Liquisolid Compact Tablet:

An Innovative Approach for Enhancing Bioavailability and Solubility

Pallavi Bhilaji Jire, Shrutika Krishnadas Patil, Nilesh Gulab Ahire, Mansi A. Dhankani,

Amitkumar R. Dhankani, Sunil P. Pawar

P.S.G.V.P Mandal’s College of Pharmacy, Shahada, Maharashtra, India.

*Corresponding Author E-mail: pallavijire06@gmail.com, skpatil2323@gmail.com,

ABSTRACT:

Liquisolid compacts represent a promising technology for improving the dissolution and bioavailability of poorly water-soluble drugs. Pharmaceutical scientists face significant challenges in formulating such drugs, as many newly discovered active pharmaceutical ingredients (APIs) exhibit solubility issues that hinder their absorption in the gastrointestinal tract. Liquisolid systems convert liquid pharmaceutical formulations into dry, free-flowing, and compressible powders by mixing non-volatile solvents with carrier and coating materials. Liquisolid Tablets offer a unique advantage for the formulation of poorly soluble drugs by enhancing dissolution and bioavailability. Compared to other drug delivery systems, they are cost-effective, easy to manufacture, and provide a stable, solid dosage form with the solubility advantages of liquids. Liquisolid tablets are especially beneficial for large-scale production, where other systems like soft gelatin capsules or nanosuspensions may be more costly and complex to produce. Liquisolid systems can be classified into powder drug solutions, powder drug suspensions, and powder liquid drugs, with further classification based on the formulation technique into Liquisolid compacts and microsystems. The main components include carrier materials, coating materials, non-volatile solvents, disintegrants, and lubricants. Despite the advantages, such as improved dissolution rates and controlled drug release, the technology is limited to water-insoluble drugs and may face challenges when dealing with high-dose formulations. This review discusses the preparation, formulation, advantages, disadvantages, and various evaluation techniques employed in Liquisolid compacts, offering insights into their potential for enhancing drug delivery and bioavailability.

KEYWORDS: Liquisolid, Dissolution, Water-Insoluble Drug, Carrier Materials, Non-Volatile Solvents.

INTRODUCTION:

Pharmaceutical scientists face significant challenges due to the poor solubility of water-insoluble medicines. Powder solutions are meant to hold liquid. Powdered pharmaceuticals have made significant progress in improving dissolving rates. Various procedures have been developed in recent years, including drug micronization, solid dispersions, co-precipitation, lyophilization, micro-encapsulation, pro-drug and drug derivatization processes, and incorporating drug solutions into soft gelatin capsules¹.

Micronization is commonly used to improve medication surface area, although its effectiveness decreases when manufactured as tablets and encapsulations^.2,3,4 In the case of soft gelatin capsules, These medications have the highest bioavailability due to their solution-based formulation. Creating soft gelatin capsules is costly and needs advanced technology. However, there are effective methods for preparing liquid oily pharmaceuticals and water-insoluble solid drug solutions⁵.

The most appropriate method is determined by factors pertaining to both the patient and the medicine. The most common way to administer medicine is orally. Because oral therapy is less expensive and more patient-acceptable, it is the preferred option. Because of their adaptability and ability to bypass pain, oral dose forms account for more than 70% of commercially available drugs⁶.

Liquisolid systems are mixtures of pharmaceutical suspensions or solutions that can be compressed and flow freely. Liquisolid is made up of the terms “solid” for powdered forms and “liquid” for medication solutions or suspensions^.7

Several active medicinal compounds have been synthesized. Approximately 40–60% of newly discovered drugs have solubility difficulties^.8 Many active pharmaceutical ingredients have solubility issues in the gastrointestinal system, including APIs like Lansoprazole, Azithromycin, Loperamide, Duloxetine, etc.

Liquisolid Compact System refers to the dry, non-adherent, free-flowing, and compressible powder mixture made from liquid drugs. The liquid medication is a solution or suspension of poorly soluble pharmaceuticals made with non-volatile solvents that are mixed with carrier and coat materials to produce a dispersible phase that is used to make granules and tablets, among other things.⁹

Classification of Liquisolid systems:

1. There are three subgroups of liquid solid systems based on the type of liquid medication they Contain:

· Powdered drug solutions

· Powdered drug suspensions

· Powdered liquid drugs.

