Pseudo-ternary Phase Diagrams Research Articles

Thermodynamically stable ionic liquid microemulsions pioneer pathways for topical delivery and peptide application

Copper peptides (GHK-Cu) are a powerful hair growth promoter with minimal side effects when compared with minoxidil and finasteride; however, challenges in delivering GHK-Cu topically limits their non-invasive applications. Using theoretical calculations and pseudo-ternary phase diagrams, we designed and constructed a thermodynamically stable ionic liquid (IL)-based microemulsion (IL-M), which integrates the high drug solubility of ILs and high skin permeability of microemulsions, thus improving the local delivery of copper peptides by approximately three-fold while retaining their biological function. Experiments in mice validated the effectiveness of our proposed IL-M system. Furthermore, the exact effects of the IL-M system on the expression of growth factors, such as vascular endothelial growth factor, were revealed, and it was found that microemulsion increased the activation of the Wnt/β-catenin signaling pathway, which includes factors involved in hair growth regulation. Overall, the safe and non-invasive IL microemulsion system developed in this study has great potential for the clinical treatment of hair loss.

Purification and Fractionation of Lignin via ALPHA: Liquid-Liquid Equilibrium for the Lignin-Acetic Acid-Water System.

In order to effectively practice the Aqueous Lignin Purification with Hot Agents (ALPHA) process for lignin purification and fractionation, the temperatures and feed compositions where regions of liquid-liquid equilibrium (LLE) exist must be identified. To this end, pseudo-ternary phase diagrams for the lignin-acetic acid-water system were mapped out at 45-95 °C and various solvent: feed lignin mass ratios (S:F). For a given temperature, the accompanying SL (solid-liquid), SLL (solid-liquid-liquid), and one-phase regions were also located. For the first time, ALPHA using acetic acid (AcOH)-water solutions was applied to a lignin recovered via the commercial LignoBoost process. In addition to determining tie-line compositions for the two regions of LLE that were discovered, the distribution of lignin and key impurities (the latter can negatively impact lignin performance for materials applications) between the two liquid phases wasalso measured. As a representative example, lignin isolated in thelignin-rich phase was reduced 7x in metals and 4x in polysaccharides by using ALPHA with a feed solvent composition of 50-55% AcOH and an S:F of 6:1, with said lignin being obtained at a yield of 50-70% of the feed lignin and having a molecular weight triple that of the feed.

Alginate raft as carrier for self-emulsifying drug delivery system of curcuminoid: In vitro and in vivo analysis

Hemorrhagic gastric ulcer can cause chronic inflammation that can lead to gastro-intestinal perforation and gastric adenocarcinoma or other serious gastric complications. Among naturally occurring treatments, curcumin (CuR) was used but it has limitations of low solubility and rapid first pass effect due to presence of diketo moiety. The present study aimed, to synthesize new synthetic derivative of CuR named curcuminoid (CuRD) and evaluate for its biological activity against gastric ulcer. Solubility and permeation of CuRD were enhanced by development of self-emulsifying drug delivery system (SEDDS). Pseudo-ternary phase diagram was constructed to identify the most efficient self-emulsification region. Optimized CuRD-SEDDS were further employed in the preparation of R-CuRD-SEDDS for local drug delivery in the stomach and all quality control test, raft resilience and strength, raft weight and volume, in-vitro dissolution, anti-oxidant and in-vitro anti-inflammatory activity were also observed. R-CuRD-SEDDS possess significant 20-fold increase in anti-oxidant and 10-fold increase in anti-inflammatory activities as compared to naturally occurring CuR. 70–80 % release within 1 hr, 85 % ulcer inhibition and 3.02 ± 1.5 ulcer index in aspirin induced ulcer was found. Newly developed R-CuRD-SEDDS with enhanced anti-oxidant and anti-inflammatory activities was an alternative approach for the treatment of gastric ulcer.

