Pseudo-ternary Phase Diagrams Research Articles

Formulation of Intranasal Mucoadhesive Thermotriggered In Situ Gel Containing Mirtazapine as an Antidepressant Drug.

The purpose of the present work was to develop nanoemulsion-based formulations of mirtazapine for intranasal delivery using a spray actuator to target the brain for treating depression. Research on the solubility of medications in different oils, surfactants, co-surfactants, and solvents has been done. Using pseudo-ternary phase diagrams, the various ratios of the surfactant and co-surfactant mix were computed. Thermotriggered nanoemulsion was formulated using different concentrations of poloxamer 407 (i.e., 15%, 15.5%, 16%, 16.5% up to 22%). Similarly, mucoadhesive nanoemulsion using 0.1% Carbopol and water-based plain nanoemulsions were also prepared for comparative assessment. The developed nanoemulsions were analyzed for physicochemical properties, i.e., physical appearance, pH, viscosity, and drug content. Drug-excipient incompatibility was determined by Fourier transform infrared spectral (FTIR) analysis and differential scanning calorimetry (DSC). In vitro drug diffusion studies were conducted for optimized formulations. Among the three formulations, RD1 showed the highest percentage of drug release. Ex vivo drug diffusion studies were conducted on freshly excised sheep nasal mucosa with Franz diffusion cell simulated nasal fluid (SNF) for all three formulations up to 6 h, and the thermotriggered nanoemulsion (RD1) showed 71.42% drug release with 42.64 nm particle size and a poly dispersity index of 0.354. The zeta potential was found to be -6.58. Based on the above data, it was concluded that thermotriggered nanoemulsion (RD1) has great potential to be used as an intranasal gel for treating depression in patients. It can offer great benefits by reducing dosing frequency and improving bioavailability of mirtazapine by direct nose-to-brain delivery.

D-Optimal Design and Development of a Koumine-Loaded Microemulsion for Rheumatoid Arthritis Treatment: In vivo and in vitro Evaluation.

Koumine (KME) is the most abundant active ingredient separated from Gelsemium elegans Benth and exhibits a significant therapeutic effect on rheumatoid arthritis (RA). It is a lipophilic compound with poor aqueous solubility, and there is an urgent need to develop novel dosage forms of KME and promote its clinical application for the treatment of RA. The aim of this study was to design and develop KME-loaded microemulsions (KME-MEs) for the effective management of RA. The composition of the microemulsion was selected by carrying out a solubility study and generating pseudoternary phase diagrams, and further optimized by D-Optimal design. The optimized KME-MEs was evaluated for particle size, viscosity, drug release, storage stability, cytotoxicity, cellular uptake, Caco-2 cell transport and everted gut sac investigations. In vivo fluorescence imaging and the therapeutic effects of KME and KME-MEs on collagen-induced arthritis (CIA) rats were also evaluated. The optimized microemulsion contained 8% oil, 32% Smix (surfactant/cosurfactant) and 60% water and was used for in vivo and in vitro studies. The optimal KME-MEs exhibited a small globule size of 18.5 ± 0.14 nm and good stability over 3 months, and the release kinetics followed a first-order model. These KME-MEs had no toxic effect on Caco-2 cells but were efficiently internalized into the cytoplasm. Compared to KME, the KME-MEs displayed significantly increased permeability and absorption in Caco-2 cell monolayer assay and ex vivo everted gut sac experiment. As expected, the KME-MEs attenuated the progression of RA in CIA rats and were more effective than free KME with a reduced frequency of administration. The KME-MEs improved the solubility and therapeutic efficacy of KME by employing formulation technology. These results provide a promising vehicle for the oral delivery of KME to treat RA and have attractive potential for clinical translation.

