Effect of a Surfactant on Absorption of AM Antibiotic from Non-Aqueous Parenteral Suspensions

Abstract

Attempts to modify the absorption of a monocyclic beta-lactam antibiotic from an oily suspension formulation were made by incorporation of the non-ionic surfactant sorbitan trioleate. Time to serum peak concentration was increased with increased level of surfactant and there anpeared to be more efficient clearance of the antibiotic from the depot with increase in level of surfactant in the formulation. The second effect may be explained in terms of the physical characteristics of the formulations whereas the alteration in time to serum peak concentrations may be due to an effect of the surfactant on transport of drug throuah tissue.     

Aspirin Degradation in Mixed Polar Solvents

Abstract

Degradation studies were conducted on 0.2% w/v aspirin liquid formulation in a wide range of water-propylene glycol mixtures and water-triethylene glycol diacetate mixtures at four temperatures. The effect of a surfactant, polyoxyethylene (20) sorbitan monolaurate, on aspirin stability was also investigated. There was a linear relationship between water content and degradation rate constants. The surfactant increased aspirin degradation in all formulations. Formulations containing the higher concentration of the surfactant showed the greater aspirin decomposition.     

Characterizing colloidal structures of pseudoternary phase diagrams formed by oil/water/amphiphile systems

Two pseudoternary phase diagrams were constructed using ethyl oleate, water, and a surfactant blend containing poly (oxyethylene 20) sorbitan monooleate and sorbitan monolaurate with or without the cosurfactant 1-butanol. Two colloidal regions were identified in the cosurfactant-free phase diagram; a microemulsion (ME) and a region containing lamellar liquid crystals (LC). The addition of 1-butanol increased the area in which systems formed microemulsions and eliminated the formation of any liquid crystalline phases. Samples that form the colloidal regions of both systems were investigated by freeze-fracture transmission electron microscopy and by viscosity and conductivity measurements. The three techniques were compared and evaluated as characterisation tools for such colloidal systems and also to identify transitions between the colloidal systems formed. A droplet ME was present at a low water volume fraction (phi w) in both systems (phi w < 0.15) as revealed by electron microscopy. At higher phi w values, LC structures were observed in micrographs of samples taken from the cosurfactant-free system while the structure of samples from the cosurfactant-containing system was that of a bicontinuous ME. The viscosity of both systems increased with increasing phi w to 0.15 and flow was Newtonian. However, formation of LC in the cosurfactant-free system resulted in a dramatic increase in viscosity that was dependent on phi w and a change to pseudoplastic flow. In contrast, the viscosity of the bicontinuous ME was independent of phi w. Three different methods were used to estimate the percolation threshold from the conductivity data for the cosurfactant-containing system. The use of nonlinear curve fitting was found to be most useful yielding a value close to 0.15 for the phi w.     

Microencapsulation of Sulfadiazine with Cellulose Acetate Pethalate

Abstract

Microencapsulation of a relatively insoluble drug sulfadiazine was carried out by allowing drops of' a suspension of the drug in an aqueous cellulose acetate phthalate solution to fall into an acetic acid hardening solution. Spherical microcapsules could readily be obtained when a surfactant polyoxyethylene 20 sorbitan monooleate was added to the suspensior. Increased drug concentration in the suspension yielded larger microcapsules with shorter disintegration times. The incorporation of viscosity agents into the suspension yielded microcapsules with altered disintegration times     

Characterizing Colloidal Structures of Pseudoternary Phase Diagrams Formed by Oil/Water/Amphiphile Systems

Two pseudoternary phase diagrams were constructed using ethyl oleate, water, and a surfactant blend containing poly (oxyethylene 20) sorbitan monooleate and sorbitan monolaurate with or without the cosurfactant 1-butanol. Two colloidal regions were identified in the cosurfactant-free phase diagram; a microemulsion (ME) and a region containing lamellar liquid crystals (LC). The addition of 1-butanol increased the area in which systems formed microemulsions and eliminated the formation of any liquid crystalline phases. Samples that form the colloidal regions of both systems were investigated by freeze-fracture transmission electron microscopy and by viscosity and conductivity measurements. The three techniques were compared and evaluated as characterisation tools for such colloidal systems and also to identify transitions between the colloidal systems formed. A droplet ME was present at a low water volume fraction (?_w) in both systems (?_w <0.15) as revealed by electron microscopy. At higher ?_w values, LC structures were observed in micrographs of samples taken from the cosurfactant-free system while the structure of samples from the cosurfactant-containing system was that of a bicontinuous ME. The viscosity of both systems increased with increasing ?_w to 0.15 and flow was Newtonian. However, formation of LC in the cosurfactant-free system resulted in a dramatic increase in viscosity that was dependent on ?_w and a change to pseudoplastic flow. In contrast, the viscosity of the bicontinuous ME was independent of ?_w. Three different methods were used to estimate the percolation threshold from the conductivity data for the cosurfactant-containing system. The use of nonlinear curve fitting was found to be most useful yielding a value close to 0.15 for the ?_w.     

