Formulation And Evaluation Of Self Emulsifying Drug Delivery System Of Lopinavir

Self-emulsifying peptide drug delivery systems: How to make them highly mucus permeating

This study presents an emerging approach for oral peptide drug delivery by designing self-emulsifying drug delivery systems (SEDDS) capable of protecting peptide drugs from intestinal brush border membrane-bound (BBM) enzymes. Tuftsin was incorporated as a model peptide into three optimized SEDDS formulations through hydrophobic ion pairing with the anionic surfactants docusate (AOT), N-octadecyl sulfate (OS), and lauryl sulfate (LS). SEDDS- 1 consisted of octyldodecanol, polyoxyethylene (10) oleyl ether, polyoxyethylene (20) oleyl ether and citronellol. SEDDS- 2 were formulated with isopropylmyristate, polyoxyethylene (20) oleyl ether and eugenol. SEDDS- 3 included caprylic acid, PEG- 35 castor oil and citronellol. The resulting nanoemulsions were characterized for droplet size, zeta potential, polydispersity index (PDI), and stability in biorelevant media. Enzymatic degradation studies with aminopeptidase N and ex vivo rat small intestine revealed remarkable protective effects. SEDDS- 3 exhibited superior performance, preserving over 80% of tuftsin after 4h, followed by SEDDS- 2 protecting 70% of tuftsin, while the unformulated peptide was entirely degraded within 20 min. Furthermore, SEDDS- 2 demonstrated enhanced permeation of tuftsin across intestinal mucosa by achieving a 4-fold increase, while SEDDS- 3 led to a 3-fold enhancement in permeation compared to the unformulated peptide. Accordingly, SEDDS- 3 demonstrates the greatest potential for peptide delivery due to its superior protective performance and enhanced permeation compared to the control. These findings underscore the potential of SEDDS as a versatile platform for safeguarding peptide drugs against enzymatic degradation in the intestinal environment. By modifying their composition, SEDDS can unlock new possibilities for efficient oral peptide drug delivery, overcoming critical enzymatic and mucosal barriers.

Comparison of the protective effect of self-emulsifying peptide drug delivery systems towards intestinal proteases and glutathione

Highly mucus permeating and zeta potential changing self-emulsifying drug delivery systems: A potent gene delivery model for causal treatment of cystic fibrosis

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 300 nm 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.

Background: Diclofenac is a potent non-steroidal anti-inflammatory drug (NSAID) with poor water solubility and gastrointestinal (GI) side effects. Conventional oral diclofenac can have delayed onset and cause GI irritation. Self-micro emulsifying drug delivery systems (SMEDDS) improve solubility of hydrophobic drugs, while oral fast-dissolving films enhance convenience and speed of administration. Combining these approaches may yield rapid, efficient diclofenac delivery. Objectives: To formulate and optimize a diclofenac-loaded SMEDDS for improved solubility and absorption, incorporate it into a self-micro emulsifying mouth dissolving film (SMMDF), and evaluate the formulation’s in vitro characteristics and in vivo performance. Materials and Methods: Solubility of diclofenac was determined in various oils, surfactants, and co-surfactants to select SMEDDS components. Pseudo-ternary phase diagrams were constructed to identify self-emulsification regions. SMEDDS formulations were prepared and optimized using a mixture design to minimize droplet size. The optimized SMEDDS was characterized for droplet size, polydispersity index (PDI), zeta potential, and self-emulsification time. SMMDFs were prepared by solvent casting of polymer matrices containing the optimized SMEDDS. Films were evaluated for uniformity, mechanical properties, disintegration time, in vitro dissolution, and morphology. An in vivo pharmacokinetic study in rats compared the SMMDF to a conventional diclofenac tablet. Results: The optimized SMEDDS (oil: Capryol 90, surfactant: Tween 80, co-surfactant: Transcutol-HP) had a droplet size ~50 nm, PDI 0.22, and zeta potential –15 mV. SMMDFs were uniform (thickness ~100 μm) with high drug content (>98%) and fast disintegration (~25 s). In vitro, SMMDF released >90% of diclofenac in 5 min versus ~60% from a tablet. In rats, SMMDF showed higher C_max (4.1 vs 2.3 μg/mL) and shorter T_max (0.5 h vs 2 h) than the tablet, with a 1.6-fold increase in AUC, indicating significantly improved bioavailability (p<0.01). Conclusions: The diclofenac SMMDF achieved rapid dissolution and enhanced systemic exposure compared to the conventional formulation. This novel combination of SMEDDS with a mouth dissolving film offers a promising strategy for improving the onset and efficacy of poorly soluble drugs like diclofenac while potentially reducing GI side effects.