Green nanoemulsion-based treatment to remove sulfamethoxazole from a contaminated water solution

Sulfamethoxazole (SUX) is a common pharmaceutical, but represents a potential global threat to human health due to its exhaustive use and consequent outflow in the environment. This situation calls for development of a cost-effective approach to remove SUX present in contaminated released from various sources. In this study, we developed green nanoemulsions to remove SUX from contaminated water samples. Parameters predicted by Hansen solubility (HSPiP software) were used to select excipients. Several trial batches (SN1–SN12) of green nanoemulsions were developed and characterized for size, zeta potential, polydispersity (PDI), and removal efficiency (%RE) to determine the input parameters (factors, levels, and responses) for an experimental design tool (Design-Expert) to identify the most critical variables controlling %RE and to optimize the nanoemulsion composition under set constraints. Transmission electron microscopy (TEM) confirmed the morphological behavior after 30 min of dispersion. Finally, the inductively coupled plasma-optical emission spectroscopy (ICP-OES) technique was used to confirm the absence of SUX in water treated with the optimized nanoemulsion. Results showed that SUX and eugenol closely interact based on Hansen solubility parameters and the experimental solubility data corroborated the predicted outcomes. Pseudo ternary-phase diagrams suggested various ratios of surfactant to co-surfactant (Smix) based on SN1–SN12 and that SN10 was the most suitable nanoemulsion for input parameters (Smix of 1:3, desired size 78 nm, lowest PDI 0.118, highest %RE 78%, and highest zeta potential +23 mV) in the experimental design program. In addition, Design-Expert identified the prime factors responsible to control %RE. OSEN1 was the most robust and optimized nanoemulsion with high overall desirability (0.94). Composition, globular size, viscosity, and contact time emerged as prime critical variables with a significant impact on the %RE of SUX from contaminated water using the green nanoemulsion. ICP-OES confirmed the absence of SUX from treated water. Overall, our results demonstrate that green nanoemulsions represent a promising and cost-effective approach to remove SUX from environmental water samples and alleviate safety concerns.

Redox-responsive microemulsion: Fabrication and application to curcumin encapsulation

HypothesisStimulus-responsive microemulsions have aroused significant attention because of their versatile and reversible switchability between stable and unstable states. However, most stimuli-responsive microemulsions are based on stimuli-responsive surfactants. We posit that the change in the hydrophilicity of a selenium-containing alcohol triggered by a mild redox reaction could also influence the stability of microemulsions and provide a new nanoplatform for the delivery of bioactive substances. ExperimentsA selenium-containing diol (3,3′-selenobis(propan-1-ol), PSeP) was designed and used as a co-surfactant in a microemulsion with ethoxylated hydrogenated castor oil (HCO40), diethylene glycol monohexyl ether (DGME), 2-n-octyl-1-dodecanol (ODD) and water. The redox-induced transition in PSeP was characterized by 1H NMR, 77Se NMR, and MS. The redox-responsiveness of the ODD/HCO40/DGME/PSeP/water microemulsion was investigated through determination of a pseudo-ternary phase diagram, analysis by dynamic light scattering, and electrical conductivity, and its encapsulation performance was evaluated by determination of the solubility, stability, antioxidant activity, and skin penetrability of encapsulated curcumin. FindingsThe redox conversion of PSeP enabled efficient switching of ODD/HCO40/DGME/PSeP/water microemulsions. Addition of oxidant (H2O2), oxidized PSeP into more hydrophilic PSeP-Ox (selenoxide), disrupting the emulsifying capacity of the combination of HCO40/DGME/PSeP, markedly reducing the monophasic microemulsion region in the phase diagram, and inducing phase separation in some formulations. Addition of reductant (N2H4·H2O), reduced PSeP-Ox and restored the emulsifying capacity of the combination of HCO40/DGME/PSeP. In addition, PSeP-based microemulsions can significantly enhance the solubility in oil (by 23 times), stability, antioxidant capacity (DPPH∙ radical scavenging by 91.74 %), and skin penetrability of curcumin, showing clear potential for encapsulation and delivery of curcumin and other bioactive substances.

