Self-microemulsifying Drug Delivery System Research Articles

Application of Simplex Lattice Mixture design and desirability function in the development and Optimization of SEDDS for protein kinase inhibitor-Pazopanib Hydrochloride

Pazopanib Hydrochloride is a tyrosine protein kinase inhibitor molecule approved by USFDA and European agencies for the treatment of renal cell carcinoma (RCC) patients and other renal malignancies, but it has very poor aqueous solubility. Therefore, it is essential need to improve the solubility and in vitro dispersion or release characteristics. The purpose of this study was to investigate the Pazopanib hydrochloride drug solubility in various vehicles and screening of suitable solubilizers for the preparation of self-emulsifying lipid-based drug delivery systems (SE-LBDDS) of a poorly water-soluble drug (BCS class II), Pazopanib HCl by using simplex lattice mixture design. Ternaryplots wereconstructed by using oil (Labrafac WL 1349l), surfactant (Labrasol), and co-surfactant (Transcutol-P), and the concentration ranges were determined by using a simplex lattice design. The composition of pazopanib HCl SEEDS was optimized through various dependent variables (responses)such as solubility (Y1), precipitation after 15 min (Y2), and, particle size (Y3).Solubility study of pazopanib HCl in different oils, surfactants, and co-surfactants was carried out by shake flask method at 37°C. Three formulation components were chosen based on the maximum solubility results inthe oil, surfactant, and co-surfactant category and included in the experimental design. The results were analyzed by model fitting using the standard least-squares method. Pazopanib HCl were shown maximum solubility i.e. 25.64±0.24mg/g, 57.84 ±2.91mg/g and, 44.61±1.51mg/g in Labrafac WL 1349 (oil), Labrasol (surfactant) and Transcutol-P (co-surfactant) respectively. Hence these chosen formulation component's concentrations were further optimized by using a simplex lattice design (SLD). Derived mathematical polynomial equations and models were exercised to evaluate the impact of formulation input variables on the output variables (responses) using JMP software. The model p-value for both the responses i.e. solubility and particle size were found less than 0.05 hence models were significant. The results of the mathematical analysis demonstrated that the formulation components have a significant impact on the studied responses. Hence simplex lattice mixture design can be used as a powerful quality design to predict the optimized SEDDS formulation.The applicability of simplex lattice design with desirability function helped optimize a SEEDS formulation of pazopanib HCl and the selected model has made it possible to identify the impact of the critical factors to optimize the required responses.

Fabrication and Optimization of Directly Compressible Self-Emulsifying Tablets Containing Cannabis Extract Obtained from Supercritical Carbon Dioxide Extraction

Δ9-Tetrahydrocannabinol and cannabidiol, which are present in cannabis extract, exhibit low bioavailability when administered orally due to significant first-pass metabolism. The use of a self-emulsifying drug delivery system (SEDDS) can enhance their dissolution and bioavailability. However, liquid SEDDS formulations are prone to inadequate stability. To address this issue, the development of a solid SEDDS formulation was explored. This study aimed to optimize directly compressible self-emulsifying tablets containing cannabis extract obtained from supercritical carbon dioxide extraction. Initially, a liquid SEDDS of cannabis extract was solidified by adsorption onto solid carriers (colloidal silicon dioxide and microcrystalline cellulose). The resulting solid mixture was then combined with other pharmaceutical excipients and compressed into tablets. Three factors were optimized using the Box-Behnken design: compressional force (1,000–2,000 psi), quantity of hydroxypropyl methylcellulose (0–6%), and quantity of croscarmellose sodium (0–6%). The results revealed that a mass ratio of colloidal silicon dioxide, microcrystalline cellulose, and liquid SEDDS of cannabis extract at 0.65:2:1 successfully solidified the mixture. The optimal tablet formulation was achieved with a compressional force of 2,000 psi, without the addition of hydroxypropyl methylcellulose or croscarmellose sodium. Verification data indicated that the predictions made by the computer software were accurate and reliable. The developed tablets exhibited improved dissolution of the cannabis extract, with Δ9-tetrahydrocannabinol demonstrating higher dissolution compared to cannabidiol. Additionally, the compressed tablets were capable of emulsifying small nano-sized droplets (approximately 200 nm). However, the droplets exhibited a larger size and broader polydispersity index compared to the liquid SEDDS. In conclusion, the study successfully developed directly compressible self-emulsifying tablets that enhanced the dissolution of cannabis extract.