Oral self-nanoemulsifying drug delivery systems for enhancing bioavailability and anticancer potential of fosfestrol: In vitro and in vivo characterization

PurposeThe objective of the current research work was to fabricate a fosfestrol (FST)-loaded self-nanoemulsifying drug delivery system (SNEDDS) to escalate the oral solubility and bioavailability and thereby the effectiveness of FST against prostate cancer. Methods32 full factorial design was employed, and the effect of lipid and surfactant mixtures on percentage transmittance, time required for self-emulsification, and drug release were studied. The optimized solid FST-loaded SNEDDS (FSTNE) was characterized for in vitro anticancer activity and Caco-2 cell permeability, and in vivo pharmacokinetic parameters. ResultsUsing different ratios of surfactant and co-surfactant (Km) a pseudo ternary phase diagram was constructed. Thirteen liquid nano emulsion formulations (LNE-1 to LNE-13) were formulated at Km = 3:1. LNE-9 exhibited a higher % transmittance (99.25 ± 1.82 %) and a lower self-emulsification time (24 ± 0.32 s). No incompatibility was observed in FT-IR analysis. Within 20 min the solidified FST loaded LNE-9 (FSTNE) formulation showed almost complete drug release (98.20 ± 1.30 %) when compared to marketed formulation (40.36 ± 2.8 %), and pure FST (32 ± 3.3 %) in 0.1 N HCl. In pH 6.8 phosphate buffer, the release profiles are found moderately higher than in 0.1 N HCl. FSTNE significantly (P < 0.001) inhibited the PC-3 prostate cell proliferation and also caused apoptosis (P < 0.001) compared to FST. The in vitro Caco-2 cell permeability study results revealed 4.68-fold higher cell permeability of FSTNE than FST. Remarkably, 4.5-fold rise in bioavailability was observed after oral administration of FSTNE than plain FST. ConclusionsFSTNE remarkably enhanced the in vitro anticancer activity and Caco-2 cell permeability, and in vivo bioavailability of FST. Thus, FST-SNEDDS could be utilized as a potential carrier for effective oral treatment of prostate cancer.

Ginger oil-based microemulsion as a strategy to improve the topical therapy of imiquimod

The Imiquimod (IMQ) formulation for cutaneous administration is challenging due to its very low solubility and its poor penetration properties. The purpose of this study was to develop medium or high fluidity microemulsions (ME) to increase the solubility and modulate the release for the topical administration of Imiquimod (IMQ), thus increasing the therapeutic efficacy of the drug. Ginger oil was selected as the oil phase, Polysorbate 80/Triton X-100 1:1 as the surfactant system, and water as the aqueous phase. From the construction of a pseudo-ternary phase diagram, it was possible to obtain ME in a wide range of combinations with medium to high density. Five ME were subjected to conductivity, drug incorporation, and in vitro release assays. From conductivity determinations, it was established that ME exhibited a characteristic profile of percolative conductivity, suggesting a phase inversion of W/O to direct micelles O/W. The release assay demonstrated the ability of the ME to deliver IMQ, where the ME1–3 had a high rate of release as a function of time, and the ME4–5, released the drug in a sustained manner. These results indicate that the ME studied may be a promising vehicle for increasing the effectiveness of IMQ in topical dosage forms.

Self-microemulsifying system of an ethanolic extract of Heliopsis longipes root for enhanced solubility and release of affinin

Self-microemulsifying or self-nanoemulsifying drug delivery systems (SMEDDS/SNEDDS) are well known to improve the dissolution and increase the oral bioavailability of hydrophobic drugs, including herbal extracts. Organic extracts of Heliopsis longipes root and affinin, its main component, induce a vasodilator effect; however, they are poorly water soluble and therefore are difficult to administer and dose by the oral route. This research aimed to develop, through pseudo-ternary phase diagrams, a self-microemulsifying system prepared from an ethanolic extract of H. longipes root (HL-SMDS). In addition, the optimized lipid-based formulation was characterized and its in vitro gastrointestinal simulated dissolution was determined. The formulation composed of Transcutol, 55% (solubilizer); Tween80/PG, 10% (surfactant/co-solvent); Labrasol, 35% (surfactant); and the herbal extract was selected as optimal and identified as a SMEDDS, since when coming into contact with water, it forms a micro-emulsion with droplet sizes less than 100 nm. The stability tests showed that HL-SMDS remained stable over time under extreme conditions. Furthermore, the amount of affinin released from HL-SMDS at pH 1 and 6.8 was higher than that of the ethanolic extract from H. longipes root. These results indicate that HL-SMDS is a novel alternative to improve the aqueous solubility and therefore the oral bioavailability of the ethanolic extract of H. longipes root.