· Based on the formulation technique used, Liquisolid systems may be classified into two categories:

· Liquisolid compacts

· Liquisolid microsystems^10,11,12

Advantages:

1. Liquisolid technology helps make solid medicines from liquids, like oily drugs.

2. Improved availability of an orally administered water-insoluble medication.

3. Production costs are lower than those for soft gelatin capsules.

4. Liquisolid systems are produced in a manner like regular tablets.

5. Improves medication release in vitro and in vivo compared to commercial products, such as soft gelatin capsules.

6. Can be used for controlled medication delivery.

7. Drug release can be controlled by employing appropriate formulation ingredients.

8. The medicine might be molecularly disseminated inside the formulation.

9. Capability of industrial production is also possible.

10. Enhanced bioavailability can be obtained as compared to conventional tablets^.13,14,15,16

Disadvantages:

1. This approach is only applicable to medications that are insoluble in water.

2. The liquisolid pill approach has difficulties when it comes to high-dose insoluble medicines.

3. To ensure suitable flow and compactability for liquisolid powder formulations, significant quantities of carrier and coating ingredients should be added.^17,18

Main components of Liquisolid system:

Component	Role in Liquisolid System	Examples	References
Non-Volatile Liquid	Solubilizes the drug, enhances wetting & dissolution	PEG 400, Capryol 90, Tween 80, Labrafil M 1944 CS	Spireas et al. (1998)¹⁶
Carrier Material	Adsorbs the liquid vehicle while maintaining flow properties	Microcrystalline Cellulose (Avicel PH 102), Lactose Monohydrate	Javadzadeh et al. (2007)¹⁹
Coating Material	Improves flowability and prevents sticking during compression	Colloidal Silicon Dioxide (Aerosil 200), Talc	Spireas et al. (1998)¹⁶
Superdisintegrant	Facilitates rapid tablet disintegration and drug release	Sodium Starch Glycolate, Crosspovidone, Croscarmellose Sodium	Bolton & Bon (2004)²⁰
Binder	Enhances compressibility and tablet integrity	Polyvinylpyrrolidone (PVP), Hydroxypropyl Methylcellulose (HPMC)	Javadzadeh et al. (2007)¹⁹
Lubricant	Reduces friction and prevents sticking during compression	Magnesium Stearate, Stearic Acid	Aulton (2002)²¹
Glidant	Improves powder flow properties before compression	Talc, Colloidal Silicon Dioxide (Aerosil)	Lachman et al. (1987)²²

Preparation and Formulation of Liquisolid:²³

Theories/ Calculation:

Regardless of whether the goal is to improve solubility or sustain release, a quantitative method must be used. This method determines the ideal coating and carrier materials to provide free flow and high powder compressibility.²⁴

For a given carrier and coating, flowable (Φ-value) and compressible (Ψ-value) liquid retention potentials are key. Φ-value indicates max liquid for flowability, while Ψ-value reflects max liquid for compressibility without leakage. Flowability is tested via Carr's index, Hauser’s ratio, and angle of repose, while compressibility is assessed through practical tests.²⁵

The excipient ratio (R), which is the ratio between the weight of the carrier (Q) and the coating material (q) in the formulation (Equation 1):

R = Q/q

Liquid load factor (Lf), which is the ratio between the weights of the liquid medication (W) to that of the carrier material (Q) (Equation 2):

Lf = W/Q

The liquid load factor that allows acceptable flow is calculated according to the following equation (Equation 3):

Φ L f = Φ+ φ (1/R)

Where Φ and ∅ are the flowable liquid retention potentials of the carrier and coating material, respectively. Similarly, the liquid load factor, which allows acceptable compressibility, can be calculated according to the following equation (Equation 4):

ΨLf = Ψ+ Ψ(1/R)

Where Ψ and Ψ are the compressible liquid retention potentials of the carrier and the coating material, respectively. The optimal liquid load factor (Lo) based on which formulation will be developed is equal to either Φ Lf or Ψ Lf, whichever has the smallest value. Accordingly, the carrier Q_o, and coating material q_o can be calculated.^{26, 27}

Qo = W/Lo (for calculate carrier material)

qo = Qo/R (For calculating coating material)

Pre-Compression evaluation:

The powder mixture evaluated for properties as follows:

1. Differential Scanning Calorimetry (DSC):²⁸

It measures heat variation needed to raise a sample's temperature compared to a standard. The sample and standard are kept at similar temperatures. DSC tests drug-excipient compatibility in the Liquisolid process. A missing drug peak in the thermogram indicates molecular dispersion in the formulation. Five mg of the sample were heated from 50° to 250°C at 10°C/min in a nitrogen atmosphere (100mL/min).