Fabrication and Evaluation of Colloidal Silica Containing Powders for Solid Self-emulsifying Drug Delivery System of Poorly Water Soluble Rivaroxaban

Fabrication and Evaluation of Colloidal Silica Containing Powders for Solid Self-emulsifying Drug Delivery System of Poorly Water Soluble Rivaroxaban

NOVEL SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEM FOR ENHANCED DIABETES MANAGEMENT: EVALUATING THE COMBINED EFFECTS OF GLIMEPIRIDE AND BOSWELLIA SERRATA EXTRACT

This study aimed to create and assess a novel self-microemulsifying drug delivery system (SMEDDS) for treating diabetes mellitus that contains glimepiride and Boswellia serrata extract. In the creation of SMEDDS formulations, Transcutol-P was employed as the base oil, while the surfactants Tween 80 and propylene glycol/polyethylene glycol 400 served as the co-surfactants. To improve the formulation, pseudoternary phase diagrams were created. While the SMEDDS of B. serrata extract showed a mean droplet size of 27.63 nm, 98.3% transmittance, a zeta potential of -0.11 mV, and a polydispersity index of 0.287, the glimepiride-optimized SMEDDS showed a mean droplet size of 14.8 nm, 98.5% transmittance, a zeta potential of -0.10 mV. In-vivo evaluation on diabetes-induced rats demonstrated significant reductions in SGOT and SGPT levels with the glimepiride and B. serrata extract SMEDDS compared to diabetic control rats and the marketed glimepiride formulation. The formulation showed promising results in controlling serum total protein, triglyceride, and cholesterol levels. The glimepiride and B. serrata extract SMEDDS also exhibited antioxidant activity, reducing malondialdehyde (MDA) absorbance. Histopathological assessment of kidney and pancreas tissues revealed the protective effects of the concomitant administration of glimepiride and B. serrata extract SMEDDS formulation against diabetes-induced damage. Overall, the developed SMEDDS formulation kit showed superior in-vitro and in-vivo performance, suggesting its potential as an effective therapeutic option for managing diabetes mellitus.

Enhancement of the Solubility of Lipophilic Drug by Self-Micro Emulsifying Drug Delivery System (SMEDDS) For Oral Administration

Enhancement of the Solubility of Lipophilic Drug by Self-Micro Emulsifying Drug Delivery System (SMEDDS) For Oral Administration

Omega-3 fatty acid-based self-microemulsifying drug delivery system (SMEDDS) of pioglitazone: Optimization, in vitro and in vivo studies

Pioglitazone (PGL) is an effective insulin sensitizer, however, side effects such as accumulation of subcutaneous fat, edema, and weight gain as well as poor oral bioavailability limit its therapeutic potential for oral delivery. Recent studies have shown that combination of both, PGL and fish oil significantly reduce fasting plasma glucose,improve insulin resistance, and mitigate pioglitazone-induced subcutaneous fat accumulation and weight gain. Nevertheless, developing an effective oral drug delivery system for administration of both medications have not been explored yet. Thus, this study aimed to develop a self-micro emulsifying drug delivery system (SMEDDS) for the simultaneous oral administration of PGL and fish oil. SMEDDS was developed using concentrated fish oil,Tween® 80, and Transcutol HP and optimized by central composite design (CCD). The reconstituted, optimized PGL-SMEDDS exhibited a globule size of 142 nm, a PDI of 0.232, and a zeta potential of −20.9 mV. The in-vitro drug release study of the PGL-SMEDDS showed a first-order model kinetic release and demonstrated remarkable 15-fold enhancement compared to PGL suspension. Additionally, following oral administration in fasting albino Wistar rats, PGL-SMEDDS exhibited 3.4-fold and 1.4-fold enhancements in the AUC0–24h compared to PGL suspension and PGL marketed product. The accelerated stability testing showed that the optimized SMEDDS formulation was stable over a three-month storage period. Taken together, our findings demonstrate that the developed fish oil-based SMEDDS for PGL could serve as effective nanoplatforms for the oral delivery of PGL, warranting future studies to explore its synergistic therapeutic potential in rats.

Development of Environmentally Responsive Self-Emulsifying System Containing Copaiba Oil-Resin for Leishmaniasis Oral Treatment.

