Introduction

Semisolids are topical dosage forms used for therapeutic, protective, or cosmetic functions. Due to the flexible behavior of semisolid dosage forms, they maintain their shape when external force is applied. Every semisolid dosage form has a stable three-dimensional structure with unique rheological characteristics. Topical drugs are frequently administered using semisolids including creams, ointments, gels, and lotions. These skin-applied formulations enable the local treatment of several disorders, including skin infections, dermatitis, psoriasis, and wound healing. Active pharmaceutical ingredients (APIs) can be delivered via semisolids to the intended site of action [1].

Gels are semi-solid dosage forms that can be topical or transdermal. They are polymeric matrix-entrapped liquid phases of aqueous colloidal suspensions. Gels typically have a clear or translucent appearance, and because of their smooth texture, it is simple to apply them evenly across vast areas of skin. They can be used as lubricants in addition to being utilized as medications [2, 3]. Gels are usually classified into several types based on their composition, structure, and application. Some of the common types of gels are hydrogels, organogels, and oleogels. The hydrogels are the ones with a large portion of water as the liquid phase. They are made of hydrophilic polymers with a high-water absorption and retention capacity. High water content and great swelling qualities are characteristics of hydrogels due to hydrophilic polymer networks arranged in three dimensions. The oleogel is a gel in which a liquid oil phase is immobilized within a three-dimensional network of solid particles or gelling agents. Unlike traditional gels, primarily water-based (hydrogels), oleogels have an oil-based matrix. They create stable, semi-solid, or gel-like structures from liquid oils [4, 5]. Oleogels are gels with an oil-based liquid phase. Solid particles or structuring agents are included in the oil during their formation to create a network that provides the gel with its structure. Due to their stability, smoothness, and controlled release qualities, oleogels are frequently utilized in food, cosmetics, and medicinal products. Hydrogels are commonly employed in biomedical applications such as drug delivery systems, wound healing, and tissue engineering scaffolds because of their high-water content, biocompatibility, and resemblance to natural tissues. The organogels are gels with an organic solvent as the liquid phase. Small molecules or polymers are dispersed in an organic liquid media to create them. Pharmaceutical formulations, cosmetics, and personal care items are just a few industries where organogels are used. They can serve as vehicles for transdermal drug administration and offer regulated release of active ingredients. Gelators, which might be organic molecules or polymers, are dispersed in an organic solvent to produce these gels. The solvent is immobilized by the self-assembling network structure that the gelators create. Due to their capacity to solubilize lipophilic chemicals and provide increased stability compared to liquid solvents, organogels find use in industries such as medicine delivery, energy storage, and sensor technologies [5,6,7].

History and Prospects

Following Thomas Graham's proposal of a nebulous definition in 1861, the understanding of what constitutes a "gel" has evolved. Dr. Dorothy Jordan Lloyd observed 65 years later that "the colloid condition, the 'gel' is simpler to identify than to precisely define.

Oleogels first emerged in the food sector, where developers engineered structural agents to solidify liquid oils. This innovation aimed to replicate the properties of solid fats in products without resorting to the use of unhealthy saturated fats.

Besides trans fats, saturated fats, primarily derived from animal sources such as meat and dairy products, can pose health risks when consumed excessively and are likely associated with conditions like diabetes, obesity, metabolic syndrome, and cardiovascular disease. According to WHO guidelines, total fat intake should not exceed 1%, 10%, or 30% of total energy consumption, respectively. To safeguard consumer health, developing and implementing innovative methods capable of solidifying liquid oils without generating trans-fatty acids and reducing saturated fatty acid levels is crucial. One promising approach investigated for mitigating the production of trans-free and saturated fats involves oil gelation using structurants, known as "oleo gelation." This technique holds promise for addressing this challenge.

Beyond their application in the food industry, oleogels hold promising prospects in the pharmaceutical sector as carriers for drug delivery systems. Their potential to revolutionize medication administration lies in their ability to enhance bioavailability and regulate the release of active ingredients.

Additionally, the emollient properties of oleogels can enhance the texture and sensory experience of skincare products, such as lotions, creams, and other formulations used in cosmetics and personal hygiene. Given their versatility, oleogels offer great promise for future use in personal care and pharmaceuticals, making them an intriguing area for ongoing research and development efforts [8].

Purpose of Oleogels

Oleogels can be used for long-term treatment as they can form a drug depot when given as an injection. They entrap the liquid oil through self-assembly, by which hydrophobic drugs can be easily entrapped in them. Therefore, it is suitable for BCS class II or IV drugs, which have low aqueous solubility [9]. BCS class II drugs like Atorvastatin, Carvediol, Ciprofloxacin, etc. can be used in oleogel formulations to increase their effectiveness by targeting solubility and direct absorption in the body [10]. Whereas for BCS class IV drugs like amphotericin, ciprofloxacin, neomycin, etc., the main attributes for improvement are solubility and permeability [11]. Such drugs can be incorporated into the oil effectively.

Because of the special composition of oleogels and lipophilic properties, they can significantly increase drug absorption via the skin and enhance its bioavailability. Oleogel formulations, as opposed to drug suspensions or gels, can improve the bioavailability of hydrophobic medications by more than 4.5 times, such as olmesartan medoxomil (OLM), as seen in one of the research conducted. In contrast to drug suspensions and gels, which only released 23.75% and 20.11% of the OLM medication after 24 h, the improved oleogel formulation released 100% of the drug. The exceptional solubilizing activity of the oleogel's constituents, such as surfactants and lavender oil, was responsible for this notable increase in drug release from the formulation [12]. In summary, the key differences between oleogels, hydrogels, and organogels lie in the liquid phase (oil, water, or organic solvent) and the gel-forming components used [13]. These differences result in unique properties and applications for each type of gel.

In the current review, we aim to gain a deeper insight into Oleogel by exploring its composition and formulation, the methods involved in its preparation where the liquid oils are first converted into emulsion and further into oleogel is shown in Fig. 1, the process of characterizing it, and the numerous applications it can be utilized for [14].

Fig. 1
figure 1

Liquid oil is transformed into an oleogel through a process involving the addition of gelling agents to an oil-water emulsion

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Composition and Formulation of Oleogels

Oleogels are formulated by mixing oleogelators like waxes, fatty acid alcohols or esters, ethyl cellulose, phospholipids, and phytosterols with edible oils as organic solvents. The qualities of the produced oleogels are directly influenced by the oleogelator chosen and the method of oleogelation.

Oleogels are three-dimensional structures prepared using liquid oils with the help of oleogelators. It is reversible and shows good viscoelastic properties. These attributes enable their self-assembly into various shapes and applications, such as controlled release and enhanced bioavailability [15].