2. Fourier transformed infrared spectroscopy:²⁸

FTIR spectra detect drug-excipient interactions by monitoring changes in functional group vibrations. Pellets were prepared using the KBr pressed pellet method and analyzed with a Bruker FTIR spectrophotometer using Opus software.

3. X Ray Diffraction (XRD):²⁸

XRD identifies and characterizes compounds through diffraction patterns, assessing the crystalline state of liquisolid compacts and drug-excipient mixtures.

4. Scanning electron microscopy:²⁸

SEM determines the presence of drug crystals or excipients. A lack of crystallinity in the image indicates complete drug dissolution in the carrier system.

5. Angle of Repose:²⁹

The fixed funnel method measured the angle of repose. Powder was poured through a fixed-height funnel onto graph paper until the pile's apex reached the tip. The angle was then calculated using the formula.

𝑇𝑎𝑛 𝜃 = ℎ / 𝑟

𝜃 = 𝑇𝑎𝑛 −1 ℎ / r

· Where, 𝜃 is the angle of repose.

· h is the height of heap.

· r is the radius of the heap circle.

6. Bulk Density:²⁹

Bulk density was measured by pouring a known sample through a funnel into a graduated cylinder. The sample's volume was recorded, and density was calculated using a formula.

Bd=W / Vb

· Where Bd = Bulk density

· W = Mass of the powder

· B = Bulk volume of the powder

7. Tapped Density:²⁹

Tapped density was measured by pouring the powder into a graduated cylinder, tapping until volume stabilized, and recording the volume change. Density was then calculated using a formula.

Dt= W / T

· Where Td= tapped density

· W=Mass of the powder

· T= Tapped volume of the powder

8. Compressibility index and Hausner’s ratio:²⁹

The compressibility index and Hausner ratio assess powder flow by measuring bulk and tapped densities. They indirectly reflect size, shape, cohesiveness, surface area, and moisture content.

I = (𝐷𝑡 – 𝐷𝑏/𝐷) × 100

· Where, I= Compressibility index

· Dt= Tapped density of the powder

· Db= Bulk density of the powder

· Hausner ratio= Dt / Db

Evaluation of Liquisolid Tablets:²⁸

1. Weight Variation Test:

Twenty tablets of each formulation were individually weighed, and their average weight was calculated. Each tablet's weight was compared to this average (Indian Pharmacopeia, 2014).

2. Friability Test:

Tablet strength was assessed using the Roche friabilator, which simulates shock abrasion by rotating at 25 rpm, dropping tablets 6 inches per turn. Six pre-weighed tablets were tested for 100 revolutions, then reweighed after dusting. A weight loss below 1% is acceptable, with % friability calculated per the Indian Pharmacopoeia (2014).

Percentage of Friability =

(Initial weight – final weight/ Initial weight) x 100

3. Hardness Test:

Tablet hardness, crucial for resistance during handling and storage, was tested using a Monsanto hardness tester. Six tablets were placed between jaws along the diametric axis, with an initial reading of 0 kg/cm³. The knob was turned until the tablet cracked, and the value was recorded.

4. Wetting Time:

A little petri dish was filled with water and a folded tissue paper. The time required for the tablet to get entirely wet was measured while it was sitting on paper.

5. Water Absorption Ratio (R):

The tablet's weight (b) was measured before it was placed in the petri dish. We removed the wetted medication and measured its weight (Wa). We then computed the water absorption ratio using the following equation: or R

R=100 x [ (Wa-Wb)/Wb]

Where, Wb = Tablet weights before absorption

Wa = Tablet weights after water absorption

6. In Vitro Release

A USP II device was used for in vitro release of liquidsolid tablets at 37ºC ± 2ºC. Studies show that lower drug concentration in the liquid formulation leads to faster release, improving absorption and bioavailability.

7. In Vivo Study

The liquisolid technique enhances the release of poorly soluble drugs. Absorption in beagle dogs showed higher bioavailability, peak plasma concentration, and AUC for liquisolid compacts versus commercial tablets. Other parameters remained unchanged, with the commercial formulation showing 15% lower bioavailability.

8. Stability Studies

Per ICH guidelines, drug content is determined by exposing drug crystals to accelerated stability conditions (Q1 R2). Samples are analyzed at set intervals using an infrared spectrophotometer.

Applications:

1. To enhance drug dissolution

Liquisolid compacts enhance drug dissolution by dispersing it in a non-volatile solvent and absorbing it onto carriers, improving wettability, and increasing the dissolution rate.³⁰

2. A tool to sustain drug release

Liquisolid systems enable instant or prolonged drug release using specific excipients.

