Formulation and optimization of lipid- and Poloxamer-tagged niosomes for dermal delivery of terbinafine: preparation, evaluation, and in vitro antifungal activity.

Fungal skin diseases are recognized as a global burden disease that affect human quality adjusted life. Terbinafine belongs to allylamine and broad-spectrum antifungal drugs but considered practically insoluble. Different lipids/surfactant with two different molar ratios were investigated with Span 40-based niosomes; characterized for size, morphology, loading capacity (EE%), in vitro release, kinetics, and antifungal activities. Vesicle sizes (0.19-1.23 µm), EE% (25-99%), zeta potential (> -32 mV), and in vitro release rates were dependent on both lipid types and ratios. Higher ratios of Poloxamer 407 preferably formed mixed micelles rather than forming noisome bilayers. Both Compritol and Precirol were deemed to be potential alternatives to cholesterol as bilayer membrane stabilizers. Terbinafine-loaded Compritol and Precirol stabilized niosomes were successfully prepared and demonstrated superior antifungal activities in vitro (inhibition zones) using Candida albicans ATCC 60913.

Using Bio-Layer Interferometry to Evaluate Anti-PEG Antibody-Mediated Complement Activation.

The purpose of this study was to develop a Bio-layer interferometry (BLI) system that could be an alternative approach for the direct evaluation of anti-polyethylene glycol (PEG) immunoglobulin M (IgM)-mediated complement activation of the accelerated blood clearance (ABC) phenomenon. Complement activation is well known to play an important role in the clearance of PEGylated and non-PEGylated nanomedicines following intravenous injection. This complement system is also thought to be responsible for the ABC phenomenon wherein repeated injections of PEGylated products are bound by anti-PEG antibodies. This study used three different sources of anti-PEG antibodies: HIK-M09 monoclonal antibodies (mAbs); HIK-M11 mAbs; and antiserum containing polyclonal anti-PEG IgMs. 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-n-[methoxy (polyethylene glycol)-2000] (mPEG2000-DSPE) was immobilized as an antigen on aminopropyl silane biosensor chips of BLI. All anti-PEG IgMs in the sources increased the signals (thickness of the layer around the sensor tip) regarding binding of anti-PEG antibodies to PEG on the chips. In all anti-PEG IgM sources, further increases in the signals were observed when incubated in naïve mouse serum, which is a complement source, but not in heat inactivated (56 °C, 30 min) mouse serum, which abolishes complement activity. These findings show that the complement activation mediated via anti-PEG IgMs, which occurred on the sensor chips, was detected via BLI analysis. The complement activation induced by all anti-PEG IgM sources was confirmed via conventional enzyme-linked immunosorbent assay (ELISA), which is the conventional mode for detection of complement activation. Our study results show that BLI is a simple alternative method for the detection of complement activation.

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.

Hyaluronic acid gel-core liposomes (hyaluosomes) enhance skin permeation of ketoprofen.

Since FDA approval of the first transdermal patch in 1979, the utilizing of skin as a route of systemic drug administration has attracted the attention of the formulation scientists. The liposomes research in the area of transdermal drug delivery has been around for decades. This study aimed at comparing the latest gel-core liposomes (hyaluosomes) with nonconventional liposomal systems such as propylene glycol (PG)-liposomes, ethosomes, transferosomes and conventional liposomes loaded with ketoprofen. The modified thin-film hydration method was used to prepare these liposomal systems; size, zeta potential, EE%, TEM, rheological properties, in vitro release and ex vivo permeation studies were performed. Vesicle size and PDI ranged from 160 nm to 700 nm and 0.15 to 0.5, respectively. More interestingly, thermal gelation and shear-thinning characteristics were only recorded with hyaluosomes; while Newtonian behavior and low viscosity values (2 mPas.s to 6 mPa.s) were shown with all other liposomal systems. Hyaluosomes recorded superior (3-fold increases) transdermal permeation characteristics (flux and permeability coefficient), compared with other liposomal systems. With the advancement in liposomal sciences, this study warrants hyaluosomes as a promising transdermal liposomal system for favorable rheological characteristics as well as superior transdermal permeation that proved greater capacity than conventional and other non-conventional liposomal systems.

Comparative studies for ciprofloxacin hydrochloride pre-formed gels and thermally triggered (in situ) gels: in vitro and in vivo appraisal using a bacterial keratitis model in rabbits.

