Effect of Terpenes on the Enhancement of Skin Permeation of Lipophilic Drugs: A Systematic Review.

Objectives: The stratum corneum (SC) remains an obstacle to the passage of drugs applied topically. Several investigations have focused on enhancing the penetration of drugs through the SC by integrating permeation enhancers (PE) into the drug formulation. Terpenes are among the PE utilized in formulations and are categorized by the regulatory bodies as generally recognized as safe (GRAS). This study aimed to comparatively analyze the skin permeation enhancing effect of terpenes on lipophilic drugs. Methods: The present study reviewed the effects of terpenes on the permeation of lipophilic small-molecule drugs through the skin using original research published between 2000 - 2022 retrieved from PubMed®. The search phrase used was (lipophilic drug) AND (terpene) AND (permeation enhancer). Results: Terpenes increase the percutaneous permeation of lipophilic small molecule drugs by 1.06 - 256.80-fold. Linear correlation analysis of terpenes' cLog P with enhancement ratio (ER) revealed moderate and strong positive correlations in pig skin (r = 0.21) and mouse skin (r = 0.27), and rat skin (r = 0.41) and human skin (r = 0.67), respectively. Drug cLog P is a poor (r = -0.06) predictor of permeation enhancement. Terpenes with cLog P higher than 2.40 had ER greater than 10. Higher ERs (>30) were recorded for nerolidol, carvacrol, borneol, terpineol, limonene, menthone, pulegone, and menthol among the terpene-chemical penetration enhancers. Conclusion: cLog P of terpene-based chemical permeation enhancers (CPE) is strongly correlated with ER of lipophilic drugs across human skin. Non-polar groups in terpenes and hydrogen bond interactions by terpenes with SC lipid enhance cutaneous drug penetration of lipophilic drugs.

Nanosuspension-Loaded Dissolving Microneedle Patches for Enhanced Transdermal Delivery of a Highly Lipophilic Cannabidiol.

Purpose: Transdermal Drug Delivery System (TDDS) offers a promising alternative for delivering poorly soluble drugs, challenged by the stratum corneum's barrier effect, which restricts the pool of drug candidates suitable for TDDS. This study aims to establish a delivery platform specifically for highly lipophilic drugs requiring high doses (log P > 5, dose > 10 mg/kg/d), to improve their intradermal delivery and enhance solubility. Methods: Cannabidiol (CBD, log P = 5.91) served as the model drug. A CBD nanosuspension (CBD-NS) was prepared using a bottom-up method. The particle size, polydispersity index (PDI), zeta potential, and concentration of the CBD-NS were characterized. Subsequently, CBD-NS was incorporated into dissolving microneedles (DMNs) through a one-step manufacturing process. The intradermal dissolution abilities, physicochemical properties, mechanical strength, insertion depth, and release behavior of the DMNs were evaluated. Sprague-Dawley (SD) rats were utilized to assess the efficacy of the DMN patch in treating knee synovitis and to analyze its skin permeation kinetics and pharmacokinetic performance. Results: The CBD-NS, stabilized with Tween 80, exhibited a particle size of 166.83 ± 3.33 nm, a PDI of 0.21 ± 0.07, and a concentration of 46.11 ± 0.52 mg/mL. The DMN loaded with CBD-NS demonstrated favorable intradermal dissolution and mechanical properties. It effectively increased the delivery of CBD into the skin, extended the action's duration in vivo, and enhanced bioavailability. CBD-NS DMN exhibited superior therapeutic efficacy and safety in a rat model of knee synovitis, significantly inhibiting TNF-α and IL-1ß compared with the methotrexate subcutaneous injection method. Conclusion: NS technology effectively enhances the solubility of the poorly soluble drug CBD, while DMN facilitates penetration, extends the duration of action in vivo, and improves bioavailability. Furthermore, CBD has shown promising therapeutic outcomes in treating knee synovitis. This innovative drug delivery system is expected to offer a more efficient solution for the administration of highly lipophilic drugs akin to CBD, thereby facilitating high-dose administration.

Lipid Nanocapsule: A Novel Approach to Drug Delivery System Formulation Development.

