ORODISPERSIBLE LIQUISOLID COMPACTS: A NOVEL APPROACH TO ENHANCE SOLUBILITY AND BIOAVAILABILITY

ABOUT AUTHORS
VINOTH KUMAR P 1,
*RAJALAKSHMI A.N.1, STEPHEN P2
1Department of Pharmaceutics, College Oof Pharmacy, Mother Theresa Postgraduate And Research Institute of Health Sciences, Puducherry-6, India
1 Department of Pharmaceutics, College of Pharmacy, Mother Theresa Postgraduate And Research Institute of Health Sciences, Puducherry-6
, India
2 Formulation Research and Development, Sai Mirra Innopharm Pvt Ltd., Chennai, India

*ocusertraji@gmail.com

ABSTRACT:
Orodispersible liquisolid system is the combination of liquisolid technique and orodispersible system. The poor dissolution rate of water insoluble drug is a major drawback for the development of pharmaceutical dosage forms. The oral absorption of drug is most often controlled by dissolution in the gastrointestinal tract. Liquisolid system has been used to enhance dissolution rate of poorly water-soluble drugs. Orodispersible tablets are given in order to provide fast action by disperse in the mouth, without the need of water and make them compliance for paediatric and geriatric patients and to bypass the liver metabolism.

INTRODUCTION
The oral route remains the preferred route of drug administration due to its convenience, good patient compliance and low production costs. In order for a drug to be absorbed into the systemic circulation following oral administration, the drug must be dissolved in the gastric fluids (Munke and Nagarsenker, 2004). For hydrophobic drugs, the dissolution process acts as the rate-controlling step and which determines the rate and degree of absorption. Bioavailability of poorly water soluble drugs is limited by their solubility and dissolution rate (Nazzal and Khan, 2006)

Liquisolid technique is a new and promising method that can change the dissolution rate of drugs. It has been used to enhance dissolution rate of poorly water-soluble drugs. The new ‘liquisolid’’ technique may be applied to formulate liquid medications (i.e. oily liquid drugs and solutions, suspensions or emulsions of water-insoluble solid drugs carried in non-volatile liquid vehicles) into powders suitable for tableting or encapsulation. Since, the liquisolid tablets contain a solution of the drug in suitable solvent; the drug surface available for dissolution is tremendously increased (Javadzadeh and Nokhodchi, 2008)

The concept of orodispersible tablet emerged with an objective to improve patient’s compliance. These dosage forms rapidly disintegrate and/or dissolve to release the drug as soon as they come in contact with saliva, thus without the need for water during administration, an attempts that makes them highly attractive for paediatric and geriatric patients (Kaushik et al 2004). When put in the mouth, these dosage forms disintegrate instantly to release the drug, which dissolves or disperses in the saliva. Thereafter, the drug may get absorbed from the pharynx and oesophagus or from other sections of GIT as the saliva travels down. In such cases, bioavailability is significantly greater than that observed from conventional tablet dosage form (Mudgal and Singhai, 2011)

LIQUISOLID SYSTEM
This technique was first introduced by Spireas et al. and applied to incorporate water insoluble drugs into rapid release solid dosage forms. The term “liquisolid compacts” as described by Spireas et.al indicates that immediate or sustained release tablets or capsules that are prepared using the technique of “liquisolid systems” combined with the inclusion of appropriate adjuvants required for tabulating or encapsulation such as lubricants and for rapid or sustained release action, such as disintegrate or binders, respectively (Shashidher and  Veer,2012)

CONCEPT OF LIQUISOLID SYSTEM
When the drug dissolved in the liquid vehicle is incorporated into a carrier material which has a porous surface and closely matted fibres in its interior such as celluloses, both absorption and adsorption take place. The liquid initially absorbed in the interior of the particles is captured by its internal structure. After the saturation of this process, adsorption of the liquid onto the internal and external surfaces of the porous carrier particles occurs. Then, the coating material having high adsorptive properties and large specific surface area provides the liquisolid system the desirable flow characteristics (Sambasiva and Naga, 2011).