This article reports on comparative in vitro characterization and in vivo evaluation of pre-formed cellulose-based gels, methylcellulose (MC) and carboxymethylcellulose sodium (CMC) and in situ gel-forming Pluronic F127 (PL) for ocular delivery of ciprofloxacin hydrochloride (Cipro) by using a bacterial keratitis model and histological corneal examination. Drug-polymer interactions were studied employing thermal analysis. Further, different concentrations (1-3% w/w or 10-30% w/w) of gels depending on the nature of the polymer used were prepared, characterized for clarity, pH, rheology and in vitro release. Selected gel formulations were evaluated for ocular delivery to Staphylococcus aureus-infected rabbit corneas; and ocular toxicity through histological examination of the cornea. The results demonstrated no Cipro-polymers physicochemical interactions and pseudoplastic flow for all gels used at 35 °C. Both polymer concentrations and drug solubility in the gels are dominantly the rate-determining factors for in vitro drug release. The corneal healing rate for all gel-based formulations was significantly faster (p < 0.05) than that for Cipro solution-treated rabbits. PL-based gel induced significant swelling/edema of the corneal stroma, compared with MC- and CMC-based gels. In conclusion, cellulose-based polymers have superior ocular tolerability/dramatically less irritant; and superior efficacy with more convenient administration compared with PL and Cipro solution, respectively.

Preparation, characterization and evaluation of novel elastic nano-sized niosomes (ethoniosomes) for ocular delivery of prednisolone.

Niosomes embodying ethanol and minimum amount of cholesterol (ethoniosomes) could be promising ocular delivery systems for water soluble and insoluble drugs. This manuscript reports on novel nano-sized elastic niosomes (ethoniosomes) composed of Span 60: cholesterol (7:3 mol/mol) and ethanol, for ocular delivery of prednisolone acetate (Pred A) and prednisolone sodium phosphate (Pred P). These ethoniosomes were prepared with the thin film hydration (TFH) and ethanol injection (EI) methods, characterized for percentage entrapment efficiency (% EE), size, zeta potential, morphology, elasticity, in vitro release and physical stability. Ocular irritation, bioavailability and anti-inflammatory effects were evaluated and compared with the conventional suspension and solution eye drops. The prepared ethoniosomal vesicles (EV) had a Z-average diameter of 267 nm, zeta potential of approximately -40 mV and % change in size after extrusion of 4%. They were physically stable for at least 2 months at 4 °C. The prepared EV showed good ocular tolerability using the modified Draize's test and the estimated relative ocular bioavailability for Pred A EV and Pred P EV was 1.54 and 1.75 times greater than that for the suspension and solution eye drops, respectively. The time required for complete healing from the clove oil-induced severe ocular inflammation was reduced to half with Pred A and Pred P EV. More interestingly, the intraocular pressure (IOP) elevation side effect recorded for Pred A and Pred P EV was significantly less than that for the conventional suspension and solution eye drops.

A simple and rapid approach to evaluate the in vitro in vivo role of release controlling agent ethyl cellulose ether derivative polymer.

Diclofenac sodium (DCL-Na) conventional oral tablets exhibit serious side effects when given for a longer period leading to noncompliance. Controlled release matrix tablets of diclofenac sodium were formulated using simple blending (F-1), solvent evaporation (F-2) and co-precipitation techniques (F-3). Ethocel® Standard 7 FP Premium Polymer (15%) was used as a release controlling agent. Drug release study was conducted in 7.4 pH phosphate buffer solutions as dissolution medium in vitro. Pharmacokinetic parameters were evaluated using albino rabbits. Solvent evaporation technique was found to be the best release controlling technique thereby prolonging the release rate up to 24 hours. Accelerated stability studies of the optimized test formulation (F-2) did not show any significant change (p<0.05) in the physicochemical characteristics and release rate when stored for six months. A simple and rapid method was developed for DCL-Na active moiety using HPLC-UV at 276nm. The optimized test tablets (F-2) significantly (p<0.05) exhibited peaks plasma concentration (cmax=237.66±1.98) and extended the peak time (tmax=4.63±0.24). Good in-vitro in vivo correlation was found (R(2)=0.9883) against drug absorption and drug release. The study showed that once-daily controlled release matrix tablets of DCL-Na were successfully developed using Ethocel® Standard 7 FP Premium.

Hybrid thermosensitive-mucoadhesive in situ forming gels for enhanced corneal wound healing effect of L-carnosine.

