**2.2 Various forms of LS systems**

	- a. Powdered liquid drugs
	- b. Powdered drug solutions
	- c. Powdered drug emulsions
	- d. Powdered drug suspensions
	- a. LS compacts
	- b. LS microsystems

The two main formulation elements of LSCs are liquid medicine and powder substrate. The major components of the powder substrate are: (a) carrier particles that are preferably big and porous to improve compression; (b) coating material particles that are ideally very fine and highly adsorptive to improve flow.

The schematic representation of various steps involved in preparation of LS formulations is shown in **Figure 2**.

*Development of Liquisolid Compacts: An Approach for Dissolution Enhancement of Poorly… DOI: http://dx.doi.org/10.5772/intechopen.108706*

**Figure 2.**

*Representation of several stages involved in development of LS formulations.*

The amounts of various excipients required for the formulation of powder solutions are predicted using a novel mathematical model expression [9]. The absorbate molecules diffuse through the absorbent until they are eventually consumed by the powder particles inside their bulk, which causes the liquid to be absorbed. Adsorption is the phenomena where liquid is not really absorbed and the molecules merely cling to the solid's accessible surface, both internal and external, rather than being disseminated throughout the solid's interior. However, sorption is a mechanism where simultaneous occurrence of both of these processes occur which majorly depends on powder characteristics.

#### **2.3 Mechanisms for enhanced drug release in LS systems**

The mechanisms for enhanced drug release in LS systems include.


#### *2.3.1 Enhanced drug surface area*

Even if the drug particles are totally dissolved in the preferred hydrophilic nonvolatile solvent in the LS system, the drug is still present in the powder substrate, either in molecularly distributed or completely solubilized state. As a result, when compared to directly compacted tablets (DCTs), the surface area of the drug in LS systems is substantially higher. However, when the drug content rises, the solubility limit rises with it. Hence, as the amount of undissolved drug in the liquid carrier

increased, the rate of drug release decreased. Furthermore, the rate of drug release increases along with the proportion of molecularly dispersed drug (FM). Spireas' percentage of the molecularly dispersed drug is the ratio of drug solubility (Sd) in the liquid vehicle to the genuine drug concentration (Cd) in the liquid vehicle transported by each system (FM). It can be calculated using Eq. (1).

$$\text{FM} = \frac{\text{Sd}}{\text{Cd}} \tag{1}$$

where, FM is equal to 1, in case if Sd ≥ Cd.

#### *2.3.2 Enhanced aqueous/water solubility of drug*

A small volume of liquid vehicle in the LS formulation may not be sufficient in the case of the LS system to entirely solubilize the medication and increase drug solubility in dissolution medium. The solvent diffusing out of an LS particle is sufficient to increase the solubility of poorly aqueous soluble drugs in the dissolution medium at the interface microenvironment of the solid particle and liquid carrier, which is the most likely explanation for the increase in aqueous solubility of poorly aqueous soluble drugs [2]. It's also feasible that a small amount of the liquid carrier diffuses with the medication from the total amount, acting as a co-solvent to boost the drug's solubility in water.

#### *2.3.3 Enhanced wetting properties*

In the instance of the LS system, the wetting property is explained by measuring the contact angles as well as the water rising times. By lowering the interfacial tension between the powder/tablet surface and the dissolution medium, a non-volatile liquid vehicle aids in the wetting of drug particles in the system. The low contact angle of LSCs compared to conventional tablets proves improved wettability. The wettability of the LS system is improved by lowering the interfacial tension when the liquid vehicle acts as a surfactant. Water growing times and contact angles were used to demonstrate the wettability of the LS system.

By measuring the contact angles and the water rising times in the case of the LS system, the wetting property is described. A non-volatile liquid vehicle facilitates the wetting of drug particles in the system by reducing the interfacial tension between the surface of the powder or tablet and the dissolving media. The superior wettable quality of LSCs is demonstrated by their low contact angle when compared to traditional tablets. When the liquid vehicle functions as a surfactant, the interfacial tension is reduced, which enhances the wettability of the LS system. Water growth times and contact angles were employed to demonstrate the wettability of the LS system.

#### **2.4 Parameters affecting LS formulations**

#### *2.4.1 Basis of selection of excipients in LS technology*

The LS technology majorly deals with the selection of suitable carrier and coating materials that are mainly responsible for loading of drug in the liquid medication. This may be liquid drug or suspension of drug in a solvent or a solution of drug in suitable liquid (non-volatile) vehicle. This is further adsorbed on the porous carrier material.