Trypsin decorated self-emulsifying drug delivery systems (SEDDS): Key to enhanced mucus permeation

This investigation sought to devise and evaluate a self-micro emulsifying drug delivery system (SMEDDS) tailored for Nebivolol hydrochloride (NBL), a potent third-generation β-1 receptor antagonist crucial in hypertension management. Despite its therapeutic efficacy, NBL faces the challenge of low bioavailability, standing at a mere 12%. To overcome this limitation, our study aimed to develop an effective SMEDDS formulation to enhance the solubility of Nebivolol hydrochloride. We conducted extensive solubility studies on various components, including Cremophore-RH 40 (Cr-RH 40), Peceol, and Gelucire 50/13 (Gel 50/13), to determine the optimal composition for SMEDDS formulation. In our methodology, we conducted solubility studies to identify the most suitable combination of Cr-RH 40, Peceol, and Gel 50/13 for the SMEDDS formulation. Additionally, we performed emulsification efficiency studies to achieve optimal emulsification of the oily phase, evaluating different surfactant mixtures to select the most suitable liquid and solid surfactants. Subsequently, the resulting formulation underwent comprehensive characterization, including analysis of particle size, zeta potential, polydispersity index, and various techniques such as differential scanning calorimetry, Infrared spectroscopy, transmission electron microscopy, permeability studies, and stability assessments. Upon formulation, our Nebivolol hydrochloride-loaded SMEDDS exhibited significant enhancements compared to the pure drug. Characterization results revealed a favorable particle size distribution, appropriate zeta potential, and a low polydispersity index. Differential scanning calorimetry and Infrared spectroscopy confirmed the compatibility of components, while transmission electron microscopy provided visual insights into morphological characteristics. Permeability studies demonstrated improved solubility, highlighting the potential of the SMEDDS formulation in addressing Nebivolol hydrochloride's bioavailability challenges. Our discussion underscored the observed enhancements in solubility and formulation characteristics, attributing the efficacy of the Nebivolol hydrochloride-loaded SMEDDS to the optimized composition, surfactant mixtures, and emulsification efficiency. Comprehensive characterization validated the stability and compatibility of the SMEDDS, offering insights into its potential as a drug delivery system for Nebivolol hydrochloride. These positive outcomes set the stage for future research aimed at enhancing Nebivolol hydrochloride's therapeutic efficacy through advanced delivery systems. In conclusion, our study successfully developed and characterized a highly lipophilic drug, Nebivolol hydrochloride, within a SMEDDS. The formulation displayed improved solubility and promising characteristics, suggesting its potential in overcoming the bioavailability challenges associated with Nebivolol hydrochloride and opening avenues for further advancements in drug delivery strategies for this antihypertensive agent.

In vivo evaluation of an oral self-emulsifying drug delivery system (SEDDS) for exenatide

Self-emulsifying drug delivery systems (SEDDS) help to deliver lipophilic drugs with improved bioavailability. The objective of this study was to develop SEDDS to improve solubility and enhance the oral absorption of the poorly water soluble drug, piroxicam. The influence of the oil, surfactant and co-surfactant types on the drug solubility and their ratios on forming efficient and stable SEDDS were investigated by construction of Pseudo ternary phase diagrams. Formulations were characterized for thermodynamic stability studies, Self-emulsification, Viscosity, Droplet size, Zeta potential, Differential Scanning Calorimetry, in vitro drug release, Diffusion and Stability studies. The drug diffusion from the optimised formulation C1 was 98.18±0.84% while from the marketed piroxicam capsule was 95.13±2.98%. The developed piroxicam SEDDS formulation showed greater dissolution, and diffusion than the pure drug and marketed capsule. Release kinetics showed that the mechanism of drug release is super class-II, as it follows zero order release and fits with korsmeyer-peppas model.

In this study, we focused on quetiapine fumarate (QTF), a class II BCS drug. QTF is an atypical antipsychotic used in the treatment of schizophrenia and bipolar disorders. Our objective was to develop a new QTF-loaded self-emulsifying drug delivery system (SEDDS) to improve the dissolution and absorption of the drug. An experimental design approach was used to develop and optimize QTF-loaded SEDDS. The optimized formulation was characterized for droplets size, zeta potential, PDI, and stability. It was then evaluated using an in-vitro combined test for dissolution and Everted gut sac technique. Mathematical modeling and Transmission electron microscopy (TEM) were used to elucidate the mechanism of release.The optimal formulation was type IIIB SEDDS, constituted of 9.1% of oleic acid, 51.6% of Tween®20, and 39.3% of Transcutol® P. It showed a droplets size of 144.8 ± 4.9nm with an acceptable PDI and zeta potential. For in-vitro evaluation tests, we noticed an enhancement of the dissolution rate of the optimal QTF-loaded SEDDS compared to the free drug (98.82 ± 1.24% for SEDDS after 30 min compared to 85.65 ± 2.5% for the pure drug). The release of QTF fitted with the Hopfenberg model indicating the drug was released by water diffusion and erosion mechanism. This result was confirmed by TEM images which showed a smaller droplet size after release. We also found an amelioration of the permeability of QTF of 1.69-fold from SEDDS compared to the free drug. Hence, the SEDDS formulation represented a new way to improve the dissolution and absorption of QTF.