The physical encapsulation and chemical fixation of Zn during thermal treatment process of municipal solid waste incineration (MSWI) fly ash

Thermal treatment is a promising treatment technology of municipal solid waste incineration (MSWI) fly ash because of its detoxication and volume reduction. However, the relationship between immobilization of heavy metals and mineral transformation during thermal treatment remains unclear. In this study, the immobilization mechanism of Zn during thermal treatment process of MSWI fly ash was investigated by experiment and calculation. The results show that addition of SiO2 facilitates transition of dominant minerals from melilite to anorthite during sintering, increases liquid content during melting and improves liquid polymerization degree during vitrification. ZnCl2 tends to be physically encapsulated by liquid phase, and ZnO is mainly chemically fixed into minerals at high temperature. Increase in both liquid content and liquid polymerization degree favors the physical encapsulation of ZnCl2. The decreasing order of chemical fixation ability of minerals to ZnO is spinel > melilite > liquid > anorthite. To better immobilize Zn during sintering and vitrification process chemical composition of MSWI fly ash should be located in melilite and anorthite primary phases of pseudo-ternary phase diagram, respectively. The results are helpful to understand immobilization mechanism of heavy metals and avoid volatilization of heavy metals during thermal treatment process of MSWI fly ash.

KETOCONAZOLE LADEN MICROEMULSION BASED GEL FORMULATION AGAINST SKIN FUNGAL INFECTION

Objective: The present research was aimed to develop ketoconazole (KT) loaded microemulsion-based gel formulation for effective topical delivery through enhanced drug solubility, improved skin permeation and reduced side effects overcoming drawbacks of conventional dosage forms. Methods: For the selection of oil, surfactant and co-surfactant mixture (Smix) ratio, the phase titration method was used and pseudo-ternary phase diagrams were prepared. D-optimal mixture design was employed to optimize the microemulsion system taking oil, Smix and water as independent variables and particle size, polydispersity index, zeta potential, % transmittance and cumulative % drug release as response variables. Finally, topical gel formulation of KT-loaded microemulsion was developed and evaluated for physico-chemical properties, rheological properties, in vitro drug release kinetics and ex-vivo drug permeation. Results: The optimized microemulsion was found to be a transparent formulation with 19.7 nm particle size, 0.268 polydispersity index,-0.2 mV zeta potential, 97.83% transmittance and 85.85% cumulative drug release at 24 h. The developed gel of optimized microemulsion possessed pH 6.20, viscosity 2178 cps, spreadability 18.634 g.cm2/sec, adhesiveness 45.989 N/mm2, and cohesiveness-85.583. The in vitro drug release was found to be 69.08 % (at 24 h), showing sustained release and Higuchi kinetic profile. The developed gel exhibited 1.84-fold higher drug permeation flux as compared to the marketed product. Conclusion: The developed gel formulation possessed all desired quality attributes and physico-chemical properties. The in vitro and ex-vivo study data proved it’s suitability as a better alternative to conventional products in the effective treatment of fungal skin infections.

Preparation and In Vitro Characterization of Alkyl Polyglucoside-Based Microemulsion for Topical Administration of Curcumin.

The skin is a complex and selective system from the perspective of permeability to substances from the external environment. Microemulsion systems have demonstrated a high performance in encapsulating, protecting and transporting active substances through the skin. Due to the low viscosity of microemulsion systems and the importance of a texture that is easy to apply in the cosmetic and pharmaceutical fields, gel microemulsions are increasingly gaining more interest. The aim of this study was to develop new microemulsion systems for topical use; to identify a suitable water-soluble polymer in order to obtain gel microemulsions; and to study the efficacy of the developed microemulsion and gel microemulsion systems in the delivery of a model active ingredient, namely curcumin, into the skin. A pseudo-ternary phase diagram was developed using AKYPO® SOFT 100 BVC, PLANTACARE® 2000 UP Solution and ethanol as a surfactant mix; caprylic/capric triglycerides, obtained from coconut oil, as the oily phase; and distilled water. To obtain gel microemulsions, sodium hyaluronate salt was used. All these ingredients are safe for the skin and are biodegradable. The selected microemulsions and gel microemulsions were physicochemically characterized by means of dynamic light scattering, electrical conductivity, polarized microscopy and rheometric measurements. To evaluate the efficiency of the selected microemulsion and gel microemulsion to deliver the encapsulated curcumin, an in vitro permeation study was performed.

