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B y
M r . M e g h r a j S u r y a w a n s h i ,
M r s . S h e f a l i D h a v a d e
G u i d e
D r . S . B . B u m r e l a
S i n h g a d I n s t i t u t e o f P h a r m a c e u t i c a l S c i e n c e s
K u s g a o n ( B k ) l o n a v a l a ,
P u n e - 4 1 0 4 0 1
“LIQUISOLID TECHNIQUE AS A TOOL FOR
ENHANCEMENT OF DISSOLUTION PROFILE OF
POORLY SOLUBLE DRUG: LORNOXICAM”
1
INTRODUCTION
 Solubility is defined as the concentration of the solute in a
saturated solution at specified condition.
 The drug solubility in solution is static property and drug
dissolution rate is dynamic property.
 Solubility is one of the important parameters to achieve
desired concentration of drug in systemic circulation for
achieving pharmacological response.
 Currently only 8% of new drug candidates have both high
solubility and permeability.
2
NEED AND OBJECTIVES
 NEED OF PRESENT INVESTIGATION:
 Liquisolid compact are used to enhance the solubility
and dissolution rate of poorly water soluble drugs.
 Lornoxicam is non-steroidal anti-inflammatory drug
(NSAIDS) that belongs to oxicam class and is freely
soluble in NaOH, whereas it is practically insoluble in
water.
 It is belongs to (CLASS II) drugs which are poorly
soluble, highly permeable.
3
OBJECTIVES
 To enhance the solubility of poorly water soluble drug like Lornoxicam.
 To formulate and evaluate liquisolid compact of Lornoxicam.
 To compare dissolution profile of liquisolid compact of Lornoxicam
with conventional tablets of Lornoxicam.
 To study the effect of different concentration of nonvolatile vehicle used
on drug release.
 To study the effect of different ratios of carrier and coating material
used on drug release.
4
Method of liqui-solid compact
Lornoxicam +
Non-volatile
vehicle
(PG, PEG,
Cremophor EL)
Carir (Avicel PH
102) + Coating
material
(Cab-O-Sil M5)
Disintegrant
(polyplasdone
XL-10)
Powder
Mixture
Compact/
Tablet
Addition Trituration
Mixing for 10min
Direct
Compression
5
Optimization
 Effect of different drug concentration in liquid vehicle on drug release
from lornoxicam liquisolid compacts by direct compression method
 Effect of different ratios of carriers on drug release of lornoxicam
liquisolid compact.
6
Characterization
 Pre-compression study
 FTIR
 DSC
 Flow properties
 Compact/tablet evaluation
 Weight variation
 Hardness
 Assay
 Content uniformity
 Friability
 In-vitro disintegration
 In-vitro dissolution
7
Saturation solubility data of lornoxicam
Solvents Solubility (mg/ml)
Cremophor-EL 0.842 mg/ml
Propylene glycol 0.2842 mg/ml
Polyethylene glycol- 400 0.75 mg/ml
Water 0.0003 mg/ml
8
Determination of angle of slide for various excipients
9
Flowable liquid retention potential for carrier and coating
material (Φ- value)
Excipient
Φ Value
PEG400 Propylene glycol CremophorEL
Avicel102 0.005 0.16 0.27
Cab-o-sil M-5 3.26 3.31 0.9
10
Liquid load factor different ratios of carrier and coating
material (Φ- value)
Sr. No
Liquid
vehicle
R value Lf value
1 PG
10 0.491
20 0.325
2 PEG400
10 0.331
20 0.168
3 Cremophor EL
10 0.360
20 0.315
11
Lornoxicam Liquisolid tablet evaluation
Liquisolid system tablet evaluation
LS
Tab.