Leishmaniasis is a disease caused by protozoa species of the Leishmania genus, and the current treatments face several difficulties and obstacles. Most anti-leishmanial drugs are administered intravenously, showing many side effects and drug resistance. The discovery of new anti-leishmanial compounds and the development of new pharmaceutical systems for more efficient and safer treatments are necessary. Copaiba oil-resin (CO) has been shown to be a promising natural compound against leishmaniasis. However, CO displays poor aqueous solubility and bioavailability. Self-emulsifying drug delivery systems (SEDDS) can provide platforms for release of hydrophobic compounds in the gastrointestinal tract, improving their aqueous solubilization, absorption and bioavailability. Therefore, the present work aimed to develop SEDDS containing CO and Soluplus® surfactant for the oral treatment of leishmaniasis. The design of the systems was accomplished using ternary phase diagrams. Emulsification and dispersion time tests were used to investigate the emulsification process in gastric and intestinal environments. The formulations were nanostructured and improved the CO solubilization. Their in vitro antiproliferative activity against promastigote forms of L. amazonensis and L. infantum, and low in vitro cytotoxicity against macrophages were also observed. More studies are necessary to determine effectiveness of SOL in these systems, which can be candidates for further pharmacokinetics and in vivo investigations.

Formulation and Evaluation of a Self-Microemulsifying Drug Delivery System of Raloxifene with Improved Solubility and Oral Bioavailability.

Poor aqueous solubility and dissolution limit the oral bioavailability of Biopharmaceutics Classification System (BCS) class II drugs. In this study, we aimed to improve the aqueous solubility and oral bioavailability of raloxifene hydrochloride (RLX), a BCS class II drug, using a self-microemulsifying drug delivery system (SMEDDS). Based on the solubilities of RLX, Capryol 90, Tween 80/Labrasol ALF, and polyethylene glycol 400 (PEG-400) were selected as the oil, surfactant mixture, and cosurfactant, respectively. Pseudo-ternary phase diagrams were constructed to determine the optimal composition (Capryol 90/Tween 80/Labrasol ALF/PEG-400 in 150/478.1/159.4/212.5 volume ratio) for RLX-SMEDDS with a small droplet size (147.1 nm) and stable microemulsification (PDI: 0.227). Differential scanning calorimetry and powder X-ray diffraction of lyophilized RLX-SMEDDS revealed the loss of crystallinity, suggesting a molecularly dissolved or amorphous state of RLX in the SMEDDS formulation. Moreover, RLX-SMEDDS exhibited significantly higher saturation solubility and dissolution rate in water, simulated gastric fluid (pH 1.2), and simulated intestinal fluid (pH 6.8) than RLX powder. Additionally, oral administration of RLX-SMEDDS to female rats resulted in 1.94- and 1.80-fold higher area under the curve and maximum plasma concentration, respectively, than the RLX dispersion. Collectively, our findings suggest SMEDDS is a promising oral formulation to enhance the therapeutic efficacy of RLX.

In Vitro and In Vivo Efficacy of Topical Dosage Forms Containing Self-Nanoemulsifying Drug Delivery System Loaded with Curcumin.

The external use of curcumin is rare, although it can be a valuable active ingredient in the treatment of certain inflammatory diseases. The aim of our experimental work was to formulate topical dosage forms containing curcumin for the treatment of atopic dermatitis. Curcumin has extremely poor solubility and bioavailability, so we have tried to increase it with the usage of self-emulsifying drug delivery systems. Creams and gels were formulated using penetration-enhancing surfactants and gelling agents. The release of the drug from the vehicle and its penetration through the membrane were determined using a Franz diffusion cell. An MTT cytotoxicity and in vitro antioxidant assays were performed on HaCaT cell line. The in vivo anti-inflammatory effect of the preparations was tested by measuring rat paw edema. In addition, we examined the degree of inflammation induced by UV radiation after pretreatment with the cream and the gel on rats. For the gels containing SNEDDS, the highest penetration was measured after half an hour, while for the cream, it took one hour to reach the maximum concentration. The gel containing Pemulen TR-1 showed the highest drug release. It was determined that the curcumin-containing preparations can be safely applied on the skin and have antioxidant effects. The animal experiments have proven the effectiveness of curcumin-containing topical preparations.

Design and Evaluation of Hydrophobic Ion Paired Insulin Loaded Self Micro-Emulsifying Drug Delivery System for Oral Delivery.

