Solubility enhancement technique of BCS Class II drug by Solvent Evaporatiom

“SOLUBILITY ENHANCEMENT TECHNIQUE OF BCS
CLASS II DRUG BY SOLVENT EVAPORATION TECHNIQUE
–
FORMULATION & EVALUATION
PRESENTED BY –
MR.KAUSTAV DEY
REGD. NO. – 1703267065
SEMESTER- 8TH
UNDER THE ESTEEMED GUIDANCE OF -
DR. GOUTAM KUMAR JENA
M.PHARM , Ph.D.
ASSOCIATEPROFESSORCUMPLACEMENTOFFICER

C O N T E N T S
1. Introduction
2. Literature Review
3. Aim of the Study
4. Objectives of the Study
5. Plan of Work
• Pharmaceutical Buffer preparation
• Formulation
• Dissolution study
• Solubility study
6. Results & Conclusion
7. References
ROLAND INSTITUTE OF PHARMACEUTICAL SCIENCES
1

I N T R O D U C T I O N
• The enhancement of oral bioavailability of poorly water-
soluble drugs remains one of the most challenging aspects of
drug development.
• The most commonly used techniques to increase dissolution
rate are particle size reduction, salt formation and
lyophilization, but all these methods have practical limitations
like improper enhancement of solubility and all the drugs are
not suitable for these techniques.
• To overcome all these, solid dispersion technique by solvent
evaporation approach is successfully applied to improve the
solubility and dissolution rate, there by bioavailability.
2

L I T E R A T U R E R E V I E W
Sr.
No.
Drugs Additives Preparation
Technique
Solubility/dissolution improvement Reference
1 Glimepiride Arginine Neat grinding A significant increase in the solubility of glimepiride in phosphate buffer pH
6.8 was observed for the eutectic mixture when compared to the drug alone.
An increase in the dissolution rate was also observed.
(Park et al.,
2020)
2 Celecoxib Adipic acid
or Saccharin
Liquid-assisted
grinding
The eutectic samples showed improved solubility in distilled water compared
to pure drug. In the IDR assay, the dissolved amounts of celecoxib in eutectic
mixtures were higher than the isolated drug and revealed the eutectic’s
dissolution rate. Powder dissolution studies showed that both eutectics
presented a significant higher dissolution profiles than raw celecoxib and
physical mixtures, in different media
(Hyun et al.,
2019)
3 Nimesulide Nicotinamid Solvent
Evaporation
Drying)
The solubility rise of eutectic sample was almost 14 times in distilled water
compared to pure drug. A significant improvement of solubility of the
mixture was also observed in other media (0.1 N HCl, phosphate buffer pH
and simulated gastric fluid). Comparison of dissolution profiles revealed that
prepared eutectic showed higher drug release (43.49%) compared to pure
drug (24.30%) within one hour
(Patel et al.,
2019)
4 Ibuprofen Poloxamer Melting/cooling
followed by
grinding
In vitro dissolution studies showed dissolution rate enhancement for eutectic
mixtures in different media. The most pronounced effect was seen for
mixture of ibuprofen: poloxamer (1:0.75) in acidic medium where the
cumulative drug release was 58.27% while for drug, it was 3.67%.
(Dugar et al.,
2016)
5 Glicazide Succinic Acid Electrospray
deposition and
liquid-assisted
grinding
Dissolution profiles obtained in acidic medium pH 1.2 showed that the
eutectic mixtures performed better than raw gliclazide. DE90min values were
significantly higher for eutectic samples. The dissolution rate of formulated
eutectic mixtures with Pluronic F68 and mannitol markedly was improved.
(Emami et al.,
2018)
.