weight
(mg)
Diameter
(mm)
Thickness
(mm)
Width
(mm)
Length
(mm)
Hardness
(N)
D.T
(min)
LS-1 136 ±5 3.8 ±0.2 4.5 ±0.2 8.1 ±0.2 40-50 1.5 ±0.3
LS-2 177±5 8.1 ±0.2 3.2 ±0.2 40-50 1.5 ±0.3
LS-3 90±5 2.7 ±0.2 4.5 ±0.2 8.1 ±0.2 40-50 2.1 ±0.3
LS-4 188±5 8.1 ±0.2 3.3 ±0.2 40-50 1.39 ±0.3
LS-5 68±5 5.3 ±0.2 2.4 ±0.2 40-50 2.8 ±0.3
LS-6 88±5 2.6 ±0.2 4.5 ±0.2 8.1 ±0.2 40-50 1.4 ±0.3
LS-7 181±5 8.1 ±0.2 3.3 ±0.2 40-50 1.53 ±0.3
LS-8 304±5 9.1 ±0.2 4.7 ±0.2 40-50 1.52 ±0.3
LS-9 121±5 3.6 ±0.2 4.5 ±0.2 8.1 ±0.2 40-50 1.5 ±0.3
LS-10 202±5 8.1 ±0.2 4.1 ±0.2 40-50 2.1 ±0.3
LS-11 90±5 2.7 ±0.2 4.6 ±0.2 8.1 ±0.2 40-50 1.31 ±0.3
LS-12 152±5 8.1 ±0.2 3.1 ±0.2 40-50 1.53 ±0.3
LS-13 170±5 8.1 ±0.2 3.1 ±0.2 40-50 1.22 ±0.3
LS-14 182±5 8.1 ±0.2 3.2 ±0.2 40-50 1.56 ±0.3
LS-15 113±5 3.1 ±0.2 4.5 ±0.2 8.1 ±0.2 40-50 1.45 ±0.3
LS-16 121±5 3.4 ±0.2 4.6 ±0.2 8.1 ±0.2 40-50 2.11 ±0.3
LS-17 85±5 2.4 ±0.2 4.5 ±0.2 8.1 ±0.2 40-50 1.39 ±0.3
LS-18 90±5 2.7 ±0.2 4.5 ±0.2 8.1 ±0.2 40-50 1.49 ±0.3
DCT 100 ±5 3.1 ±0.2 4.4 ±0.2 8.1 ±0.2 40-50 1.39 ±0.3
12
Assay, Content uniformity and Friability data for
lornoxicam liquisolid tablet
Liquisolid System % Assay
Content
Uniformity (%)
Friability (%)
LS-1 89.31± 5 97.2 ± 2 0.126
LS-2 105.6 ± 4.1 98.2 ± 3.1 0.156
LS-3 96.25 ± 3.5 101.2 ± 2.1 0.135
LS-4 106.2 ± 4.6 99.2 ± 1.1 0.128
LS-5 91 ± 5.3 99 ± 1.6 0.102
LS-6 95.2 ± 2 98.3 ± 1.3 0.11
LS-7 96.8 ± 6 97.9 ±2.1 0.187
LS-8 100.6 ± 3.2 100.2 ±3.1 0.17
LS-9 108.7 ± 6.3 100.6 ± 2.1 0.131
LS-10 90.8 ± 5.2 101 ± 1.5 0.0152
LS-11 96.8 ± 6.1 98.9 ± 1.6 0.166
LS-12 100.6 ± 1.5 99.2 ± 1.3 0.162
LS-13 101.25 ± 4 99.8 ± 1.4 0.103
LS-14 98.75± 2.6 100.6 ± 2.4 0.0891
LS-15 100.62 ± 2.5 100.1 ±2.1 0.126
LS -16 94.3 ± 3.6 98.6 ± 2.6 0.156
LS-17 96.25 ±4.8 97.8 ± 2.7 0.105
LS-18 99.37 ± 3.7 100.1 ± 1.9 0.154
DCT 100 ± 6.1 99.2 ± 2.3 0.013
13
14
Conclusion
 The studies suggested that lower drug concentration in Cremophor EL
gives enhanced dissolution profile.
 LS-LXM-14 formulation showed complete release of drug within 10min
in phosphate buffer pH 7.4 dissolution media.
 Powder substrate ratio(R=20) was found to give good release profile as
compare to other ratioR20>R10.
 The present investigation showed that liquisolid formulation can be
used to enhance the solubility of poorly soluble drug like LXM.
15
References
 Jain P, Goel A, Sharma S. and Parmar M. Solubility enhancement techniques with special
emphasis on hydrotrophy. International Journal of Pharmacy Research. 2010; 1(1):34-45.
 Yellela S. Pharmaceutical technologies for enhancing oral bioavailability of poorly
soluble drugs. Journal of Bioequivalence and Bioavailability. 2010; 29(2):028 – 036.
 Vemula V, Lagishetty V and Lingala S. Solubility enhancement techniques. International
Journal of Pharmaceutical Science Review and Research. 2010; 5(1): 41 – 51.
 Mohanachandran P, Sindhumol P. and Kiran T. Enhancement of solubility and
dissolution rate: An overview, International Journal of Comp. Pharmacy.2010;4(1): 1-10.
 Aulton M. Pharmaceutics: The science of dosage form design. 2nd Edition. USA: Churchill
Livingstone.2002; 15.