Oral administration of Huanglian-Houpo herbal nanoemulsion loading multiple phytochemicals for ulcerative colitis therapy in mice

How to achieve stable co-delivery of multiple phytochemicals is a common problem. This study focuses on the development, optimization and characterization of Huanglian-HouPo extract nanoemulsion (HLHPEN), with multiple components co-delivery, to enhance the anti-ulcerative colitis (UC) effects. The formulation of HLHPEN was optimized by pseudo-ternary phase diagram combined with Box-Behnken design. The physicochemical properties of HLHPEN were characterized, and its anti-UC activity was evaluated in DSS-induced UC mice model. Based on preparation process optimization, the herbal nanoemulsion HLHPEN was obtained, with the droplet size, PDI value, encapsulation efficiency (EE) for 6 phytochemicals (berberine, epiberberine, coptisine, bamatine, magnolol and honokiol) of 65.21 ± 0.82 nm, 0.182 ± 0.016, and 90.71 ± 0.21%, respectively. The TEM morphology of HLHPEN shows the nearly spheroidal shape of particles. The optimized HLHPEN showed a brownish yellow milky single-phase and optimal physical stability at 25 °C for 90 days. HLHPEN exhibited the good particle stability and gradual release of phytochemicals in SGF and SIF, to resist the destruction of simulated stomach and small intestine environment. Importantly, the oral administration of HLHPEN significantly restored the shrunk colon tissue length and reduced body weight, ameliorated DAI value and colon histological pathology, decreased the levels of inflammatory factors in DSS-induced UC mice model. These results demonstrated that HLHPEN had a significant therapeutic effect on DSS-induced UC mice, as a potential alternative UC therapeutic agent.

Formulation of Microemulsions Containing Rambutan Peel Extract and Their Antibacterial Activities

Nowadays, numerous pathogens have become increasingly resistant to antibiotics. To address this issue, it is important to undertake additional research to develop alternative antibacterial agents. The goal of this investigation was to fabricate microemulsions from rambutan (Nephelium lappaceum L.) peel extract and test their antibacterial activity. The cytotoxicity of the rambutan peel extract was studied. The other assessments were conducted on the visual, physical, and electrical properties of microemulsions, which include their appearance, phase separation, viscosity, and conductivity. Moreover, the research also examined the potential antibacterial effects of microemulsions against both gram-negative (Escherichia coli) and gram-positive (Staphylococcus aureus) bacteria by exploring their ability to inhibit bacterial growth. The findings indicated that even when the extract was used at the highest concentration (100 µg/mL), there were no cytotoxic effects on skin keratinocyte cells. Using the pseudoternary phase diagram, a blend of rosemary oil, water, and a combination of surfactant (Tween® 80) and co-surfactant (Ethanol) were employed to create microemulsions containing different quantities of rambutan peel extract. According to the results, a stable microemulsion was observed as the ratio of Tween® 80 and ethanol was higher than 38%. The microemulsions containing extract at concentrations of 1% w/w, 5% w/w, and 10% w/w were clear and transparent, with no phase separation. All formulations were physiochemically acceptable. Microemulsions containing 1% w/w – 10% w/w rambutan peel extracts were shown to be efficient in suppressing only gram-positive S. aureus.&nbsp

Natural Oil Nanoemulsion-Based Gel Vehicle for Enhancing Antifungal Effect of Topical Luliconazole