Nanocapsules are polymeric nanoparticles encased in a polymeric coating composed of a predominantly non-ionic surfactant, macromolecules, phospholipids, and an oil core. Lipophilic drugs have been entrapped using various nanocarriers, including lipid cores, likely lipid nanocapsules, solid lipid nanoparticles, and others. A phase inversion temperature approach is used to create lipid nanocapsules. The PEG (polyethyleneglycol) is primarily utilised to produce nanocapsules and is a critical parameter influencing capsule residence time. With their broad drug-loading features, lipid nanocapsules have a distinct advantage in drug delivery systems, such as the capacity to encapsulate hydrophilic or lipophilic pharmaceuticals. Lipid nanocapsules, as detailed in this review, are surface modified, contain target-specific patterns, and have stable physical and chemical properties. Furthermore, lipid nanocapsules have target-specific delivery and are commonly employed as a marker in the diagnosis of numerous illnesses. This review focuses on nanocapsule synthesis, characterisation, and application, which will help understand the unique features of nanocapsules and their application in drug delivery systems.

Effect of Terpenes on the enhancement of skin permeation of lipophilic drugs: A systematic review

Objectives@#The stratum corneum (SC) remains an obstacle to the passage of drugs applied topically. Several investigations have focused on enhancing the penetration of drugs through the SC by integrating permeation enhancers (PE) into the drug formulation. Terpenes are among the PE utilized in formulations and are categorized by the regulatory bodies as generally recognized as safe (GRAS). This study aimed to comparatively analyze the skin permeation enhancing effect of terpenes on lipophilic drugs. @*Methods@#The present study reviewed the effects of terpenes on the permeation of lipophilic small-molecule drugs through the skin using original research published between 2000 - 2022 retrieved from PubMed®. The search phrase used was (lipophilic drug) AND (terpene) AND (permeation enhancer). @*Results@#Terpenes increase the percutaneous permeation of lipophilic small molecule drugs by 1.06 – 256.80-fold. Linear correlation analysis of terpenes’ cLog P with enhancement ratio (ER) revealed moderate and strong positive correlations in pig skin (r = 0.21) and mouse skin (r = 0.27), and rat skin (r = 0.41) and human skin (r = 0.67), respectively. Drug cLog P is a poor (r = -0.06) predictor of permeation enhancement. Terpenes with cLog P higher than 2.40 had ER greater than 10. Higher ERs (>30) were recorded for nerolidol, carvacrol, borneol, terpineol, limonene, menthone, pulegone, and menthol among the terpene-chemical penetration enhancers. @*Conclusion@#cLog P of terpene-based chemical permeation enhancers (CPE) is strongly correlated with ER of lipophilic drugs across human skin. Non-polar groups in terpenes and hydrogen bond interactions by terpenes with SC lipid enhance cutaneous drug penetration of lipophilic drugs.

Exploring LIPIDs for their potential to improves bioavailability of lipophilic drugs candidates: A review.

This review aims to provide a thorough examination of the benefits, challenges, and advancements in utilizing lipids for more effective drug delivery, ultimately contributing to the development of innovative approaches in pharmaceutical science. Lipophilic drugs, characterized by low aqueous solubility, present a formidable challenge in achieving effective delivery and absorption within the human body. To address this issue, one promising approach involves harnessing the potential of lipids. Lipids, in their diverse forms, serve as carriers, leveraging their unique capacity to enhance solubility, stability, and absorption of these challenging drugs. By facilitating improved intestinal solubility and selective lymphatic absorption of porously permeable drugs, lipids offer an array of possibilities for drug delivery. This versatile characteristic not only bolsters the pharmacological efficacy of drugs with low bioavailability but also contributes to enhanced therapeutic performance, ultimately reducing the required dose size and associated costs. This comprehensive review delves into the strategic formulation approaches that employ lipids as carriers to ameliorate drug solubility and bioavailability. Emphasis is placed on the critical considerations of lipid type, composition, and processing techniques when designing lipid-based formulations. This review meticulously examines the multifaceted challenges that come hand in hand with lipid-based formulations for lipophilic drugs, offering an insightful perspective on future trends. Regulatory considerations and the broad spectrum of potential applications are also thoughtfully discussed. In summary, this review presents a valuable repository of insights into the effective utilization of lipids as carriers, all aimed at elevating the bioavailability of lipophilic drugs.

