Liquid Crystal Gel Based Formulation:

Strategies to Enhance Solubility and Absorption of Poorly Soluble Drug

Shethia Aashutosh Narendra, Sulbha G. Patil

P.S.G.V.P. Mandal's college of Pharmacy Shahada (Maharashtra) Dist. Nandurbar, Maharashtra, India.

*Corresponding Author E-mail: aashushethia07@gmail.com

ABSTRACT:

Repaglinide is a poorly water-soluble antidiabetic drug, and its low solubility limits oral bioavailability and therapeutic efficiency. The present approach focuses on the development of a repaglinide liquid crystal gel as a novel drug-delivery system to improve its solubility and dissolution characteristics. Liquid crystal gels possess an ordered internal structure capable of solubilizing lipophilic drugs and providing controlled drug release. Incorporation of repaglinide into the liquid crystalline matrix enhances its solubility, improves bioavailability, and ensures sustained release, thereby reducing dosing frequency and fluctuations in plasma drug levels. The formulation also offers good physical stability and patient acceptability. Overall, repaglinide liquid crystal gel represents a promising strategy for overcoming solubility-related limitations and improving the therapeutic performance of repaglinide in the management of type 2 diabetes mellitus.

KEYWORDS: Repaglinide, Liquid crystal gel, Solubility enhancement, Controlled drug release, Antidiabetic drug.

INTRODUCTION:

Repaglinide is a newer blood glucose lowering medication from the carbamoyl methyl benzoic acid class. It promotes insulin release from pancreatic beta-cells by closing K+ ATP channels, and it is quickly absorbed and removed from the body. Repaglinide was created to alleviate the drawbacks of existing anti-diabetic medications. Hypoglycemia, subsequent failure, and cardiovascular adverse effects are among them.

Although repaglinide shares some chemical similarities with glibenclamide, a sulphonylurea-type anti-diabetic medication, it differs from other sulphonylureas in both action profile and excretion mechanism. Other sulphonylureas bind to other receptor sites than repaglinide. As a result, it is 3–5 times more effective than glibenclamide, and it does not induce insulin release in the absence of glucose, unlike glibenclamide. The medicine repaglinide is classified as a BCS Class II drug. In the upper section of the intestine, it is weakly absorbed. With a claimed bioavailability of 56%, it undergoes significant hepatic first-pass metabolism.

Liquid crystal:

The characteristics of both liquid and solid states are combined in the liquid crystalline state. Solids have a crystalline structure and are organized, whereas liquids are characterized by their capacity to flow. In 1888, Austrian botanist Friedrich Reinitzer began researching liquid crystals. Reinitzer, were studies on substances that display a phase of matter with characteristics halfway between those of a traditional liquid and solid crystal are called liquid crystals. It is frequently referred to as a condition of matter or a mesomorphic state. The degree of molecular order in a mesomorphic state is intermediate between that of isotropic liquids, gases, and amorphous solids, which lack long range order, and that of perfect three-dimensional, long-range positional and orientational order seen in solid crystals. Another name for it is meso intermediate.²

Transdermal gel:

The transdermal drug delivery may offer several advantages over oral delivery. It eliminates the degradation of the drug by first-pass metabolism and delivers the drug over a longer period of time with less fluctuation. The permeation and penetration of the drug through the stratum corneum may perform as a rate-restricting phase in many transdermal delivery systems. Therefore, penetration enhancers are added to improve drug penetration.³ Fatty acids are well-known penetration enhancers. Their effect depends on their structure, degree of saturation, and the extent of the alkyl chain. According to the FDA, fatty acids are generally recognized as safe (GRAS), and their use is approved. The addition of permeation enhancers to SPLs may have a synergistic effect in improving drug penetration into the skin and eyes.

Advantages of Liquid Crystal Transdermal Gel:

· Enhanced Drug Permeation:

Liquid crystals can improve drug penetration through the skin due to their unique lipid-like structure, which mimics the stratum corneum lipids.

