Self-microemulsifying Drug Delivery System Research Articles

Development, Analysis, and Determination of Pharmacokinetic Properties of a Solid SMEDDS of Voriconazole for Enhanced Antifungal Therapy

Background: Voriconazole is an antifungal drug, which is classified under Bio-Classification System-II and has low water solubility (0.71 mg/mL) and high permeability. Hardly any endeavors have been made to increase the bioavailability of voriconazole. Objective: To develop and evaluate a solid SMEDDS (self-microemulsifying drug delivery system) for antifungal activity. Methods: Based on solubility studies of Labrafil-M 1994 CS (oil), Cremophor-RH 40 (a surfactant) and Transcutol-HP (a co-surfactant) were selected as components of the SMEDDS and a pseudo-ternary phase diagram was prepared. Thereafter, the oil, surfactant, and co-surfactant were mixed with altered weight ratios (1:1/1:2/2:1) and evaluated through various in vitro, in vivo analyses. Results: The particle size of the optimized formulation was observed to be 19.04 nm and the polydispersity index (PDI) value was found to be 0.162 with steady-state zeta potential. The optimized liquid SMEDDS was converted into a solid SMEDDS. Various adsorbents, such as Aerosil-200, Avicel-PH101, Neusilin-US2, and Neusilin UFL2 were screened to better detect the oil-absorbing capacity and flow properties of the powder. Neusilin UFL2 was selected as an adsorbent due to its better oil-absorbing capacity. DSC, X-ray diffraction, and dissolution studies were carried out to characterize the formulation. Further, the Pharmacokinetic profile was also studied in Wistar rats and the Cmax, tmax, and AUC0®t were calculated. The Cmax and AUC0®t plasma concentration is considerably better for the SMEDDS than for the pure drug and marketed formulation. Conclusions: This investigation clearly reveals the potential of developing a solid SMEDDS for candidiasis and invasive aspergillosis treatment, with better efficacy as compared to the commercially available marketed formulation.

Nanotechnology in Drug Delivery: Overcoming Poor Solubility Challenges through Nanoformulations

Abstract: The pharmaceutical sector continues to face difficulties with poorly soluble drug solubility. Insufficiently soluble drugs have low bioavailability, and their effectiveness is frequently affected. Numerous approaches have been developed in response to this challenge, including using various dosage forms, solid dispersions, nano-suspensions, self-emulsifying drug delivery systems, and cyclodextrin complexes. By improving drug dissolving, decreasing drug particle size, and increasing drug dispersion, these dosage forms seek to increase drug solubility. Nanotechnology is one of the latest advances that has the potential to revolutionize the delivery of drugs and significantly improve the solubility of drugs that are now poorly soluble. Since they have a larger surface area and can pass through biological barriers, nanoparticles are particularly well suited for the delivery of drugs. These technologies can potentially enable the development of more effective and efficient drug formulations for the treatment of various diseases. In addition, the review highlights recent advances in the field, including emerging technologies such as nanotechnology, which can revolutionize drug delivery and significantly improve the solubility of poorly soluble drugs with their potential applications.

Locally Acting Budesonide-Loaded Solid Self-Microemulsifying Drug Delivery Systems (SMEDDS) for Distal Ulcerative Colitis

Locally Acting Budesonide-Loaded Solid Self-Microemulsifying Drug Delivery Systems (SMEDDS) for Distal Ulcerative Colitis

Development of a novel apixaban-loaded solid self-emulsifying drug delivery system for oral administration: physicochemical characterization and pharmacokinetics in rats

Development of a novel apixaban-loaded solid self-emulsifying drug delivery system for oral administration: physicochemical characterization and pharmacokinetics in rats