16

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Liquisolid technique as a tool for enhancement

  • 1. B y M r . M e g h r a j S u r y a w a n s h i , M r s . S h e f a l i D h a v a d e G u i d e D r . S . B . B u m r e l a S i n h g a d I n s t i t u t e o f P h a r m a c e u t i c a l S c i e n c e s K u s g a o n ( B k ) l o n a v a l a , P u n e - 4 1 0 4 0 1 “LIQUISOLID TECHNIQUE AS A TOOL FOR ENHANCEMENT OF DISSOLUTION PROFILE OF POORLY SOLUBLE DRUG: LORNOXICAM” 1
  • 2. INTRODUCTION  Solubility is defined as the concentration of the solute in a saturated solution at specified condition.  The drug solubility in solution is static property and drug dissolution rate is dynamic property.  Solubility is one of the important parameters to achieve desired concentration of drug in systemic circulation for achieving pharmacological response.  Currently only 8% of new drug candidates have both high solubility and permeability. 2
  • 3. NEED AND OBJECTIVES  NEED OF PRESENT INVESTIGATION:  Liquisolid compact are used to enhance the solubility and dissolution rate of poorly water soluble drugs.  Lornoxicam is non-steroidal anti-inflammatory drug (NSAIDS) that belongs to oxicam class and is freely soluble in NaOH, whereas it is practically insoluble in water.  It is belongs to (CLASS II) drugs which are poorly soluble, highly permeable. 3
  • 4. OBJECTIVES  To enhance the solubility of poorly water soluble drug like Lornoxicam.  To formulate and evaluate liquisolid compact of Lornoxicam.  To compare dissolution profile of liquisolid compact of Lornoxicam with conventional tablets of Lornoxicam.  To study the effect of different concentration of nonvolatile vehicle used on drug release.  To study the effect of different ratios of carrier and coating material used on drug release. 4
  • 5. Method of liqui-solid compact Lornoxicam + Non-volatile vehicle (PG, PEG, Cremophor EL) Carir (Avicel PH 102) + Coating material (Cab-O-Sil M5) Disintegrant (polyplasdone XL-10) Powder Mixture Compact/ Tablet Addition Trituration Mixing for 10min Direct Compression 5
  • 6. Optimization  Effect of different drug concentration in liquid vehicle on drug release from lornoxicam liquisolid compacts by direct compression method  Effect of different ratios of carriers on drug release of lornoxicam liquisolid compact. 6
  • 7. Characterization  Pre-compression study  FTIR  DSC  Flow properties  Compact/tablet evaluation  Weight variation  Hardness  Assay  Content uniformity  Friability  In-vitro disintegration  In-vitro dissolution 7
  • 8. Saturation solubility data of lornoxicam Solvents Solubility (mg/ml) Cremophor-EL 0.842 mg/ml Propylene glycol 0.2842 mg/ml Polyethylene glycol- 400 0.75 mg/ml Water 0.0003 mg/ml 8
  • 9. Determination of angle of slide for various excipients 9
  • 10. Flowable liquid retention potential for carrier and coating material (Φ- value) Excipient Φ Value PEG400 Propylene glycol CremophorEL Avicel102 0.005 0.16 0.27 Cab-o-sil M-5 3.26 3.31 0.9 10
  • 11. Liquid load factor different ratios of carrier and coating material (Φ- value) Sr. No Liquid vehicle R value Lf value 1 PG 10 0.491 20 0.325 2 PEG400 10 0.331 20 0.168 3 Cremophor EL 10 0.360 20 0.315 11