Preparation and Characterization of Amorphous Solid Dispersions for the Solubilization of Fenretinide.

Fenretinide (4-HPR), a retinoid derivative, has shown high antitumor activity, a low toxicological profile, and no induction of resistance. Despite these favorable features, the variability in oral absorption due to its low solubility combined with the high hepatic first pass effect strongly reduce clinical outcomes. To overcome the solubility and dissolution challenges of poorly water-soluble 4-HPR, we prepared a solid dispersion of the drug (4-HPR-P5) using a hydrophilic copolymer (P5) previously synthesized by our team as the solubilizing agent. The molecularly dispersed drug was obtained by antisolvent co-precipitation, an easy and up-scalable technique. A higher drug apparent solubility (1134-fold increase) and a markedly faster dissolution were obtained. In water, the colloidal dispersion showed a mean hydrodynamic diameter of 249 nm and positive zeta potential (+41.3 mV), confirming the suitability of the formulation for intravenous administration. The solid nanoparticles were also characterized by a high drug payload (37%), as was also evidenced by a chemometric-assisted Fourier transform infrared spectroscopy (FTIR) investigation. The 4-HPR-P5 exhibited antiproliferative activity, with IC50 values of 1.25 and 1.93 µM on IMR-32 and SH-SY5Y neuroblastoma cells, respectively. Our data confirmed that the 4-HPR-P5 formulation developed herein was able to increase drug apparent aqueous solubility and provide an extended release over time, thus suggesting that it represents an efficient approach to improve 4-HPR bioavailability.

Recent Progress of Lipid Nanoparticles-Based Lipophilic Drug Delivery: Focus on Surface Modifications.

Numerous drugs have emerged to treat various diseases, such as COVID-19, cancer, and protect human health. Approximately 40% of them are lipophilic and are used for treating diseases through various delivery routes, including skin absorption, oral administration, and injection. However, as lipophilic drugs have a low solubility in the human body, drug delivery systems (DDSs) are being actively developed to increase drug bioavailability. Liposomes, micro-sponges, and polymer-based nanoparticles have been proposed as DDS carriers for lipophilic drugs. However, their instability, cytotoxicity, and lack of targeting ability limit their commercialization. Lipid nanoparticles (LNPs) have fewer side effects, excellent biocompatibility, and high physical stability. LNPs are considered efficient vehicles of lipophilic drugs owing to their lipid-based internal structure. In addition, recent LNP studies suggest that the bioavailability of LNP can be increased through surface modifications, such as PEGylation, chitosan, and surfactant protein coating. Thus, their combinations have an abundant utilization potential in the fields of DDSs for carrying lipophilic drugs. In this review, the functions and efficiencies of various types of LNPs and surface modifications developed to optimize lipophilic drug delivery are discussed.

The clinical effect of intravenous lipid emulsion on rabbits medicated with diazepam.

Intravenous lipid emulsions (ILE) have been increasingly used to reverse a wide range of lipophilic drug intoxications. However, it is still unknown if these emulsions interfere with other lipophilic drugs routinely used while treating intoxicated patients, such as diazepam, one of the main antiepileptic drugs. Therefore, the objective of the present study was to evaluate whether the administration of a 20% ILE interferes with diazepam's clinical effect. We randomly allocated thirty rabbits to five groups. Three of those groups received diazepam (1.0 mg/kg, IV), one of which did not receive any additional treatment, while the two remaining groups were treated with ILE or lactated ringer solution (1.5 mL/kg followed by 0.25 mL/kg/min for 30 min). The fourth group only received lipid emulsion, and the fifth only lactated ringer. Successive neurological exams at 20 min intervals for a total of 100 min were performed to assess the rabbits' neurological state. We concluded that the ILE did not interfere with diazepam's clinical effect but, although unlikely, the possibility of recurrence of a sedative effect should be considered.

Solid Lipid Nanoparticles (SLNs): Advancements in Modification Strategies Toward Drug Delivery Vehicle.