Lipid-Based Nanoformulations for Drug Delivery: An Ongoing Perspective

Oils and lipids help make water-insoluble drugs soluble by dispersing them in an aqueous medium with the help of a surfactant and enabling their absorption across the gut barrier. The emergence of microemulsions (thermodynamically stable), nanoemulsions (kinetically stable), and self-emulsifying drug delivery systems added unique characteristics that make them suitable for prolonged storage and controlled release. In the 1990s, solid-phase lipids were introduced to reduce drug leakage from nanoparticles and prolong drug release. Manipulating the structure of emulsions and solid lipid nanoparticles has enabled multifunctional nanoparticles and the loading of therapeutic macromolecules such as proteins, nucleic acid, vaccines, etc. Phospholipids and surfactants with a well-defined polar head and carbon chain have been used to prepare bilayer vesicles known as liposomes and niosomes, respectively. The increasing knowledge of targeting ligands and external factors to gain control over pharmacokinetics and the ever-increasing number of synthetic lipids are expected to make lipid nanoparticles and vesicular systems a preferred choice for the encapsulation and targeted delivery of therapeutic agents. This review discusses different lipids and oil-based nanoparticulate systems for the delivery of water-insoluble drugs. The salient features of each system are highlighted, and special emphasis is given to studies that compare them.

Self-microemulsifying drug delivery system-based gastroretentive in situ raft of pazopanib with enhanced solubility and bioavailability.

Pazopanib hydrochloride (PZH) is a Biopharmaceutics Classification System class II drug that faces challenges at the formulation forefront including low aqueous solubility (0.043 mg/mL) and poor oral bioavailability (14-39%). The present investigation aimed to develop a self-microemulsifying drug delivery system (SMEDDS) of PZH using a blend of Capryol® 90, Labrasol®, and propylene glycol to improve its solubility. Furthermore, a sustained-release SMEDDS-based gastroretentive floating system was developed and optimized using the Central Composite Design approach of DoE. The optimized SMEDDS-based in situ gelling raft, R-SM-PZH, exhibited minimal floating lag time (3.09 ± 0.8 s), optimal viscosity (1229.4 ± 20.9 cP) and density (0.327 ± 0.15 g/mL) as compared to other formulations under study. Additionally, R-SM-PZH was evaluated for its in vitro dissolution in FaSSGF and FeSSGF, pharmacokinetic profile, and MTT assay (against NCI-H460 lung cancer cells) compared to pure PZH. A 12 h sustained release, three-fold augmentation in dissolution rate and bioavailability, and 15-fold enhancement in cytotoxicity were observed in comparison to pure PZH. Thus, the SMEDDS-based in situ gelling raft presents a promising approach to advancing the developability potential of PZH.

The role of coatings and plasticizers compatibility in stability of advanced gastro-resistant self-emulsifying pellets designed for the delivery of volatile compounds: A combined solid-state NMR and dissolution study

The gastro-resistant behaviour of solid self-emulsifying drug delivery systems (S-SEDDS) represents a significant and innovative advancement in delivering poorly soluble drugs. Due to the complexity of these systems and the liquid nature of SEDDS, thorough investigation is essential. This study explored the stability of self-emulsifying (SE) pellets containing the volatile compound thymol coated with gastro-resistant Eudragit® L 30 D-55 water dispersion. The SE pellet cores, composed of Neusilin® US2 with adsorbed SEDDS (thymol, triacylglycerol, Labrasol®, and propylene glycol), microcrystalline cellulose, and chitosan, were prepared using the extrusion/spheronization method and demonstrated optimal technological properties. The 6-month stability of three coating compositions, differing in thickness and triethyl citrate (TEC) concentration in the Eudragit® L topcoat, or the application of an ethylcellulose (EC, Surelease®) sub-coat, was investigated using the combined in vitro dissolution testing and solid-state nuclear magnetic resonance (ss-NMR) for detailed structural characterization. The dissolution data of samples with Eudragit® L topcoat data showed an acceleration of thymol release in acidic conditions, preventing the SE pellets from achieving gastro-resistance. The ss-NMR analysis revealed an incompatibility between TEC and SEDDS (specifically propylene glycol), identified as a TEC phase transition to a liquid phase independent of TEC concentration. Additionally, ss-NMR analysis revealed that neat thymol negatively affected coating layer stability by promoting the plasticization of Eudragit® L. The inclusion of a 10 % Surelease® sub-coat yielded positive results, maintaining the gastro-resistant properties of SE pellets stored under 25 °C/60 % RH for 6 months. However, ss-NMR analysis confirmed ongoing TEC liquefaction after 3 and 6 months, indicating that the oleic acid and triglycerides in Surelease® as plasticizers contributed to this instability. Therefore, this formulation cannot be deemed stable, and using Surelease® as a sub-layer is only a temporary solution. Overall, while plasticizers are commonly used in pharmaceutical technology, they can introduce significant problems in S-SEDDS development, and their use in sub- or topcoats should be carefully considered or avoided. At the same time, it became evident that in-vitro dissolution testing alone cannot capture the slow processes and interactions occurring within the internal structure of these systems.

