Enhanced stability and permeation potential of nanoemulsion containing sefsol-218 oil for topical delivery of amphotericin B

Aim: To characterize the enhanced stability and permeation potential of amphotericin B nanoemulsion comprising sefsol-218 oil at varying pH and temperature of aqueous continuous phase.

Methodology: Several batches of amphotericin B loaded nanoemulsion were prepared and evaluated for their physical and chemical stability at different pH and temperature. Also, a comparative study of ex vivo drug permeation across the albino rat skin was investigated with commercial Fungisome® and drug solution at 37?°C for 24?h. The extent of drug penetrated through the rat skin was thereby evaluated using the confocal laser scanning microscopy (CLSM).

Results and conclusions: The optimized nanoemulsion demonstrated the highest flux rate 17.85?±?0.5?µg/cm²/h than drug solution (5.37?±?0.01?µg/cm²/h) and Fungisome® (7.97?±?0.01?µg/cm²/h). Ex vivo drug penetration mechanism from the developed formulations at pH 6.8 and pH 7.4 of aqueous phase pH using the CLSM revealed enhanced penetration. Ex vivo drug penetration studies of developed formulation comprising of CLSM revealed enhanced penetration in aqueous phase at pH 6.8 and 7.4. The aggregation behavior of nanoemulsion at both the pH was found to be minimum and non-nephrotoxic. The stability of amphotericin B was obtained in terms of pH, optical density, globular size, polydispersity index and zeta potential value at different temperature for 90 days. The slowest drug degradation was observed in aqueous phase at pH 7.4 with shelf life 20.03-folds higher when stored at 4?°C (3.8 years) and 5-fold higher at 25?°C (0.951 years) than at 40?°C. The combined results suggested that nanoemulsion may hold an alternative for enhanced and sustained topical delivery system for amphotericin B.     

Development and in vitro evaluation of a nanoemulsion for transcutaneous delivery

Objective: The purpose of this study is to develop a nanoemulsion formulation for its use as a transcutaneous vaccine delivery system.

Materials and methods: With bovine albumin-fluorescein isothiocyanate conjugate (FITC-BSA) as a vaccine model, formulations were selected with the construction of pseudo-ternary phase diagrams and a short-term stability study. The size of the emulsion droplets was furthered optimized with high-pressure homogenization. The optimized formulation was evaluated for its skin permeation efficiency. In vitro skin permeation studies were conducted with shaved BALB/c mice skin samples with a Franz diffusion cell system. Different drug concentrations were compared, and the effect of the nanoemulsion excipients on the permeation of the FITC-BSA was also studied.

Results: The optimum homogenization regime was determined to be five passes at 20?000?psi, with no evidence of protein degradation during processing. With these conditions, the particle diameter was 85.2?nm?±?15.5?nm with a polydispersity index of 0.186?±?0.026 and viscosity of 14.6 cP?±?1.2 cP. The optimized formulation proved stable for 1 year at 4?°C. In vitro skin diffusion studies show that the optimized formulation improves the permeation of FITC-BSA through skin with an enhancement ratio of 4.2 compared to a neat control solution. Finally, a comparison of the skin permeation of the nanoemulsion versus only the surfactant excipients resulted in a steady state flux of 23.44?μg/cm²/h for the nanoemulsion as opposed to 6.10?μg/cm²/h for the emulsifiers.

Conclusion: A novel nanoemulsion with optimized physical characteristics and superior skin permeation compared to control solution was manufactured. The formulation proposed in this study has the flexibility for the incorporation of a variety of active ingredients and warrants further development as a transcutaneous vaccine delivery vehicle.     