Solid lipid nanoparticles are at the cornerstone of the swiftly growing area of medical nanotechnology, having several potential functions in drug delivery, research, clinical care, and a variety of other fields. They provide the opportunity of developing novel therapies due to their unique properties, such as small particle size and being prepared from physiological biodegradable lipids. The loading of bioactive molecules into nanocarriers is a novel drug delivery prototype employed for various drug targeting levels. Hence, SLNs hold a great promise for achieving the aim of targeted and controlled drug delivery. For this reason, they have attracted the extensive attention of scientists and researchers. This review is based on recent studies and research, and here we present advantages, disadvantages, and preparation methods, several advanced modifications, targeting strategies, and recent applications of solid lipid nanocarriers in drug delivery systems.

A Comprehensive Insight on Recent Advancements in Self-emulsifying Drug Delivery Systems.

A large proportion of new chemical moieties are poorly water-soluble. As a result, the biggest challenge for researchers is to enhance the solubility and oral bioavailability of lipophilic drugs. Self-emulsifying systems offer immense potential for improving lipophilic drugs' oral bioavailability and solubility through various mechanisms such as: inhibiting efflux transporters, absorption of the lipophilic drug through the lymphatic system, and bypassing hepatic first-pass metabolism. These systems dissolve hydrophobic drugs, allowing them to be delivered in a unit dose form for oral administration. Despite much potential, issues like stability, low drug loading, packaging, etc., are associated with the self-emulsifying technique. This review discusses conventional Self-Emulsifying Drug Delivery Systems (SEDDS), which deliver poorly water-soluble drugs. Recent advancements in self-emulsifying systems to solve the issues associated with conventional SEDDS are described exhaustively, including their methodologies and excipients utilized for preparation. The current article also furnishes a literature review on recent advancements in self-emulsifying systems. Recent advances in SEDDS are a great option for overcoming oral bioavailability, stability, and solubility issues of lipophilic drugs. Solid-self emulsifying system can be used to improve the stability of the formulation, hydrophobic ion-pairing for improving mucus permeation properties, while supersaturated self-emulsifying systems with a low concentration of surfactant to overcome issues such as precipitation of drug after dilution and gastrointestinal related side effects. The day will come when medicine companies will see the value of selfemulsifying system developments and adopt this technology for next-generation product releases.

Molecular Dynamics Simulations of Self-Assembling Colloids in Fed-State Human Intestinal Fluids and Their Solubilization of Lipophilic Drugs.

Bioavailability of oral drugs often depends on how soluble the active pharmaceutical ingredient is in the fluid present in the small intestine. For efficient drug discovery and development, computational tools are needed for estimating this drug solubility. In this paper, we examined human intestinal fluids collected in the fed state, with coarse-grained molecular dynamics simulations. The experimentally obtained concentrations in aspirated duodenal fluids from five healthy individuals were used in three simulation sets to evaluate the importance of the initial distribution of molecules and the presence of glycerides in the simulation box when simulating the colloidal environment of the human intestinal fluid. We observed self-assembly of colloidal structures of different types: prolate, elongated, and oblate micelles, and vesicles. Glycerides were important for the formation of vesicles, and their absence was shown to induce elongated micelles. We then simulated the impact of digestion and absorption on the different colloidal types. Finally, we looked at the solubilization of three model compounds of increasing lipophilicity (prednisolone, fenofibrate, and probucol) by calculating contact ratios of drug-colloid to drug-water. Our simulation results of colloidal interactions with APIs were in line with experimental solubilization data but showed a dissimilarity to solubility values when comparing fasted-/fed-state ratios between two of the APIs. This work shows that coarse-grained molecular dynamics simulation is a promising tool for investigation of the intestinal fluids, in terms of colloidal attributes and drug solubility.

LC-MS/MS method for the determination of a semi-synthetic phenolic antioxidant 2,6-diisobornyl-4-methylphenol in rats after different administration routes.

