Fluconazole and Curcumin Loaded Nanoemulsion Against Multiple Drug Resistance Dermatophytes

Purpose: Topical nanoemulsion comprising of fluconazole and curcumin was developed to target multiple drug resistance dermatophytes infection and to facilitate cutaneous delivery of these poorly water soluble drugs. Methods: Almond oil, sesame oil and paraffin light were used to formulate nanoemulsions and screened for the stability. The solubility of fluconazole and curcumin in surfactants, co-surfactants and oils was screened to decide the various components of the nanoemulsion. The oil phase was light paraffin whereas tween 80 and span 80 were the surfactants and ethanol was used as a co-surfactant. To identify the area of nanoemulsion existence, a pseudoternary diagram was drawn and optimum systems were developed. Drug-loading efficiency was assessed and the developed nanoemulsions were characterized for globule size, stability, robustness to dilution and pH. The optimized nanoemulsion was further evaluated for drug content, viscosity, skin permeation study (ex vivo) and assay of antifungal activity. Results: The globule size was below 200 nm and uniform for the optimized nanoemulsion formulation. It showed enhanced skin permeation (ex vivo) and better antifungal efficacy as compared to the native form of fluconazole and curcumin suspensions. Antimicrobial assay confirmed the synergistic effect of fluconazole and curcumin combination against multiple drug resistance Trychophytum rubrum and Trichophyton metagrophytes as compared to the fluconazole alone. Conclusion: The results clearly indicate an optimized delivery of fluconazole and curcumin in a synergistic way from the nanoemulsion formulation. This resulted in better penetration of these poorly soluble molecules and overall enhanced antifungal activity as compared to these drugs as such against multiple drug resistance dermatophytes.

Human milk-based fortifier is associated with less alteration of milk fat globule size than cow milk-based fortifier

We aimed to evaluate if human milk-based fortifier (HMBF) affects human milk fat globule (MFG) size less than cow milk-based fortifier (CMBF), which may impact overall infant feeding tolerance. Measurements of donated human milk were performed before fortification as well as at 1 hour, 24 hours, and 48 hours after fortification with CMBF or HMBF. MFG size in each sample of fortified milk was measured by laser light scattering. MFG size in the fortified milks increased gradually over time. At 24 and 48 hours after fortification, MFG size in the milk with CMBF was larger than that in the milk with HMBF (4.8 ± 0.5 vs 4.3 ± 0.3 μm, p<0.01, 5.1 ± 0.7 vs 4.5 ± 0.4 μm, p = 0.03, respectively). HMBF is associated with less alteration of MFG size than CMBF. This may have an impact on feeding tolerance of very preterm infants.

Ultrasound homogenization of milk cream at low temperature

Ultrasonication has been identified as a particularly promising technology for homogenization of dairy products. Homogenization of cream, by reducing fat globule size, can be utilized to inhibit creaming. The homogenization of cream usually leads to increased viscosity. Cream with fat level greater than 17% cannot be homogenized with satisfactory results since conventional homogenization methods cause coalescence and mostly agglomeration. The aim of this study was to investigate the influence of ultrasonication on milk cream (5-30% fat) and to study the phenomenon of formation of fat clusters during sonication (0.5-15 mins) at low temperature (2°C). The results showed that ultrasonication can reduce the fat globule size, although it resulted in the formation of fat clusters at short time (<1min), but at longer time, fat clusters can be broken. On the other hand, ultrasound homogenization tends to increase the viscosity of cream at various fat contents. Microstructure of solid phase showed that there was formation of double emulsions and partial fat coalescence. Ultrasound homogenization with the addition of SDS as small-molecule surfactant can prevent the formation of fat clusters. Fatty acid composition in solid phase shows that it consists of long-chain fatty acids in higher amount compared to that present in the liquid fraction. Whereas the concentration of short and medium chain fatty acids in the liquid phase was higher compared to that in solid phase. The utilization and optimization of ultrasound for cream homogenization has a potency to solve the limitation of conventional method (pressure homogenizer) which commonly used in dairy industry.

Formulation and Optimization of Self Emulsifying Drug Delivery System For Effective Anthelmintic Therapy

The present study aims to develop and optimize a self-emulsifying drug delivery system for paediatric patients to improve the oral bioavailability of the anthelmintic drug, Praziquantel (PZQ) and to perform it’s in-vitro dissolution study. The solubility of PZQ was estimated in various vehicles to select proper component combination. Capmul MCM (oil), Cremophore RH40 (surfactant) and PEG400 (co-surfactant) were employed to construct pseudo-ternary phase diagrams. Eight formulations composed of Capmul MCM, at Smix ratios (1:1, 2:1 & 3:1) were selected. The optimized formulation F7 has a mean globule size 14.73 nm with a negative zeta potential -44.43 mV. The results indicated that PZQ loaded SEDDS, showed enhanced solubilization and nanosizing potential to improve the absorption of the drug.