Novel lipid-based nanocarrier of nitrofurantoin for improved oral bioavailability and reduced variability in absorption

The current research aims to improve oral bioavailability, reduce the variability in absorption, and decrease GI intolerance of Nitrofurantoin (NFT) by presenting in a lipid-based liquid self-nanoemulsifying drug delivery system (L-SNEDDS). L-SNEDDS formulations were developed using a thermosolvency technique. Physicochemical properties including in-vitro drug diffusion were exercised to optimize the formula, further, comparative ex-vivo permeability, in-vitro cell line, in-vitro anti-microbial, and in-vivo pharmacokinetic evaluation of optimized formulation was carried out. Based on the highest saturation solubility, soybean oil, oleoyl polyoxyl-6-glycerides, and diethylene glycol monoethyl ether were selected as oil, surfactant, and co-surfactant, respectively. A Smix ratio of 1:2 was selected based on pseudoternary phase diagrams. The formulation prepared with an equal ratio of oil and Smix exhibited the lowest globule size (59.4 ± 0.8 nm), optimum zeta potential (−21.3 ± 1.1 mV), and faster drug release (95.4 ± 4.2 % in 30 min), and hence was selected for further evaluation. Optimized formulation (SF5) was found stable and showed improved membrane permeability against pure drug suspension (1.84 times) and marketed suspension formulation (1.15 times). SF5 exhibited similar % cell viability and % cell toxicity in Caco-2 cell lines compared to the marketed suspension. However, it showed the highest zone of inhibition against both the gram-negative and gram-positive organisms. The relative bioavailability of NFT-loaded L-SNEDDS was enhanced by 1.46 and 1.55 times compared to the marketed and pure drug, respectively. Thus, it can be concluded that the variability of oral absorption is minimized, and oral bioavailability is improved by the novel lipid-based nanocarrier system of NFT.

Solubility enhancement of fexofenadine using self-nano emulsifying drug delivery system for improved biomimetic attributes

Fexofenadine is a poorly water-soluble drug, which limit its bioavailability and ultimately therapeutic efficacy. Liquid self-nano emulsifying drug delivery system (L-SNEDDs) is an approach that can enhance the solubility of fexofenadine by increasing its surface area and reducing the particle size, which increases the rate and extent of drug dissolution. In this investigation, L-SNEDDs of fexofenadine was made up using surfactants and co-surfactant. The SNEDDS formulation was optimized using a pseudo-ternary phase diagram and characterized. The optimized L-SNEDDS incorporated fexofenadine were thermodynamically stable and showed mean droplet size and zeta potential of 155nm and -18mV, respectively unaffected by the media pH. In addition, the viscosity, and refractive index were observed 18.4 and 1.49cps, respectively for optimized L-SNEDDS fortified fexofenadine. The results of Fourier transform infrared spectroscopy revealed an insignificant interaction between the fexofenadine and excipients. A drug loading efficiency of 94.20% resulted with a complete in vitro drug release in 2h, compared with the pure drug, which demonstrate significant improvement in the efficacy. Moreover, these results signify that on further in vivo assessment L-SNEDDS fortified fexofenadine can indicate improvement in pharmacokinetic and clinical outcome. Thus, the investigation revealed that, the L-SNEDDs incorporated fexofenadine was most effective with a mixture of surfactant and co-surfactant with improved solubility intend to relieve pain associated with inflammation with single-dose oral administration.

TOPICAL NANOEMULSION-BASED GEL OF ISOCONAZOLE NITRATE

This study aimed to make an o/wnanoemulsion of isoconazole the drugnitrate (ISN) for topical use. Low aqueous solubility is a characteristicfeature of the imidazole antifungal ISN. Therefore, ISN nanoemulsion would increase dispersibility and decreases skin resistance by enhancing the drug penetration to the first layers of skin (stratum corneum). The work included constructing the pseudo-ternary phase diagrams by using the aqueous titration method. The prepared o/w nanoemulsions were composed of oil, Smix (a mixture of surfactant and co-surfactant) and deionized water (DW). ISN nanoemulsions were subjected to characterization studies to choose the best formula. According to the characterization studies, the optimal formula, designated NE14 contains 1% ISN, 66% Smix ((1:3) tween60: propylene glycol:ethanol), 7% oleic acid, and 27% deionized water was reached. FormulaNE14 is characterized by having a polydispersity index of (0.146), pH (5.76), droplet size (84.6 nm), percent transmittance (98.8%), viscosity (80m Pa.s) and a high release of isoconazole propably due low viscosity. The droplet size of NE14 (84.6nm) was alsoconfirmed by an atomic force microscopy (AFM) research. The improved formula (ISN NE14) was found to be a promising nanoemulsion formula for enhancing the topical bioavailability of ISN and thus could increase its efficacy for the treatment of topical fungal infections.