IBP (2,6-diisobornyl-4-methylphenol) is a small drug molecule with antioxidant properties considered to be a promising neuro-, cardio-, and retinoprotective agent. In this study, a bioanalytical LC-MS/MS method for its determination in rat plasma was developed using 11H-indeno[1,2-b]quinoxalin-11-one oxime as an internal standard (IS). The analytes were extracted from plasma by liquid-liquid extraction technique using isopropyl alcohol:chloroform mixture (1:5, v/v) followed by evaporation and reconstitution of the residues in acetonitrile. The chromatographic separation was carried out on the EC Nucleodur C8 ec column (150 × 4.6 mm, 5 µm) under an isocratic elution mode using acetonitrile and water containing 0.1% (v/v) formic acid (97:3, v/v) as a mobile phase at a flow rate of 0.55 mL/min (40 °C). The IS and IBP were eluted at 3.79 ± 0.02 and 6.30 ± 0.02 min, respectively. The total analysis time was 7.00 min. Multiple reaction monitoring was used to conduct the MS/MS detection in the negative ion mode with transitions at m/z 245.9 â†’ 214.9 (IS) and 379.2 â†’ 256.0 (IBP). Validation studies of the developed method revealed good linearity over the range of 10-5,000 ng/mL. Within- and between-run accuracy was in the range of 92-110%, while within- and between-run precision was below 8%. Additionally, low matrix effects and high recovery (above 98%) were observed. IBP remained stable in rat plasma at room temperature for 4 h, at -80 °C for 21 days, over three freeze-thaw cycles, under vacuum concentrator (45 °C, dried residues) and auto-sampler (15 °C, processed samples) temperatures for 1 h and 24 h, respectively. Subsequently, the validated LC-MS/MS method has been successfully applied to quantitate IBP in actual plasma samples after a single oral, intramuscular, and subcutaneous dose of IBP (10 mg/kg in the peach oil) to rats. Pharmacokinetic studies show that more rapid and complete IBP absorption with a satisfactory excretion rate were observed after oral administration route compared to the intramuscular and subcutaneous ones.

Distinguishing nanoparticle drug release mechanisms by asymmetric flow field-flow fractionation.

This research demonstrates the development, application, and mechanistic value of a multi-detector asymmetric flow field-flow fractionation (AF4) approach to acquire size-resolved drug loading and release profiles from polymeric nanoparticles (NPs). AF4 was hyphenated with multiple online detectors, including dynamic and multi-angle light scattering for NP size and shape factor analysis, fluorescence for drug detection, and total organic carbon (TOC) to quantify the NPs and dissolved polymer in nanoformulations. The method was demonstrated on poly(lactic-co-glycolic acid) (PLGA) NPs loaded with coumarin 6 (C6) as a lipophilic drug surrogate. The bulk C6 release profile using AF4 was validated against conventional analysis of drug extracted from the NPs and complemented with high performance liquid chromatography - quadrupole time-of-flight (HPLC-QTOF) mass spectrometry analysis of oligomeric PLGA species. Interpretation of the bulk drug release profile was ambiguous, with several release models yielding reasonable fits. In contrast, the size-resolved release profiles from AF4 provided critical information to confidently establish the release mechanism. Specifically, the C6-loaded NPs exhibited size-independent release rate constants and no significant NP size or shape transformations, suggesting surface desorption rather than diffusion through the PLGA matrix or erosion. This conclusion was supported through comparative experimental evaluation of PLGA NPs carrying a fully entrapped drug, enrofloxacin, which showed size-dependent diffusive release, along with density functional theory (DFT) calculations indicating a higher adsorption affinity of C6 onto PLGA. In summary, the development of the size-resolved AF4 method and data analysis framework fulfills salient analytical gaps to determine drug localization and release mechanisms from nanomedicines.

SEDDS Basic Design and Recent Formulation Advancement: A Concurrent Review.