Oil

The gelling agent and gelling solvent employed during the creation of oleogels have a considerable impact on their properties, such as texture, thermal behavior, and rheology. The behavior of the gel and the absorption of lipid droplets or bio-actives in the gastrointestinal phase are significantly influenced by the oil phase in oleogels. Oleogels chemical composition, particularly the length of their fatty acid chains and the presence of unsaturated fatty acids, affects how they gel. Wax was used as the gelling agent in a study to examine the ability of several oils including corn, sunflower, rice bran, and high oleic sunflower oil, to form gel at various saturation and unsaturation levels. The oils with higher saturation levels contributed to stronger oleogels. The oil viscosity and polarity are additional oil properties that substantially impact the kinetics of gelation and crystallization of oleogels. Oils with greater polarity produced weaker gels because of significant interactions between the gelator and solvent [16, 17].

Higher viscosity and longer carbon chain oils produce gels with greater hardness. Additionally, more spatial twisting in the oil phase results from more unsaturation, which improves the oil's hydrophobicity and lowers interaction energy. Thus, stronger oleogels can be created using oils with lower polarity, higher unsaturation levels, and higher viscosity [18].

Oleogelators

Low Molecular Weight (LMW) Oil Gelators

The solid fibers serve as stabilizers for LMW organogelators prepared gels. The gelator is dissolved in an organic solvent at a higher temperature, and the finished product is cooled to room temperature to create them. During the cooling process, there are three possible outcomes: highly ordered aggregation producing crystals, random aggregation producing an amorphous precipitate, or an intermediary aggregation process producing a gel [19].

n-alkanes

N-alkanes, sometimes referred to as paraffin, are saturated hydrocarbon chains made up of hydrogen-bonded carbon-carbon bonds. In organic solvents, these chemicals can create lamellar crystal structures. By combining into crystal platelets, the lamellas engage in weak physical interactions such as Van der Waals, electrostatic, p-p stacking, and london dispersion forces to form a three-dimensional network. Given that functional groups required for other molecular interactions are absent in n-alkanes, London dispersion forces are thought to be the primary driving force behind self-assembly in these molecules [20].

In silicon oil, N-alkanes with carbon chains ranging from 24 to 36 displayed the ability to gel, with longer chains necessitating lower molecular concentrations. Due to variations in sublimation temperatures and solubilities, increasing the hydrocarbon length improved gel stability. An examination of the C-36 alkane's molecular packing revealed the development of lamellar platelets that interconnected to form a 3D crystal network. These systems are used in the petrochemical sector to treat oil spills. It is advised that functionalized groups be used to change the leading alkane chains to improve the stability and performance of the network. In n-alkanes, adding functional groups, such as hydroxyl end categories, on either end of the chain of carbons can result in additional molecule-based interactions, like hydrogen bonding and dipole-dipole interactions. These changes can improve physical interactions inside the system [21,22,23].

Waxes and Shellac

Natural waxes can use low quantities of liquid oils (1-4 wt%) to create oleogels by building a three-dimensional network that traps the oil inside of its pores and absorbs it on the network's surface [24]. Wax in liquid oil is heated to a temperature over its melting point and subsequently cooled under shear or quiescent circumstances. The chemical composition of waxes, including the relative amounts of elements of fatty acids, fatty alcohols, and hydrocarbon chains, which depend on their source, impacts the gelation behavior. The oil's quality also matters since better gelation results from higher saturation levels.

Wax-based oleogels have several advantages, including the capacity to make water-in-oil patterned emulsions without emulsifiers, affordability, food-grade qualities, and ease of availability. Due to its thermo-reversible behavior, temperature control in food applications is possible. Carnauba wax, rice bran wax, bees candelilla wax, and sunflower seeds wax are typical food-grade waxes used in oleogel applications. These oleogels' 3-D network configuration and crystal morphology are typical factors that influence how well they bind oil; a higher oil-binding capacity was linked to larger crystal size and an even distribution of mass. The speed of cooling significantly affects how quickly shellacs crystallize. When making oleogels, slower cooling rates lead to larger, denser crystals, whereas faster cooling rates produce less dense crystals with more surface area. Faster cooling increases the surface area of lesser dense crystals, encouraging greater crystal-crystal interactions and the development of crystal networks [10, 19, 20].

Triacyl glycerol derivatives

Oil structuring systems can be utilized to self-assemble the capacity of triacylglycerols (TAGs) that comprise the crystal network known as fat. Various techniques of oil structuring are illustrated in Fig. 2. It has been investigated whether mixes of TAGs with low and high melting points can produce oleogels [25]. When compared to the distinct qualities of high and low melting TAGs, it was found that melting/crystallization temperatures, gel properties, shape, and solid fat content differed in the mixed state. As oil structuring agents, monoglycerides (MAGs) have also been the subject of substantial research, with various MAG and oil types tested for effectiveness [26,27,28].

Fig. 2
figure 2

Various oil structuring techniques currently in use

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Ceramides

The most basic sphingolipids, ceramides, are created by amidating lipids with sphingosine. They can be produced synthetically via enzymatic or chemical catalysis, with a variety of structures depending on the length of the chain and sugar side group. Ceramides have been related to lowered cholesterol and the growth of cancer. Ceramides can organize canola oil by producing lamellar ceramide bilayers, enabling persistent gels formation at concentrations as low as 2 weight percent [28, 29].

Phytosterols Based Oleogels

Numerous studies have been conducted on the oleogelation capabilities of plant sterols, including cholesterol levels, ergosterol, and cholestenol. They have an aliphatic side chain, a hydroxyl group, and a steroid skeleton. The rice bran contains a different phytosterol-based gelator termed γ-oryzanol, composed of triterpene alcohols and ferulic acid, which are esters of phytosterols. At modest concentrations (2%), the synergistic combination of these gelators produces powerful oleogels. Vegetable oils and the ratio of γ-oryzanol to β-sitosterol impact the crystal structure, affecting the rate of oil trapping and the ability of oleogels to absorb oil. Different ratios of γ-oryzanol and β-sitosterol were used to study canola oil to examine its polymorphism build-up, melting temperatures, and morphological features [30,31,32].

High Molecular Weight Oil Gelators

Proteins and polysaccharides, which have high molecular weights, can build a three- dimensional network by hydrogen bonding, which can effectively trap oil and produce oleogels. The molecular mass, structure, and amount of the polymers greatly impact the viscoelastic characteristics of oleogels created by polymeric oleogelators.