Development of Bedaquiline-Loaded SNEDDS Using Quality by Design (QbD) Approach to Improve Biopharmaceutical Attributes for the Management of Multidrug-Resistant Tuberculosis (MDR-TB).

Background: The ever-growing emergence of antibiotic resistance associated with tuberculosis (TB) has become a global challenge. In 2012, the USFDA gave expedited approval to bedaquiline (BDQ) as a new treatment for drug-resistant TB in adults when no other viable options are available. BDQ is a diarylquinoline derivative and exhibits targeted action on mycobacterium tuberculosis, but due to poor solubility, the desired therapeutic action is not achieved. Objective: To develop a QbD-based self-nanoemulsifying drug delivery system of bedaquiline using various oils, surfactants, and co-surfactants. Methods: The quality target product profile (QTPP) and critical quality attributes (CQAs) were identified with a patient-centric approach, which facilitated the selection of critical material attributes (CMAs) during pre-formulation studies and initial risk assessment. Caprylic acid as a lipid, propylene glycol as a surfactant, and Transcutol-P as a co-surfactant were selected as CMAs for the formulation of bedaquiline fumarate SNEDDS. Pseudo-ternary phase diagrams were constructed to determine the optimal ratio of oil and Smix. To optimize the formulation, a Box-Benkhen design (BBD) was used. The optimized formulation (BDQ-F-SNEDSS) was further evaluated for parameters such as droplet size, polydispersity index (PDI), percentage transmittance, dilution studies, stability studies, and cell toxicity through the A549 cell. Results: Optimized BDQ-F-SNEDDS showed well-formed droplets of 98.88 ± 2.1 nm with a zeta potential of 21.16 mV. In vitro studies showed enhanced drug release with a high degree of stability at 25 ± 2 °C, 60 ± 5% and 40 ± 2 °C, 75 ± 5%. Furthermore, BDQ-F-SNEDDS showed promising cell viability in A549 cells, indicating BDQ-F-SNEDDS as a safer formulation for oral delivery. Conclusion: Finally, it was concluded that the utilization of a QbD approach in the development of BDQ-F-loaded SNEDDS offers a promising strategy to improve the biopharmaceutical properties of the drug, resulting in potential cost and time savings.

Preparation and Characterization of Prednisolone Acetate Microemulsion for Ophthalmic Use

Background: Prednisolone acetate is an ester form of prednisolone. It is used topically as an ophthalmic suspension to treat many inflammatory ocular conditions, where its absorption from suspension is highly variable and has poor dose accuracy. Objectives: The main objective of this research is to formulate and evaluate prednisolone acetate microemulsion for ophthalmic use to increase solubility, residence time, and corneal permeability of the drug to enhance patient compliance and treatment efficacy. Methods: Twenty-four prednisolone acetate-loaded microemulsion (0.5%w/w) formulas were prepared using oleic acid, isopropyl myristate as (oil phase) (1:1), tween 80, labrasol, and cremophor EL as (surfactant), ethanol, polyethylene glycol 400, propylene glycol, transcutol P as co-surfactant and Sörensen isotonic phosphate buffer saline pH 7.4 as the aqueous phase at different Smix ratios (1:1), (1:2) and (2:1) by aqueous titration method to construct pseudoternary phase diagram to determine the existence of microemulsion region. All the prepared formulas were subjected to different evaluation tests to determine the optimum formula. Results: observations of the microemulsion showed that it had a clear and transparent yellowish color, formulation F9 composed of oleic acid and isopropyl myristate in a ratio (1:1) as oil, twee80 as a surfactant, and propylene glycol: ethanol (1:1) in a ratio (2:1) as cosurfactant gave the best particle size (10.18nm), polydispersity index (0.2216), zeta potential (-25,91), % of transmittance (99.382%±0. 09), and drug content (100±0.16). Microemulsion formulation provided considerably higher permeability than the marketed eye drop suspension (Optipred®) and improved bioavailability. Conclusions: The microemulsion-containing prednisolone acetate is a promising ocular carrier for the controlled release of prednisolone acetate in treating anterior segment inflammation. Received: Dec. 2022 Accepted March 2023 Published: Oct.2023