In the present scenario, lipid-based novel drug delivery systems are the area of interest for the formulation scientist in order to improve the bioavailability of poorly water-soluble drugs. A selfemulsifying drug delivery system (SEDDS) upon contact with the gastrointestinal fluid, forms an o/w emulsion. SEDDS has gained popularity as a potential platform for improving the bioavailability of the lipophilic drug by overcoming several challenges. The various advantages like improved solubility, bypassing lymphatic transport, and improvement in bioavailability are associated with SMEDDS or SNEDDS. The extent of the formation of stable SEDDS depends on a specific combination of surfactant, co-surfactant, and oil. The present review highlighted the different aspects of formulation design along with optimization and characterization of SEDDS formulation. It also gives a brief description of the various aspects of the excipients used in SEDDS formulation. This review also includes the conflict between types of SEDDS based on droplet size. There is an extensive review of various research regarding different solidification techniques used for SEDDS in the last three years.

Lipomics: A Potential Carrier for the Intravenous Delivery of Lipophilic and Hydrophilic Drugs.

In the present work, we propose the development of a novel carrier that does not need organic solvents for its preparation and with the potential for the intravenous delivery of lipophilic and hydrophilic drugs. Named lipomics, this is a mixed colloid of micelles incorporated within a liposome. This system was designed through ternary diagrams and characterized by physicochemical techniques to determine the particle size, zeta potential, shape, morphology, and stability properties. The lipomics were subjected to electron microscopy (SEM, TEM, and STEM) to evaluate their physical size and morphology. Finally, pharmacokinetic studies were performed by radiolabeling the lipomics with Technetium-99m chelated with BMEDA to evaluate the in vivo biodistribution through techniques of molecular imaging (microSPECT/CT) in rats. Radiolabeling efficiency was used to compare the encapsulation efficiency of the hydrophilic and lipophilic molecules in lipomics and liposomes. According to the results, lipomics are potentially carriers of lipophilic and hydrophilic drugs.

Lactose hydrate can increase the transcellular permeability of ß-naphthol in rat jejunum and ileum.

BACKGROUND: The unstirred water layer (UWL) is an integral part of the apical surface of mucosal epithelia and comprises mucins (MUC), for which there are many molecular species. Galectins, a family of ß-galactoside-binding lectins, form a lattice barrier on surface epithelial cells by interacting with MUC. Lactose inhibits the galectin-MUC interaction. Therefore, the present study investigated the galectin-MUC interaction in the mucosa of the gastrointestinal tract and its role in intestinal barrier functions. MATERIALS AND RESULTS: The effects of lactose hydrate (LH) on the membrane permeability of the rat small intestine and Caco-2 cells were examined. LH enhanced the membrane permeability of the rat small intestine, which contains the UWL, via a transcellular route, for which the UWL is the rate limiting factor. The membrane permeability of Caco-2 cells, in which the UWL is insufficient, was not affected by LH. The apparent permeability coefficient (Papp) of a paracellular marker was not significantly altered in the rat small intestine or Caco-2 cells treated with LH at any concentration. Furthermore, the Papp of ß-naphthol which is a transcellular marker was not significantly altered in Caco-2 cells treated with LH, but was significantly increased in the rat small intestine in a LH concentration-dependent manner. CONCLUSIONS: The present results demonstrate that the physical barrier has an important function in gastrointestinal membrane permeability, and LH-induced changes increase the transcellular permeability of ß-naphthol in rat small intestine.

Solid lipid nanoparticles and nanostructured lipid carriers: a review of the methods of manufacture and routes of administration.

The bioavailability of drugs is dependent on several factors such as solubility and the administration route. A drug with poor aqueous solubility, therefore, poses challenges with regards to its pharmaceutical advance and ultimately its biological usage. Lipid nanoparticles have been used in pharmaceutical science due to their importance in green chemistry. Their biochemical properties as 'green' materials and biochemical processes as 'green' processes mean they can be environmentally sustainable. Generally, lipid nanoparticles can be employed as carriers for both lipophilic and hydrophilic drugs. The proposed administration route for nanoparticles can present advantages and disadvantages which should be considered by a formulator. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are attractive delivery systems because of their ease of manufacture, biocompatibility, biodegradability, and scale-up capacity of formulation constituents. The easy and simple scalability of novel SLNs and nano lipid carriers, along with their various processing procedures, recent developments, limitation and toxicity, formulation optimization and approaches for the manufacture of lipid nanoparticles, lyophilization and drug release are comprehensively discussed in this review. This review also summarizes the research data related to the various preparation methods and excipients used for SLNs and NLCs in recent years.