PURPOSE: Thermosensitive in situ gels have been around for decades but only a few have been translated into ophthalmic pharmaceuticals. The aim of this study was to combine the thermo-gelling polymer poloxamer 407 and mucoadhesive polymers chitosan (CS) and methyl cellulose (MC) for developing effective and long-acting ophthalmic delivery systems for L-carnosine (a natural dipeptide drug) for corneal wound healing. METHODS: The effect of different polymer combinations on parameters like gelation time and temperature, rheological properties, texture, spreading coefficients, mucoadhesion, conjunctival irritation potential, in vitro release, and ex vivo permeation were studied. Healing of corneal epithelium ulcers was investigated in a rabbit's eye model. RESULTS: Both gelation time and temperature were significantly dependent on the concentrations of poloxamer 407 and additive polymers (chitosan and methyl cellulose), where it ranged from <10 s to several minutes. Mechanical properties investigated through texture analysis (hardness, adhesiveness, and cohesiveness) were dependent on composition. Promising spreading-ability, mucoadhesion, transcorneal permeation of L-carnosine, high ocular tolerability, and enhanced corneal epithelium wound healing were recorded for poloxamer 407/chitosan systems. CONCLUSION: In situ gelling systems comprising combinations of poloxamer-chitosan exhibited superior gelation time and temperature, mucoadhesion, and rheological characteristics suitable for effective long-acting drug delivery systems for corneal wounds.

Vardenafil Oral Dispersible Films (ODFs) with Advanced Dissolution, Palatability, and Bioavailability.

Oral, quick response, and on demand, also known as a spontaneous oral treatment for erectile dysfunction, is highly needed by both patients and physicians. Vardenafil is selective (fewer side effects) and more effective in difficult-to-treat conditions than sildenafil. This study aims at fostering the dual objectives of using biomolecules such as artificial sweetening agents to solubilize and mask the bitterness of vardenafil loaded on biodegradable polymeric materials (PVA, MC, SA, and PVP K30) to fabricate oral, fast-dissolving films (vardenafil ODFs) in the mouth without the need for water to ingest the dosage form. Furthermore, coprecipitated-dispersed mixtures of vardenafil and three sweeteners (sorbitol, acesulfame K, and sucralose) were prepared and characterized using FTIR, DSC, and solubility studies. Moreover, eight different vardenafil ODFs were prepared using the solvent-casting method. Modified gustatory sensation test, in vitro disintegration, and release studies were performed. In addition, the optimized ODF (F8) was compared with the commercial film-coated tablets pharmacokinetically (relative bioavailability, onset, and duration of actions were estimated). The results indicated that the three sweetening agents had comparable solubilizing capacity. However, both sucralose- and acesulfame K-based ODFs have a more enhanced sweet and palatable taste than sorbitol-sweetened ODF. The SA- and PVP K30-based ODFs showed significantly faster disintegration times and release rates than MC. In conclusion, PVA has good film-forming properties, but a higher ratio of PVA adversely affected the disintegration and release characteristics. The % relative bioavailability for ODF was 126.5%, with a superior absorption rate constant (Ka) of 1.2-fold. The Cmax and estimated Tmax were compared to conventional film-coated tablets.

Polymeric long-acting drug delivery systems (LADDS) for treatment of chronic diseases: Inserts, patches, wafers, and implants.

Non-oral long-acting drug delivery systems (LADDS) encompass a range of technologies for precisely delivering drug molecules into target tissues either through the systemic circulation or via localized injections for treating chronic diseases like diabetes, cancer, and brain disorders as well as for age-related eye diseases. LADDS have been shown to prolong drug release from 24 h up to 3 years depending on characteristics of the drug and delivery system. LADDS can offer potentially safer, more effective, and patient friendly treatment options compared to more invasive modes of drug administration such as repeated injections or minor surgical intervention. Whilst there is no single technology or definition that can comprehensively embrace LADDS; for the purposes of this review, these systems include solid implants, inserts, transdermal patches, wafers and in situ forming delivery systems. This review covers common chronic illnesses, where candidate drugs have been incorporated into LADDS, examples of marketed long-acting pharmaceuticals, as well as newly emerging technologies, used in the fabrication of LADDS.

Design, characterization and in vivo evaluation of modified release baclofen floating coated beads.