Polysaccharide-Based Oleogels

By using the direct dispersion method, ethyl cellulose (EC), a polysaccharide of food grade, is frequently used for the structure of edible oils. It is a cellulose derivative that is semi- crystalline and has ethyl groups in place of the hydroxyl groups. EC has specific functional characteristics depending on the molecular mass and level of substitution. EC can form gels in liquid oil due to its hydrophobic properties and semicrystalline structure. The gelation process involves heating EC above its glass transition temperature (about 130°C), followed by chilling to promote the development of stiff hydrogen bonds and intermolecular interactions. As a result, a three-dimensional network is created, trapping the oil within the one-dimensional polymer strands [33,34,35].

Protein-Based Oleogelators

The hydrophilic nature of the protein limits their capacity to create networks in hydrophobic oils, which limits their potential for use in the production of oleogels. However, two strategies have been put out for organizing oils using proteins: the solvent transfer technique and the emulsion pattern technique. In the emulsion template approach, proteins are used as emulsifiers to make emulsions, which are then removed to form maximum inner-phase pickering emulsions. The protein's ability to organize into networks at their interfaces and control the characteristics of the ensuing HIPE (high internal phase pickering emulsions) which are specialized emulsions characterized by having a very high volume fraction of internal phase compared to the external phase are both dependent on the interfacial tension. Stable emulsions are made by restricting the coalescence of scattered oil droplets and strengthening the interfacial network [36, 37].

Preparation of Oleogel

The preparation of oleogels involves the dispersion of a structuring agent into an oil phase, by various techniques, including hot or cold homogenization, solvent evaporation, and melt blending. Each method offers unique advantages and is selected based on the nature of the structuring agent and the desired characteristics of the final oleogel product. There are multiple steps in the typical oleogel preparation process. The choice of ingredients is important first and foremost. This requires selecting an appropriate oil or a combination of oils depending on the desired release profile, stability, and compatibility with the intended medicine. A suitable gelator, which can be a polymer or a tiny organic molecule, must also be chosen. The capacity to create a stable gel structure and compatibility with the selected oil are important factors.

Hot or Cold Homogenization

Hot homogenization combines the oil phase and the oleogelator, which is the substance responsible for creating the gel network, at a temperature surpassing its melting point. This facilitates the dispersion of oleogelator molecules or particles throughout the oil phase. Subsequently, the mixture undergoes homogenization, either through a high-speed blender or a high-pressure homogenizer, to subject it to strong shear pressures. This process breaks up any aggregates and ensures uniform distribution of the oleogelator throughout the oil phase, forming a stable and homogeneous gel network. Following homogenization, the liquid cools, prompting the gel network to form as the temperature decreases [16, 38,39,40].

Unlike hot homogenization, which requires heating the mixture, cold homogenization combines the oleogelator and the oil phase at or below room temperature. Cold homogenization is often preferred when working with temperature-dependent oleogelators or when the desired gel structure is best achieved at lower temperatures in the final product [41, 42]

Solvent Evaporation

The solvent evaporation process involves dissolving the oleogelator in a suitable solvent and blending it with the oil phase. By carefully controlling the evaporation of the mixture, the solvent is removed, leaving the oleogelator dispersed throughout the oil phase. Solvent evaporation can be carried out using various methods such as vacuum drying, rotational evaporation, or allowing the solvent to evaporate naturally in the open air. This technique is particularly beneficial when dealing with oleogelators that are challenging to dissolve in oils or when precise control over the gel structure is necessary.

Porous additives with high surface areas and hydrophilic qualities are utilized in the creation of oleogels due to their ability to absorb significant amounts of hydrophobic oil in the presence of water. This results in oleogels with enhanced consistency, flowability, and texture. During the solvent exchange process, proteins and polysaccharides are the building blocks for producing these oleogels [16, 43].

Melt Blending

Melt blending involves promptly merging the oleogelator and oil phase at a temperature exceeding the oleogelator's melting point. The mixture is stirred through agitation or similar means until the oleogelator disperses evenly within the oil phase. This method of melt blending is user-friendly and doesn't necessitate specialized equipment like solvents or homogenizers. However, it may not be suitable for all oleogelators, especially those susceptible to structural degradation or changes under high temperatures [44]. According to the intended formulation, the prescribed amounts of oil and gelator are carefully weighed. Then, these components are blended in a spotless, dry container. The mixture is then heated to promote dissolution and homogeneity. A suitable heating technique, such as a water bath or heating mantle, can be used to accomplish this. It is crucial to keep the temperature above the melting point of the gelator but below the temperatures at which oil and medication degrade. Achieving appropriate dissolution and homogeneity during the heating process is facilitated by gently swirling or agitating the mixture. After heating and blending, the mixture is allowed to cool gradually while gently stirring. Optimizing the cooling rate is critical because it can affect the final gel structure. The gelator molecules arrange into a three-dimensional network as the mixture cools, trapping the oil inside. Creating an oleogel with a gel-like consistency results from this gradual cooling process [1].

During the cooling process, optional additions such as antioxidants, preservatives, permeation enhancers, and drug-specific may be added to the mixture. Care should be taken when including these additions to guarantee correct mixing and homogeneity within the oleogel. The oleogel goes through several characterization and evaluation stages after it is created. The appearance of the oleogel, including color, transparency, and homogeneity, can be seen through visual inspection. Texture analysis measures the gel's strength and consistency using rheological and penetration testing methods. These analyses include details about the gel's viscoelastic, viscosity, and hardness. While this general procedure gives an overview of the creation of oleogels as shown in Fig. 3, it is crucial to remember that exact processes and requirements can change based on the application, kind of gelator, and desired qualities [45, 46].

Fig. 3
figure 3

Oleogel formation involves adding oleogelators to liquid oil, placing the mixture in a water bath, homogenizing, and then cooling. Cooling solidifies the oil, creating an oleogel with a semi-solid or solid texture

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Characterization of Oleogels

Numerous tests and analyses are used to evaluate oleogels to comprehend their functional, chemical, and physical characteristics. The standard approach to oleogel evaluation is presented below in a systematic manner.

Organoleptic Characters

The consistency, roughness, grease, color, texture, and physical appearance of the formulation are evaluated. The oleogel is examined visually and by applying the gel to the skin and putting a tiny amount of the gel between fingers. The test is conducted on oleogels to assess various sensory attributes and physical properties influencing their acceptability and performance [47].

Gel–Sol Transition

The formation of bonds between particles or molecular sp

ecies, forming a three-dimensional solid network, is termed the sol-gel transition. This transition converts a sol, or colloidal solution, into a gel [48]. Stable oleogels must maintain their gel structure throughout processing and storage to prevent phase separation or syneresis. By comprehending the factors affecting the gel-sol transition, such as selecting appropriate gelling agents and formulation variables, it becomes feasible to enhance the long-term stability of oleogel-based drug delivery systems. Managing drug release rates is crucial to the gel-sol transition in drug delivery systems such as Oleogels [49].