Despite several novel and innovative approaches, clinical translation of oral insulin delivery into commercially viable treatment is still challenging due to its poor absorption and rapid degradation in GIT. Thus, an insulin-SDS hydrophobic ion pair loaded self-microemulsifying drug delivery system (SMEDDS) was formulated to exploit the hypoglycemic effects of orally delivered insulin. Insulin was initially hydrophobically ion paired with sodium dodecyl sulphate (SDS) to enhance its lipophilicity. The successful complexation of Insulin-SDS was confirmed by FTIR and surface morphology was evaluated using SEM. Stability of insulin after its release from HIP complex was evaluated using SDS PAGE. Subsequently, Ins-SDS loaded SMEDDS was optimized using two factorial designs. In vitro stability of insulin entrapped in optimized SMEDDS against proteolytic degradation was also assessed. Further, antidiabetic activity of optimized Ins-SDS loaded SMEDDS was evaluated in diabetic rats. Insulin complexed with SDS at 6:1 (SDS/insulin) molar ratio with almost five-fold increased lipophilicity. The SMEDDS was optimized at 10% Labraphil M2125 CS, 70% Cremophore EL, and 20% Transcutol HP with better proteolytic stability and oral antidiabetic activity. An Ins-SDS loaded SMEDDS was successfully optimized. Compared with insulin and Ins-SDS complex, the optimized SMEDDS displayed considerable resistance to GI enzymes. Thus, the SMEDDS showed potential for effective delivery of macromolecular drugs with improved oral bioavailability.

Nanocellulose-Based Film-Forming Hydrogels for Improved Outcomes in Atopic Skin.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by impaired skin barrier function. Amongst the various dermal formulations that are being used and/or investigated for AD treatment, one of the advanced approaches is the use of hydrogels as film-forming systems that are applied directly to the skin and have the added value of providing a physical barrier, which is lacking in atopic skin. Novel film-forming hydrogels based on two different nanocrystalline celluloses (NCCs) in combination with one of two natural polymers (alginate or pectin) were developed for incorporation of betamethasone dipropionate (BDP). Initially, the low water solubility of BDP was resolved by prior dissolution in a self-microemulsifying drug delivery system (SMEDDS). The mixture of Kolliphor® EL/Capryol® 90 in a ratio of 8/2 was chosen on the merit of its high BDP-saturated solubility and no BDP precipitation upon water dilution, enabling BDP to remain dissolved after incorporation into hydrogels. The solvent evaporation method was used to prepare the films, and their high water retention capacity was confirmed in vitro on artificial membranes and pig ear skin. The presented results thus confirm NCC-based film-forming hydrogels as a very promising drug delivery system for AD treatment.

Formulation Development and Evaluation of Solid Self Microemulsifying Drug Delivery System of Azelnidipine

This study aimed to develop a self-micro emulsifying drug delivery system (SMEDDS) for poorly soluble azelnidipine using Capryol 90 as the oil, Tween 80 as the surfactant, and transcutol-HP as the co-surfactant. A factorial design was used to optimize the formulation, and Neusilin UFL2 was used as an adsorbent to convert the liquid SMEDDS to solid SMEDDS. The optimized formulation had a particle size of 80.5nm, a transmittance of 98.2%, a zeta potential of -3.1 mV, and a polydispersibility index of 0.226. The solid SMEDDS tablet exhibited improved drug release (99.4% in 60 minutes) compared to the marketed tablet (67.09.75%) and pure drug (26.17%). This study demonstrates the potential of the SMEDDS approach to enhance the solubility and in-vitro drug release of poorly soluble drugs such as azelnidipine.

Self-emulsifying drug delivery systems and the application in drugs and cosmetics

Self-emulsifying drug delivery systems (SEDDS) have the potential to enhance the bioavailability and therapeutic impact of active ingredients that are poorly water-soluble, low pemeability and unstable. The active ingredient, oil, surfactant, co-surfactant and/or co-solvent are the main elements of SEDDS. Supersaturable SEDDS have been developed to increase the efficiency of active ingredient loading by incorporating precipitation inhibitors (PIs) into SEDDS that help maintain the supersaturated state, preventing drug precipitation in the gastrointestinal tract. Due to these benefits, SEDDS have been studied and applied in drugs and cosmetics in various dosage forms including solidification (S-SEDDS) by different techniques to create powder, granules, pellets to apply to tablets, hard capsules as well as soft capsules, lotions, and some other semi-solid dosage forms... This review mainly focuses on the components, formulation, and applications of SEDDS in the pharmaceutical and cosmetic products.