Baclofen is a centrally acting skeletal muscle relaxant approved by the US Food and Drug Administration (FDA) for the treatment of muscle spasticity, but the immediate release mode of administration and rapid absorption has been associated with adverse effects. The main objective of this study was to prepare modified release floating beads of baclofen in order to decrease the unwanted side effects. The beads were prepared using alginate and coated with Eudragit RS100, Eudragit L100 and cetyl alcohol. They were evaluated for their encapsulation efficiency, buoyance characteristics, morphology, and in vitro release. They have also been tested in vivo for their oral bioavailability and potential side effects. The prepared beads showed floating properties up to 12 h with different lag times ranging from 45.67 to 72.33 sec. Morphological evaluation using scanning electron microscopy (SEM) revealed that the coated beads show smooth with no pores or cracks surfaces. Real-time morphology of the beads during in vitro release testing was studied by the SEM. Optimized formulation of baclofen coated beads exhibited favorable mechanical properties, in addition, it provided extended baclofen release for up to 6 h. In addition, in vivo studies showed that the coated beads effectively decreased the hypotensive side effect associated with rapid plasma peaking from Baclofen® immediate-release tablets. In addition, there were significant differences between the values of Cmax, Tmax, and AUC0-24 of optimized modified release baclofen floating formulations when compared to Baclofen® immediate-release tablets.

Formulation of controlled-release baclofen matrix tablets. II. Influence of some hydrophobic excipients on the release rate and in vitro evaluation.

The aim of this study was to investigate the influence of polymer level and type of some hydrophobic polymers, including hydrogenated castor oil (HCO); Eudragit RS100 (E-RS100); Eudragit L100 (E-L100), and some fillers namely mannitol [soluble filler], Dibasic calcium phosphate dihydrate (Emcompress) and anhydrous dibasic calcium phosphate [insoluble fillers] on the release rate and mechanism of baclofen from matrix tablets prepared by a hot-melt granulation process (wax tablets) and wet granulation process (E-RS100 and E-L100 tablets). Statistically significant differences were found among the drug release profile from different classes of polymeric matrices. Higher polymeric content (40%) in the matrix decreased the release rate of drug because of increased tortuosity and decreased porosity. At lower polymeric level (20%), the rate and extent of drug release was elevated. HCO was found to cause the strongest retardation of drug. On the other hand, replacement of Emcompress or anhydrous dibasic calcium phosphate for mannitol significantly retarded the release rate of baclofen, except for E-L100 (pH-dependent polymer). Emcompress surface alkalinity and in-situ increase in pH of the matrix microenvironment enhanced the dissolution and erosion of these matrix tablets. The release kinetics was found to be governed by the type and content of the excipients (polymer or filler). The prepared tablets showed no significant change in drug release rate when stored at ambient room conditions for 6 months.

Formulation of controlled-release baclofen matrix tablets: influence of some hydrophilic polymers on the release rate and in vitro evaluation.

This work aims at investigating different types and levels of hydrophilic matrixing agents, including methylcellulose (MC), sodium alginate (Alg), and sodium carboxymethylcellulose (CMC), in an attempt to formulate controlled-release matrix tablets containing 25 mg baclofen. The tablets were prepared by wet granulation. Prior to compression, the prepared granules were evaluated for flow and compression characteristics. In vitro, newly formulated controlled-release tablets were compared with standard commercial tablets (Lioresal and baclofen). The excipients used in this study did not alter physicochemical properties of the drug, as tested by the thermal analysis using differential scanning calorimetry. The flow and compression characteristics of the prepared granules significantly improved by virtue of granulation process. Also, the prepared matrix tablets showed good mechanical properties (hardness and friability). MC- and Alg-based tablet formulations showed high release-retarding efficiency, and good reproducibility and stability of the drug release profiles when stored for 6 months in ambient room conditions, suggesting that MC and Alg are good candidates for preparing modified-release baclofen tablet formulations.

Comparison of the effect of tromethamine and polyvinylpyrrolidone on dissolution properties and analgesic effect of nimesulide.