Background: Luliconazole, a newer class of imidazole anti-fungal agent, is very effective against several species of fungi, especially dermatophytes. It has very low aqueous solubility acting as barrier for topical delivery and limiting its dermal availability. Aim of the study: This study aimed to formulate luliconazole oil/water nanoemulsion by the aqueous titration method. Methods: Solubility study resulted in selecting peppermint oil, tween 80 and transcutol p as oil phase, surfactant and cosurfactant respectively, although pseudoternary phase diagram construct nanoemulsion area for picking formulations. Fifteen o/w nanoemulsion formulations prepared and characterised for droplet size, polydispersity index, pH values, percent transmittance, luliconazole content. Among formulations, eight preparations introduced to enhance the viscosity of prepared nanoemulsion by combining 0.5% carbopol 934 as gelling agent. Results: The selected preparations demonstrated homogeneous nanoemulgels with pH values appropriate for skin application and accepted luliconazole content. Viscosity results manifested non-newtonian pseudo plastic behavior with shear-thinning viscosity profile. In vitro release studies revealed dissimilar release profile (f2˂50) than that of pure luliconazole dispersion. The results revealed that the formula NG-1 with oil: Smix(2:1):water (15:40:43.5) ratio containing 1% drug and 0.5% carbopol 934 was the optimised formula with excellent spreadability. Conclusion: The study concluded that nanoemulsion-based gel is contemplated an encouraging and proceed technique for the topical preparation and upgrade solubility, dissolution rate and permeability of insufficient water-soluble drugs across the skin.

Design and dermatokinetic appraisal of lornoxicam-loaded ultrafine self-nanoemulsion hydrogel for the management of inflammation: In vitro and in vivo studies

The present study aimed to evaluate the impact of ultrafine nanoemulsions on the transdermal delivery of lornoxicam (LOR) for management of the inflammation. The transdermal administration of LORNE could increase the efficacy of LOR with a reduction in side effects. Merging the beneficial properties of ultrafine nanoemulsions and their components (penetration enhancers) can lead to good solubilization, a small droplet size, and more effective LOR carriers. Therefore, this study aims to develop and evaluate the potential use of ultrafine nanoemulsions of LOR (LORNE) to elucidate their skin targeting for the treatment of inflammation. Based on solubility and pseudo ternary phase diagram tests, ultrafine LORNE composed of Labrafil M 2125 CS, Cremophor RH40, and Transcutol HP to deliver LOR was developed and characterized for its physicochemical properties, emulsification, and in vitro release. The selected LORNE was incorporated into carbopol gel (LORNE-Gel) and examined for ex vivo skin permeation, retention, dermatokinetics, anti-inflammatory efficacy, and skin irritation. The selected LORNE12-Gel could improve skin permeation, retention, and dermatokinetic results significantly (p < 0.05) with enhanced CSkin max and AUC0-48h compared to LOR-Gel. Moreover, LORNE12-Gel showed a remarkable anti-inflammatory effect compared to LOR-Gel after topical application. No signs of skin irritation were observed following treatment, indicating the safety of LORNE12-Gel. Thus, this study demonstrated that LOR-loaded LORNE12-Gel could be promising as an efficient transdermal nanocarrier for an anti-inflammatory alternative.

Enhanced bioavailability and pharmacokinetics parameters of Enalapril solid self nanoemulsifying oral dispersible tablet: formulation, in vitro and in vivo evaluation

Enalapril (EN) is an antihypertensive drug that is sparingly soluble in water with limited oral bioavailability. Successfully prepared self-nanoemulsifying systems (SNES) loaded with EN were developed. The solubility of EN in different oils, surfactants, and cosurfactants was tested. Pseudoternary phase diagrams were developed, and various SNES formulations were prepared and evaluated regarding content uniformity, emulsification time, droplet size (DS), and zeta potential (ZP). The selected system was examined using transmission electron microscopy. Solid Self-Nanoemulsifying Systems (SSNES) were formulated using Avicel® PH101 carrier and Aerosil® 200 adsorbent to form a free-flowing powder. The powder was formulated as an oral disintegrating tablet (ODT) using superdisintegrants and tested for physicochemical properties and stability. Finally, an in vivo pharmacokinetic study in healthy human volunteers was carried out. The composition of the selected SNES was 10% Labrafil®, 60% Tween 80, and 30% Transcutol® HP. It developed with an emulsification time of 21 sec, DP range of 60.16 nm, ZP of 1.17 mV, and spherical-shaped globules. The accelerated stability testing proved that there was no significant difference in physical properties after storage for 3 months. The percentage of relative bioavailability for formula F2 was 112.04%. The results of this study proved that the prepared EN-SSNES ODT represents a novel formulation alternative to the currently marketed tablet.