Antibiotics modified by hydrophobic ion-pairing – A solution world's problems with resistant bacteria?

Resistance to antibiotics is one of the greatest dangers to the humanity, according to the World Health Organization. To reduce the amount of used antibiotics, various targeted drug delivery is considered, e.g., biopolymeric micro- or nanoparticles, electrospun nanofibers, or self-emulsifying drug delivery systems. In the case of hydrophilic antibiotics, there is an issue of relatively low encapsulation efficiencies and too rapid release, due to chemical character impairment (hydrophobic carrier – hydrophilic antibiotic). It results in not only lower clinical success rate, but also in creating a huge antibiotic waste when the manufacturing process is converted to the industrial conditions. A possible solution to overcome these problems is changing the chemical character of the antibiotics by a simple reaction of ion pairing with either cationic or ionic surfactants that may decrease water solubility of antibiotics without any loss, or with even better, bactericidal properties. This approach increases encapsulation efficiency up to nearly 100%. As the result, lower doses of antibiotics can be used in drug delivery systems that provide a more sustainable release. However, there is a risk of a higher toxicity due to the presence of surfactants and the origin of improved antibacterial properties have not yet been fully explained. Herein, we present the review of the current achievements in the field of antibiotics hydrophobized by hydrophobic ion pairing (HIP) for various drug delivery systems with the special regard to the antibacterial properties and biocompatibility.

Lycopene from Red Guava (Psidium guajava L.): From Hepatoprotective Effect to Its Use as Promising Self-Emulsifying Drug Delivery System for Anti-Inflammatory and Antioxidant Applications.

Lycopene is a carotenoid with potential use in the treatment of chronic illnesses. Here, different formulations of lycopene were studied: lycopene-rich extract from red guava (LEG), purified lycopene from red guava (LPG) and a self-emulsifying drug delivery system loaded with LPG (nanoLPG). The effects of administering orally various doses of LEG to hypercholesterolemic hamsters were evaluated regarding the liver function of the animals. The cytotoxicity of LPG in Vero cells was analyzed by a crystal violet assay and by fluorescence microscopy. In addition, nanoLPG was employed in stability tests. LPG and nanoLPG were tested for their cytotoxic effect on human keratinocytes and antioxidant capacity on cells in an endothelial dysfunction model in an isolated rat aorta. Finally, the effect of different nanoLPG concentrations on the expression of immune-related genes (IL-10, TNF-α, COX-2 and IFN-γ) from peripheral blood mononuclear cells (PBMC) using real-time PCR was also analyzed. Results suggest that LEG, despite not being able to improve blood markers indicative of liver function in hypercholesterolemic hamsters, reduced hepatic degenerative changes. Additionally, LPG did not show cytotoxicity in Vero cells. In relation to nanoLPG, the effects produced by heat stress evaluated by Dynamics Light Scattering (DLS) and visually were loss of color, texture change and phase separation after 15 days without interfering with the droplet size, so the formulation proved to be efficient in stabilizing the encapsulated lycopene. Although LPG and nanoLPG showed moderate toxicity to keratinocytes, which may be related to cell lineage characteristics, both revealed potent antioxidant activity. LPG and nanoLPG showed vasoprotective effects in aortic preparations. The gene expression assay indicates that, although no significant differences were observed in the expression of IL-10 and TNF-α, the PBMCs treated with nanoLPG showed a reduction in transcriptional levels of IFN-γ and an increased expression of COX-2. Thus, the work adds evidence to the safety of the use of lycopene by humans and shows that tested formulations, mainly nanoLPG due to its stability, stand out as promising and biosafe products for the treatment of diseases that have oxidative stress and inflammation in their etiopathology.

Celecoxib Oral Solution and the Benefits of Self-Microemulsifying Drug Delivery Systems (SMEDDS) Technology: A Narrative Review.

