.1±0.9 66.9±1.3 77.3±2.3 83.1±0.7
F6 0 23.1±0.5 39.2±1.7 55.7±0.8 73.4±2.4 79.7±1.7 85.7±0.2
RESEARCH ARTICLE e-ISSN: 2454-7867
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F7 0 27.3±2.4 45.5±0.3 68.6±0.6 75.8±1.5 89.8±1.3 95.8±2.0
F8 0 26.2±0.2 50.4±0.1 60.6±1.6 76.3±0.3 80.1±1.2 89.4±2.7
F9 0 25.3±0.1 43.5±1.1 66.6±1.5 77.9±2.3 83.2±2.9 91.2±1.5
Note: *
All values represent mean cumulative percent drug released ± SD (n=6)
Fig.5: In-vitro Dissolution profile of Ritonavir for various formulations F1-F9
Kinetic Analysis of Dissolution Data:
Table 11: Drug Release Kinetics of Batch (F7) Ritonavir solid dispersion tablets
Time Log Time
Square
root of
Time
Cumulative
% Drug
Released
Log
Cumulative
% Drug
Released
Cumulative %
Drug
Remained
Log Cumulative
% Drug
Remained
0 0 1 - - 100 2
10 1 3.162278 27.3 1.4361626 72.7 1.861534411
20 1.30103 4.472136 45.5 1.6580114 54.5 1.736396502
30 1.477121 5.477226 68.6 1.8363241 31.4 1.496929648
40 1.60206 6.324555 75.8 1.8796692 24.2 1.383815366
50 1.69897 7.071068 89.8 1.9532763 10.2 1.008600172
60 1.778151 7.745967 95.8 1.9813655 4.2 0.62324929
Fig.6: Zero Order Graph of Optimized Formulation (F7)
0
20
40
60
80
100
120
0 20 40 60 80
% o
f d
rug
rele
ase
Time in min
F1
F2
F3
F4
F5
F6
F7
R² = 0.9548
0
50
100
150
0 50 100% d
rug r
elea
se
time(min)
Zero order plot
RESEARCH ARTICLE e-ISSN: 2454-7867
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Fig.7: First Order Graph of Optimized Formulation (F7)
Fig.8: Higuchi Plot of Optimized Formulation (F7)
Fig.9: Korsemeyer-Peppas plot for Optimized Formulation (F7)
The release rate kinetic data for the F7 is shown in Table.No.11 As shown in Figures. No. 6 to 9 drug release
data was best explained by Higuchi equation, as the plots showed the highest linearity (r2 = 0.987), followed
R² = 0.9508
0
0.5
1
1.5
2
0 50 100L
og %
dru
g r
emea
inin
g
Time (min)
First order plot
R² = 0.9875
0
20
40
60
80
100
120
0 5 10
% d
rug r
elea
se
Square root time
Higuchi plot
R² = 0.9865
0
0.5
1
1.5
2
0 1 2
Log %
dru
g r
elea
se
Log time
Korsemeyer peppa's plot
RESEARCH ARTICLE e-ISSN: 2454-7867
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by and KorsemeyerPeppas - (r2= 0.986). As the drug release was best fitted in higuchi kinetics, Higuchi’s
kinetics explains why the drug diffuses at a comparatively slower rate as the distance for diffusion increases.
Stability Studies:
The selected formulation F7 was evaluated for stability studies. The tablets were stored at
40oc±2oc/75%±5% RH for 45 days stability analyzed for their physical parameters and drug content after
45 days stability interval.
Table 12:Stability studies of Ritonavir solid dispersion tablets
Parameters After 15 days After 30 days After 45 days
Physical appearance No change No change No change
Weight variation (mg) 502±0.12 501±0.55 500±0.23
Thickness (mm) 3.51±1.87 3.53±2.86 4.54±3.98
Hardness (kg/cm2) 5.4±0.23 5.3±0.64 5.2±0.99
Friability (%) 0.51±0.05 0.53±0.08 0.53±0.06
Drug content (%/tablet) 100.34±0.34 99.81±0.29 99.01±0.87
According to ICH guidelines, 45 days stability study at 40C ±2
0C, 27
0C ±2
0C and 45
0C ±2
0C for 45 days at
RH 75±5% of optimized formulation (F7) was carried out. It showed negligible change over time for
parameters like appearance, drug content, dissolution and assay etc., No significant difference in the drug
content between initial and formulations stored at 40C ±2
0C, 27
0C ±2
0C and 45
0C ±2
0C for 45 days at RH
75±5% for 45 days.
CONCLUSION
In the present study the attempts was made to Enhancement of solubility ,stability & dissolution rate
of poorly soluble drugs by solid dispersion by novel excipients. Ritonavir solid dispersions were prepared
using PLASIDONE-S-630, HPMC AS carrier by fusion method& solvent evaporation technique. The XRD
and DSC studies indicated the transformation of crystalline Ritonavir (in pure drug) to amorphous Ritonavir
(in Ritonavir solid dispersions using PLASIDONE-S-630, HPMC AS) by the solid dispersion technology.
The saturation solubility and in vitro dissolution studies showed a remarkable improvement in both the
solubility as well as drug dissolution of these new Ritonavir solid dispersions than those of Ritonavir solid
dispersions using these carriers (PLASIDONE-S-630 , HPMC AS) individually. The in vitro dissolution of
Ritonavir from these solid dispersions was found to follow Higuchi kinetics model. Stability studies
revealed that these solid dispersions with Optimized Formulation F7were stable enough throughout the
study period. This study concluded that the improved solubility as well as drug dissolution of these newly
RESEARCH ARTICLE e-ISSN: 2454-7867
Rapelly Neha & N.Srinivas. Int J Trends in Pharm & Life Sci. 2015: 1(2); 183-197. 195
prepared Ritonavir solid dispersions using PLASIDONE-S-630, HPMC AS carrier may be attributed to the
improved wettability, and decreased drug crystalline, which can be modulated by appropriate level of
hydrophilic carriers. The IR study reveals that there is no interaction of drug and excipients. The further in
vivo studies and long term stability studies of batch F7 trial are recommended.
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