Preparation of nano emulsion with high salt resistance

In this paper, the high salt shale reservoir as the research object, through the combination of microemulsion dilution method and pseudo-ternary phase diagram to screen the salt resistance of good nano emulsion. In the system, D-limonene was used as the oil phase, and the surfactant CAB-35 and AOS were selected by pseudo-ternary phase diagram method as the surfactant in the ratio of 1:1, and then mixed with n-butanol in the ratio of 1:1 to obtain the best microemulsion effect. The nano emulsion system was prepared by diluting the microemulsion. By testing the interfacial tension, the optimum preparation conditions of nano emulsion were screened. The results showed that the nano emulsion prepared by dilution under the condition of 5:5 oil/water ratio of microemulsion system had the best ability to reduce the interfacial tension between oil and water.

Improvement of dissolution profile of eplerenone with solidified self-emulsifying drug delivery systems (S-SEDDS)

Context Eplerenone is a member of antihypertensives used individually or in combination with other medicines. Eplerenone exhibits poor solubility and is considered a class II drug. Objective Increasing the solubility of eplerenone by using both liquid and solid self-emulsifying drug delivery systems as an alternative to its marketed tablet product. Methods Solubility studies of eplerenone were done with different oils, surfactants, and co-surfactants to determine which one has the highest solubility for eplerenone and determine the preference in the formulations of liquid self-emulsifying drug delivery system. The solidification process was carried out with the adsorption to solid carrier method. Optimal ratios of components were specified with the pseudo-ternary phase diagram technique. Self-emulsifying drug delivery system formulations were characterized in terms of chemical interaction, droplet size/distribution, crystallization behaviors, and rheological evaluation. In vitro drug release studies were conducted and compared to pure drugs and marketed products. Results The solubility screening results showed high solubility of EPL in triacetin (11.99 mg/mL) as oil, Kolliphor®EL (≈ 2.65 mg/mL), and Tween80 (≈ 1.91 mg/mL) as surfactant and polyethylene glycol 200 (PEG200) (≈ 8.50 mg/mL), dimethyl sulfoxide (≈ 7.57 mg/mL), TranscutolP (≈ 6.03 mg/mL) as co-surfactant, respectively. Rheology studies revealed that liquid self-emulsifying drug delivery formulations exhibited non-Newtonian pseudoplastic flow. Conclusion Solid self-emulsifying drug delivery systems prepared with Aerosil and Neusilin have shown tremendous improvement in terms of eplerenone dissolution by releasing the entire dose with boosted effect within 5 and 30 min respectively compared to the marketed product and pure eplerenone (p < 0.05).

Design and Characterization of Microemulsion System for Fentanyl citrate

This research was aimed to formulate and characterize micro-emulsion systems as a sublingual delivery system of fentanyl citrate an opioid pain medicine used for treatment of breakthrough cancer pain that is not controlled by other medicines. The three phases i.e. oil, surfactant and co-surfactant were selected on the basis of their drug solubility and their efficiency to form ME. Pseudo-ternary phase diagrams were constructed and on the basis of ME existence ranges various formulations of FC were developed. The influence of Smix ratio on the ME formation and in vitro permeation of ME through cellophane membrane was studied respectively. The optimized ME formulation C2 consists of a globule size of 96.9 nm, polydispersity index of 0.263, pH 4.18, viscosity 20.4 cps, a zeta potential of -8.5and conductance of 131.7±0.42µS. The optimized ME formulation C2 exhibited a steady state flux of about 361.92±0.57 and thus exhibiting higher drug permeation through ME for mulations. Apart from this, the formulation was also evaluated for drug content, centrifugation and stability study. The results indicate that, the investigated MEmay be used as a promising alternative for FC therapy for breakthrough pain management.