· Controlled/Sustained Release:

LC gels can provide a controlled or sustained release of the drug, reducing dosing frequency and improving patient compliance.

· High Drug Loading:

They can solubilize both hydrophilic and lipophilic drugs efficiently.

· Biocompatibility and Safety:

Many LC systems use biocompatible surfactants and lipids, minimizing irritation.

· Stability:

The ordered structure of LCs can protect the drug from degradation.

· Aesthetic Appeal:

They are non-greasy, spread easily, and are generally cosmetically acceptable.

Disadvantages of Liquid Crystal Transdermal Gel:

· Complex Formulation:

Preparing LC gels requires careful control of composition and temperature to maintain the desired mesophase.

· High Cost:

The surfactants, lipids, and equipment used can make the formulation more expensive than conventional gels.

· Physical Stability Issues:

Changes in temperature, pH, or mechanical stress can disrupt the LC structure, affecting drug release.

· Limited Drug Types:

Not all drugs are suitable; some may destabilize the LC structure or have poor compatibility.

· Skin Irritation Risk:

Certain surfactants or co-surfactants in the formulation may cause irritation in sensitive individuals.

Classification of Liquid Crystals:

Liquid crystalline compounds are differentiated into two types: thermotropic and lyotropic. The liquid crystals that change their phase upon heating or cooling are thermotropic. The mesophase is called enantiotropic when the phase is obtained upon both heating and cooling. When added in a suitable solvent, lyotropic phases are formed, and the appearance of the mesophase is dependent on both concentration and temperature.

· Thermotropic Liquid Crystals:

Thermotropic LCs are the ones that are extensively recognized due to their application in televisions, laptops, mobile phones, and tablet displays. According to the structural features, thermotropic liquid crystals are subdivided into two main groups. The rod-like molecules are calamitic and the disc-like molecules are discotic.

· Lyotropic Liquid Crystals:

Lyotropic substances are strongly birefringent. Mesophase in binary systems of amphiphiles and water may be classified as (a) the neat phase, (b) the middle phase, (c) the viscous isotropic phase, (d) the isotropic phase, and (e) the inverse phase. Lyotropic substances with other solvents are also studied. Mesophases of lyotropic liquid crystals are also affected by temperature changes. Lyotropic liquid crystals of hydrated phospholipids are studied as a model medium for studies of antimicrobial agent activity.

Fig. 2. Classification of liquid crystals.

Methods for Preparing Liquid Crystals:

· Synthetic approaches to prepare calamitic liquid crystals:

Hydroxyl (-OH) and carboxylic acid (-COOH) functionalized aromatic rings can be esterified to provide ester-bridged liquid crystals. Traditionally, the acid group was converted into an acid chloride derivative using oxalyl chloride or thionyl chloride, followed by the reaction with a hydroxyl functionalized group in the presence of a base. A new simple method has been developed where the esterification reaction is carried out using 4- (N, N-dimethylamino) pyridine (DMAP) base and N, N-dicyclohexylcarbodiimide (DCC) catalyst at room temperature, A long, linear architecture favors liquid crystal formation, and the simplest structures are 4,4'- disubstituted. Multiaryls are difficult to synthesize directly. One solution for this problem is the Palladium- catalyzedcross-coupling reactions, which allow the formation of a carbon-carbon bond between, for example.

two benzene rings or a benzene ring and an acetylene unit. Their development has enabled the synthesis of a wide range of liquid crystals that would otherwise have been extremely difficult or even impossible to make.

The presence of pyrimidine rings in a compound enhances liquid crystal properties and introduces, in some cases, nematic and smectic C phases. Coupling methodology provides an efficient route for the synthesis of phenyl pyrimidine and fluorophenyl pyrimidines. Palladium- catalyzed cross-coupling reactions are also used for inserting important terminal groups required for liquid crystal structure.

