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Liquisolid Technology:
The concept of liquisolid compacts can be used to formulate liquid medication such as oily liquid drug and solutions or suspensions of water-insoluble solid drugs in non-volatile vehicles, into acceptably flowing and compressible powders.5

Using this new formulation technique, a liquid medication may be converted into a dry-looking, non-adherent, free flowing and readily compressible powder by a simple blending with selected powder excipients referred to as carrier and coating materials. Various grades of cellulose, starch, lactose, etc, may be used as the carrier, whereas a very fine particle size silica powder may be used as the coating material. Liquisolid compacts are acceptably flowing and compressible powdered forms of liquid medications and they are industrially applicable.

In addition, the term “liquid medication” does not only imply drug solutions, as in “powdered solutions”, but also drug suspensions, emulsions, or liquid oily drugs. Therefore, in contrast to “powdered solutions”, the term “liquisolid compacts” is more general and it may encompass for different formulation systems, namely, “powdered drug solutions”, “powdered drug suspensions”, “powdered drug emulsions”, and “powdered liquid drug”. Furthermore, the older term of “powdered solutions” seems to be inadequate even in describing the original systems, since it has not been proven that the remains in solutions in the liquid vehicle after its deposition on the extremely large powder surfaces of silica used.

The various definition and terms which are used in liquisolid technology are:
Liquid medication: Includes liquid lipophilic drugs and drug suspensions or solutions of solid water insoluble drugs in suitable non-volatile solvent systems.

Liquisolid systems: Refers to powdered forms of liquid medications formulated by converting liquid lipophilic drugs or drug suspensions or solutions of water insoluble solid drugs in suitable nonvolatile solvent systems, into dry, non-adherent, free-flowing and readily compressible powder admixtures by blending with selected carrier and coating materials.

Carrier material: These are compression-enhancing, relatively large, preferably porous material possessing sufficient absorption properties which contributes in liquid absorption. e.g. Microcrystalline and amorphous cellulose,various grades of cellulose, starch, lactose, sorbitol, Avicel PH 102 and 200, Eudragit RL and RS, amorphous cellulose etc.6,7,8

Coating material: Refers to a material possessing fine and highly adsorptive particles, such as various types of silica, which contributes in covering the wet carrier particles and displaying a dry looking powder by adsorbing any excess liquid.These are flow-enhancing, very fine (10 nm to 5,000 nm in diameter) particles. e.g. silica of various grades like Cab-O-Sil M5, Aerosil 200, Syloid 244FP etc.

Non-volatile solvents: Inert, high boiling point, preferably water-miscible and not highly viscous organic solventsystems. Various non-volatile solvents used for the formulation of liquisolid systems includepolyethylene glycol 200 and 400, glycerin, polysorbate 80 and propylene glycol, liquid polyethylene glycol, polysorbate, glycerin, N, N dimethylacetamide, fixedoils etc.

Disintegrants: Disintegrants are those materials which are required to disintegrate the tablet after administration inside the body.Most commonly used Disintegrants is sodium starch glycolate (Explotab13, Pumogel etc.).

Preparation of liquisolid tablets:
The calculated quantities of drug and non-volatile liquid are accurately weighed in a glass beaker and then the beaker is sonicated for homogeneous mixing. The resulting medication is incorporated into other beaker Calculated quantities of carrier and coating materials are added and stirring is done completely. Later each selected liquisolid formula is blended with certain amount of superdisintegrant (used in formulations) and prepared liquisolid systems that are proved to have acceptable flowability and compressibility are compressed into tablets of desired weight using press with appropriate diameter of punch and die.9

Fig: preparation of liquisolid tablets

Classification of liquisolid systems:
Based on the type of liquid medication contained therein, liquisolid systems may be classified into three sub-groups:
1)Powdered drug solutions
2)Powdered drug suspensions
3)Powdered liquid drugs

Powdered drug solutions and suspensions may be produced by the conversion of drug solutions or drug suspensions into liquisolid systems and powdered liquid drugs are produced from the formulation of liquid drugs into liquisolid systems. Simultaneously, based on the formulation technique used, liquisolid systems may be classified into two categories namely,
· Liquisolid compacts
· Liquisolid Microsystems

The term “liquisolid compacts” refers to immediate or sustained release tablets or capsules prepared, combined with the inclusion of appropriate adjuvants required for tabletting or encapsulation, such as lubricants, and for rapid or sustained release action, such as Disintegrants or binders, respectively.