Preparation and quality evaluation of total flavonoids microemulsion of "Pueraria lobata-Hovenia dulcis"

The effective components of flavonoids in the &quot;Pueraria lobata-Hovenia dulcis&quot; drug pair have low bioavailability in vivo due to their unstable characteristics. This study used microemulsions with amphoteric carrier properties to solve this problem. The study drew pseudo-ternary phase diagrams through titration compatibility experiments of the oil phase with emulsifiers and co-emulsifiers and screened the prescription composition of blank microemulsions. The study used average particle size and PDI as evaluation indicators, and the central composite design-response surface method(CCD-RSM) was used to optimize the prescription; high-dosage drug-loaded microemulsions were obtained, and their physicochemical properties, appearance, and stability were evaluated. The results showed that when ethyl butyrate was used as the oil phase, polysorbate 80(tween 80) as the surfactant, and anhydrous ethanol as the cosurfactant, the maximum microemulsion area was obtained. When the difference in results was small, K_(m )of 1∶4 was chosen to ensure the safety of the prescription. The prescription composition optimized by the CCD-RSM was ethyl butyrate(16.28%), tween 80(9.59%), and anhydrous ethanol(38.34%). When the dosage reached 3% of the system mass, the total flavonoid microemulsion prepared had a clear and transparent appearance, with average particle size, PDI, and potential of(74.25±1.58)nm, 0.277±0.043, and(-0.08±0.07) mV, respectively. The microemulsion was spherical and evenly distributed under transmission electron microscopy. The centrifugal stability and temperature stability were good, and there was no layering or demulsification phenomenon, which significantly improved the in vitro dissolution of total flavonoids.

The Development of Dermal Self-Double-Emulsifying Drug Delivery Systems: Preformulation Studies as the Keys to Success.

Self-emulsifying drug delivery systems (SEDDSs) are lipid-based systems that are superior to other lipid-based oral drug delivery systems in terms of providing drug protection against the gastrointestinal (GI) environment, inhibition of drug efflux as mediated by P-glycoprotein, enhanced lymphatic drug uptake, improved control over plasma concentration profiles of drugs, enhanced stability, and drug loading efficiency. Interest in dermal spontaneous emulsions has increased, given that systems have been reported to deliver drugs across mucus membranes, as well as the outermost layer of the skin into the underlying layers. The background and development of a double spontaneous emulsion incorporating four anti-tubercular drugs, clofazimine (CFZ), isoniazid (INH), pyrazinamide (PZY), and rifampicin (RIF), are described here. Our methods involved examination of oil miscibility, the construction of pseudoternary phase diagrams, the determination of self-emulsification performance and the emulsion stability index of primary emulsions (PEs), solubility, and isothermal micro calorimetry compatibility and examination of emulsions via microscopy. Overall, the potential of self-double-emulsifying drug delivery systems (SDEDDSs) as a dermal drug delivery vehicle is now demonstrated. The key to success here is the conduct of preformulation studies to enable the development of dermal SDEDDSs. To our knowledge, this work represents the first successful example of the production of SDEDDSs capable of incorporating four individual drugs.

Phase diagrams and property of colloidal systems prepared with an alkyl polyglucoside surfactant and the essential oil of Melaleuca alternifolia (tea tree)

BackgroundThe purpose of this study was to develop the colloidal formulation, based on microemulsions and hydrogels, of Melaleuca alternifolia oil (aka tea tree oil, TTO) using a sustainable and biocompatible alkyl polyglucoside (APG) surfactant, Glucopon 600 CSUP (G600), commonly formulated for personal-care and home-care products. MethodsThe pseudo-ternary phase diagram of TTO-mixed surfactant-water was established with the water titration method at 25 °C. The mixed surfactants were composed of G600 and propylene glycol (PPG) as a co-surfactant at G600/PPG = 1/1, 2/1 and 3/1 (m/m). Colloid samples of one phase were further characterized with rheological measurements and dynamic light scattering (DLS) at 25 °C. Significant findingsThe samples containing TTO/mixed surfactant = 1/9 (m/m) and water show single phase only. With increasing water contents, the aforesaid system changed from Newtonian to pseudo-plastic, reflecting the transition from micellar solution / microemulsion to hydrogel. Especially, the gel-like behavior was confirmed with the dynamic oscillatory measurements, in which storage moduli were always larger than loss moduli at any time and any frequency under a constant strain of 0.5 %. Microemulsions made of 1 wt% tea tree oil and 9 wt% mixed surfactants were stable for > 1 month as monitored by aggregate size by DLS.