Enhanced transdermal delivery of carvedilol using nanoemulsion as a vehicle

The aim of the present study was to develop nanoemulsion as a possible vehicle for enhanced transdermal penetration of carvedilol (CVD). For screening of nanoemulsion components, solubility of CVD in oils, surfactants and co-surfactants was determined. Various surfactants and co-surfactants were screened for their ability to nanoemulsify the selected oily phases. The obtained results indicated that Acconon CC6® had shown good nanoemulsification efficiency (minimum surfactant required S _min?=?46.52%?w/w) among the selected surfactants and further improved in presence of CO-20® (S _min?=?37.11%?w/w). The ranges of nanoemulsion existence were delineated through the construction of the pseudo-ternary phase diagram at different ratio of surfactant mixture (S/CoS), and various nanoemulsions were selected from phase diagram of S/CoS ratio 1?:?1. The effect of content of oil and S/CoS (1?:?1) on the skin permeation of CVD was evaluated through an excised wistar rat skin using Franz diffusion cell. All the nanoemulsions showed a high skin permeation rate (92.251–161.53?µg/cm²/h), good enhancement ratio (3.5–6.2) and high permeability coefficient in comparison to control groups. The optimised nanoemulsion formulation with the highest skin permeation rate (161.53?µg/cm²/h) consisted of 0.25%?w/w CVD, 12.5%?w/w Miglyol 810®, 50%?w/w Acconon CC6®/CO-20® (1?:?1) and water. The above formulation had the smallest mean globules size (9.28?nm). The superior transdermal flux of CVD may be due to nanorange size of oil globules that lead to intimate contact with the skin layer. These studies suggest that the nanoemulsion system is a promising vehicle for the transdermal delivery of CVD.     

Influence of omega fatty acids on skin permeation of a coenzyme Q10 nanoemulsion cream formulation: characterization,in silico and ex vivo determination

Objective: The aim of this study was to develop a coenzyme Q10 nanoemulsion cream, characterize and to determine the influence of omega fatty acids on the delivery of coenzyme Q10 across model skin membrane via ex vivo and in silico techniques.

Methods: Coenzyme Q10 nanoemulsion creams were prepared using natural edible oils such as linseed, evening primrose, and olive oil. Their mechanical features and ability to deliver CoQ10 across rat skin were characterized. Computational docking analysis was performed for in silico evaluation of CoQ10 and omega fatty acid interactions.

Results: Linseed, evening primrose, and olive oils each produced nano-sized emulsion creams (343.93–409.86?nm) and exhibited excellent rheological features. The computerized docking studies showed favorable interactions between CoQ10 and omega fatty acids that could improve skin permeation. The three edible-oil nanoemulsion creams displayed higher ex vivo skin permeation and drug flux compared to the liquid-paraffin control cream. The linseed oil formulation displayed the highest skin permeation (3.97?±?0.91?mg/cm²) and drug flux (0.19?±?0.05?mg/cm²/h).

Conclusion: CoQ10 loaded-linseed oil nanoemulsion cream displayed the highest skin permeation. The highest permeation showed by linseed oil nanoemulsion cream may be due to the presence of omega-3, -6, and -9 fatty acids which might serve as permeation enhancers. This indicated that the edible oil nanoemulsion creams have potential as drug vehicles that enhance CoQ10 delivery across skin.     

Development,optimization, and characterization of a novel tea tree oil nanogel using response surface methodology

Purpose: To develop and optimize nanoemulsion (NE)-based emulgel (EG) formulation as a potential vehicle for topical delivery of tea tree oil (TTO).

Methodology: Central composite design was adopted for optimizing the processing conditions for NE preparation by high energy emulsification method viz. surfactant concentration, co-surfactant concentration, and stirring speed. The optimized NE was developed into emulgel (EG) using pH sensitive polymer Carbopol 940 and triethanolamine as alkalizer. The prepared EG was evaluated for its pH, viscosity, and texture parameters, ex vivo permeation at 37?°C and stability. Antimicrobial evaluation of EG in comparison to conventional gel and pure TTO was also carried out against selected microbial strains.

Results and discussion: Optimized NE had particle size and zeta potential of 16.23?±?0.411?nm and 36.11?±?1.234?mV, respectively. TEM analysis revealed the spherical shape of droplets. The pH of EG (5.57?±?0.05?) was found to be in accordance with the range of human skin pH. EG also illustrated efficient permeation (79.58?μL/cm²) and flux value (J_SS) of 7.96?μL cm²/h through skin in 10?h. Viscosity and texture parameters, firmness (9.3?±?0.08?g), spreadability (2.26?±?0.06?mJ), extrudability (61.6?±?0.05?mJ), and adhesiveness (8.66?±?0.08?g) depict its suitability for topical application. Antimicrobial evaluation of EG with same amount of TTO as conventional gel revealed broader zones of growth inhibitions against all the selected microbial strains. Moreover, EG was also found to be nonirritant (PII 0.0833). These parameters were consistent over 90 d.