Dolutegravir Loaded Solid Self-Micro-Emulsifying Drug Delivery System for Enhanced Solubility and Dissolution

Dolutegravir sodium (DG) is a recently approved antiretroviral drug belonging to BCS class II having poor aqueous solubility and only 16% oral bioavailability. Hence aim of the present work was to develop solid self micro-emulsifying drug delivery system (S-SMEDDS) of Dolutegravir for enhanced solubility and dissolution behaviour. Initially, solubility of DG was checked to select oil, surfactant, and co-surfactant. Pseudo ternary phase diagram was constructed to identify microemulsion region. Liquid SMEDDS of DG were prepared using Campul MCM, Tween 80 and Transcutol P as oil, surfactant, and co-surfactant, respectively. The effect of different oil, surfactant and co-surfactant concentrations on particle size, zeta potential and %transmittance was studied using Box–Behnken factorial design. The obtained liquid SMEDDS was evaluated for its thermodynamic stability, globule size, robustness to dilution, viscosity, dye solubilization test, cloud point, etc. Satisfactory formulations of liquid SMEDDS were converted to solid form by adsorption technique using Neusilin US2 as a solid carrier. Evaluation of S-SMEDDS showed that solubility of DG in S-SMEDDS increases from 0.270 to 33.52 mg/mL. In-vitro drug release of S-DG4 showed 99.86 ± 1.47% drug release within 120 minutes while plain DG showed 32.55 ± 1.52%. Hence study revealed that S-SMEDDS is a promising approach to enhance solubility, dissolution and hence bioavailability of poorly aqueous soluble drug like DG.

Development and characterization of clove oil microemulsion

Clove oil is one type of essential oil from clove flower buds (Syzygium aromaticum) which contains eugenol compounds. Clove oil is volatile in nature and highly affected by heat, thus incorporating it in a microemulsion system can increase its shelf life of the oils. This study aimed to formulate and characterize microemulsion preparations with clove flower essential oil. The microemulsion existence region was determined by constructing a pseudo-ternary phase diagrams and prepared with four components, i.e. isopropyl myristate, tween-80 as a surfactant, polyethylene glycol 400 (PEG 400) as a co-surfactant, and water as the aqueous phase. The optimized clove oil microemulsion formulation was subjected to an evaluation of various parameters, such as organoleptic properties, %transmittance, pH, viscosity, stability, particle size, zeta potential, and polydispersity index (IP). Based on the results of the study, the highest compound component in clove oil was eugenol with a % area of ​​63.79%. The results revealed that the construction of a phase diagram and the use of the phase titration method constituted a suitable technique for the preparation of microemulsions as most of the formulations were transparent. It was found that the tween-80:PEG 400 ratio of 2:1 with an oil:S-mix ratio of 1:9 generated an optimum results. The clove oil microemulsion had a globule size of 17.69±0.025nm, a polydispersity index value of 0.057±0.0043, zeta potential of-5.36±0.23mV, and a pH value of 7.3±0.1, a viscosity value of 466.7±9.06., and %transmittance of 99.9±0.1. According to these findings, the microemulsion formulation might serve as a suitable drug delivery system.

Enhanced Intestinal Permeability of Cefixime by Self-Emulsifying Drug Delivery System: In-Vitro and Ex-Vivo Characterization.