In liquisolid systems, the drug is already in solution form in liquid vehicle, while at the same time, it is carried by powder. The wettability of the compacts in the dissolution media is one of the proposed mechanisms for explaining the enhanced dissolution rate from the liquisolid compacts.

THEORETICAL CONCEPT OF LIQUISOLID SYSTEM
FIG-1:THEORETICAL CONCEPT OF LIQUISOLID SYSTEM

Non-volatile solvent present in the liquisolid system facilitates wetting of drug particles by decreasing interfacial tension between dissolution medium and tablet surface. Thus, due to substantial increase in wettability and effective surface area for dissolution, liquisolid compacts may be expected to reveal enhanced release profiles of water-insoluble drugs.

MATHEMATICAL MODEL TO DESIGN LIQUISOLID SYSTEM:
For getting good flow behaviour and compressibility of liquisolid systems, a mathematical model designed by Spireas et al. was used as formulation design model for the liquisolid tablets (Bhise et al., 2009). Prerequisites for this include suitable drug candidate, suitable non-volatile solvent, carrier and coating materials. The amounts of excipients (carrier and coating materials) used to prepare liquisolid compacts depend on the flowable liquid retention potential values (Ф-value) and the liquid loading factors (Lf).
Flowable liquid retention potential values (Ф- value)

The flowable liquid retention potential (Φ-value) of a powder is defined as the maximum amount of a given non-volatile liquid that can be retained inside its bulk (w/w) while maintaining acceptable flowability.

Therefore, in order to calculate the quantity of excipients, we need to determine the liquid retention potential value for both carrier (ФCA-value) and coating (ФCO-value) materials for each formulation. These values are constant for the given vehicle/powder system.

Liquid loading factors (Lf)
It is defined as the weight ratio of the liquid formulation (W) and the carrier material (Q) in the system:

Lf = W/Q------ (1)
(W is the weight of the liquid medication (the drug + non-volatile liquid vehicle) and Q is the weight of the carrier.)

R represents the ratio between the weights of the carrier (Q) and the coating (q) material present in the formulation. Then optimum weight of the coating material (q) could also be obtained (Equation 2).
R =Q/q------ (2)

The liquid load factor that ensures acceptable flowability (Lf) can be determined by:
Lf = ФCA + ФCO (1/R) ----- (3)
By calculating Lf and W, we can calculate the amount of Q and required for the liquisolid system

TABLE-1: LIQUISOLID FORMULATION PARAMETERS OF VARIOUS POWDER EXCIPIENTS WITH COMMONLY USEDLIQUID VEHICLES (Abdul Hasan Sathali and Deepa, 2013)

 

Non-volatile solvents

Φ-value for carrier
material (Avicel PH102)

Φ-value for coating
material (Aerosil 200)

1.Propylene glycol

0.16

3.31

2.polyethylene glycol400

0.005

3.26

3.Tween 80

0.003

3.95

4.Cremophor EL

0.18

0.80

5.capryol 90

0.16

0.40

COMPONENTS OF LIQUISOLID SYSTEMS
The major formulation components of liquisolid compacts are (Yadav et al., 2010)
1. Carrier Material
These are compression-enhancing, relatively large, preferably porous particles possessing a sufficient absorption property which contributes in liquid absorption.
E.g. various grades of cellulose, starch, lactose, sorbitol, Avicel PH 102 and 200, Eudragit RL and RS, amorphous cellulose etc.

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

3. Non-Volatile Solvents
Inert, high boiling point, preferably water-miscible and not highly viscous organic solvent systems. Various non-volatile solvents used for the formulation of liquisolid systems include Polyethylene glycol 200 and 400, glycerin, polysorbate 80 and propylene glycol, polysorbates, glycerin, N, N- dimethylacetamide, fixed oils, etc.

4. Disintegrant
Superdisintegrants increases the rate of drug release, water solubility and wettability of liquisolid granules. Mostly Superdisintegrants like sodium starch glycolate and crosspovidone and croscarmellose sodium are used.

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