Research Progress on Peptide Drugs for Type 2 Diabetes and the Possibility of Oral Administration

Diabetes is a global disease that can lead to a range of complications. Currently, the treatment of type 2 diabetes focuses on oral hypoglycemic drugs and insulin analogues. Studies have shown that drugs such as oral metformin are useful in the treatment of diabetes but can limit the liver’s ability to release sugar. The development of glucose-lowering peptides has provided new options for the treatment of type 2 diabetes. Peptide drugs have low oral utilization due to their easy degradation, short half-life, and difficulty passing through the intestinal mucosa. Therefore, improving the oral utilization of peptide drugs remains an urgent problem. This paper reviews the research progress of peptide drugs in the treatment of diabetes mellitus and proposes that different types of nano-formulation carriers, such as liposomes, self-emulsifying drug delivery systems, and polymer particles, should be combined with peptide drugs for oral administration to improve their absorption in the gastrointestinal tract.

Design of self-emulsifying oral delivery systems for semaglutide: reverse micelles versus hydrophobic ion pairs.

It was the aim of this study to evaluate the potential of reverse micelles (RM) and hydrophobic ion pairs (HIP) for incorporation of semaglutide into self-emulsifying oral drug delivery systems. Reverse micelles loaded with semaglutide were formed with a cationic (ethyl lauroyl arginate, ELA) and an anionic surfactant (docusate, DOC), whereas HIP were formed between semaglutide and ELA. Maximum solubility of the peptide and the rate of dissolution was evaluated in various lipophilic phases (glycerol monocaprylocaprate:caprylic acid 1:4 (m/m), glycerol monolinoleate:caprylic acid 1:4 (m/m) and glycerol monocaprylocaprate:glycerol monolinoleate 1:4 (m/m)). Self-emulsifying drug delivery systems (SEDDS) loaded with RM and HIP were characterized regarding size distribution, zeta potential, cytocompatibility and Caco-2 permeability. Droplet sizes between 50 and 300nm with polydispersity index (PDI) around 0.3 and zeta potentials between - 45 mV (RMDOC) and 36 mV (RMELA) were obtained. RM provided an almost 2-fold higher lipophilicity of semaglutide than HIP resulting in a 4.2-fold higher payload of SEDDS compared to HIP. SEDDS containing RM or HIP showed high cytocompatibilities with a cell survival above 75% for concentrations up to 0.1% on Caco-2 cells and acceptable hemolytic activity. Permeation studies across Caco-2 monolayer revealed an at least 2-fold increase in permeability of semaglutide for the developed formulations.