An essential indicator of gel stability and shelf life is the gel melting temperature (Tg). It can be found via the bubble motion method, the glass ball drop method, or the straightforward tube inversion method. Tg is dependent on the solvent's and organogelator's chemical and physical characteristics, as well as any interactions between them. It rises as the concentration of the gelator does. Calculating Tg versus gelator concentration allows for the investigation of the thermal stability of organic gels. Gel-sol transition is absent from permanent gels created by the chemical reaction of massive polymeric molecules [50].

Analysis of texture

Penetration testing is used to gauge the gel's tensile strength and uniformity. It involves penetrating the gel with a cone or needle and measuring the force or depth needed to break through. This method details the gel's hardness or softness [51]. Texture characterization is crucial for pharmaceutical formulations as it directly impacts various factors such as product performance, stability, and patient acceptance. The texture of pharmacological formulations, whether applied topically or orally, significantly influences their ease of application. By utilizing oleogels with optimal spreadability and glide qualities, patients can apply them smoothly and evenly to the skin or mucosal surfaces, enhancing comfort and compliance with treatment protocols. Texture analysis enables the optimization of formulation parameters to achieve the desired application qualities, thereby promoting patient adherence to treatment regimens. Variations in texture can indicate phases of melting, crystallization, or gelation in oleogel compositions. Texture characterization helps identify critical processing temperatures or ranges associated with these transitions, which may affect the shelf life and stability of the product. Monitoring texture changes over time can reveal physical instabilities such as phase separation or syneresis, prompting timely action to maintain product efficacy and quality.

The type and amount of oleogelators added significantly influence the texture of oleogels. Also, increasing the quantity of oleogelators in oleogel formulations leads to decreased hardness, adhesivity, and increased spreadability. This is particularly crucial for various applications such as dressings, sauces, spreads, and desserts. However, the excessive addition of an oleogelator is not optimal [42].

Rheology of oleogels

The rheology of the oleogels is an important parameter in determining the stability of the formulation. Rheometry and other related techniques are frequently used to characterize the rheological properties of oleogels to evaluate their viscoelasticity, viscosity, flow behavior, and stress response. Under stress, oleogels can display both viscous (flowing) and elastic (solid-like) qualities. This is known as their viscoelastic behavior. The type and concentration of gelling agents employed in the formulation of oleogels are among the elements that affect their viscoelastic qualities. An essential rheological characteristic of oleogels that governs their capacity to retain their structural integrity and shape is their strength. By changing variables like the concentration of gelling agents and the manufacturing conditions, oleogels' gel strength may be customized.

One of the parameters studied is steady shear characterization wherein the sample's response to varying flow rates is estimated through viscosity measurement and the oscillatory shear provides information about how the sample will behave in different temperature changes and its stability [52]. Compared to hydrogels and organogels, oleogels show viscoelastic behavior that demonstrates both elastic and viscous properties under stress. They undergo swelling in the presence of aqueous solutions. Hydrogels have a comparatively stable cross-linked structure that shows both viscous and elastic behavior without external stimuli. The properties might differ based on the type of hydrocolloid used in the preparation. Rheological properties of the organogels can be found in their gel strength and viscoelasticity results. The properties can be adjusted based on the gelling agents and the dispersion medium used. The viscoelastic values will differ for different types of samples, and they can't be generalized [53,54,55].

Based on the sources, the given range of acceptable viscoelastic values for oleogels usually comprises a storage modulus (G') between 13,000 and 101,000 Pa and a loss modulus (G") between 12,000 and 14,000 Pa in the applied frequency range. Furthermore, the storage modulus values (G' > G") are typically larger than the loss modulus values, suggesting that oleogels have a true-gel state and a solid-like character. Understanding the structural integrity and behavior of oleogels in various applications requires understanding these viscoelastic properties [56, 57]. Depending on the particular formulation and composition, organogels can have different values for the storage modulus (G') and loss modulus (G"). In one of the research studies, the loss modulus (G") varied from 12,000 to 14,000 Pa within the applied frequency range, while the storage modulus (G') of the organogel samples ranged from 16,000 to 101,000 Pa. In general, the storage modulus (G') was greater than the loss modulus (G"), suggesting that the organogels were in a true-gel state that resembled a solid. An evaluation was also conducted on the loss factor (tan δ = G"/G'), with the allowable range varying based on the particular application and the required viscoelastic properties of the organogel [54, 56, 58].

Instruments Used to Evaluate Rheology of Oleogels

"Rheometer by definition is a tool that measures various physical parameters based on which the rheological parameters of viscous fluids can be estimated" [59]. There are five types of rheometers that work on different principles such as concentric cylinder rotary viscometer, rotating cylinder, cone and plate or plate and plate rotary rheometer, capillary tube rheometer, and vane rheometer. The rheometer will be selected based on the thickness of the fluid or paste [52].

Measurements of Rheology

The rheometer fitted with a cone-plate fixture is used to measure the rheology, and the oleogel formulations will be subjected for a stress relaxation test. The plate's surface will be covered with oleogels. The cone and surface have a set gap angle (θ) of 5 degrees and a 0.5 mm spacing between them. The samples are subjected to a 10% shear strain while at room temperature. The degradation of the oleogels', stress parameter was observed as a function of time. The Following equation determines the prepared oleogels' percent stress relaxation (%SR) under stressed situations, where σmin is the lowest stress achieved after the rest, and σmax is the greatest stress reached when the strain is applied [60].

$$\%SR=\frac{\sigma max-\sigma min}{\sigma max}$$

In Vitro Drug Release Studies

In vitro release tests are performed on oleogels designed for drug delivery. A modified Franz diffusion cell is usually used to perform the in vitro drug release study on oleogels. The drug release over time is measured by adding a known quantity of oleogel to an appropriate dissolution device. The known amount of precisely weighed drug-loaded oleogel will be applied to the membrane. The phosphate buffer (pH 5.8), maintained at 32 ± 0.5°C simulating skin conditions, is used as release media. This assessment aids in understanding the oleogel's drug release profile and release kinetics [61].

Thermal Properties

The thermal properties of oleogels are determined by differential scanning calorimetry or thermal gravimetry analysis to assess the melting point and Tg.

Solid State Characterizations

For the characterization of oleogels, analytical methods such as Fourier-transform infrared spectroscopy (FT-IR) imaging, Nuclear Magnetic Resonance (NMR) spectroscopy, and the analysis of X-ray diffraction are used [62]. These techniques yield important insights into the molecular interactions that occur when organogelator molecules aggregate. Profitable information on hydrogen bonding is provided by FT-IR [63].