Hydrophilic carriers like MCC enhance release, while hydrophobic carriers or polymers like HPMC prolong it, allowing tailored drug delivery.³⁰

3. To Improve Drug Photostability in Solid Dosage Forms:

Liquisolid systems enhance the photostability of light-sensitive drugs using coatings like Silicon Dioxide, which deflect light and prevent degradation, outperforming conventional formulations.³⁰

4. Minimized Influence of pH Variations:

Liquisolid compacts stabilize drug release across pH variations, reducing fluctuations in dissolution, absorption, and bioavailability for consistent therapeutic effects.³¹

Table: List of Published Wo. Rks on Liquisolid Delivery Systems

Drug	Vehicle used	Carrier Material	Coating material	Result	References
Labetalol hydrochloride	Propylene glycol	Avicel pH102	Aerosil 200	Labetalol hydrochloride was successfully formulated as a liquisolid tablet using the direct compression method. Compatibility studies (DSC and FTIR) showed no interactions, and in vitro testing confirmed enhanced drug release. Stability studies indicated the formulation remained stable.	Vinayak Mastiholimath et. al,³²
Furosemide	Polyethylene glycol 400	Avicel ph 102	Aerosil 200	The liquisolid technique effectively enhanced the dissolution rate of poorly soluble furosemide. Optimized 40 mg tablets achieved acceptable size, mass, and rapid, complete drug release.	Zainab E. Jassim³³
Ketoconazole	Polyethylene glycol 400	Microcrystalline cellulose	Colloidal silica	Microcrystalline cellulose, colloidal silica, PEG 400, and Polyvinyl Pyrrolidone were used in KCZ liquisolid compacts as carriers, coatings, solvents, and additives. This approach enhanced the dissolution of the previously insoluble drug.	Mir-Ali Molaei, et al³⁴
Lornoxicam	Polyethylene glycol 400	Avicel ph 200	Calcium silicate	The enhanced dissolution of Lornoxicam liquisolid tablets was due to improved wetting and increased drug surface area. Despite being a solid dosage form, the drug remained in a solubilized state within the powder, ensuring better dissolution and acceptable tablet properties	Asma A. Mokashia, et al,³⁵
Valsartan	Propylene glycol	Avicel	Aerosil 200	The liquisolid technique significantly improved Valsartan dissolution compared to the marketed product, making it a promising approach for poorly soluble drugs.	Chella, N, et al,³⁶
Olanzapine	Kolliphor el	Avicel	Aerosil	Kolliphor EL enhanced the dissolution rate of OLZ in liquisolid tablets, while precompression powders showed improved flow properties.	Korni, R.D, et al,³⁷
Nebivolol Hydrochloride	Polyethylene Glycol 400	Fujicalin	Aerosil 200	The liquisolid technique with Fujicalin successfully produced Nebivolol compacts with improved flow properties and a desirable release profile.	Ramya Sri Sura, et al,³⁸
Pioglitazone Hydrochloride	Polyethylene Glycol 400	Neusilin Us2	Aerosil 200	Pioglitazone HCl liquisolid tablets were formulated using Neusilin US2 and PEG 400 to enhance solubility. Solubility studies confirmed increased aqueous solubility of the drug.	Bhushan Rajendra Rane, et al,³⁹

CONCLUSION:

In conclusion, Liquisolid compact technology offers a viable solution to the challenge of improving the solubility and bioavailability of poorly water-soluble drugs. By converting liquid formulations into free-flowing, compressible powders, this approach enhances the dissolution rate of drugs, thus improving their absorption in the gastrointestinal tract. The technique is cost-effective compared to soft gelatin capsules and can be easily incorporated into standard tablet production processes. Despite its advantages, such as improved drug release and the potential for controlled delivery, Liquisolid systems have limitations, particularly in the formulation of high-dose drugs and those that are highly insoluble in water. Further research into optimizing carrier and coating materials, as well as refining formulation techniques, is necessary to overcome these challenges. Overall, Liquisolid technology holds significant promise for enhancing the therapeutic efficacy of poorly soluble drugs and could play a crucial role in the future of pharmaceutical drug development.

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Received on 19.03.2025 Revised on 07.04.2025

Accepted on 21.04.2025 Published on 09.05.2025

Available online from May 12, 2025

Res. J. Pharma. Dosage Forms and Tech.2025; 17(2):143-148.

DOI: 10.52711/0975-4377.2025.00021

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