The term “liquisolid Microsystems” refers to capsules prepared by combining the drug with carrier and coating materials, combined with inclusion of an additive e.g., PVP in the liquid medication wherein the resulting unit size may be as much as five times that of liquisolid compacts.

Wettability of liquisolid tablet:-
Wetting is the ability of a liquid to maintain contact with a solid surface, resulting from intermolecular interactions when the two are brought together. The degree of wetting (wettability) is determined by a force balance between adhesive and cohesive forces.The wettability of the compacts by the dissolution media is one of the proposed mechanisms for explaining the enhanced dissolution rate from the liquisolid compacts. Non-volatile solvent present in the liquisolid system facilitates wetting of drug particles by decreasing interfacial tension between dissolution medium and tablet surface.

Figure shows lower contact angle of liquisolid compacts than the conventional tablets and thus improved wettability.

Fig: Wettability of liquisolid tablet

1. Liquisolid systems are low cost formulations than soft gelatin capsules.
2. Drug release can be modified using suitable formulation ingredients
3. Drug can be molecularly dispersed in the formulation.
4. Industrial production is also possible.
5. Enhanced bioavailability can be obtained as compared to conventional tablets.
6. Several slightly, very slightly water-soluble, practically water-insoluble liquid and solid drugs can be formulated into liquisolid systems.
7. Even though the drug is in a tablet or capsule form, it is held in a solubilised liquid state, which contributes to increased drug wetting properties, thereby enhancing drug dissolution.

  1. Rapid release liquisolid tablets or capsules of water insoluble drugs exhibit enhanced in-vitro and in-vivo drug release when compared to their commercial counter parts, including soft gelatincapsules preparation.
  2. Sustained release liquisolid tablets or capsules of water insoluble drugs exhibit constant dissolution rates (zero-order release) comparable only to expensive commercial preparations that combine osmotic pump technology and laser-drilled tablets.10,
  3. Can be applied to formulate liquid medications such as oily liquid drugs.
  4. Better availability of an orally administered water insoluble drug.
  5. Production of liquisolid systems is similar to that of conventional tablets.
  6. Can be used for formulation of liquid oily drugs.
  7. Can be used in controlled drug delivery.10

1. Not applicable for formulation of high dose insoluble drugs.
2. If more amount of carrier is added to produce free-flowing powder, the tablet weight increases to more than one gram which is difficult to swallow.
3. Acceptable compression properties may not be achieved since during compression liquid drug may be squeezed out of the liquisolid tablet resulting in tablets of unsatisfactory hardness.
4. Introduction of this method on industrial scale and to overcome the problems of mixing small quantities of viscous liquid solutions onto large amounts of carrier material may not be feasible.


Solubility and dissolution improvement:
In order to overcome the limited solubility of the pharmaceuticals, these are formulated as liquisolid tablets. The method of preparation of liquisolid tablets as well as the effect of various formulation and processing variables on the preparation and the release properties of the tablets are studied by number of scientists. This technique is successfully applied for low dose water insoluble drugs. However, formulation of the high dose insoluble drugs as liquisolid tablets is one of the limitations of the liquisolid technique. In fact, when the therapeutic dose of drug is more than 50 mg, dissolution enhancement in the presence of low levels of hydrophilic carrier and coating material is not significant. But by adding some materials such as polyvinyl pyrrolidone (PVP) to liquid medication (Microsystems), it would be possible to produce dry powder formulations containing liquid with high concentration of drug. By adding such materials to the liquid medication, low amount of carrier is required to obtain dry powder with free flow ability and good compatibility.11

Flowability and compressibility:
Liquisolid compacts possess acceptable flow ability and compressibility properties. They are prepared by simple blending with selected powder excipients referred to as the carriers and the coating materials. Many grades of cellulose, starch, lactose, etc. can be used as carriers, whereas silica’s of very fine particle size can be used as coating materials.