The solubilizing and absorption enhancer properties towards nimesulide (ND) of tromethamine (Tris) and polyvinylpyrrolidone (PVP) have been investigated. Solid binary systems were prepared at various drug-polymer ratios by mixing or coprecipitation, characterized by differential scanning calorimetry, X-ray diffractometry, and Fourier transform infrared spectroscopy, and tested for dissolution behavior. Both carriers improved drug dissolution and their performance depended on concentration of the hydrophilic carrier in coprecipitates. Tris was more effective than PVP, despite the amorphizing power of PVP as revealed by solid state analyses. Complete drug amorphiztion was attained at 1:3 (wt/wt) drug:PVP, 25% (wt/wt) ND in PVP. According to thermal behavior of ND and Tris, ND-Tris systems present a eutectic behavior. The eutectic composition was 30% ND-70% Tris at approximately 129 degrees C. Amorphous ND-PVP and eutectic ND-Tris mixtures showed an improvement of 5.55 and 6.6 times of drug dissolution efficiency, respectively. In vivo experiments in mice demonstrated that administration of 50 mg/kg of drug coprecipitated with PVP or Tris resulted, respectively, in a 50% and 94% reduction of acetic acid-induced writhings in comparison with pure drug, which, instead, was statistically ineffective as compared with the control group. Moreover, the eutectic mixture of ND-Tris demonstrated antiwrithing potency 1.88 times higher than amorphous ND-PVP coprecipitate. Thus, the solubilizing power, dissolution-enhancing effect, and analgesic effect enhancer ability toward the drug make Tris particularly suitable for developing a reduced-dose, fast-release solid oral dosage form of nimesulide.

Vitamin B12-Loaded Buccoadhesive Films as a Noninvasive Supplement in Vitamin B12 Deficiency: In Vitro Evaluation and In Vivo Comparative Study With Intramuscular Injection.

This study aimed to formulate and evaluate vitamin B12-loaded buccal mucoadhesive hydrogel films. Various film formulations were prepared using chitosan and polyvinyl alcohol. The prepared films were characterized for thickness, weight variation, drug content, percentage moisture uptake and moisture content, surface pH, mechanical properties, in vitro release, and mucoadhesion. Vitamin B12 bioavailability from the optimized formulation was studied on rabbits by the aid of enzyme-linked immunosorbent assay. Neuroton® I.M. injection was used for comparison. The films had acceptable mechanical and mucoadhesion properties. The percentages of moisture content of the optimized formulation were 3.2 ± 0.95, whereas the percentage drug released was 98.59 ± 1.41% at the end of 40 min. FTIR revealed the incidence of drug/polymer interaction. Differential scanning calorimetry revealed the possibility of the dispersion of cyanocobalamin in a molecular state with complete amorphization in the polymers. The estimated AUC0-8h showed 1.5-fold increases in the bioavailability of cyanocobalamin from the optimized formulation compared with the marketed I.M. injection. These findings warrant that vitamin B12 buccal film formulation can be considered as an effective alternative portal with noninvasive and more convenient characteristics compared with the I.M. injection dosage form.

Phytosome-hyaluronic acid systems for ocular delivery of L-carnosine.

This study reports on L-carnosine phytosomes as an alternative for the prodrug N-acetyl-L-carnosine as a novel delivery system to the lens. L-carnosine was loaded into lipid-based phytosomes and hyaluronic acid (HA)-dispersed phytosomes. L-carnosine-phospholipid complexes (PC) of different molar ratios, 1:1 and 1:2, were prepared by the solvent evaporation method. These complexes were characterized with thermal and spectral analyses. PC were dispersed in either phosphate buffered saline pH 7.4 or HA (0.1% w/v) in phosphate buffered saline to form phytosomes PC1:1, PC1:2, and PC1:2 HA, respectively. These phytosomal formulations were studied for size, zeta potential, morphology, contact angle, spreading coefficient, viscosity, ex vivo transcorneal permeation, and cytotoxicity using primary human corneal cells. L-carnosine-phospholipid formed a complex at a 1:2 molar ratio and phytosomes were in the size range of 380-450 nm, polydispersity index of 0.12-0.2. The viscosity of PC1:2 HA increased by 2.4 to 5-fold compared with HA solution and PC 1:2, respectively; significantly lower surface tension, contact angle, and greater spreading ability for phytosomes were also recorded. Ex vivo transcorneal permeation parameters showed significantly controlled corneal permeation of L-carnosine with the novel carrier systems without any significant impact on primary human corneal cell viability. Ex vivo porcine lenses incubated in high sugar media without and with L-carnosine showed concentration-dependent marked inhibition of lens brunescence indicative of the potential for delaying changes that underlie cataractogenesis that may be linked to diabetic processes.

Formulation and clinical evaluation of silymarin pluronic-lecithin organogels for treatment of atopic dermatitis.