The oral route of drug delivery is the most widespread and preferred route of administration, but it has several limitations, including variable pharmacokinetics (PK), reduced dissolution and absorption, and gastrointestinal irritation. Further, many compounds have low aqueous solubility, which also limits intestinal absorption. For this narrative review, we conducted a literature search of PubMed until August 2022, focusing on emulsions, microemulsions, nanoemulsions, and self-emulsifying drug delivery systems. The self-microemulsifying drug delivery system (SMEDDS) overcomes these limitations of hydrophobic compounds to enhance their bioavailability. A SMEDDS formulation is a clear, thermodynamically stable, oil-in-water emulsion of lipid, solubilized drug, and two surfactants, which spontaneously forms droplets < 100nm in diameter. These components help deliver presolubilized drugs to the gastrointestinal tract, while protecting them from degradation in gastric acid or first-pass hepatic metabolism. SMEDDS formulations have improved oral drug delivery in the treatment of cancer (paclitaxel), viral infections (ritonavir), and migraine headache (ibuprofen and celecoxib oral solution). The American Headache Society recently updated their consensus statement for the acute treatment of migraine and included a selective cyclo-oxygenase-2 selective inhibitor formulated in SMEDDS, celecoxib oral solution. This SMEDDS formulation showed pronounced improvement in bioavailability compared with celecoxib capsules, allowing for a low dose of celecoxib in the oral solution to provide safe and effective acute migraine treatment. Here, we will focus on SMEDDS formulations, what differentiates them from other analogous emulsions as vehicles for poorly soluble drugs, and their clinical application in the acute treatment of migraine. Oral drugs reformulated in SMEDDS have shown accelerated times to peak plasma drug concentrations and increased maximum plasma concentrations, compared with capsules, tablets, or suspensions. SMEDDS technology increases both drug absorption and bioavailability of lipophilic drugs, compared with other formulations. Clinically, this allows the use of lower doses with improved PK profiles without compromising efficacy, as shown with celecoxib oral solution for the acute treatment of migraine.

Nose-to-brain delivery of perampanel formulated in a self-microemulsifying drug delivery system improves anticonvulsant and anxiolytic activity in mice

Perampanel (PER) is a potent third-generation antiepileptic drug only available for oral administration. Additionally, PER has shown potential in managing epilepsy comorbidities such as anxiety. Previously, we demonstrated that the intranasal (IN) administration of PER, loaded in a self-microemulsifying drug delivery system (SMEDDS), improved brain-targeting and exposure in mice. Herein, we investigated PER brain biodistribution, its anticonvulsant and anxiolytic effects, and its potential olfactory and neuromotor toxicity after IN administration to mice (1 mg/kg). PER showed a rostral-caudal brain biodistribution pattern when administered intranasally. At short times post-nasal dosing, high PER concentrations were found in olfactory bulbs (olfactory bulbs/plasma ratios of 1.266 ± 0.183 and 0.181 ± 0.027 after IN and intravenous administrations, respectively), suggesting that a fraction of the drug directly reaches brain through the olfactory pathway. In the maximal electroshock seizure test, IN PER protected 60% of mice against seizure development, a substantially higher value than the 20% protected after receiving oral PER. PER also demonstrated anxiolytic effects in open field and elevated plus maze tests. Buried food-seeking test showed no signs of olfactory toxicity. Neuromotor impairment was found in rotarod and open field tests at the times of PER maximum concentrations after IN and oral administrations. Nevertheless, neuromotor performance was improved after repeated administrations. Compared with IN vehicle, PER IN administration decreased brain levels of L-glutamate (0.91 ± 0.13 mg/mL vs 0.64 ± 0.12 mg/mL) and nitric oxide (100 ± 15.62% vs 56.62 ± 4.95%), without interfering in GABA levels. Altogether, these results suggest that the IN PER delivery through the developed SMEDDS can be a safe and promising alternative to the oral treatment, which supports the design of clinical studies to evaluate the IN PER delivery to treat epilepsy and neurological-related conditions as anxiety.

Formulasi Self Nano-Emulsifying Drug Delivery System (SNEDDS) Ibuprofen dengan VCO dan Kombinasi Surfaktan