A I M O F T H E S T U D Y
• The aim of this present investigation is to enhance solubility of
Ibuprofen by formulating as solid dispersions.
• To effectuate this formulation, solubility trials are performed
with carrier like Ethyl Cellulose (EC) to enhance the solubility,
dissolution rate and consequently bioavailability of the drug.
• Further various molecular weight grades of these polymers are
used to prepare the solid dispersion.
3

O B J E C T I V E S O F T H E S T U D Y
Solubility and Dissolution enhancement of Ibuprofen by using Ethyl Cellulose
(EC) polymer with the help of Solvent evaporation method
Comparing dissolution of formulated Drug-polymer complex with raw drug
To evaluate the drug release from the tablets prepared with solid dispersion
by invitro dissolution studies.
Choosing appropriate Drug-polymer complex ratio among various ratios.
The study is intended to select the best possible ratio of drug and polymer.
The impact of polymers ratio on various properties of the tablet will be
determined
4

P L A N O F W O R K
Pharmaceutical
Buffer
Preparation
Formulation of
Various Drug
Polymer complex
1.Dissolution
Study
1.Solubility Study
5

PHARMACEUTICAL BUFFER PREPARATION
KH2PO4
(28.2 g)
K2HPO4
(11.45 g)
Distilled Water
(1000 ml)
Standard
Phosphate Buffer
Stock Solution
(pH 6.8)
Buffer Solution (10 ml)
+
Drug(10 mg)
2 ml was taken out
Volume made upto 1000 ml
(50 times dilution= 20 µg/ml)
2 µg/ml
4 µg/ml
6 µg/ml
8 µg/ml
10 µg/ml
Blank
Solution
6

PHARMACEUTICAL BUFFER PREPARATION (contd.)
Concentration Absorbance
10 0.022
20 0.044
30 0.065
40 0.087
50 0.109
y = 0.0022x + 0.0003
R² = 0.9999
0
0.02
0.04
0.06
0.08
0.1
0.12
0 10 20 30 40 50 60
Absorbance
Concentration
Standard Calibration Curve of Ibuprofen in
Phosphate Buffer(pH 6.8)
7

F O R M U L A T I O N
Drug + Polymers
in different ratios
Sieved through
Sieve #100
1.Mixed with
solvent
1.Kept in Hot air
Oven
2.(40°-45°C for
30 min)
1.Trituration of
solid mass
1.Kept in
Dessicator for 48
hrs
8

F O R M U L A T I O N ( c o n t d . )
Formulation
Drug: Polymer
Ratio
Drug Polymer Total Weight
F1 1:1 400 mg 400 mg 800 mg
F2 1:2 400 mg 800 mg 1200 mg
F3 1:3 400 mg 1200 mg 1600 mg
F4 1:4 400 mg 1600 mg 2000 mg
9

D I S S O L U T I O N S T U D Y
100 mg Equivalent Solid
dispersions obtained from
each formulation
Mixed with standard
Phosphate buffer stock
solution (pH 6.8)
USP Dissolution Apparatus- II
(37°±0.5°C/60 min/50 rpm)
At every 15 min intervals for
the next 1 hour, solution was
withdrawn & replaced with
5ml PB 6.8 solution
Filtered & 1ml solution is
procured and diluted to 10
ml with PB 6.8 solution
UV Absorbance measured
% cumulative drug release
was calculated
Compared with raw drug by
data visualization
10

D I S S O L U T I O N S T U D Y ( c o n t d . )
Time(in
minutes)
Pure
Drug
F1 F2 F3 F4
15 0.106 0.141 0.142 0.174 0.138
30 0.087 0.051 0.088 0.104 0.089
45 0.096 0.029 0.051 0.051 0.103
60 0.083 0.082 0.058 0.105 0.058
Time (in
minutes)
Pure
Drug
F1 F2 F3 F4
0 0 0 0 0 0
15 49 55 65 75 66
30 51 59 68 79 71
45 62 65 70 87 73
60 65 69 71 93 81
Time v/s Absorbance
Chart of Dissolution
% Cumulative drug release
of Various Formulations
11

D I S S O L U T I O N S T U D Y ( c o n t d . )
12
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
%
RELEASE
TIME (IN MINUTES)
% CUMMULATIVE DRUG RELEASE
Pure Drug F1 F2 F3 F4

S O L U B I L I T Y S T U D Y
10 mg Equivalent Solid dispersions
Mixed with 20 ml water
Kept in Mechanical Shaker for 24 hrs at 25°C
Filtered & 1ml solution is procured and diluted to 10 ml with PB 6.8
solution
UV Absorbance measured & compared with raw drug
13

