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Liquisolid drug delivery system

Introduction:-The term Liquisolid Technique is a:-Novel concept of drug delivery.Drugs belonging to Biopharmaceutics classification system(BCS) Class II (poor water solubility).Suitable for lipophilic and water insoluble drug.Changes the dissolution rate of water insoluble drug.

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Liquid medication such as solutions or suspensions of water insoluble drug in suitable non-volatile liquid vehicle can be easily converted into powder with acceptable flow properties and compression behaviour using suitable powder excipients.

By the use of this technique a liquid medication is converted into a dry-looking ,non-adherent ,free flowing and readily compressible powder by a simple blending with a powder excipient

Better bioavailability of poorly soluble drug achived when drug is present in solution as in liquisolid formulation.

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Need Of Liquisolid Technique:- For poorly soluble,insoluble liquid drugs or

lipophilic drug. For poorly flowable powder admixture. To aid direct compression. To improve efficiency of tablet

manufacturing.

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Materials Used In Preparation Of Liquisolid System:-

Drugs:Poorly soluble or insoluble in water .e.g,Hydrocortisone,Hydrochlorothiazide.

Non-volatile Solvent:Hydrophilic or Lipophilic nature.Selection of solvent based on type of formulation like immediate or control release.Water miscible and not highly viscous organic solvent system are suitable as vehicle.e.g. Propylene glycol, Polyethylene glycol,Tween 80,20, Span 80,20etc.

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Carrier Material: Coarser and granular for acceptable flow. Preferably porous particles possessing a sufficient absorption property.

e.g,cellulose,lactose,sorbitol.etc.

Coating Material:

These are flow enhancing ,very fine(10nm to 5,000nm in diameter)

Highly absorptive coating particles.(e.g ,various grades of silica)

Disintegrant: Most commonly Sodium Starch Glycolate is used.

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Mathematical Model For Designing Liquisolid System:-

To achieve good flow behaviour and compressibility of liquisolid system a mathematical model designed by Spireas et al. was used as formulation designed model for the liquisolid tablet.This model is based on new fundamental properties of powder called ‘’Flowable Liquid Retaintion Potential’’(Φ value) and

”Compressible Liquid Retaintion Potential’’(Ψ value) of powder excipient used in formulation.

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Excipients Ratio (R) : R=Q/q

Where,R represents the ratio between the weights of carrier (Q) and coating material(q).

Liquid Load Factor(Lf):Lf=W/Q

Where, Lf is the ratio of liquid medication(W) to weight of carrier material(Q) in system.

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Cont…

The Liquid Load factor (Lf) to produce acceptable flowability can be determined by:

Lf = Φ + φ.(1/R)

Where, Φ and φ are the Φ-values (Flowable Liquid Retaintion Potential) of the carrier and coating material, respectively.

Similarly,the Liquid Load factor for production of liquisolid system with acceptable compactability (ΨLf ) can be determined by:

ΨLf= Ψ + Ψ .(1/R)

Where, Ψ and Ψ are the Ψ values(Compressible Liquid Retaintion Potential) of the carrier and coating matrial, respectively.

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Method Of Prepration:-Both solid as well as liquid drugs can be used for prepration of liquisolid tablet.If the drug is solid it must be initially dissolved or supended in a suitable non-volatile solvent to produce drug solution or suspension .The prepared drug solution or suspension or liquid drug is incorporated into carrier material.Carrier material should be of porous nature and possessing sufficient absorption properties.

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Cont… Resultant wet mixture converted into a dry-

looking ,non-adherent,free flowing and readily compressible powder by addition of coating material.

Mixing is an important step in formulation as it distributes the liquid medication in powder.

Also allows the drug solution to be absorbed in the interior of powder particles.

This formulation is compressed.11

Liquid Medication

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Solid

Drug

Non-volatile Solvent system

Drug solution or Drug Suspension

Liquid

drug

orCrrier Materi

al

Coating

Material

Wet Particle

s

Liquisolid

systemFinal

FormulationTabletting

Fig: Steps involved in prepration of Liquisolid system

Mechanisms Of Enhanced Drug Release From Liquisolid System:-

Incresaed surface area.Increased aqueous solubility of drug.Improved wetting properties.