Cefixime (CFX) belongs to a group of third-generation cephalosporin antibiotics with low water solubility and low intestinal permeability, which ultimately leads to significantly low bioavailability. This study aimed to increase solubility, improve drug release, and intestinal permeability of CFX by loading into SEDDS. Suitable excipients were selected based on drug solubility, percent transmittance, and emulsification efficiency. Pseudo-ternary phase diagram was fabricated for the identification of effective self-emulsification region. The best probably optimized formulations were further assessed for encumbered drug contents, emulsification time, cloud point measurement, robustness to dilution, mean droplet size, zeta potential, polydispersity index (PDI), and thermodynamic and chemical stability. Moreover, in vitro drug release studies and ex vivo permeation studies were carried out and apparent drug permeability Papp of different formulations was compared with the marketed brands of CFX. Amongst the four tested SEDDS formulations, F-2 formulation exhibited the highest drug loading of 96.32%, emulsification time of 40.37 ± 3 s, mean droplet size of 19.01 ± 1.12 nm, and demonstrated improved long-term thermodynamic and chemical stability when stored at 4 °C. Release studies revealed a drug release of 97.32 ± 4.82% within 60 min in simulated gastric fluid. Similarly, 97.12 ± 5.02% release of CFX was observed in simulated intestinal fluid within 120 min; however, 85.13 ± 3.23% release of CFX was observed from the marketed product. Ex vivo permeation studies displayed a 2.7-fold increase apparent permeability compared to the marketed product in 5 h. Owing to the significantly improved drug solubility, in vitro release and better antibacterial activity, it can be assumed that CFX-loaded SEDDS might lead to an increased bioavailability and antibacterial activity, possibly leading to improved therapeutic effectiveness.

Design, characterization and pharmacokinetic studies of anti-Malarial drug Artemisinin by optimized self-emulsifying nano drug delivery system (SNEDDS)

Owing to deprived hydrophilicity, Artemisinin (ART) is known as Class II biopharmaceutical (BCS). The goal of the existing endeavor is to formulate ART self-nanoemulsifying drug delivery systems (ART-SNEDDS) that will increase its solubility in water. Thus, excipients were screened in pre-formulation experiments for solubility and emulsification effectiveness. Moreover, blends of the oil soy bean, surfactant tween 80 and co-surfactant soy lecithin were used to create pseudo ternary phase diagrams at different ratios. Further, the prepared ART-SNEDDS were evaluated visually, for thermodynamic stability, time to self nano-emulsify, the impact of dilution and pH, % transmittance, droplet size, poly dispersity index (PDI), surface morphology studies, zeta potential, in-vitro release rate, and for oral pharmacokinetic studies. The ART-SNEDDS were prepared to increase the quantity of loaded ART into the formulation. Nevertheless, in-vitro dissolution studies of the ART-SNEDDS formulation demonstrated an increased dissolution with improved solubility. It was found through oral bio-availability experiments in rats that there was an improvement in rate of absorption as well. As a result, a formulation to increase the drug’s solubility and perhaps bioavailability was developed.

Topical Delivery of Diacetyl Boldine in a Microemulsion Formulation for Chemoprotection against Melanoma.

This study aimed to develop a microemulsion formulation for topical delivery of Diacetyl Boldine (DAB) and to evaluate its cytotoxicity against melanoma cell line (B16BL6) in vitro. Using a pseudo-ternary phase diagram, the optimal microemulsion formulation region was identified, and its particle size, viscosity, pH, and in vitro release characteristics were determined. Permeation studies were performed on excised human skin using Franz diffusion cell assembly. The cytotoxicity of the formulations on B16BL6 melanoma cell lines was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay. Two formulation compositions were selected based on the higher microemulsion area of the pseudo-ternary phase diagrams. The formulations showed a mean globule size of around 50 nm and a polydispersity index of <0.2. The ex vivo skin permeation study demonstrated that the microemulsion formulation exhibited significantly higher skin retention levels than the DAB solution in MCT oil (Control, DAB-MCT). Furthermore, the formulations showed substantially higher cytotoxicity toward B16BL6 cell lines than the control formulation (p < 0.001). The half-maximal inhibitory concentrations (IC50) of F1, F2, and DAB-MCT formulations against B16BL6 cells were calculated to be 1 µg/mL, 10 µg/mL, and 50 µg/mL, respectively. By comparison, the IC50 of F1 was 50-fold lower than that of the DAB-MCT formulation. The results of the present study suggest that microemulsion could be a promising formulation for the topical administration of DAB.