Antifungal Topical Nanoemulgel Containing Miconazole Nitrate

Nanomulgel have emerged as one of the most interesting topical drug delivery system as it has dual release control system i.e. nanoemulsion and gel. Also the stability of nanoemulsion is increased when it is incorporated in gel. Miconazole nitrate is an antifungal medication topically administered to treat skin infections such as athlete’s foot, jock itch and ringworm. The aim of the present research work was to investigate the potential of nanoemulgel in enhancing the topical delivery of hydrophobic drug. MCZ nanoemulsions were prepared using span 80, tween 80, propylene glycol and different conc. of sunflower oil by High pressure homogenization technique. The prepared nanoemulsions were evaluated for pH, drug content, centrifugation, globule size and zeta potential.F2 showed highest drug content 91.26%.The globule size are found to be satisfactory range of nanoemulsion. The drug release kinetics is in the order of F2>F3>F4>F5>F1.And Nanoemulgel is prepared by using Carbopol 934 as gelling agent The release kinetics of nanoemulgel was found to obey zero order kinetics. The nanoemulgel was found to be stable with respect to physical appearance, pH, rheological properties spreadability and drug content at all temperature and conditions for two month. Hence, in the present study it can be concluded that Miconazole Nitrate nanoemulgel formulation is a promising system for the topical drug delivery and also an alternative method to deliver the hydrophobic drugs in water soluble gel bases. Key words: Hydrophobic drugs, Nanoemulgel, Miconazole nitrate, Topical drug delivery.

Development of Piperine-Loaded Solid Self-Nanoemulsifying Drug Delivery System: Optimization, In-Vitro, Ex-Vivo, and In-Vivo Evaluation

Hypertension is a cardiovascular disease that needs long-term medication. Oral delivery is the most common route for the administration of drugs. The present research is to develop piperine self-nanoemulsifying drug delivery system (PE-SNEDDS) using glyceryl monolinoleate (GML), poloxamer 188, and transcutol HP as oil, surfactant, and co-surfactant, respectively. The formulation was optimized by three-factor, three-level Box-Behnken design. PE-SNEDDs were characterized for globule size, emulsification time, stability, in-vitro release, and ex-vivo intestinal permeation study. The optimized PE-SNEDDS (OF3) showed the globule size of 70.34 ± 3.27 nm, percentage transmittance of 99.02 ± 2.02%, and emulsification time of 53 ± 2 s Finally, the formulation OF3 was transformed into solid PE-SNEDDS (S-PE-SNEDDS) using avicel PH-101 as adsorbent. The reconstituted SOF3 showed a globule size of 73.56 ± 3.54 nm, PDI of 0.35 ± 0.03, and zeta potential of −28.12 ± 2.54 mV. SEM image exhibited the PE-SNEDDS completely adsorbed on avicel. Thermal analysis showed the drug was solubilized in oil, surfactant, and co-surfactant. S-PE-SNEDDS formulation showed a more significant (p < 0.05) release (97.87 ± 4.89% in 1 h) than pure PE (27.87 ± 2.65% in 1 h). It also exhibited better antimicrobial activity against S. aureus and P. aeruginosa and antioxidant activity as compared to PE dispersion. The in vivo activity in rats exhibited better (p < 0.05) antihypertensive activity as well as 4.92-fold higher relative bioavailability than pure PE dispersion. Finally, from the results it can be concluded that S-PE-SNEDDS might be a better approach for the oral delivery to improve the absorption and therapeutic activity.