Aceclofenac/Citronellol Oil Nanoemulsion Repurposing Study: Formulation, In Vitro Characterization, and In Silico Evaluation of Their Antiproliferative and Pro-Apoptotic Activity against Melanoma Cell Line.

Aceclofenac (ACF) is a widely used non-steroidal anti-inflammatory drug (NSAID) known for its effectiveness in treating pain and inflammation. Recent studies have demonstrated that ACF possesses antiproliferative properties, inhibiting the growth of cancer cells in various cancer cell lines. Citronellol, a monoterpenoid alcohol found in essential oils, exhibits antioxidant properties and activities such as inhibiting cell growth and acetylcholinesterase inhibition. In this study, the objective was to formulate and evaluate an aceclofenac/citronellol oil nanoemulsion for its antiproliferative effects on melanoma. The optimal concentrations of citronellol oil, Tween 80, and Transcutol HP were determined using a pseudoternary phase diagram. The formulated nanoemulsions were characterized for droplet size, zeta potential, thermophysical stability, and in vitro release. The selected formula (F1) consisted of citronellol oil (1 gm%), Tween 80 (4 gm%), and Transcutol HP (1 gm%). F1 exhibited a spherical appearance with high drug content, small droplet size, and acceptable negative zeta potential. The amorphous state of the drug in the nanoemulsion was confirmed by Differential Scanning Calorimetry, while FTIR analysis indicated its homogenous solubility. The nanoemulsion showed significant antiproliferative activity, with a lower IC50 value compared to aceclofenac or citronellol alone. Flow cytometric analysis revealed cell cycle arrest and increased apoptosis induced by the nanoemulsion. In silico studies provided insights into the molecular mechanism underlying the observed antitumor activity. In conclusion, the developed aceclofenac/citronellol oil nanoemulsion exhibited potent cytotoxicity and pro-apoptotic effects, suggesting its potential as a repurposed antiproliferative agent for melanoma treatment. In a future plan, further animal model research for validation is suggested.

PREPARATION AND OPTIMIZATION OF CILOSTAZOL NANOEMULSION ORAL LIQUID DOSAGE FORM

Objective: Cilostazol has poor water solubility and low oral bioavailability. Therefore, the formulation of cilostazol as a nanoemulsion may enhance its solubility and improve oral bioavailability. Hence, the aim of this study was to formulate and characterize an oil-in-water (o/w) nanoemulsion of cilostazol as an oral liquid dosage form. Methods: Pseudo-ternary phase diagrams were constructed using the aqueous titration method. Formulations of pseudo-ternary phase plots consisting of oil, various weight ratios of S mix (mixture of surfactant and co-surfactant), and deionized water were made. Different characterization studies, droplet size measurement, polydispersity index, drug content, zeta potential measurement, and in vitro release have been conducted to choose the optimized formula. Results: The characterization studies have demonstrated that the optimized formula is (F-6), consisting of 20 % S mix (3:1), 10% ginger oil, and 70% deionized water. This formula had the following characteristics; droplet size (72.9-110 nm), polydispersity index (0.22), percentage of drug content (99.8%), and in vitro release of cilostazol nanoemulsion was significantly higher (P&lt;0.05) in comparison with other formulations. A Scanning probe microscopy (SPM) study has revealed that the droplet size of F-6 was at the nano-scale. Conclusion: In conclusion, the optimized cilostazol formula (F-6) is a promising formula which may have the capability of improving the oral bioavailability of cilostazol.