Ibuprofen is one of the Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) class of propionic acid derivatives which has potent anti-inflammatory and antipyretic activity. The solubility of ibuprofen is disadvantageous because it is practically insoluble and has poor dissolution. The aim of this study was to overcome the solubility of ibuprofen through a stable SNEDDS formula. One way to overcome the solubility of ibuprofen is to prepare nanoemulsions using the Self-Emulsifying Drug Delivery System (SNEDDS) technique. SNEDDS is a form of preemulsion drug which spontaneously forms nanoemulsion when it encounters the aqueous phase in the digestive tract. Parameters for the success of the SNEDDS formula include emulsification time, stability, and droplet size using a particle size analyzer (PSA). The SNEDDS formulation was carried out by mixing span 80 and tween 20, PEG 400 and VCO as the oil phase. The characteristics of SNEDDS ibuprofen include homogeneity of SNEDDS, clarity, transmittance, emulsification time, and droplet size. The composition of the optimum formula for SNEDDS ibuprofen is 1 mL of VCO; 1 mL PEG; 7 mL tween 20; 1 mL span 80. The formula shows good homogeneity, is clear with emulsification time of 15 seconds, transmittance is 92.69%, and droplet size is 221.9 nm.

Development of positively charged amphiphile containing self-nanoemulsifying drug delivery system for improved therapeutic efficacy of metronidazole against Helicobacterpylori

Metronidazole (MTZ) has been extensively used to treat bacterial infections for over five decades, but MTZ bacterial resistance has been on the rise, making it less effective against Bacteroides species. This study aimed to improve the antibacterial activity of MTZ-loaded self-emulsifying drug delivery systems (SNEDDS) against H. pylori by the incorporation of alkylated morpholine serving as a positively charged amphiphile. The studies of drug solubility and emulsification led to the development of a ternary phase diagram for selecting formulation ingredients. The key ingredients of the formulation were selected as cinnamon oil (lipid), cremophor EL (surfactant), and polyethylene Glycol (PEG) 200 (co-surfactant). The optimized formulations were characterized for various physicochemical properties. The average droplet size and zeta potential of MTZ-SNEDDS were determined to be 146.03 ± 2.1 nm and −15.3 ± 0.50 mV while for alkylated morpholine incorporated MTZ-SNEDDS, these were 183.36 ± 21.42 nm and −16.2 ± 1.30 mV, respectively. The thermodynamically robust alkylated morpholine incorporated SNEDDS was successful in maintaining the chemical integrity of the MTZ. The antibacterial potential of MTZ-SNEDDS was significantly enhanced against H. pylori upon the incorporation of alkylated morpholine. It can be concluded that incorporating amphiphilic positively charged morpholine into SNEDDS can lead to more intake of them by H. pylori, and prolonging the contact duration of the SNEDDS with the outer membrane of H. pylori increased the transmembrane penetration of SNEDDS.

Self-emulsifying drug delivery systems: A versatile approach to enhance the oral delivery of BCS class III drug viahydrophobic ion pairing.

Biopharmaceutical classification systems (BCS) class III drugs belongs to a group of drugs with high solubility in gastrointestinal (GI) fluids and low membrane permeability result in significantly low bioavailability. Self-emulsifying drug delivery systems (SEDDS) considered a suitable candidate to enhance the bioavailability of poorly soluble drugs by improving their membrane permeability, however, incorporating hydrophilic drugs in to these carriers remained a great challenge. The aim of this study was to develop hydrophobic ion pairs (HIPs) of a model BCS class-III drug tobramycin (TOB) in order to incorporate into SEDDS and improve its bioavailability. HIPs of TOB were formulated using anionic surfactants sodium docusate (DOC) and sodium dodecanoate (DOD). The efficiency of HIPs was estimated by measuring the concentration of formed complexes in water, zeta potential determination and log P value evaluation. Solubility studies of HIPs of TOB with DOC were accomplished to screen the suitable excipients for SEDDS development. Consequently, HIPs of TOB with DOC were loaded into SEDDS and assessed the log DSEDDS/release medium and dissociation of these complexes at different intestinal pH over time. Moreover, cytotoxic potential of HIPs of TOB and HIPs loaded SEDDS formulations was evaluated. HIPs of TOB with DOC exhibited the maximum precipitation efficiency at a stoichiometric ratio of 1:5. Log P of HIPs of TOB improved up to 1500-fold compared to free TOB. Zeta potential of TOB was shifted from positive to negative during hydrophobic ion pairing (HIP). HIPs of TOB with DOC was loaded at a concentration of 1% (w/v) into SEDDS formulations. Log DSEDDS/release medium of loaded complexes in to oily droplets was above 2 and dissociated up to 20% at various pH within 4 h. Finding of this study suggested that improvement of the lipophilic character of BCS class-III drugs followed by incorporation into oily droplets can be deliberated as a promising tool to enhance the permeation across biological membranes.