Silymarin is a naturally occurring flavonoid drug; evidence from recent research has highlighted its use as a potential treatment for atopic dermatitis (AD). Both poor water solubility and drug permeability have hindered the percutaneous absorption of silymarin. Formulation of silymarin into pluronic-lecithin organogel (PLO) basis for topical skin delivery is the main aim of this work. Six different PLO formulations were prepared containing various pluronic to lecithin ratios using two cosolvent systems of ethyl alcohol and dimethyl sulfoxide. Formulation 2 (20% pluronic and 3% lecithin) was found to be the optimal base for topical delivery of silymarin as it showed optimum pH, viscosity, drug content, and satisfactory in vitro silymarin permeation. The silymarin PLO formulation significantly relieved inflammatory symptoms of AD such as redness, swelling, and inflammation. These findings warrant the ability for application of these novel silymarin PLO formulations as a novel treatment for AD.

Design and characterisation of a polyethylene oxide matrix with the potential use as a teat insert for prevention/treatment of bovine mastitis.

This manuscript reports (for the first time) on antibiotic-free polymeric inserts for the prevention and/or treatment of bovine mastitis. Polyethylene oxide (PEO)-based inserts were prepared using different concentrations of various hydrophilic polymers and water-soluble and water-insoluble drug-release-modifying excipients. A simple and scalable melt-extrusion method was employed to prepare the inserts. The prepared inserts were characterised for their dimension, rheological and mechanical properties. The in vitro release of a model bacteriostatic drug (salicylic acid) from the prepared inserts was studied to demonstrate the effectiveness and reproducibility of the melt-extrusion manufacturing method. Further, the in vitro stability of the inserts was evaluated using gel permeation chromatography (GPC) to monitor any change in molecular weight under real-time and accelerated storage conditions. The investigated inserts were stable at accelerated storage conditions over a period of 6 months. PEO inserts have the potential to serve a dual purpose, act as a physical barrier against pathogens invading the teat canal of cows and possibly control the release of a drug.

Recent advances in non-ionic surfactant vesicles (niosomes): self-assembly, fabrication, characterization, drug delivery applications and limitations.

Non-ionic surfactant vesicles, simply known as niosomes are synthetic vesicles with potential technological applications. Niosomes have the same potential advantages of phospholipid vesicles (liposomes) of being able to accommodate both water soluble and lipid soluble drug molecules control their release and as such serve as versatile drug delivery devices of numerous applications. Additionally, niosomes can be considered as more economically, chemically, and occasionally physically stable alternatives to liposomes. Niosomes can be fabricated using simple methods of preparations and from widely used surfactants in pharmaceutical technology. Many reports have discussed niosomes in terms of physicochemical properties and their applications as drug delivery systems. In this report, a brief and simplified summary of different theories of self-assembly will be given. Furthermore manufacturing methods, physical characterization techniques, bilayer membrane additives, unconventional niosomes (discomes, proniosomes, elastic and polyhedral niosomes), their recent applications as drug delivery systems, limitations and directions for future research will be discussed.

Eutectic, monotectic and immiscibility systems of nimesulide with water-soluble carriers: phase equilibria, solid-state characterisation and in-vivo/pharmacodynamic evaluation.

OBJECTIVES: The solid-state interactions of fused mixtures nimesulide (ND) with polyethylene glycol (PEG) 4000, urea or mannitol were studied through constructing thaw-melt phase equilibrium diagrams. METHODS: The solid-state characteristics were investigated using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Various types of interactions were identified such as the formation of a eutectic system of ND-PEG 4000, monotectic system of ND-urea and complete solid immiscibility of ND with mannitol. The effects of carrier concentrations on the equilibrium solubility and in-vitro dissolution characteristics were studied. KEY FINDINGS: Linear increases (R(2) > 0.99) in the aqueous solubility of ND in various concentrations of PEG 4000 and urea were obtained, whereas mannitol did not exhibit any effect on the solubility of ND. Similar trends were obtained with the dissolution efficiency of the fused mixtures of ND with PEG 4000 and urea compared with the corresponding physical mixtures and untreated drug. The analgesic effects of untreated ND and the selected formulations were investigated by evaluating the drug's ability to inhibit the acetic acid-induced writhing response. CONCLUSIONS: The analgesic effect of ND in a eutectic mixture with PEG 4000 and a monotectic mixture with urea was potentiated by 3.2 and 2.7-fold respectively compared with the untreated drug.