NMR Spectroscopy

It serves as a useful tool for confirming the existence of intermolecular hydrogen bonding. The small-angle neutron scattering (SANS) method may be used to study the fibrillar network's shape in organogelators, providing valuable insights into their structural characteristics [64]. NMR spectroscopy stands as a sophisticated method for characterization, allowing for the determination of a sample's molecular structure at the atomic level. Widely utilized in pharmaceutical research and development, NMR spectroscopy provides crucial insights throughout the drug development process, including the identification of drug impurities. NMR spectroscopy enables the detection of various properties such as phase changes, solubility, conformational and configurational alterations, and diffusion potential. Additionally, quantifying the ingredients in pharmaceutical formulations can be achieved using NMR spectroscopy. The relative concentrations of each component can be determined by measuring peak intensities in the NMR spectra. This data evaluates the formulation's consistency, stability, and composition [65].

NMR measurement provides information about the specific interactions, internal mobility of the constituents, and molecular organization of oleogels [66, 67]. By observing the shifting and splitting of signals, NMR can reveal molecular characteristics like chemical composition, shape, bonding, and dynamics, aiding in understanding the general structure and behavior of molecules. Researchers can gain valuable insights into the physical characteris

tics and behavior of oleogels by analyzing and interpreting NMR spectra, which offer indirect information about morphology [68].

Liquid Chromatography-Mass Spectroscopy (LC-MS)

LC-MS, a widely used analytical technique, merges mass spectrometry (MS) with liquid chromatography (LC). The advanced sensitivity of modern MS has led to the replacement of numerous immunoassays by LC-MS. The superior sensitivity and specificity of LC-MS have enhanced the efficiency of drug discovery processes.

LC-MS analysis of oleogels allows for the identification and quantification of various components including the structural agent, different lipid elements, contaminants, and other small compounds. This analytical technique enables the determination of the gel's composition, stability, changes over time, and the presence of impurities or degradation products. Such information is crucial for quality assurance, formulation optimization, and understanding the characteristics and potential applications of oleogels in various fields such as food products, medications, and cosmetics. To ascertain the chain length of chemical components such as free fatty acids (FFA) and fatty alcohols (FAL), and to elucidate the diverse chemical constituents of waxes commonly employed in oleogelation, samples previously separated using High-Performance Liquid Chromatography (HPLC) can be analyzed using gas chromatography-mass spectrometry with an evaporative light scattering detector (HPLC-ELSD). Due to the polar and non-volatile nature of FFA and FAL, they necessitated derivatization to facilitate column mobility [69, 70].

HPLC

HPLC remains one of the most vital analytical tools for quantifying and fingerprinting bioactive chemicals. Its utility is particularly evident in assessing the stability, quality, and chemical composition of oleogels. Furthermore, HPLC is instrumental in estimating the molecular weight of polymers due to their linear polymer backbone. In situations where only a few components are suspected to be present, thin-layer chromatography (TLC) or HPLC can aid in determining sample composition. Initial examinations often employ qualitative or semiquantitative methods. It is the most appropriate and extensively employed analytical technique for quantifying organic compounds [71, 72].

Ultraviolet-Visible Spectroscopy

UV-visible spectroscopy is a common method employed to structurally analyze oleogels and their constituent parts. This non-destructive analytical technique exploits the absorption of UV and visible light by molecules to provide insights into the stability, concentration, and chemical composition of substances within oleogels. Over time, oleogel stability can be monitored using UV-visible spectroscopy. Changes in absorption spectra, such as shifts in peak position or intensity y, can indicate potential oxidation, degradation, or other chemical alterations in the oleogel composition [73].

pH

The pH of the formulation can be determined by directly inserting the electrode of a pH meter into the formulation[74].

Viscosity

Viscosity is a crucial criterion for characterizing oleogels as it influences the texture and spreadability of the product. Measurement of viscosity is typically conducted using viscometers. Subsequently, the viscosity measurements can be plotted against temperature [75].

Extrudability and Spreadability

To measure oleogel extrusion, the time taken for the gel ribbon to extrude from a collapsible tube in ten seconds can be recorded. Approximately one gram of the oleogel can be sandwiched between two glass slides of equal size, weight, and thickness. Initially, the first spreading diameter (Di) is noted. Subsequently, a load of 10, 20, 50, or 100 g can be applied to the upper slide for one minute in each case, and the ultimate spreading diameter (Df) of the gel is recorded. Extrudibility is measured in cm/s, while spreadability is expressed as a percentage[66].

The spreadability percentage can be calculated using the following equation:

$$\%\;Spreadability=\left(Df-Di\right)/Di\times100$$

Advantages and Disadvantages of Oleogels

Oleogels hold promise as an ideal matrix for medication delivery, with a significant portion of research focused on their applications. Oleogels are well-suited for long-term medication delivery due to their non-covalent, self-assembling nature, offering flexibility and reversibility. It emphasizes the ease of combining medication with oleogels, which can be tailored to deliver various medications. There is an additional benefit of employing oleogels in medication delivery, as many are composed of biocompatible substances such as lipids and fatty acids, boasting excellent safety records for human application. In a recent review paper, the researcher outlines ingredients and methods food scientists use to enhance oleogels, exploring potential medicinal applications. These biocompatible materials, comprised of tiny, amphiphilic molecules, utilize non-covalent interactions to capture liquid oil while self-assembling. They possess qualities conducive to slow-release medications, particularly those used in treating mental illness or cancer. Oleogels exhibit viscosity loss under mechanical force, yet regain it upon force release, offering protective properties. Compared to other types of gels, oleogels offer increased stability and simplicity in preparation, along with enhanced drug permeability. They are unaffected by moisture and incur reduced expenses due to fewer ingredients. Oleogels exhibit stability in the short term and are suitable for drugs requiring controlled release, extended shelf life, low half-lives, and long-term effects. They eliminate the need for frequent medication doses and are easier to remove from the skin with less oily residue.

However, oleogel formulations have certain drawbacks. Inappropriate partition coefficients may compromise skin permeability, making them unsuitable for medications causing skin irritation or sensitivity. Storage requirements are also critical, as impurities can prevent gelling. Additionally, swelling may occur when the gel absorbs liquid exceeding its volume, while spontaneous contraction and liquid release, known as syneresis, can be undesirable [11, 76].

Stability Problems Associated with the Oleogelators

A significant obstacle to the commercial adoption of oleogels as fat substitutes is the lack of robust data on their safety and potential health benefits. Often, the presumed health advantages of oleogels are attributed to their higher content of unsaturated fatty acids compared to saturated fats. Certain gelling agents, such as wax, may fail to produce oleogels with the desired solid fat-like structure at low concentrations. Conversely, excessive incorporation of oleogelators, like wax, into oleogels may adversely affect the mouthfeel and consumer perception of final food products.