Conclusion: TTO EG turned out to be a promising vehicle for the topical delivery of TTO with enhanced therapeutic efficacy.     

Development of novel amisulpride-loaded liquid self-nanoemulsifying drug delivery systems via dual tackling of its solubility and intestinal permeability

Objective: The aim of the current investigation was at enhancing the oral biopharmaceutical behavior; solubility and intestinal permeability of amisulpride (AMS) via development of liquid self-nanoemulsifying drug delivery systems (L-SNEDDS) containing bioenhancing excipients.

Methods: The components of L-SNEDDS were identified via solubility studies and emulsification efficiency tests, and ternary phase diagrams were constructed to identify the efficient self-emulsification regions. The formulated systems were assessed for their thermodynamic stability, globule size, self-emulsification time, optical clarity and in vitro drug release. Ex vivo evaluation using non-everted gut sac technique was adopted for uncovering the permeability enhancing effect of the formulated systems.

Results: The optimum formulations were composed of different ratios of Capryol? 90 as an oil phase, Cremophor^® RH40 as a surfactant, and Transcutol^® HP as a co-surfactant. All tested formulations were thermodynamically stable with globule sizes ranging from 13.74 to 29.19?nm and emulsification time not exceeding 1?min, indicating the formation of homogenous stable nanoemulsions. In vitro drug release showed significant enhancement from L-SNEDDS formulations compared to aqueous drug suspension. Optimized L-SNEDDS showed significantly higher intestinal permeation compared to plain drug solution with nearly 1.6–2.9 folds increase in the apparent permeability coefficient as demonstrated by the ex vivo studies.

Conclusions: The present study proved that AMS could be successfully incorporated into L-SNEDDS for improved dissolution and intestinal permeation leading to enhanced oral delivery.     

Curcumin nanoemulsion for transdermal application: formulation and evaluation

The aim of this work is to develop a curcumin nanoemulsion for transdermal delivery. The incorporation of curcumin inside a nanoglobul should improve curcumin stability and permeability. A nanoemulsion was prepared by the self-nanoemulsification method, using an oil phase of glyceryl monooleate, Cremophor RH40 and polyethylene glycol 400. Evaluation of the nanoemulsion included analysis of particle size, polydispersity index, zeta potential, physical stability, Raman spectrum and morphology. In addition, the physical performance of the nanoemulsion in Viscolam AT 100P gel was studied. A modified vertical diffusion cell and shed snake skin of Python reticulatus were used to study the in vitro permeation of curcumin. A spontaneously formed stable nanoemulsion has a loading capacity of 350?mg curcumin/10?g of oil phase. The mean droplet diameter, polydispersity index and zeta potential of optimized nanoemulsion were 85.0?±?1.5?nm, 0.18?±?0.0 and ?5.9?±?0.3?mV, respectively. Curcumin in a nanoemulsion was more stable than unencapsulated curcumin. Furthermore, nanoemulsification significantly improved the permeation flux of curcumin from the hydrophilic matrix gel; the release kinetic of curcumin changed from zero order to a Higuchi release profile. Overall, the developed nanoemulsion system not only improved curcumin permeability but also protected the curcumin from chemical degradation.     

Intradermal and follicular delivery of adapalene liposomes

Abstract

Background: Adapalene is a widely used topical anti-acne drug; however, it has many side effects. Liposomal drug delivery can play a major role by targeting delivery to pilosebaceous units, reducing side effects and offering better patient compliance.

Objective: To prepare and evaluate adapalene-encapsulated liposomes for their physiochemical and skin permeation properties.