  • 12. Lornoxicam Liquisolid tablet evaluation Liquisolid system tablet evaluation LS Tab. weight (mg) Diameter (mm) Thickness (mm) Width (mm) Length (mm) Hardness (N) D.T (min) LS-1 136 ±5 3.8 ±0.2 4.5 ±0.2 8.1 ±0.2 40-50 1.5 ±0.3 LS-2 177±5 8.1 ±0.2 3.2 ±0.2 40-50 1.5 ±0.3 LS-3 90±5 2.7 ±0.2 4.5 ±0.2 8.1 ±0.2 40-50 2.1 ±0.3 LS-4 188±5 8.1 ±0.2 3.3 ±0.2 40-50 1.39 ±0.3 LS-5 68±5 5.3 ±0.2 2.4 ±0.2 40-50 2.8 ±0.3 LS-6 88±5 2.6 ±0.2 4.5 ±0.2 8.1 ±0.2 40-50 1.4 ±0.3 LS-7 181±5 8.1 ±0.2 3.3 ±0.2 40-50 1.53 ±0.3 LS-8 304±5 9.1 ±0.2 4.7 ±0.2 40-50 1.52 ±0.3 LS-9 121±5 3.6 ±0.2 4.5 ±0.2 8.1 ±0.2 40-50 1.5 ±0.3 LS-10 202±5 8.1 ±0.2 4.1 ±0.2 40-50 2.1 ±0.3 LS-11 90±5 2.7 ±0.2 4.6 ±0.2 8.1 ±0.2 40-50 1.31 ±0.3 LS-12 152±5 8.1 ±0.2 3.1 ±0.2 40-50 1.53 ±0.3 LS-13 170±5 8.1 ±0.2 3.1 ±0.2 40-50 1.22 ±0.3 LS-14 182±5 8.1 ±0.2 3.2 ±0.2 40-50 1.56 ±0.3 LS-15 113±5 3.1 ±0.2 4.5 ±0.2 8.1 ±0.2 40-50 1.45 ±0.3 LS-16 121±5 3.4 ±0.2 4.6 ±0.2 8.1 ±0.2 40-50 2.11 ±0.3 LS-17 85±5 2.4 ±0.2 4.5 ±0.2 8.1 ±0.2 40-50 1.39 ±0.3 LS-18 90±5 2.7 ±0.2 4.5 ±0.2 8.1 ±0.2 40-50 1.49 ±0.3 DCT 100 ±5 3.1 ±0.2 4.4 ±0.2 8.1 ±0.2 40-50 1.39 ±0.3 12
  • 13. Assay, Content uniformity and Friability data for lornoxicam liquisolid tablet Liquisolid System % Assay Content Uniformity (%) Friability (%) LS-1 89.31± 5 97.2 ± 2 0.126 LS-2 105.6 ± 4.1 98.2 ± 3.1 0.156 LS-3 96.25 ± 3.5 101.2 ± 2.1 0.135 LS-4 106.2 ± 4.6 99.2 ± 1.1 0.128 LS-5 91 ± 5.3 99 ± 1.6 0.102 LS-6 95.2 ± 2 98.3 ± 1.3 0.11 LS-7 96.8 ± 6 97.9 ±2.1 0.187 LS-8 100.6 ± 3.2 100.2 ±3.1 0.17 LS-9 108.7 ± 6.3 100.6 ± 2.1 0.131 LS-10 90.8 ± 5.2 101 ± 1.5 0.0152 LS-11 96.8 ± 6.1 98.9 ± 1.6 0.166 LS-12 100.6 ± 1.5 99.2 ± 1.3 0.162 LS-13 101.25 ± 4 99.8 ± 1.4 0.103 LS-14 98.75± 2.6 100.6 ± 2.4 0.0891 LS-15 100.62 ± 2.5 100.1 ±2.1 0.126 LS -16 94.3 ± 3.6 98.6 ± 2.6 0.156 LS-17 96.25 ±4.8 97.8 ± 2.7 0.105 LS-18 99.37 ± 3.7 100.1 ± 1.9 0.154 DCT 100 ± 6.1 99.2 ± 2.3 0.013 13
  • 14. 14
  • 15. Conclusion  The studies suggested that lower drug concentration in Cremophor EL gives enhanced dissolution profile.  LS-LXM-14 formulation showed complete release of drug within 10min in phosphate buffer pH 7.4 dissolution media.  Powder substrate ratio(R=20) was found to give good release profile as compare to other ratioR20>R10.  The present investigation showed that liquisolid formulation can be used to enhance the solubility of poorly soluble drug like LXM. 15
  • 16. References  Jain P, Goel A, Sharma S. and Parmar M. Solubility enhancement techniques with special emphasis on hydrotrophy. International Journal of Pharmacy Research. 2010; 1(1):34-45.  Yellela S. Pharmaceutical technologies for enhancing oral bioavailability of poorly soluble drugs. Journal of Bioequivalence and Bioavailability. 2010; 29(2):028 – 036.  Vemula V, Lagishetty V and Lingala S. Solubility enhancement techniques. International Journal of Pharmaceutical Science Review and Research. 2010; 5(1): 41 – 51.  Mohanachandran P, Sindhumol P. and Kiran T. Enhancement of solubility and dissolution rate: An overview, International Journal of Comp. Pharmacy.2010;4(1): 1-10.  Aulton M. Pharmaceutics: The science of dosage form design. 2nd Edition. USA: Churchill Livingstone.2002; 15. 16