Many food manufacturing processes involve high shear forces, such as dough mixing, which can disrupt the self-assembled fibrillar networks formed by low-molecular-weight oleogelators, leading to a loss of solid-like structure and impacting the texture and overall acceptability of the product. Moreover, some oleogelators, such as phytosterols like oryzanol and sitosterol, are highly sensitive to water, resulting in instability when incorporated into foods with high water content.

The instability of sterol-based oleogelators in water-rich foods may be attributed to water binding to the hydroxyl group of sitosterol, forming hydrate crystals that disrupt the hydrogen-bonded network. Furthermore, while oleogels made from natural waxes exhibit desirable qualities, their stability may be compromised during prolonged storage due to the vulnerability of waxes to post-crystallization alterations, including crystal aggregation [77].

Applications of Oleogels

There are various applications of oleogels as summarized in the Fig. 4.

Fig. 4
figure 4

Applications of oleogels

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Oleogels in the Delivery of Nutraceuticals

Foods or food ingredients known as nutraceuticals can either treat or prevent disease [78]. B-carotene, lycopene, curcumin, docosahexaenoic acid (DEA), eicosapentaenoic acid, linoleic acid, linolenic acid, the tannins, flavanols, and phytosterols are a few examples of soluble in fat nutraceutical substances [76]. By employing oleogels for controlled release, these substances' therapeutic efficacy can be increased. Vegetable fats, frequently used as the liquid continuous stage in oleogels, are a natural source of nutrients because they are a good source of phytosterols and their esters. When phytosterols are included in oleogels, they erratically travel to an application site alongside therapeutic or bioactive substances. Phytosterols, including b-sitosterol, dehydrocholesterol, stigma sitosterol, and lipids, can function as oleogelators as well as nutraceuticals. They have been combined with g-oryzanol to form gels of sunflower seed oil, producing clear oleogels with tiny, brief fibrils [31]. Consuming the phytosterols ceramides, and fatty acids from the ceramide group resulted in 30% reduced serum cholesterol levels and improved general serum lipoprotein composition in rats [79, 80]. A policosanol/olive made from oil oleogel is also created to give the nutraceutical component ferulic acid orally. Due to its antioxidant qualities, ferulic acid has potential uses in treating diabetes, Alzheimer's disease, cancer, and other degenerative disorders [81, 82]. In summary, the case study delves into utilizing oleogels as carriers for nutraceuticals, renowned for their capacity to prevent or alleviate ailments. When integrated into oleogels, nutrients such as ferulic acid and phytosterols have exhibited the potential to reduce cholesterol levels and address various degenerative conditions. Oleogels offer controlled release mechanisms, augmenting the bioavailability and effectiveness of these compounds, thereby presenting opportunities to optimize health outcomes.

Oleogels in Cosmetics

In comparison to the substantial study on oleogels in food and medicine, cosmetics study is still in its earliest stages. Most of the bioactive compounds used in cosmetics are lipophilic molecules, including the vitamins A, D, K, and E, coenzyme Q10, glucosamine, N-acetyl glucosamine, ferulic acid, and other antioxidants. However, most research is concentrated on employing organic solvents as carriers rather than vegetable oils to deliver the bioactive chemicals. The worse organoleptic qualities of vegetable oils might cause this. Because they have both hydrophilic and lipophilic characteristics, The liquid continuous medium used in lecithin organogels is an appealing delivery system for cosmetic compounds [83].

Most skin care products on the market today are emulsion-based, which means they have a lipid and oil phases. This category includes oleogels as well as oils. They are utilized in dermatological cosmetics because they are particularly suggested for skin types with issues. Problem solutions for this population are becoming increasingly important as more people, in particular those with skin barrier diseases, rely on physiological lipids in large dosages. In this situation, oleogels, also referred to as lipogels, are advised. Oleogels, in contrast to liquid oils, have a semi-solid, gel-like consistency, much like cream emulsions. This consistency will be reached with the help of additives, which form a sponge-like structure and enable them to absorb enormous amounts of lipids [84].

When utilizing oleogels, skin hydration rises more slowly than when using emulsions. Additionally, unlike emulsions, there won't be an external water source. Therefore hydration will only be possible through internal skin processes. By lowering trans epidermal water loss (TEWL), the oleogels' lipids contribute to this process. Additionally, oleogels can incorporate naturally occurring water-retaining ingredients like urea, which has antipruritic properties. There won't be any issues with the urea's long-term stability here, unlike emulsions containing water [1, 85].

In contrast to their established roles in food and medicine, oleogels are still undergoing exploration in cosmetics, as detailed in the case study. While lipophilic substances like antioxidants and vitamins are common in cosmetics, research has predominantly favored organic solvents over vegetable oils due to sensory concerns. However, oleogels, characterized by their semi-solid consistency, are gaining popularity, particularly in dermatological products targeting skin barrier issues. Their incorporation of water-retaining agents like urea and gradual hydration offers advantages, alongside stability and antipruritic properties. Overall, oleogels hold promise for effectively delivering lipophilic compounds and addressing various skincare concerns in cosmetics.

Oleogels in the Food Industry

Oleogels are primarily used in the food business to substitute solid fats, which harm health. These oleogel components are rich in unsaturated fats, considered healthier than solid fats [86]. However, the limited availability of affordable food-grade oleogels restricts their application in the food sector. For instance, candelilla wax combined with canola oil can impart a soft texture to cookies [87]. In frankfurters, porkback fat is replaced with oleogel emulsions containing γ-oryzanol and β-sitosterol to reduce saturated fat content. In recent years, oleogels have been found to be used in ice cream, chocolate, margarine, shortening, and meat products [16]. Cakes made with shellac oleogels exhibit notable distinctions in size, volume, stickiness, and sponginess compared to cakes produced using shortenings [88]. Shortenings are commonly preferred due to their ability to aerate without disrupting the batter's consistency. Oleogels can provide chocolates with thermal stability and display foamability similar to traditional shortenings. Shellac resins serve as structural agents in chocolates [45, 88, 89]. Thus, the application of oleogels in the food industry can be explored as a healthier alternative to unhealthy solid fats. Oleogels, being rich in unsaturated fats, offer a healthier fat option. Various applications include using oleogels to impart a soft texture to cookies by blending candelilla wax and canola oil, substituting pork back fat in frankfurters with oleogel emulsions containing γ-oryzanol and β-sitosterol to reduce saturated fat content, etc.