OPTIMIZATION AND CHARACTERIZATION OF ESSENTIAL OILS FORMULATION FOR ENHANCED STABILITY AND DRUG DELIVERY SYSTEM OF MEFLOQUINE

Objective: This work aims to choose suitable essential oil formulations to improve the bioavailability and long-term aqueous stability of mefloquine in drug delivery systems. Methods: Oil phases of pomegranate oil, black cumin seed oil, and garlic oil. To choose the proper oil and surfactant for creating pseudo-ternary phase diagrams, cremophore EL, tween®20 and tween®80 (surfactants), and brij 35 (co-surfactants) were used in a variety of concentrations and combinations (Smix). Mefloquine was estimated to be soluble in a variety of oils, surfactants, and co-surfactants. Drug solubility, drug release research, thermodynamic stability, mean hydrodynamic size and zeta potential. Results: Garlic with smix of cremophore EL and brij 35, Pomegranate with Tween 2.0, and Black cumin seed oil with Tween 80 showed the highest solubilization and emulsification capabilities and were further investigated using ternary phase diagrams. When combined with the co-surfactants under investigation, cremophore EL demonstrated a greater self-emulsification zone than tween® 80 and tween 20. Garlic oil, cremophore EL, and brij 35 nanoemulsion showed smaller size, greater zeta potential, less emulsification time, high transmittance, and better drug solubility than microemulsion formulations on especially those made with tween®20 and tween 80. Mefloquine loaded garlic oil nanoemulsion showed considerably low release in body fluid (32.48%) and a good release in intestinal fluid (82.78%) by 12 h in a drug release study. Conclusion: Garlic oil as the oil phase and a mixture of cremophore EL and brij 35 as the surfactant phase are ideal surfactants and co-surfactant for mefloquine loaded garlic oil nanoemulsion with greater drug release in release kinetics investigation.

Nanoemulsion-Based Strategy for Maximizing Nitrofurantoin Absorption: In-vitro and In-vivo Investigations.

The main objective of the current research work is to improve the absorption of Nitrofurantoin (NFT) by minimizing gastrointestinal (GI) intolerance and variations in its absorption by formulating the drug into a nanoemulsion (NE). Based on the highest saturation solubility of NFT, soybean oil, transcutol HP, and labrafil M1944CS were selected as oil, co-surfactant, and surfactant, and a Smix ratio of 1:2 was selected based on pseudoternary phase diagrams. The formulation prepared with an equal ratio of oil and Smix exhibited the lowest globule size, highest zeta potential, and higher drug release and hence was selected for further evaluation. Optimized formulation (NF5) showed improved membrane permeability against pure drug suspension (2.30 times) and marketed suspension formulation (1.43 times). NF5 exhibited similar % cell viability and % cell toxicity in Caco-2 cell lines compared to the marketed suspension. The relative bioavailability of NFT-NE was enhanced by 1.10 and 1.17 times compared to the marketed and pure drug suspension, respectively. Thus, it can be concluded that the optimized nanoemulsion formulation of NFT exhibited improved membrane permeability, comparable cell viability, and increased relative bioavailability. These findings suggest the potential of the nanoemulsion approach as a strategy to overcome the variability of oral absorption and GI intolerance of NFT.

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.

Topical Delivery of Eberconazole Nitrate Loaded Microemulsion: Formulation, Design and Evaluation

The objective of the present research work was to develop a microemulsion for the transdermal delivery of eberconazole nitrate (EBZ). Initially, oil, surfactant and co-surfactant were selected based on their solubility and emulsification study. A pseudoternary phase diagram was constructed to optimize the surfactant-co surfactant (Smix) ratio. Eberconazole nitrate (EBZ) loaded microemulsion was optimized using central composite design (CCD) with amount of Capmul MCM (X1), tween 80 (X2) and transcutol (X3) as independent variables along with the cumulative amount of drug release (Q24) (Y1), flux (Jss) (Y2) and lag time (tL) (Y3) as dependent variables. Drug release study of all the design batches showed successfully increased permeation of drug which might be due to the compositional characteristics of ME. The globule size of the optimized batch of EBZ loaded ME (153.6 nm) confirms the micrometer size of the formulation. Zeta potential and polydispersity index (PDI) of the optimized batch was found to be -30.5 mV and 0.253, respectively, proving stability and uniform distribution of dispersed systems. The optimized batch of MEs has a pH value of 6.96 ± 0.21, indicating no chance of skin irritation. Further morphological and structural examination of the optimized batch of EBZ loaded ME was done by transmission electron microscope (TEM) and images illustrated the spherical micelles with size range of 100 to 200 nm which evidently may support the high absorption and results into the enhancement of drug permeation which may increase the therapeutic effect, decrease the dose frequency and improving the patience compliance for topical drug delivery.