Lyotropic liquid crystal and self-emulsifying drug delivery systems nanoparticles as artesunic acid and praziquantel carriers: An innovative approach for formulation of anti-malaria and schistosomicidal drugs

Praziquantel (PZQ) is the drug of choice for treating cestode and trematode infections, and it is currently the only option against schistosomiasis. Artesunic acid (AcART) is effective against several parasites and has emerged as an alternative for schistosomiasis treatment. However, AcART and PZQ have limited bioavailability due to poor water solubility, low permeability, and rapid cell clearance. To address these challenges, this study aimed to develop self-emulsifying drug delivery systems to develop SEDDS and NPs-LLC to overcome the low water solubility affecting AcART and PZQ bioavailability. The study involved validating the HPLC analytical methodology for AcART, SEDDS, and NPs-LLC formulations, and conducting physicochemical characterization and ex-vivo intestinal permeation assays. The composition of formulations was determined by the solubility balance of AcART and PZQ. The drug content ranged between 83 and 90 %. The anionic zeta potential was attributed to Myverol®, and the particle diameter increased slightly after the drug incorporation, while the polydispersity index indicated the relatively narrow particle size distribution. Additionally, the DSC thermogram confirmed that PZQ and AcART are in solution within SEDDS and NPs-LLC. The FTIR analysis suggests that components of SEDDS and NPs-LLC and drugs do not react to form new chemical species. The selection of specific compound formulations was based on achieving the best solubility balance. The nanostructures were stable and exhibited a surface charge favorable to mucosal permeation, with slightly superior performance for SEDDS. The innovative formulations, SEDDS and NPs-LLC, are suitable and effective carriers for AcART and PZQ.

Review article on self emulsifying system

The solubility challenges faced by the pharmaceutical industry, particularly with orally administered drugs, are indeed significant. Low aqueous solubility often leads to poor dissolution and subsequently, low bioavailability, which can result in inconsistent drug effects among patients. Various methods have been explored to address this issue, including salt formation, solid dispersion, and complex formation.Among these approaches, Self-Emulsifying Drug Delivery Systems (SEDDS) have emerged as a promising solution for enhancing the solubility of lipophilic drugs. SEDDS consist of isotropic mixtures of hydrophilic solvents, co-solvents, and surfactants. They possess the unique ability to form fine oil-in-water micro emulsions upon mild agitation and dilution in aqueous media, such as gastrointestinal fluids.The advancement in SEDDS technology encompasses improvements in composition, evaluation methods, development of different dosage forms, and techniques for converting liquid SEDDS into solid forms. These advancements not only enhance solubility but also offer versatility in administration routes and dosage forms, thereby expanding the potential applications of SEDDS in pharmaceutical formulations.This comprehensive review provides valuable insights into the latest developments in SEDDS, offering a detailed account of its composition, evaluation parameters, diverse dosage forms, and innovative techniques for solidification. Moreover, it highlights the diverse applications of SEDDS across various therapeutic areas, underscoring its growing significance in modern pharmaceutical research and development.

Single-Step Extrusion Process for Formulation Development of Self-Emulsifying Granules for Oral Delivery of a BCS Class IV Drug.

This study aimed to develop and optimize formulations containinga BCS Class IV drug by improving its solubility and permeability. Herein development of self-emulsifying solid lipid matrices was investigated as carrier systems for a BCS Class IV model drug. Self-emulsifying drug delivery systems (SEDDS) have been extensively investigated for formulating drugs with poor water solubility. However, manufacturing SEDDS is challenging. These systems usually have low drug-loading capacities, and the incorporated drugs tend to recrystallize during storage, which severely impacts the storage stability in vitro and performance in vivo. Moreover, they require greater amounts (>80%) of lipid carriers, cosolvents, surfactants, and other excipients to keep them from recrystallizing. This in turn is again challenging for high-dose drugs as it affects the size of the final drug product (tablets and capsules). Also, the final liquid nature of the formulation affects the handling and processability of the formulation, which poses challenges during the manufacturing and packaging steps. In this work, we have studied the feasibility of a single-step extrusion process to formulate and optimize solid self-emulsifying granules with a relatively higher drug loading of Ritonavir (RTV), a BCS Class IV drug. Further, we have compared the performance of using these granules as the feedstock for direct powder extrusion-based 3D printing as opposed to the use of physical blends. The stability and solubility-permeability advantage of these granules was also evaluated where SEDDS showed about 27 and 20 fold increase in apparent solublity and permeability compared to bulk drug, respectively. Combining the capabilities of HME to form drug-loaded homogeneous granules as a continuous process along with application of direct printing extruiosn (DPE) 3D printing improves the drug delivery prospects for such candidates.