Oleogels as Lubricants

Lubricants are used to improve mechanical performance and lower friction between moving parts. Phyllosilicates, metallic soaps, or polyurea derivatives are used to thicken gel-like solutions of colloidal particles that make up traditional lubricating greases. Depending on the requirements, these oils might or might not include antioxidants and anticorrosion agents [90,91,92]. In recent years, there has been a noticeable trend towards using environmentally friendly products made from renewable resources, which has led to the hunt for alternatives to traditional lubricants. Over the past two decades, the use of vegetable oil in place of mineral oil in lubricant compositions has increased [93, 94]. Vegetable oils present several benefits, such as being environmentally friendly, having low toxicity, high load-carrying capacity, minimal evaporation, and adequate solvency for additives. However, they also have drawbacks, including inadequate oxidation stability, subpar performance at low temperatures, and elevated costs [95, 96].

Low-viscosity vegetable oils, like soybean and rapeseed oils, were also used to create oleogels. Stronger oleogels were produced when glyceryl monostearate (GMS) rather than sorbitan monostearate was utilized as the gelator. It has been discovered that oleogels created with low-viscosity oils like rapeseed and soybean have higher linear viscoelastic characteristics than oleogels produced with high-viscosity oils like castor oil. It is thought that the greater dissolution of gelators in low-viscosity oils helps to reinforce the network of structures in these oleogels. The rheological response of sorbitan monostearate oleogels is significantly influenced by the pace of cooling during manufacturing [53, 90, 92, 97, 98]. Hence, incorporating oleogels into lubricants emerges as a more environmentally friendly alternative to conventional options. While diverse compounds are typically employed to thicken lubricating greases, the rising popularity of vegetable oils stems from their commendable load-carrying capacity and minimal toxicity.

Oleogels in Pharmaceuticals

Typically, finding an effective vehicle for delivering lipophilic bioactive chemicals is more challenging than it is for hydrophilic bioactive agents. From this perspective, emulsions are frequently employed to administer lipophilic substances, such as vitamins, antioxidants, sterols, etc. Oleogels can deliver the active lipophilic compounds used instead of emulsions. Due to their beneficial characteristics, oleogels have attracted a lot of attention in the fields of drug delivery and the administration of nutraceuticals. The capability to carry and break down lipophilic substances, thermoreversibility, the ability to change mechanical and textural properties, and controlled drug release are a few of these. Oleogels are frequently resistant to contamination by bacteria and moisture because they don't contain water. The use of oleogels in various administration techniques, including transdermal, parenteral, topical, and oral drug delivery applications, is therefore being researched and is summarized in Table I [99, 100].

Table I Application of Oleogels in Pharmaceuticals
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Topical and Transdermal Delivery

When compared to alternative drug delivery strategies, crossing the skin to provide medication is by far the most convenient method. This method of drug delivery has the benefits of avoiding first-pass metabolism, compliance from patients, and non-invasiveness. However, there aren't as many delivery options as possible for moving medications across the skin. Distribution of medications is difficult due to their lipophilic nature and the stratum corneum's lipid bilayer. Oleogels are seen as a promising remedy to address these problems and enable the efficient administration of lipophilic medications. Oleogels are most suited for topical and transdermal distribution, even if they have the potential to be utilized in other delivery methods. Due to their lipophilic nature, oleogels improve medication penetration into the stratum corneum's lipid bilayer [107].

Numerous oleogel components act as permeation enhancers, which is why drug penetration has increased. The main oleogel permeability enhancers are saturated and unsaturated fatty acids linked to vegetable oils. The stratum corneum's lipid bilayers are penetrated by fatty acids, which split the permeable routes into their domains. Oleogels are frequently supplemented with permeation enhancers, such as surfactants as well as phospholipids glycols, terpenes, and lecithin to improve medicine permeability through the skin barrier and boost their stability. Depending on the kind of oleogel and the purpose for which it is designed, these enhancers may be added. The stratum corneum absorbs surfactants and phospholipids, which results in the hydration of tissues. They disturb corneocytes by fluidizing the lipid bilayer, which enhances drug penetration and breaks the lipid bilayer [108].

For the local treatment of skin infections such as acne vulgaris and skin wound infections, azithromycin oleogel is used. Creating an azithromycin topical formulation is widely favored to prevent unwanted systemic side effects like diarrhea, nausea, and stomach pain. Such a formulation would allow for easy administration to the affected area, prevent first-pass metabolism, enhance patient acceptance, give individuals unable to take oral drugs an option and provide a non-invasive and useful delivery route [49]. The topical drug delivery (Oleogel) system of Serteconazole was developed to decrease the amount of active medicine that causes side effects, increase patient compliance, and improve local onset absorption and action. The cytochrome P-450 (C-450) enzyme 14-demethylase, which converts lanosterol into ergosterol, interacts with saraconazole. The ergosterol found in fungal cell membranes is essential. Inhibiting its synthesis causes cells to become more permeable, which causes their contents to flow out [101]. Other formulations of olmesartan medoxomil with oleogel were developed to reduce the side effects and increase its therapeutic effectiveness and bioavailability. The ingredients in olesartan oleogel compositions included Tween 20, Aerosil 200, and lavender oil [12].

Persian medicine (PM), in particular, offers a possible source for cutting-edge migraine remedies. PM has always utilized traditional chamomile oil, which is extracted in sesame oil, as a migraine pain treatment. Chamazulene (an aromatic oil marker) and apigenin were determined using gas chromatography (GC) and HPLC to standardize the formulation. The outcomes demonstrated that chamomile oleogel effectively treats migraines without aura [109].

By lowering swelling and inflammation, NSAIDs, or nonsteroidal anti-inflammatory drugs, can be utilized for treating periodontitis. NSAIDs can be given locally using drug delivery systems for this reason. The study used three distinct gel formulations—hydrogel, oleogel, and bi-gel- to assess the effectiveness of local delivery of the NSAID model medication, ibuprofen, for treating periodontitis. The findings demonstrated that the mechanical qualities (rheological and bioadhesive qualities) were affected by the gel formulation chosen (hydrogel, oleogel, or bigel). The most promising prospective drug delivery technologies for locally treating periodontitis were ibuprofen bigel and oleogel. Additionally, oleogel and bi-gel formulations may effectively deliver water-insoluble medications locally as shown in Fig. 5 [110]. Additionally, oleogel and bi-gel formulations may prove to be effective means of delivering water-insoluble medications locally [110].