FORMULATION AND DEVELOPMENT OF CURCUMIN BASED EMULGEL IN TREATMENT AND RECURRENCE OF VAGINAL CANDIDIASIS

Objective: The main causative agent of vaginal candidiasis is Candida albicans and it develops resistance against several synthetic antifungal drugs and it has a high rate of infection in women. According to WHO report, around 75% of women are infected by Candida albicans and 50 % are infected a second time by Candida albicans. Therefore, we choose Curcumin an antifungal agent that had reported antifungal properties against the various fungal species. The Curcumin-containing emulgel based microemulsion system was prepared for greater retention time and penetration across the vaginal mucosa. Methods: The screening of oil phase, surfactant, and cosurfactant for microemulsion formulation was selected based on the solubility study and followed by the construction of the pseudoternary phase diagram. The oil phase, surfactant and co-surfactant are selected from the pseudoternary phase diagram for the formulation of a stable microemulsion. The prepared Curcumin-loaded microemulsion was characterized by globule size, polydispersity index, Zeta potential, accelerated stability study, drug content, percent transmittance and antifungal assay by broth microdilution technique. The formulated microemulsion was converted into a vaginal emulgel by using Pluronic@F127. The formulated curcumin-loaded emulgel was characterized by different evaluation parameters and antifungal study by agar well diffusion method. Results: The result showed that the average globule size of emulgel was 286.3 nm, polydispersity index was 0.241, Zeta potential was+19.20 mv, conductivity was 0.0390 mS/cm, and drug content was found to be 95.58%. The texture of formulated emulgel was found to be soft and smooth, with shear-thinning, pseudoplastic behavior, and easily spreadable. The in vitro permeability study of emulgel shows slow and complete release of curcumin in 10 h. The microemulsion and developed emulgel showed promising antifungal activity against Candida albicans. Conclusion: The developed curcumin-loaded emulgel showed promising antifungal activity against Candida albicans as compared to the Fluconazole as an standard antifungal antibiotic. Our formulated Curcumin-containing emulgel can be a potential alternative as compared to the conventional dosage form for the treatment of vaginal candidiasis.

THE EVALUATION OF ACTIVITY AND STABILITY OF ISOLATED BROMELAIN FROM PINEAPPLE CORES (ANANAS COMOSUS [L.] MERR) AND IN VITRO PENETRATION TEST OF NANOEMULSION TOPICAL BASE

Objective: Oral administration of bromelain as an anti-inflammation therapy still faces several challenges, such as the risk of contact with the gastric fluid and its low absorption rate. Therefore, bromelain isolated from the pineapple core will be formulated as a topical base in a nanoemulsion to increase its stability, activity, and ability to penetrate the skin. Methods: Bromelain was isolated from pineapple core using ammonium sulfate precipitation and dialysis, and then the isolated fraction was loaded into topical nanoemulsion for subsequent evaluation of its characteristics, stability, enzymatic activity, and for in vitro study of penetration using Franz diffusion cell. Results: The highest specific activity of bromelain fractions found in ammonium sulfate concentration is around 20–50%. After being dialyzed, the bromelain fraction showed an increase in specific activity 2.78-fold as compared to crude extract. The characteristics of bromelain nanoemulsion showed a globule size of 21.37±1.8 nm with a polydispersity index (pdI) 0.323±0.049, oil in water (o/w) type, and the type of rheology was plastic flow. The nanoemulsion stability base was observed, and there was no phase separation after centrifugation. Bromelain in nanoemulsion base showed a proteolytic activity of 5.00 U/ml with a protein content of 154.28 mg/l. In vitro penetration studies using Franz diffusion cell for 8 h showed isolated bromelain in nanoemulsion base has a total cumulative number value of 1386.94 μg/cm2 with penetrated velocity/flux (J) of 45.93 μg/cm2 h. Conclusion: The results showed promise for bromelain loaded into nanoemulsion as a vehicle for topically administered therapeutic enzymes.

Box-Behnken Design Optimization of Etoposide Loaded Nanoemulsion: Formulation Development, Cellular Uptake Analysis and Pharmacokinetic Evaluation

Etoposide is widely used in the management of different solid tumors as well as leukemias but low aqueous solubility and poor intestinal permeability limit its oral efficacy. The present investigation aimed to enhance the oral bioavailability of etoposide through formation of nanoemulsion employing Box-Behnken design for formulation optimization. The effect of nanoemulsion composition (concentration of labrasol and solutol HS 15) and process parameters (sonication time) on globule size and polydispersity index were investigated. The optimized formulation was found to be with globule size <200 nm and PDI of 0.129. The zeta potential value −35.8 mV for nanoemulsion indicated the formation of a stable colloidal system. The in-vitro release of etoposide from optimized nanoemulsion was conducted with the help of USP dissolution apparatus type-II in 250 ml of gastric fluid of pH = 1.2 and intestinal fluid of pH 6.8 at 37±0.5 °C using dialysis bag. High drug release was achieved in case of nanoemulsion (47.127±0.82%) as compared to the marketed capsule (25.877±1.33%) and drug suspension (21.374±1.69%) in the simulated intestinal fluid of pH 6.8 after 4 h. The developed delivery system exhibited pH-independent dissolution profile of the loaded etoposide. Confocal laser scanning microscopy (CLSM) study of developed nanoemulsion system was done on intestinal tissue of Wistar rats and optical cross sections revealed deeper penetration of Rhodamine B compared to the dye solution. A comparative in-vivo bioavailability profile of developed formulation, marketed product, and API suspension was also investigated after oral administration in Wistar rats. The relative bioavailability of etoposide loaded nanoemulsion system was 2.5 times higher than the drug suspension and 1.7 times higher than the marketed capsule (Posid®). The findings of the current investigation proved that the developed nanoemulsion system is helpful to improve the bioavailability of P-gp substrate drugs like etoposide that have low oral absorption.