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Table : Formulations of liquisolid systems with enhanced drug release

Drug Liquid Vehicle Carrier & Coating Material

Hydrochlorothiazide

PEG 200 MCC + Magnesium carbonate & Colloidal Silica

Hydrocortisone PG MCC & Colloidal Silica

Carbamazepine PEG 200 MCC & Colloidal Silica

Nifedipine PEG 400 MCC and Colloidal silica with HPMC

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Table : Optimization of formulation parameters for liquisolid systems with enhanced drug release

Sr. No

Formulation parameters

Optimization Effect

1. Liquid vehicle High drug solubility in vehicle

Increased fraction of the molecularly dispersed drug .

2. Carrier and Coating material

High specific surface area

Increased Liquid load factor (Lf)

3. Addition of excipient Polyvinyl pyrollidone (PVP) Superdisintegrant

Increased liquid load factor (Lf), Increased viscosity of liquid vehicle.

4 Excipient ratio (R) High R-value Fast disintegration

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Evaluation Of Liquisolid System:-

Pre-compression Studies:Flow Properties.Differentail Scanning Calorimetry.X-Ray Diffraction.Scanning Electron Microscopy.

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Post-compression Studies:

Tablet Dimensions.Tablet Hardness.Friability.Weight Variation Test.Disintegration Test.Dissolution Test.

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ADVANTAGES OF LIQUISOLID SYSTEMS:-

Number of water-insoluble solid drugs can be formulated into liquisolid systems.

Better availability of an orally administered water insoluble drug.

Lower production cost than that of soft gelatin capsules

Production of liquisolid systems is similar to that of conventional tablets.

Exhibits enhanced in-vitro and in-vivo drug release as compared to commercial tablets.

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Cont… Can be used in controlled drug delivery. Drug release can be modified using suitable

formulation ingredients . Drug can be molecularly dispersed in the

formulation. Capability of industrial production is also possible. Enhanced bioavailability can be obtained as

compared to conventional tablets.

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LIMITATIONS:- Low drug loading capacities. Requirement of high solubility of drug in non-volatile

liquid vehicles. To achieve aceeptable flowability and compactabilty of

liquisolid powder formulation high level of carrier and coating material should be added.

This will increases weight of tablet to above one gram. Results in difficulty to swallowing. Not applicable for formulation of high dose insoluble

drug. 20

Application Of Liquisolid System:- Solubility and dissolution improvement.

Improvement in Flowability and Compressability:

Excipients possessing large surface area,fine particle size produces good flow and compression properties.

Bioavailabilty Improvement:Due to increased in wetting properties and surface availble

for dissolution ,this technique enhances drug release.

For Designing Of Sustain Release Tablet

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References:-1. Ajit S. Kulkarni*, Nagesh H. Aloorkar, Madhav S. Mane and

Jayashree B. Gaja Liquisolid Systems. Volume 3 April – June 2010.

2. Shashidher Burra*, Madhusudhanrao Yamsani, Venkateswarlu Vobalaboina, The Liquisolid technique: an overview, Brazilian Journal of Pharmaceutical Sciences ,vol. 47, n. 3, jul./sep., 2011,Pg.no:476-479.

3. Spireas S, Jarowski CI, B Rohera. Powdered Solution Technology: Principles and Mechanism. Pharm Res 1992; 9: 1351-1358.

4. Karmarkar AB, Gonjari AD, Hosmani AH. Liquisolid Technology for dissolution rate enhancement or sustained release. Expert Opin Drug Del 2010; 7: 1227-1234.

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5. Sambasiva Rao. A*, Naga Aparna. T*, Liquisolid Technology: An Overview, International Journal of Research in Pharmaceutical and Biomedical Sciences, Vol. 2 (2) Apr – Jun 2011,Pg.no:402-408.

6. Spireas S. Liquisolid System and method of preparing same. U.S Patent 6423339B1, 2002.

7. Vijay kumar Nagabandi*, T.Ramarao, K.N.Jayaveera,LIQUISOLID Compacts: A Novel Approach to Enhance Bioavailability of Poorly Soluble Drugs, International Journal of Pharmacy and Biological Sciences, Volume 1, JULY-SEPT, 2011,89-102.

THANK YOU…

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