In this study, four fluorescein hydrophobic ionic complexes were formed with the cationic polymers Eudragit RS, Eudragit RL, Eudragit E, and polyethyleneimine (PEI) to provide fluorescein sustained release, sustained cellular uptake, and stability. Complexes were loaded in a self-emulsifying drug delivery system (SEDDS) composed of 40% Tween 80, 20% Kolliphor EL, 15% 2-n-Octyl-1-dodecanol, and 25% dipropylene glycol. SEDDS were investigated regarding their size, polydispersity index (PDI), zeta potential, and cytotoxicity. Fluorescein release from SEDDS was performed in phosphate buffer (pH 6.8 and pH 8), and the released fluorescein was evaluated for cellular uptake. Moreover, fluorescein from all of the SEDDS pre-concentrates was released at different time points to check its long-term stability over six months. The average fluorescein load in SEDDS was 0.045%. SEDDS showed an average droplet size of 24.9 ± 1.6 nm with PDI ≤ 0.3. SEDDS complexes diluted 1:100 increased the zeta potential from -7.3 mV to +3.7 mV and provided > 85% cell viability. A 92.27 ± 3.18% fluorescein exhibited a few seconds of immediate release when used as control or PEI complex in SEDDS. On the contrary, Eudragit-fluorescein complexes in SEDDS showed sustained release of 87.01 ± 5.22% fluorescein in ≤ 70 min with 22.19 ± 14.56% and 59.27 ± 16.57% released at 10 min in pH 6.8 and pH 8 release media, respectively. Comparatively, the medium at pH 6.8 maintained a significantly improved sustained fluorescein release (p ≤ 0.001). Furthermore, Eudragit RS/RL compared to Eudragit E, significantly exhibited a slower fluorescein release rate from SEDDS (p ≤ 0.01). The cellular uptake of the released fluorescein was 72.4 ± 8.2% for all SEDDS complexes after 3 h. Eudragit complexes compared to PEI complex in SEDDS significantly showed m ore sustained fluorescein cellular uptake at 1 h and 2 h (p ≤ 0.001). However, SEDDS complexes showed the longest fluorescein stability with PEI after six months, whereas fluorescein stability for SEDDS containing fluorescein as Eudragit complex and control showed 39.1% and 82.5% fluorescence decrease, respectively, after three months. In the developed SEDDS, the presence of hydrophobic ionic complexes can significantly promote longer stability and sustained cellular uptake of fluorescein while releasing in a sustained manner.

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-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs

Self-emulsifying drug delivery systems (SEDDS) represent an innovative approach to improving the solubility and bioavailability of poorly water-soluble drugs, addressing significant challenges associated with oral drug delivery. This review highlights the advancements and applications of SEDDS, including their transition from liquid to solid forms, while addressing the formulation strategies, characterization techniques, and future prospects in pharmaceutical sciences. The review systematically analyzes existing studies on SEDDS, focusing on their classification into liquid and solid forms and their preparation methods, including spray drying, hot-melt extrusion, and adsorption onto carriers. Characterization techniques such as droplet size analysis, dissolution studies, and solid-state evaluations are detailed. Additionally, emerging trends, including 3D printing, hybrid systems, and supersaturable SEDDS (Su-SEDDS), are explored. Liquid SEDDS (L-SEDDS) enhance drug solubility and absorption by forming emulsions upon contact with gastrointestinal fluids. However, they suffer from stability and leakage issues. Transitioning to solid SEDDS (S-SEDDS) has resolved these limitations, offering enhanced stability, scalability, and patient compliance. Innovations such as personalized 3D-printed SEDDS, biologics delivery, and targeted systems demonstrate their potential for diverse therapeutic applications. Computational modeling and in silico approaches further accelerate formulation optimization. SEDDS have revolutionized drug delivery by improving bioavailability and enabling precise, patient-centric therapies. While challenges such as scalability and excipient toxicity persist, emerging technologies and multidisciplinary collaborations are paving the way for next-generation SEDDS. Their adaptability and potential for personalized medicine solidify their role as a cornerstone in modern pharmaceutical development.