Synergistic antimicrobial effect of daptomycin and ethyl lauroyl arginate containing self-emulsifying drug delivery system against bacterial infections

This study aimed to enhance the antimicrobial properties of daptomycin by ion-pairing with ethyl lauroyl arginate (ELA) and incorporation in a self-emulsifying drug delivery system (SEDDS).Daptomycin was ion-paired with the ELA and the hydrophobic ion pair (HIP) was loaded into SEDDS. SEDDS 1 consisted of 15% oleic acid, 5% soy phosphatidylcholine, 10% cetyltrimethylammonium bromide (CTAB) in medium-chain triglycerides (MCT) at a concentration of 250 mg/ml, 20% benzyl alcohol, and 50% PG-4 caprate. SEDDS 2 comprised 10% soy phosphatidylcholine in MCT at a concentration of 53 mg/ml, 10% CTAB, 20% benzyl alcohol, and 60% PG-4 caprate. SEDDS were characterized regarding droplet size, polydispersity index (PDI), zeta potential, and stability. Cytotoxicity was evaluated on Caco-2, HeLa, and SW620 cells. Antimicrobial activity was assessed by agar diffusion studies and time-kill assays with Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans.Both formulations showed a droplet size below 200 nm with a PDI < 0.4, a positive zeta potential, and robust thermodynamic stability. They exhibited low toxicity profiles while maintaining full antimicrobial efficacy on all tested pathogens. Compared to unformulated daptomycin, SEDDS 1 and 2 lowered the minimum inhibitory concentration (MIC) 5- and 8- fold for S. aureus and 10- and 30- fold for S. epidermidis, respectively. Bacterial killing time was 105 -fold shortened with SEDDS 1 and 106 -fold with SEDDS 2. Furthermore, HIP and SEDDS enhanced antibacterial activity against Candida albicans and Pseudomonas aeruginosa. According to these results, ion pairing of daptomycin with ELA and incorporation into SEDDS is a promising approach to improve the antimicrobial activity of this drug.

Self-microemulsifying drug delivery system (SMEDDS) for oral delivery of zafirlukast: Design, formulation, and pharmacokinetic evaluation

The current research aimed to develop a self-microemulsifying drug delivery system (SMEDDS) of zafirlukast to enhance its oral bioavailability by increasing its solubility and overcoming the negative food effect. For the formulation of SMEDDS, the solubility of zafirlukast was determined in different oils, surfactants, and cosurfactants. Based on this study's results, pseudo-ternary phase diagrams were plotted to select the efficient self-emulsification region. Eudragit EPO was employed as a precipitation inhibitor to avoid the supersaturation of zafirlukast in the SMEDDS system. The formulated system was evaluated for transparency, cloud point, optical birefringence, and globule size analysis using techniques like DLS, SANS and TEM. The SMEDDS preconcentrate was solidified by adsorbing it on Neusilin US2 and further formulated as a tablet. It was then evaluated for in vitro drug release against the marketed tablet. The optimized composition of zafirlukast SMEDDS and suspension of the plain drug were evaluated for a pharmacokinetic profile in rats for both fed and fasted conditions. The SMEDDS yielded microemulsion found transparent and homogeneous with globule size less than 50 nm by DLS, SANS and TEM techniques. On dilution with water, the microemulsion was found robust without any phase separation even after 24 h of storage. The tablet form of SMEDDS was stable and passed all the IPQC tests for a tablet. The optimized SMEDDS tablet form exhibited a superior in vitro dissolution profile than a marketed tablet. The pharmacokinetic study of optimized SMEDDS showed improved value for Cmax and AUC in both fed and fasted conditions compared to the plain drug.