In order to have acceptable flow ability and compatibility for liquisolid powder formulation, high levels of carrier and coating materials should be added and that in turn will increase the weight of each tablet above 1 gm which is very difficult to swallow. Therefore, in practice it is impossible with conventional method to convert high dose drugs to liquisolid tablet with the tablet weight of less than 1 gm.

In such systems, the drug existed in a molecular state of subdivision and systems were free flowing, on-adherent, dry looking powders. In further studies, compression enhancers were added to these powdered solutions like microcrystalline cellulose. However, the compression of these latter systems resulted in a significant ‘Liquid Squeezing Out’ phenomenon

In this system liquid medication is to be mixed with the excipients and then compressed to tablets. It was proved that the smaller the drug concentration in the liquid medication, the more rapid the release rates, since drugs in a high concentration tend to precipitate within the polymers pores .Polymers possessing large surface areas, and diluents like microcrystalline cellulose of fine particle size and granular grades produced good flow and compression properties, resulting in acceptable tablets.

Designing of sustained release tablet:
Development of sustained release oral dosage forms is beneficial for optimal therapy in terms of efficacy, safety and patient compliance. Ideally, a controlled release dosage form will provide therapeutic concentration of the drug in the blood that is maintained throughout the dosing interval. There are several techniques for the preparation of sustained release formulations, among which control of drug dissolution is one of the best and most successful methods due to its simplicity and low cost. To achieve this aim, several methods have been developed such as preparation of salt form of drug, coating with special materials and incorporation of drugs into hydrophobic carriers.

Liquisolid technique is a new and promising method that can change the dissolution rate of drugs. It is claimed that if hydrophobic carriers such as Eudragit RL and RS are used instead of hydrophilic carries in liquisolid systems, sustained release systems can be obtained. Therefore, it is suggested that the method have the potential to be optimized for the reduction of drug dissolution rate and thereby production of sustained release systems.

Bioavailability improvement:
In the liquisolid and powdered solution systems the drug might be in a solid dosage form, it is held within the powder substrate in solution, or in a solubilised, almost molecularly dispersed state. Therefore, due to their significantly increased wetting properties and surface of drug available for dissolution, liquisolid compacts of water- insoluble substances may be expected to display enhanced drug release properties, and consequently, improved bioavailability.

Mechanism of enhanced drug release from liquisolid systems:
The three recommended mechanisms include an increased surface area of drug available for release, an increased aqueous solubility of the drug, and an improved wettability of the drug particles.

Increased drug surface area:
When the drug within the liquisolid system is absolutely dissolved in the liquid vehicle it is positioned in the powder substrate in a solubilised, molecularly dispersed state. Therefore, the surface area of drug available for release is much greater than that of drug particles within directly compressed tablets.

Consequently, with increasing drug content beyond the solubility limit and thus, increasing fraction of undissolved drug in the liquid vehicle the release rate decreases. It has been pragmatic with various drugs that the release rates are directly proportional to the fraction of the molecularly dispersed drug (FM) in the liquid formulation. FM is defined by Spireas as the ratio between the drug's solubility (Sd) in the liquid vehicle and the actual drug concentration (Cd) in this vehicle carried by each system.

Sd/Cd Where FM =1 if Sd ≥ Cd

Increased aqueous solubility of the drug:
In addition to the first mechanism of drug release enhancement it is expected that Cs, the solubility of the drug, might be increased with liquisolid systems. In fact, the relatively small amount of liquid vehicle in a liquisolid compact is not sufficient to increase the overall solubility of the drug in the aqueous dissolution medium. However, at the solid/liquid interface between an individual liquisolid primary particle and the release medium it is possible that in this microenvironment the amount of liquid vehicle diffusing out of a single liquisolid particle together with the drug molecules might be sufficient to increase the aqueous solubility of the drug if the liquid vehicle acts as a co solvent. The overall increase in the solubility of drugs caused by liquisolid system.



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