Evaluation of Liquid Crystal Gel:

· Physical Appearance:

The prepared Repaglinide liquid crystal gel was visually inspected against black and white backgrounds to check uniformity, presence of particulate matter, and phase separation.

· pH Determination:

One gram of gel was dispersed in 10 mL of distilled water and allowed to equilibrate for 2 hours. The pH was measured using a calibrated digital pH meter at room temperature.

· Drug Content Uniformity:

A quantity of gel equivalent to the required dose of Repaglinide was accurately weighed and dissolved in methanol (or suitable solvent). The solution was sonicated, filtered, and analyzed using UV spectrophotometry at λmax ≈ 241–245nm or by HPLC. Drug content was calculated using a calibration curve.

· Viscosity Measurement:

Viscosity of the liquid crystal gel was measured using a Brookfield viscometer fitted with an appropriate spindle at different rotational speeds (e.g., 10–100rpm) at 25± 1°C.

· Rheological Behavior:

Shear stress was measured at increasing shear rates using a rheometer. A plot of shear stress versus shear rate was used to determine pseudoplastic or Newtonian behavior.

· Spreadability:

An excess of gel was placed between two glass slides. A known weight was applied on the upper slide and the time taken for the slides to separate was recorded.

· Texture Profile Analysis:

Texture profile analysis was performed using a texture analyzer by compressing the gel twice with a cylindrical probe and measuring mechanical parameters.

· In-Vitro Drug Release Study:

In-vitro drug release was carried out using Franz diffusion cell or USP dissolution apparatus with dialysis membrane. Phosphate buffer pH 7.4 was used as receptor medium. Samples were withdrawn at predetermined intervals and analyzed by UV/HPLC.

· Skin Irritation Study (for topical/transdermal gel):

The gel was applied on shaved skin of rats and observed for erythema or edema over 24–72 hours.

· Stability Studies:

Formulations were stored at 25°C/60% RH and 40°C/75% RH as per ICH guidelines. Samples were evaluated periodically for pH, drug content, viscosity, and in-vitro release.

Applications of Repaglinide Liquid Crystal Gel:

Repaglinide liquid crystal gel is an advanced pharmaceutical formulation developed to enhance the therapeutic effectiveness of repaglinide in the management of type 2 diabetes mellitus. The liquid crystalline gel system provides controlled and sustained release of the drug due to its highly ordered internal structure, which helps maintain consistent plasma drug levels and prolonged glucose control. This controlled release reduces the frequency of dosing and minimizes fluctuations in blood glucose levels, thereby lowering the risk of hypoglycemic episodes commonly associated with conventional immediate-release tablets.

In addition, repaglinide liquid crystal gel is extensively studied for transdermal drug delivery applications. By delivering the drug through the skin, the formulation bypasses first-pass hepatic metabolism, leading to improved bioavailability and reduced gastrointestinal side effects. The gel form is non-invasive, easy to apply, and enhances patient compliance, especially in patients who have difficulty swallowing oral medications. Furthermore, liquid crystal gels offer high drug-loading capacity, good physical stability, and the ability to respond to physiological conditions, making them suitable for innovative antidiabetic drug-delivery research and development.

CONCLUSION:

the repaglinide liquid crystal gel is an effective approach to improve the solubility of repaglinide, a poorly water-soluble drug. The liquid crystalline system enhances drug solubilization by incorporating repaglinide within its organized lipid structure, leading to improved dissolution and bioavailability. This formulation also supports controlled drug release and better therapeutic performance, making it a promising strategy for overcoming solubility-related limitations and enhancing the overall effectiveness of repaglinide in diabetes management.

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Received on 12.03.2026 Revised on 02.05.2026

Accepted on 05.06.2026 Published on 06.07.2026

Available online from July 20, 2026

Asian J. Pharm. Res. 2026; 16(3):363-367.

DOI: 10.52711/2231-5691.2026.00053

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