Methods: A liposomal formulation of adapalene was prepared by the film hydration method and characterized for shape, size, polydispersity index (PDI), encapsulation efficiency and thermal behavior by techniques such as Zetasizer®, differential scanning calorimetry and transmission electron microscopy. Stability of the liposomes was evaluated for three months at different storage conditions. In vitro skin permeation studies and confocal laser microscopy were performed to evaluate adapalene permeation in pig ear skin and hair follicles.

Results: The optimized process and formulation parameters resulted in homogeneous population of liposomes with a diameter of 86.66?±?3.5?nm in diameter and encapsulation efficiency of 97.01?±?1.84% w/w. In vitro permeation studies indicated liposomal formulation delivered more drug (6.72?±?0.83?μg/cm²) in hair follicles than gel (3.33?±?0.26?μg/cm²) and drug solution (1.62?±?0.054?μg/cm²). Drug concentration delivered to the skin layers was also enhanced compared to other two formulations. Confocal microscopy images confirmed drug penetration in the hair follicles when delivered using the liposomal formulation.

Conclusion: Adapalene was efficiently encapsulated in liposomes and led to enhanced delivery in hair follicles, the desired target site for acne.     

Self-emulsifying drug delivery system for enhanced solubility of asenapine maleate: design,characterization, in vitro,ex vivo and in vivo appraisal

Self-emulsifying drug delivery systems (SES) were developed to improve oral bioavailability of asenapine maleate (ASM), an antipsychotic drug with challenging amphiphobic nature and extensive pre-systemic metabolism. ASM-SES was prepared by choosing the proportion of oil, surfactant, co-surfactant from constructed phase diagram. The in vitro and ex vivo evaluation was done. In vivo evaluation was done through pharmacokinetic and pharmacodynamic studies. Role of lymphatic absorption was studied by lymphatic absorption inhibition study. A formulation consisting of 9.9%, 59.4%, 29.7% and 1% of oil, surfactant, co-surfactant, and drug respectively was considered as optimized formulation. After various evaluation test, the globule size and zeta potential for optimized formulation (SES₄) were found to be 137.9?nm and ?28.8?mV respectively. A maximum of 99.64?±?0.16% of ASM was released from SES₄ in 60?minutes of time. The flux (ex vivo study) increased by 2.33 folds, which prove the enhanced release and permeation of ASM when loaded into SES. The animals administered with SES₄ showed higher activity and good pharmacodynamic response than the control and ASM-Suspension, which may be due to the greater availability of the drug. The maximum pharmacodynamic response was observed at the t_max determined by Pharmacokinetic studies. The bioavailability increased by 1.64 folds with 16.55?±?3.11% as extend of lymphatic absorption (r?=?0.9732). Good in vitro in vivo correlation was observed. ASM-SES is a novel approach to effectively deliver ASM and improve the oral bioavailability.     

Impact of various solid carriers and spray drying on pre/post compression properties of solid SNEDDS loaded with glimepiride: in vitro-ex vivo evaluation and cytotoxicity assessment

Development of self-nanoemulsifying drug delivery systems (SNEDDS) of glimepiride is reported with the aim to achieve its oral delivery. Lauroglycol FCC, Tween-80, and ethanol were used as oil, surfactant, and co-surfactant, respectively as independent variables. The optimized composition of SNEDDS formulation (F1) was 10% v/v Lauroglycol FCC, 45% v/v Tween 80, 45% v/v ethanol, and 0.005% w/v glimepiride. Further, the optimized liquid SNEDDS were solidified through spray drying using various hydrophilic and hydrophobic carriers. Among the various carriers, Aerosil 200 was found to provide desirable flow, compression, dissolution, and diffusion. Both, liquid and solid-SNEDDS have shown release of more than 90% within 10?min. Results of permeation studies performed on Caco-2 cell showed that optimized SNEDDS exhibited 1.54 times higher drug permeation amount and 0.57 times lower drug excretion amount than that of market tablets at 4?hours (p?p?>?.05, i.e. 0.74). The formulation was found stable with temperature variation and freeze thaw cycles in terms of droplet size, zeta potential, drug precipitation and phase separation. Crystalline glimepiride was observed in amorphous state in solid SNEDDS when characterized through DSC, PXRD, and FT-IR studies. The study revealed successful formulation of SNEDDS for glimepiride.     