#### *Development of Liquisolid Compacts: An Approach for Dissolution Enhancement of Poorly… DOI: http://dx.doi.org/10.5772/intechopen.108706*

A liquid layer starts forming on the surface of the particles, when once the carrier material is saturated with liquid, a moist or sticky blend is formed [10]. Dry and free flowing and compressible powder is obtained upon addition of dry coating material that physically exists in a very fine powder, instantly adsorbs fine layer of drug solution over the carrier material. Various forms of microcrystalline cellulose (such as MCC, Avicel PH101, Avicel PH102) are used as carrier materials and mostly amorphous silicon dioxide is used as coating material. Application of LS technique to poorly aqueous soluble drug enhances the drug release due to increased surface area of the drug, that in turn lead to increased solubility and improved wettability of the drug particles. The LS technology may also be applied to prolong the drug release. According to the principle, sustained release or extended release dosage forms provide desirable therapeutic plasma levels which are maintained throughout the therapy. It has been stated that usage of hydrophobic carriers like Eudragit® RL and RS instead of hydrophilic carriers or by addition of a matrix forming polymers like HPMC, sustained release formulations are developed. It was observed that the enhancement in solubility or release characteristics has been successfully improved in case of low dose poorly water-soluble drugs by the application of LS technology. The drug release rate is exactly proportional to the percentage of molecularly (FM) dispersed drug in the liquid vehicle, according to the main concept of LS technology [11].

It is obvious that only a definite amount of powder can absorb or absorb a limited volume of non-volatile solvent to preserve acceptable flow and compression properties. Hence, high amounts of carrier and coating materials are required in case of large volume of liquid medication if high dose drug is used. This result in increase in weight of the tablet eventually leads to formation of bulky tablet. Hence it is required to minimize tablet weight and increase the liquid adsorption capacity. By adding carrier and coating materials or binding agents to the liquid medication with a high specific surface area (SSA) liquid adsorption capacity is obtained. Therefore, higher the SSA of the carrier material, higher will be the liquid load factor. It has been stated that the liquid adsorption capacity of the granular cellulose that is experimental grade exhibits SSA of 24.22 m<sup>2</sup> /g which is higher than that of microcrystalline cellulose (MCC). Similarly, carrier materials such as Avicel PH102(SSA = 1.10 m<sup>2</sup> /g) and Avicel PH 101 (SSA = 1.07 m<sup>2</sup> /g) have been frequently used in the studies due to their higher SSA values. Moreover, it has to be highlighted that the physicochemical characteristics such as viscosity, polarity, lipophilicity and chemical structure of the liquid used for solubilizing or suspending the drug cannot be ignored which could also affect the adsorption capacity of both the carrier and coating materials. Subsequently, the liquid adsorption capacity of a blend of carrier and coating material not only depends on their SSA, but also depends on the liquid vehicle involved.

#### *2.4.2 Ratio of carrier and coating material (R) importance*

The pre-compression properties and drug release characteristics of LS systems increase from 5 to 1 to 50 to 1 for excipient ratios denoted by R. The reciprocal of the powder excipient ratios (1/R) and the liquid load factors (Lf) have a linear connection. The powder excipients ratio R affects the dissolving rate profiles of LS systems, with results visible within 5 minutes of the dissolution process against R values in the 5 to 20 range. At powder excipients ratios >20, the dissolving rates have risen proportionally to R until they reached an obvious maximum plateau. Lower R values should indicate medication dissolution patterns that are less than ideal. Increases in R excipient ratios cause a modest drop-in dissolution rate until the maximum degree of

dissolution is attained at R values of 35 to 45. The R values greater than 50 indicate that the drug solution was embedded during the formulation process.

Carrier agents are usually able to absorb the solvent in their interiors of matrices. The production of dry-looking, non-sticky liquid pharmaceuticals necessitates large quantities of these carriers. Due to its huge specific area in comparison to other carriers such as lactose and starch, Avicel PH 102 outperformed the others [12]. As a result, the unit size of LS tablets may vary depending on the composition of the carrier material. The more uniformly the drug is adsorbed on the coated material or absorbed into the carrier material, the higher the concentration of Avicel PH 102. The strength and cohesiveness of the LSCs are provided by the H-bonds on the cellulose molecules in Avicel PH 102. Compression transforms them plastically, creating a potent compact [13].

A surface-active substance called polysorbate 80 aids in drug particle wetting by lowering the interfacial tension between the LSC surface and the dissolving solution. As a result, it has been discovered that one of the primary explanations for an increase in dissolving rate is an increase in the wetting qualities of LSCs created by the dissolution media. More uniform drug distribution in the carrier medium was indicated by higher R values, which ranged from 30 to 60 [14].