S O L U B I L I T Y S T U D Y ( c o n t d . )
Solution Absorbance
Pure drug 0.101
F1 0.137
F2 0.156
F3 0.178
F4 0.166
14
0.101
0.137
0.156
0.178
0.166
0
0.02
0.04
0.06
0.08
0.1
0.12
0.14
0.16
0.18
0.2
Pure drug F1 F2 F3 F4
Solubility Study

R E S U L T S & C O N C L U S I O N
• The drug release from solid dispersions were in the order of
F3>F4>F2>F1>Pure Drug.
• In case of physical mixtures prepared in the ratio of 1:3 of drug
polymer (Ibuprofen: Ethyl cellulose) ratio shows better release
than other drug polymer ratios. Thus, F3 is the best suitable
formulation among all other formulations.
• The result of present study clearly indicated promising
potential of solid dispersion of Ibuprofen and ethyl cellulose
by solvent evaporation method in enhancing the solubility and
from these methods could be viewed as alternative to
conventional method of solubility enhancement of poorly
soluble drugs.
15

R E F E R E N C E S
1. . Alex, R., & Bodmeier, R. (1990). Encapsulation of water-soluble drugs by a modified solvent evaporation method. I. Effect of process and
formulation variables on drug entrapment. Journal of Microencapsulation, 7(3), 347-355. https://doi.org/10.3109/02652049009021845
2. Amasya, G., Badilli, U., Aksu, B., & Tarimci, N. (2016). Quality by design case study 1: Design of 5-fluorouracil loaded lipid nanoparticles by the
W/O/W double emulsion - Solvent evaporation method. Eur J Pharm Sci, 84, 92-102. https://doi.org/10.1016/j.ejps.2016.01.003
3. Arabi, H., Hashemi, S. A., & Fooladi, M. (1996). Microencapsulation of allopurinol by solvent evaporation and controlled release investigation of
drugs. Journal of Microencapsulation, 13(5), 527-535. https://doi.org/10.3109/02652049609026038
4. Asghari-Varzaneh, E., Shahedi, M., & Shekarchizadeh, H. (2017). Iron microencapsulation in gum tragacanth using solvent evaporation method.
Int J Biol Macromol, 103, 640-647. https://doi.org/10.1016/j.ijbiomac.2017.05.047
5. Assimopoulou, A. N., Papageorgiou, V. P., & Kiparissides, C. (2003). Synthesis and release studies of shikonin-containing microcapsules prepared
by the solvent evaporation method. Journal of Microencapsulation, 20(5), 581-596. https://doi.org/10.3109/02652040309178348
6. Badmeier, R., & Chen, H. (1993). Hydrolysis of Cellulose Acetate and Cellulose Acetate Butyrate Pseudolatexes Prepared by a Solvent
Evaporation-Microfluidization Method. Drug Development and Industrial Pharmacy, 19(5), 521-530.
https://doi.org/10.3109/03639049309062964
7. Bodmeier, R., & McGinity, J. W. (1987). Polylactic acid microspheres containing quinidine base and quinidine sulphate prepared by the solvent
evaporation technique. I. Methods and morphology. Journal of Microencapsulation, 4(4), 279-288. https://doi.org/10.3109/02652048709021820
8. Choi, J. S., Lee, S. E., Jang, W. S., Byeon, J. C., & Park, J. S. (2018). Solid dispersion of dutasteride using the solvent evaporation method:
Approaches to improve dissolution rate and oral bioavailability in rats. Mater Sci Eng C Mater Biol Appl, 90, 387-396.
https://doi.org/10.1016/j.msec.2018.04.074
9. Deng, Y., Yang, F., Zhao, X., Wang, L., Wu, W., Zu, C., & Wu, M. (2018). Improving the skin penetration and antifebrile activity of ibuprofen by
preparing nanoparticles using emulsion solvent evaporation method. Eur J Pharm Sci, 114, 293-302. https://doi.org/10.1016/j.ejps.2017.12.024
10. Deshmukh, R., Wagh, P., & Naik, J. (2016). Solvent evaporation and spray drying technique for micro- and nanospheres/particles preparation: A
review. Drying Technology, 34(15), 1758-1772. https://doi.org/10.1080/07373937.2016.1232271

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