Optimization of nutraceutical coenzyme Q10 nanoemulsion with improved skin permeability and anti-wrinkle efficiency

Coenzyme Q10 (CoQ10) is an insoluble, poorly permeable antioxidant with great biological value which acts as anti-aging and anti-wrinkle agent. To improve its permeability through topical application, the current study aimed at formulating oil/water (o/w) nanoemulsion (NE) as an efficient vehicle for delivering (CoQ10) through the skin barriers. The solubility of (CoQ10) was tested for various oils, surfactants (S), and co-surfactants (CoS). The NE region was determined by constructing pseudoternary phase diagrams. NE formulae containing 1, 2, and 3% w/w drug have been subjected to thermodynamic stability test. The formulae that passed thermodynamic stability tests were characterized by physical properties as pH, viscosity, refractive index, droplet size, zeta-potential, TEM, electroconductivity, in vitro release, and ex vivo permeation. The formula ‘F2’ containing 10% w/w isopropyl myristate (oil phase), 60% w/w of Tween 80: Transcutol HP mixture (S/CoS_mix) at ratio 2:1, 30% w/w water and 2% w/w drug was evaluated for its anti-wrinkle efficiency using an animal model. The ‘F2’ formula showed 11.76?±?1.1?nm droplet size, 1.4260?±?0.0016 refractive index, 0.228 PDI, ?14.7?±?1.23?mv zeta potential, 7.06?±?0.051?pH, 199.05?±?0.35?cp viscosity, and the highest percentage of drug release in the selected dissolution media. About 47.21% of the drug was released in phosphate buffer 7.4 containing 5% w/v Labrasol and 5% w/v isopropyl alcohol through 24?h. It also showed the highest drug flux (J_ss?=?3.164?µg/cm²/h), enhancement ratio (E_r?=?8.32), and permeability coefficient (K_p?=?22.14?×?10^?4 cm²/h). CoQ10 NE reduced the skin wrinkles and gave the skin smooth appearance. Our investigation suggests the potential use of NE as a vehicle for enhancing solubility and permeability of CoQ10 and thus improving its anti-wrinkle efficiency.     

Self-microemulsifying smaller molecular volume oil (Capmul MCM) using non-ionic surfactants: a delivery system for poorly water-soluble drug

The main purpose of this work is to formulate self-microemulsifying drug delivery system (SMEDDS) using smaller molecular oil with Atorvastatin calcium as a model drug. Solubility of the selected drug was accessed in oils and surfactants. Percent transmittance (%T) test study was performed to identify the efficient self-microemulsifying formulations. Those formulations which showed higher value for %T were evaluated for droplet size, polydispersity index, ζ potential, refractive index and cloud point measurement. Effect of drug loading on droplet size, increasing dilution in different media, thermodynamic stability and in vitro dissolution was performed to observe the performance of the selected formulation. Further cytotoxicity and permeation enhancement studies were carried out on Caco2 cell lines. Of all the oils accessed for drug solubility, Capmul MCM showed higher solubility capacity for Atorvastatin calcium. Capmul MCM was better microemulsified using combination of Tween 20 and Labrasol surfactant. Droplet size was as low as 86.93?nm with polydispersity index and ζ potential at 0.195?±?0.011 and ?7.27?±?3.11 mV respectively. The selected undiluted formulation showed refractive index values ranging from 1.40 to 1.47 indicating the isotropicity of the formulation. The selected formulation was robust to dilution in different media and thermodynamically stable. Dissolution profile was enhanced for the selected drug as compared to marketed formulation with t85% and DE values at 10?min and 80.15 respectively. Also cytotoxicity measurement showed minimum effect with good permeation enhancing capacity. Thus our study demonstrates the use of smaller molecular oil (Capmul MCM) for developing self-microemulsifying drug delivery system for better in vitro and in vivo performance.     