Fig. 5
figure 5

Drug Delivery into Periodontitis Pocket. Ibuprofen Bigel and oleogel are top contenders for treating periodontitis locally

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Due to poor skin permeability, using upconversion nanoparticles (UCNP) as a theranostic agent in skincare is constrained. The study investigates the transdermal delivery for UCNP through an oleogel-based local formulation to improve penetration into the inner skin structure,. A heat-cool approach was used to insert oleylamine-coated UCNP (OA-UCNP) into oleogels with different concentrations. Based on photoluminescence spectroscopy, the UCNP-oleogel with the greatest OA-UCNP concentration (UG4) displayed the highest luminosity. The ability of UCNP to permeate skin tissue when administered topically was proven in vitro testing utilizing gel made from agarose and animal skin models [111].

Ocular Drug Delivery

The barrier to drug transport to the back of the eye is one of the main challenges in treating posterior segment illnesses. Topical distribution via eye drops is unsuccessful due to quick clearance from tears and the huge barrier provided by the conjunctiva-sclera layers, while systemic delivery is ineffective due to the massive retina blood barrier [112,113,114,115]. Most retinal illnesses are now treated with intravitreal injections, which are invasive and can have major side effects like retinal detachment [116,117,118,119]. Several methods, such as sclera implants, iontophoresis, microneedling, sub-tenon injections, ocular inserts, and sub-tenon injections, are being researched to deliver medications for retinal illnesses [120,121,122]. Even though bioavailability is exceedingly low due to the quick evacuation of tears, eye drops are still thought to be a possibility [123,124,125]. Although each strategy shows promise, there are issues, such as clinical consequences, difficult device insertion, ineffectiveness, expenses, etc. Ophthalmic medicines cannot be delivered via topical or systemic routes to treat retinal disorders [126,127,128,129].

Dexamethasone was loaded into oleogels that had ethyl cellulose as the gelator at a concentration of 10% (wt.%) in soybean oil, exceeding the drug's solubility limit, and then expelled from the syringe to form cylindrical rods for prolonged drug delivery. Drug release was evaluated in a buffer under sink conditions [103], through intravitreal Injections, as shown in the Fig. 6. Drug release was evaluated in a buffer under sink conditions after the devices were photographed to investigate particle distribution.

Fig. 6
figure 6

Intra-vitreal injections utilized for delivery of drugs to Retina

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Research on oleogel-based formulations for ocular drug delivery (ODD) has dominated in recent years. Groundnut oil (GNO), the acid stearic (SA), and graphene oxide (GO), among others, were used to make nanocomposite oleogels in a variety of concentrations. The oleogels turned black with higher GO concentrations. At lower GO concentrations, confocal imaging showed greater branches in the fibrillar arrangement of fat crystals. The amount of medication absorbed through the caprine cornea was increased by a factor of two when the oleogel contained 0.05% GO. The created oleogels had significant antibacterial properties against E. coli and showed cytocompatibility against human mesenchymal stem cells. These results demonstrate the potential of nanocomposite oleogels based on GNO/SA/GO for ODD applications [104].

Due to the blood-retina barriers and drug elimination mechanisms, systemically and local delivery systems have difficulty successfully delivering drugs to the back of the eye. Drug delivery techniques that are controlled and prolonged can assist lessen the need for repeated injections and lower the likelihood of side effects. Even above their solubility threshold, metformin HCl and timolol maleate are integrated into oleogels made of 10% ethyl cellulose in soybean oil, causing the drug particles to disperse throughout the gelled oil. Another method involves gelling the oil phase after hydrophilic medicines have been dissolved in the water phase of water-in-oil emulsions. These methods allow for regulated and prolonged drug administration, which decreases the need for repeated injections and lessens the side effects that go along with them. [105].

A study illustrates the adaptability of oleogels in accommodating hydrophilic drugs for intravitreal, subconjunctival, or intracameral injections aimed at treating eye ailments. Using metformin hydrochloride and timolol maleate as model drugs, the study explored two methods of drug integration: directly into the oily phase or within a water-oil emulsion. Findings indicated prolonged release durations, ranging from 120 to 1400 h for metformin HCl and from 400 to 2200 h for timolol maleate, contingent upon drug loading concentrations and formulation strategies. These outcomes underscore oleogels' potential as effective carriers for hydrophilic drugs, offering sustained release profiles crucial for managing various ocular disorders [105].

Challenges and Future Prospects of Oleogels

Oleogels hold promising prospects in the pharmaceutical sector, offering versatile solutions for drug delivery across various contexts. As researchers delve deeper into their properties and potential applications, oleogels can address persistent challenges in pharmaceutical formulations. Their capability to deliver drugs through the skin presents an opportunity to transform the treatment of skin disorders like inflammation, wound infections, and acne. Their ability to deliver drugs to the eyes suggests a new and innovative approach to treating ocular conditions.

Moreover, the recent approval by the FDA of oleogel-based products underscores the growing acceptance of these formulations within the pharmaceutical industry, paving the way for further advancements and innovation in drug delivery techniques. Thus, pharmaceutical oleogels hold a promising future, offering opportunities to enhance treatment accessibility, patient outcomes, and therapeutic effectiveness.

Injectable Depots

Long-acting injectables are explored nowadays to obtain sustained drug release. Tenofovir drug-loaded chitosan nanoparticles were formulated and spray-dried. The NPs were incorporated with the oleogel matrix and were tested for their stability through non-newtonian rheological properties. More than 40-60% sustained release was observed compared to chitosan nanoparticles and standards. The results could be attributed to both the NPs and the oleogel for sustained drug release [106]. In a study, sustained release characteristics of the extended-release long-acting oleogel formulation of bupivacaine were demonstrated, with an increase in the concentration of vegetable oils. The drug was completely dissolved in the non-polar organic phase and slowly released whenever necessary [130]. FDA approved an oleogel named Filsuvez, a topical gel for treating partial thickness wounds and Junctional Epidermolysis Bullosa (JEB) on 19th December 2023. The primary endpoint of the clinical trial was based on the complete closure of the wound within 45 days of the treatment [131].

Conclusion

In conclusion, oleogels represent a versatile and innovative semi-solid solution in the pharmaceutical industry, offering stable and scalable platforms for delivering diverse active pharmaceutical ingredients (APIs). Various structuring agents allow precise control over rheological properties, enabling tailored drug release profiles. Oleogels boast advantages over conventional dosing forms, including enhanced stability, prolonged shelf life, and improved API bioavailability. Their customizable rheological features make them suitable for prolonged or targeted drug delivery applications across topical, transdermal, oral, and ocular formulations [132, 133]. Oleogels find applications across therapeutic fields such as ophthalmology, dermatology, wound healing, and pain management, effectively delivering medications to target sites regardless of hydrophilic or lipophilic nature.

The addition of active substances further enhances their therapeutic potential. As research and development continue, oleogels promise to revolutionize pharmaceutical formulations, offering improved therapeutic effects and patient satisfaction.