Comparing Low-Dose Carvedilol Continuous Manufacturing by Solid and Liquid Feeding in Self-Emulsifying Delivery Systems via Hot Melt EXtrusion (SEDEX)

Background/Objectives: This study compared two pilot scale continuous manufacturing methods of solid self-emulsifying drug delivery systems (SEDDSs) via hot melt extrusion (HME). Methods: A model poorly water-soluble drug carvedilol in low dose (0.5–1.0% w/w) was processed in HME either in a conventional powder form or pre-dissolved in the liquid SEDDS. Results: HME yielded a processable final product with up to 20% w/w SEDDS. Addition of carvedilol powder resulted in a non-homogeneous drug distribution in the extrudates, whereas a homogeneous drug distribution was observed in pre-dissolved carvedilol. SEDDSs were shown to have a plasticizing effect, reducing the HME process torque up to 50%. Compatibility between excipients and carvedilol in the studied ratios after HME was confirmed via DSC and WAXS, demonstrating their amorphous form. Solid SEDDSs with Kollidon® VA64 self-emulsified in aqueous medium within 15 min with mean droplet sizes 150–200 nm and were independent of the medium temperature, whereas reconstitution of Soluplus® took over 60 min and mean droplet size increased 2-fold from 70 nm to 150 nm after temperature increased from 25 °C to 37 °C, indicating emulsion phase inversion at cloud point. Conclusions: In conclusion, using Kollidon® VA64 and pre-dissolved carvedilol in SEDDS has shown to yield a stabile HME process with a homogenous carvedilol content in the extrudate.

Microemulsion Drug Delivery of Anti-malarial.

Malaria affects millions of people every year, especially in our world. The main treatments are oral antibiotics and vaccines. The rise of the malaria parasite, now resistant to most anti-viral drugs, is causing a global crisis. Furthermore, low water solubility and permeability of both new and old antibiotics cause limited oral bioavailability and non-compliance from patients. Lipid formulations are frequently employed to lessen toxicity, boost solubility, and improve effectiveness. The findings of studies on oral-specific lipophilic drug delivery systems, such as self-emulsifying drug delivery systems, are reviewed in this article. (SEDDS). SEDDS increases the absorption of anti-inflammatory drugs by promoting the formation of liquid emulsions that dissolve the drug in the intestine. However, traditionally used SEDDS are usually in liquid form, administered into the oral cavity, and have poor safety. This article discusses a new solidification process that can be easily and economically scaled up by using existing equipment. This strategy might also increase patient compliance and product stability. Oral SEDDS has a substantial potential influence in the fight against malaria.

Responding to Hitch in Fighting Mycobacterium Tuberculosis Through Arginine Multi Functionalized Mucoadhesive SNEDDS of Rifampicin.

The study aimed to develop thiolated pluronic-based self-emulsifying drug delivery system (SNEDDS) targeted delivery of Rifampicin coated by arginine for enhanced drug loading, mucoadhesion, muco penetration, site-specific delivery, stabilized delivery against intracellular mycobacterium tuberculosis (M. tb), decreased bacterial burden and production by intracellular targeting. Oleic oil, PEG 200 and Tween 80 are selected as oil, co-surfactant and surfactant based on solubilizing capacity and pseudo ternary diagram region. Coating of thiolated polymer on SNEDDS with ligand arginine (Arg-Th-F407 SNEDDDS) decreased bacterial burden and production by intracellular targeting in macrophages. Formulation are evaluated through scanning electron microscope (SEM), EDAX analysis, diffraction laser scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, and thermal analysis (DSC & TGA). Hydrodynamic diameter of thiolated polymeric SNEDDS (Th-F407 SNEDDS) and Arg-Th-F407 SNEDDS is observed to be 148.4 and 188.5nm with low PDI of 0.4 and 0.3, respectively. Invitro drug release study from Arg-Th-F407 SNEDDS indicates 80% sustained release in 72h under controlled conditions. Arg-Th-F407 SNEDDDS shows excellent capability of killing M.tb strains in macrophages even at low dose as compared to traditional rifampicin (RIF) and is found biocompatible, non-cytotoxic, and hemocompatible. Therefore, Arg-Th-F407 SNEDDDS of RIF proved ideal for targeting and treating M.tb strains within macrophages.