Hydrogel containing adapalene- and dapsone-loaded lipid-core nanocapsules for cutaneous application: development,characterization, in vitro irritation and permeation studies

Lipid-core polymeric nanocapsule suspensions containing adapalene and dapsone (AD-LCNC) were developed and incorporated in a Carbopol 940® hydrogel (AD-LCNC HG). A nanoemulsion (AD-NE), similarly prepared but omitting the polymer, was developed and also incorporated in a Carbopol 940^® hydrogel (AD-NE HG) to evaluate the polymer effect. Physicochemical characteristics were evaluated. AD-LCNC suspensions containing 0.07% of dapsone and 0.025% of adapalene presented an average size of 194.9?±?0.42?nm, zeta potential of ?15?±?1.2?mV and polydispersity index of 0.12?±?0.02, using electrophoretic light scattering (n?=?3). The granulometric profiles showed unimodal size distributions for AD-LCNC suspensions, demonstrating that no microscopic population is present in the formulation. No instability phenomena were observed by multiple light-scattering analysis. Photomicrographs obtained by TEM showed homogeneous- and spherical-shaped particles. The encapsulation efficiency was 99.99% for dapsone and 100% for adapalene. The pH values for AD-LCNC suspensions were 5.1 and 7.6 for AD-LCNC HG. Formulations were classified as nonirritant in the HET-CAM test. Rheological analysis demonstrated a non-Newtonian pseudoplastic profile. The in vitro skin permeation studies showed a higher amount of adapalene in epidermis (130.52?±?25.72?ng/mg) and dermis (4.66?±?2.5?ng/mg) for AD-NE HG. The AD-LCNC HG presented higher amount of dapsone in both the skin layers (73.91?±?21.64?ng/mg in epidermis and 4.08?±?0.85?ng/mg in dermis). The assay showed significant difference between AD-LCNC HG and AD-NE HG (p?相似文献   

Formulation and evaluation of thymoquinone niosomes: application of developed and validated RP-HPLC method in delivery system

Abstract

A rapid, accurate, and sensitive reverse phase high-performance liquid chromatographic (RP-HPLC) method was developed and validated for the estimation of Thymoquinone (TMQ) in API as well as in noisome. The chromatograms were developed with the mobile phase – water: 2-propanol: methanol (50:45:5 v/v/v) as a solvent system at 254?nm. The method was validated as per ICH guidelines for different parameters and the recovery of TMQ was calculated in developed niosomes. Further, TMQ loaded niosomes (TMQNIOS) were prepared and evaluated for different parameters. The optimized TMQNIOS (F3) was further evaluated for surface morphology, in vitro drug release, permeation study, and confocal laser scanning microscopic (CLSM) study. The method showed linearity range between 6.25 and 100?µg/ml with low detection limit and quantitation limit with a value of 2.08 and 6.25?µg/ml. The developed formulations showed the vesicle size and encapsulation efficiency in the range of 157.32?±?3.15 to 211.44?±?5.23?nm and 59.32?±?4.87 to 83.21?±?3.55%, respectively. The drug release result showed the significant higher release from TMQNIOS in compared to TMQDIS, and the release kinetics data showed Higuchi's equation with highest regression coefficient values. The permeation study and the confocal laser microscopy study further confirmed the enhancement in permeation of TMQ in the intestinal mucosa.     

Lipid nanoparticles of zaleplon for improved oral delivery by Box–Behnken design: optimization,in vitro and in vivo evaluation

Purpose: Zaleplon (ZL) is a hypnotic drug prescribed for the management of insomnia and convulsions. The oral bioavailability of ZL was low (～30%) owing to poor water solubility and hepatic first-pass metabolism. The cornerstone of this investigation is to develop and optimize solid lipid nanoparticles (SLNs) of ZL with the aid of Box–Behnken design (BBD) to improve the oral bioavailability.

Methods: A design space with three formulation variables at three levels were evaluated in BBD. Amount of lipid (A₁), amount of surfactant (A₂) and concentration of co-surfactant (%) (A₃) were selected as independent variables, whereas, particle size (B₁), entrapment efficiency (B₂) and zeta potential (ZP, B₃) as responses. ZL-SLNs were prepared by hot homogenization with ultrasonication method and evaluated for responses to obtain optimized formulation. Morphology of nanoparticles was observed under SEM. DSC and XRD studies were examined to understand the native crystalline behavior of drug in SLN formulations. Further, in vivo studies were performed in Wistar rats.