Development and pharmacokinetic evaluation of a self-nanoemulsifying drug delivery system for the oral delivery of cannabidiol.

The number of lipophilic drug candidates in pharmaceutical discovery pipelines has increased in recent years. These drugs often possess physicochemical properties that result in poor oral bioavailability, and their clinical potential may be limited without adequate formulation strategies. Cannabidiol (CBD) is an excellent example of a highly lipophilic compound with poor oral bioavailability, due to low water solubility and extensive first-pass metabolism. An approach that may overcome these limitations is formulation of the drug in self-nanoemulsifying drug delivery systems (SNEDDS). Herein, CBD-SNEDDS formulations were prepared and evaluated in vitro. Promising formulations (F2, F4) were administered to healthy female Sprague-Dawley rats via oral gavage (20 mg/kg CBD). Resulting pharmacokinetic parameters of CBD were compared to those obtained following administration of CBD in two oil-based formulations: a medium-chain triglyceride oil vehicle (MCT-CBD), and a sesame oil-based formulation similar in composition to an FDA-approved formulation of CBD, Epidiolex® (SO-CBD). Compared to MCT-CBD, administration of the SNEDDS formulations led to more rapid absorption of CBD (median Tmax values: 0.5 h (F2), 1 h (F4), 6 h (MCT-CBD)). Administration of F2 and F4 formulations also improved the systemic exposure to CBD by 2.2 and 2.8-fold compared to MCT-CBD; however, no improvement was found compared to SO-CBD.

Therapeutic nanoemulsions in ophthalmic drug administration: Concept in formulations and characterization techniques for ocular drug delivery.

The eye is the specialized part of the body and is comprised of numerous physiological ocular barriers that limit the drug absorption at the action site. Regardless of various efforts, efficient topical ophthalmic drug delivery remains unsolved, and thus, it is extremely necessary to advance the contemporary treatments of ocular disorders affecting the anterior and posterior cavities. Nowadays, the advent of nanotechnology-based multicomponent nanoemulsions for ophthalmic drug delivery has gained popularity due to the enhancement of ocular penetrability, improve bioavailability, increase solubility, and stability of lipophilic drugs. Nanoemulsions offer the sustained/controlled drug release and increase residence time which depend on viscosity, compositions, and stabilization process, etc.; hence, decrease the instillation frequency and improve patient compliance. Further, due to the nanosized of nanoemulsions, the sterilization process is easy as conventional solutions and cause no blur vision. The review aims to summarizes the various ocular barriers, manufacturing techniques, possible mechanisms to the retention and deep penetration into the eye, and appropriate excipients with their under-lying selection principles to prevent destabilization of nanoemulsions. This review also discusses the characterization parameters of ocular drug delivery to spike the interest of those contemplating a foray in this field. Here, in short, nanoemulsions are abridged with concepts to design clinically advantageous ocular drug delivery.

Alginate-based drug oral targeting using bio-micro/nano encapsulation technologies.

INTRODUCTION: Oral delivery is the most common administrated drug delivery path. However, oral administration of lipophilic drugs has some limitations: they have poor dose-response due to low and varied dissolution kinetics and oral bioavailability with sub-optimal dissolution within the aqueous gastrointestinal microenvironment. Therefore, there is a need for robust formulating methods that protect the drug until it reaches to its optimum absorption site, allowing its optimum pharmacological effects via increasing its intestinal permeation and bioavailability. AREA COVERED: Herein, we provide insights on orally administered lipophilic drug delivery systems. The detailed description of the obstacles associated with the oral bioavailability of lipophilic drugs are also discussed. Following this, techniques to overcome these obstacles with much emphasis on optimal safety and efficacy are addressed. Newly designed ionic vibrational jet flow encapsulation technology has enormous growth in lipophilic drug delivery systems, which is discussed thereafter. EXPERT OPINION: Researchers have shown interest in drug's encapsulation. A combination of drug-bile acid and microencapsulation methods can be one promising strategy to improve the oral delivery of lipophilic drugs. However, the most critical aspect of this approach is the selection of bile acids, polymer, and encapsulation technology.