Nanocarrier-Based Delivery Approaches of Mangiferin: An Updated Review on Leveraging Biopharmaceutical Characteristics of the Bioactive.

In recent years, bioactive constituents from plants have been investigated as an alternative to synthetic approaches of therapeutics. Mangiferin (MGF) is a xanthone glycoside extracted from Mangifera indica and has shown numerous medicinal properties, such as antimicrobial, anti-diarrhoeal, antiviral, anti-inflammatory, antihypertensive, anti-tumours, and anti-diabetic effects. However, there are numerous challenges to its effective therapeutic usage, including its low water solubility, limited absorption, and poor bioavailability. Nano formulation approaches in recent years exhibited potential for the delivery of phytoconstituents with key benefits of high entrapment, sustained release, enhanced solubility, stability, improved pharmacokinetics, and site-specific drug delivery. Numerous techniques have been employed for the fabrication of MGF-loaded Nano formulations, and each technique has its advantages and limitations. The nanocarriers that have been employed to fabricate MGF nanoformulations for various therapeutic purposes include; polymeric nanoparticles, nanostructure, lipid carriers, polymeric micelles, Nano emulsions, microemulsion & self-microemulsifying drug delivery system, solid lipid nanoparticles, gold nanoparticles, carbon nanotubes, transfersomes, nanoliposomes, ethosomes & transethosomes, and glycethosomes. Different biopharmaceutical characteristics (size, shape, entrapment efficiency, zeta potential, in vitro drug release, ex vivo drug permeation,, and in vivo studies) of the mentioned MGF-loaded nanocarriers have been methodically discussed. Patent reports are also included to further strengthen the potential of MGF in the management of diseases.

Wheatgrass-Tulsi Self-Emulsifying Drug Delivery System (WT-SEDDS): Preclinical Evaluation Of Synergistic Anticancer Activity

Wheatgrass-Tulsi Self-Emulsifying Drug Delivery System (WT-SEDDS): Preclinical Evaluation Of Synergistic Anticancer Activity

Enhanced diclofenac sodium delivery through advanced self-microemulsifying pectin-based transdermal patches

Diclofenac sodium (DCFNa) presents significant challenges in local pain relief due to its poor solubility and limited skin permeability. This study aimed to enhance the solubility and skin permeation of DCFNa by developing DCFNa-loaded self-microemulsifying drug delivery system (SMEDDS) embedded pressure-sensitive adhesive (PSA) patch. The solubility of DCFNa in various solvents was evaluated, and a ternary phase diagram was constructed to optimize the SMEDDS formulation. The transdermal patch, composed of pectin and polyacrylate, was optimized using a simplex lattice experimental design to achieve the desired adhesion strength and to select the most suitable patch for skin drug accumulation study. Clove oil, Tween® 80, and propylene glycol were identified as the appropriate oil, surfactant, and co-surfactant, respectively, for achieving highest DCFNa solubility. The SMEDDS was formed with a ratio of 5:35:60 (oil: Smix [1:1 surfactant: co-surfactant]: water), yielding nano-sized droplets (22.64 ± 0.74 nm) and significantly enhancing DCFNa solubility (329.62 ± 10.16 mg/mL) compared to phosphate buffer (5.03 ± 1.01 mg/mL). The DCFNa-loaded SMEDDS demonstrated a 9-fold increase in skin permeability compared to the DCFNa solution. The optimized PSA patch, containing 20 % pectin and 40 % polyacrylate, exhibited superior tacking and peel strength. Additionally, a 1 % DCFNa-loaded SMEDDS patch delivered twice greater drug accumulation in the skin and showed no skin irritation, maintaining better adhesion for up to 24 h compared to commercial patches.