Results: The optimized formulation with 132.89?mg of lipid, 106.7?mg of surfactant and 0.2% w/v of co-surfactant ensued in the nanoparticles with 219.9?±?3.7?nm of size, ?25.66?±?2.83?mV surface charge and 86.83?±?2.65% of entrapment efficiency. SEM studies confirmed the spherical shape of SLN formulations. The DSC and XRD studies revealed the transformation of crystalline drug to amorphous form in SLN formulation. In conclusion, in vivo studies in male Wistar rats demonstrated an improvement in the oral bioavailability of ZL from SLN over control ZL suspension.

Conclusions: The enhancement in the oral bioavailability of ZL from SLNs, developed with the aid of BBD, explicated the potential of lipid-based nanoparticles as a potential carrier in improving the oral delivery of this poorly soluble drug.     

Development of a nanoemulsion of Phyllanthus emblica L. branch extract

For potential topical administration, we formulated a nanoemulsion containing phenolic constituents of Phyllanthus emblica branch extract. The nanoemulsion has high entrapment efficiency, small particle size, is stable, and can release its main chemical components. Branches of P. emblica were extracted with 50% ethanol (EPE) with 5.4% yield. HPLC analysis indicated several phenolic compounds, including gallic acid, vanillic acid, epigallocatechin (EGC), epigallocatechin gallate (EGCG) and ellagic acid. These were selected as chemical markers of EPE in the nanoemulsion development. The nanoemulsion was prepared by microemulsion techniques with hot high pressure homogenization. A ternary phase diagram was constructed to obtain the optimized nanoemulsion. The obtained transparent EPE nanoemulsion is composed of isopropyl myristate (0.6% w/w), Brij® 78 (0.35% w/w), and 0.15% (w/w) EPE. The optimized EPE nanoemulsion had a median particle size of 191.63?±?4.07?nm with a narrow particle size distribution, a zeta potential of ?10.19?±?0.54?mV, high entrapment efficiency at 67.99?±?0.87% and good stability at 4?°C after 90?d of storage. The release of active ingredients from the EPE nanoemulsion was slower than that of the EPE aqueous formulation. The loading ratios of the five phenolic compounds were high, with relative order of EGC?>?EGCG?>?vanillic acid?>?gallic acid?>?ellagic acid, resulting in slow release profiles of EGC and EGCG in the EPE nanoemulsion. In conclusion, the obtained EPE nanoemulsion has good characteristics for future clinical trials.     

Magnetophoresis in combination with chemical enhancers for transdermal drug delivery

Purpose: The objective of the present work was to investigate the effect of combination of a novel physical permeation enhancement technique, magnetophoresis with chemical permeation enhancers on the transdermal delivery of drugs.

Methods: The in vitro drug transport studies were carried out across the freshly excised abdominal skin of Sprague-Dawley rats using transdermal patch systems (magnetophoretic and non-magnetophoretic) of lidocaine hydrochloride (LH). LH gel prepared using hydroxypropyl methylcellulose (HPMC) was spread over the magnets as a thin layer. To investigate the effect of chemical permeation enhancers, menthol, dimethyl sulfoxide, sodium lauryl sulfate and urea (5% w/v) were incorporated in the gels prior to loading on the patch system.

Results: The flux of lidocaine from magnetophoretic patch was ~3-fold higher (3.07?±?0.43 µg/cm²/h) than that of the control (non-magnetophoretic patch) (0.94?±?0.13 µg/cm²/h). Incorporation of chemical permeation enhancers in the gel enhanced the magnetophoretic delivery flux by ~4 to 7-fold.

Conclusions: The enhancement factor due to combination of chemical permeation enhancer was additive and not synergistic. Mechanistic studies indicated that magnetophoresis mediated drug delivery enhancement was via appendageal pathway.     

Design of antihistaminic transdermal films based on alginate–chitosan polyelectrolyte complexes: characterization and permeation studies

The purpose of this study was to develop suitable matrix-type transdermal drug delivery systems of Ketotifen fumarate (KF) as antiasthmatic drugs. Chitosan–alginate polyelectrolyte complex (PEC) films were used as drug release regulators for KF. Antihistaminic films with variable PEC compositions were prepared using different ratios of chitosan (CTS) to sodium alginate (ALG). Propylene glycol (PG) was used as plasticizer; Tween 80 (T₈₀) and Span 20 (S₂₀) were used as permeability enhancers. Nine formulations were obtained by film casting method and characterized in terms of weight uniformity, thickness, folding endurance, moisture lost, and moisture absorption. In addition, drug release and permeation through rat abdominal skin mounted in Franz cell were investigated. All formulations were found to be suitable in terms of physicochemical characteristics, and there was no significant interaction between the used drug and polymers. It was noticed that when T₂₀ is used as permeation enhancer, a satisfactory drug release pattern was found where 99.88% of drug was released and an amount of 2.121?mg/cm² of KF was permeated after 24?h. For the optimal formulation, a permeability coefficient of 14.00?±?0.001?cm h^?1 and a latency time of 0.35?±?0.02?h were found. The in-vitro analysis showed controlled release profile which was fitted by Korsmeyer–Peppas model (R²?=?0.998). The obtained results suggested that new controlled release transdermal formulations of asthmatic drugs could be suitably designed as an alternative to the common forms.     

Formulation of solid self-nanoemulsifying drug delivery systems using N-methyl pyrrolidone as cosolvent

Atorvastatin calcium (ATRC) is a poor water soluble drug used for treatment of hypercholesterolemia. This research is aimed to improve solubility and dissolution rate of ATRC by formulating into solid self-nanoemulsifying drug delivery system (S-SNEDDS) using N-methyl pyrrolidone (NMP) as cosolvent. Solubility of ATRC was determined in various vehicles. Ternary phase diagrams were constructed to identify stable nanoemulsion region. SNEDDS formulations were evaluated for robustness to dilution, thermodynamic stability study, % transmittance, self-emulsification time, globule size and transmission electron microscopy. The optimized liquid SNEDDS showed robust to all dilutions exhibiting no signs of phase separation or precipitation for 24?h. Liquid SNEDDS was transformed into S-SNEDDS using different adsorbents. Differential scanning calorimetry and scanning electron microscopy studies unravel the transformation of native crystalline state to amorphous state/solubilized state. In vitro dissolution study of S-SNEDDS was found to be significantly higher in comparison to that from plain drug, irrespective of pH (p?ex vivo permeation studies showed a 4.45-fold improvement in apparent permeability coefficient (P_app) from S-SNEDDS compared to plain drug. In conclusion, S-SNEDDS prepared using NMP as cosolvent provides an effective approach for improved oral delivery of ATRC.     

Vitamin B12 buccoadhesive tablets: auspicious non-invasive substitute for intra muscular injection: formulation,in vitro and in vivo appraisal

Attempting to prepare a convenient bioavailable formulation of vitamin B₁₂ (cyanocobalamin), 17 tablet formulations were prepared by direct compression. Different concentrations of hydroxypropyl methyl cellulose (HPMC), carbopol 971p (CP971p), and chitosan (Cs) were used. The tablets were characterized for thickness, weight, drug content, hardness, friability, surface pH, in vitro drug release, and mucoadhesion. Kinetic analysis of the release data was conducted. Vitamin B₁₂ bioavailability from the optimized formulations was studied on rabbits by the aid of enzyme-linked immunosorbent assay. Neurotone^® I.M. injection was used for comparison. HPMC (F1-F4), CP971p (F5-F8), and HPMC/CP971p (F12-F15)-based formulations showed acceptable mechanical properties. The formulated tablets showed maximum swelling indices of 232?±?0.13. The surface pH values ranged from 5.3?±?0.03 to 6.6?±?0.02. Bioadhesive force ranged from 66?±?0.6 to 150?±?0.5?mN. Results showed that CP971p-based tablets had superior in vitro drug release, mechanical, and mucoadhesive properties. In vitro release date of selected formulations were fitted well to Peppas model. HPMC/CP971p-based formulations showed bioavailability up to 2.7-folds that of Neurotone^® I.M. injection.