Aspirin Degradation in Mixed Polar Solvents

Degradation studies were conducted on 0.2% w/v aspirin liquid formulation in a wide range of water-propylene glycol mixtures and water-triethylene glycol diacetate mixtures at four temperatures. The effect of a surfactant, polyoxyethylene (20) sorbitan monolaurate, on aspirin stability was also investigated. There was a linear relationship between water content and degradation rate constants. The surfactant increased aspirin degradation in all formulations. Formulations containing the higher concentration of the surfactant showed the greater aspirin decomposition.     

Preparation of Polymeric Microcapsules: Formulation Studies

Air-filled microcapsules were prepared by freeze-drying different oil-in-water emulsions containing biodegradable polyester as the wall-forming material. The aim of this work was to find an acceptable formulation with respect to the microcapsule suspension and the stability of the emulsion during the production process. The influence of various formulation parameters (concentrations of mannitol, polymer, and surfactant; pH; oil-in-water phase ratio) was investigated in a factorial design. The results were treated by ordinary least-square (OLS) regression and partial least-square regression (PLSR). In a previous work, air-filled microcapsules were successfully made using human serum albumin as the surfactant in the emulsion . In the present work, a new block copolymer based on poly(ethylene glycol) (PEG) was implemented as the surfactant to replace human serum albumin. It was found that the new block copolymer is a suitable replacement for human serum albumin. The concentration of the polymer in water and the concentration of the surfactant in the oil phase and the interaction between these variables had a significant influence on the stability of the emulsion at 60°C. A surfactant concentration of approximately 2% (w/v) in water was necessary when the concentration of the wall-forming polymer was below 5% (w/v) in (-)-camphene. The concentration of the polymer in the oil phase influenced the yield, measured as the volume concentration of particles in suspension per milligram of polymer added and as acoustic effect per milligram of polymer. Low levels of polymer concentration in (-)-camphene (<5% w/v) gave the highest yield. Excess polymer in the oil phase did not form microcapsules, but precipitated in the suspension or was included in the wall of the microcapsules. Addition of mannitol protected the microcapsules from being destroyed during freeze-drying and resulted in freeze-dried products with few cracks, little shrinkage, and higher suspension yield.     

Preparation of polymeric microcapsules: formulation studies

Air-filled microcapsules were prepared by freeze-drying different oil-in-water emulsions containing biodegradable polyester as the wall-forming material. The aim of this work was to find an acceptable formulation with respect to the microcapsule suspension and the stability of the emulsion during the production process. The influence of various formulation parameters (concentrations of mannitol, polymer, and surfactant; pH; oil-in-water phase ratio) was investigated in a factorial design. The results were treated by ordinary least-square (OLS) regression and partial least-square regression (PLSR). In a previous work, air-filled microcapsules were successfully made using human serum albumin as the surfactant in the emulsion (1). In the present work, a new block copolymer based on poly(ethylene glycol) (PEG) was implemented as the surfactant to replace human serum albumin. It was found that the new block copolymer is a suitable replacement for human serum albumin. The concentration of the polymer in water and the concentration of the surfactant in the oil phase and the interaction between these variables had a significant influence on the stability of the emulsion at 60 degrees C. A surfactant concentration of approximately 2% (w/v) in water was necessary when the concentration of the wall-forming polymer was below 5% (w/v) in (-)-camphene. The concentration of the polymer in the oil phase influenced the yield, measured as the volume concentration of particles in suspension per milligram of polymer added and as acoustic effect per milligram of polymer. Low levels of polymer concentration in (-)-camphene (< 5% w/v) gave the highest yield. Excess polymer in the oil phase did not form microcapsules, but precipitated in the suspension or was included in the wall of the microcapsules. Addition of mannitol protected the microcapsules from being destroyed during freeze-drying and resulted in freeze-dried products with few cracks, little shrinkage, and higher suspension yield.     

Preformulation studies on Freund's incomplete adjuvant emulsion

Freund's Incomplete Adjuvant (FIA), which is used in vaccine therapy, is a water-in-oil emulsion delivery system consisting of an aqueous internal phase containing an antigenic protein dispersed in an external phase containing a mixture of mannide monooleate and light mineral oil. Preformulation studies are reported in this investigation for FIA emulsion. The preformulation studies included the determination of the critical micelle concentration (CMC) of the formulations investigated, the surface activity of mannide monooleate at the interface between the oil phase and the aqueous phase containing ovalbumin as the model antigenic protein, and the effect of ovalbumin on the surface activity at the interface. The influence of the concentration of mannide monooleate and/or ovalbumin on the interfacial tension between light mineral oil and either purified water or 0.9% w/v normal saline solution was measured by the DuNouy Ring Method at 25 degrees C. The CMC was determined experimentally from the relationship between the concentration of the surface active agent in each formulation and the interfacial tension. The number of moles of the surface active agent per unit area at the interface (surface excess concentration) was calculated from the Gibbs' Adsorption equation. The results indicated that mannide monooleate was an effective surface active agent since the formulation containing only mannide monooleate provided the lowest magnitude of CMC. The presence of the surface active agent, mannide monooleate and/or ovalbumin, in the formulations studied reduced the interfacial tension between the two phases. The surface activity was influenced by the presence of an electrolyte (sodium chloride), a protein (ovalbumin), or mannide monooleate in the formulation. The presence of antigenic proteins in the aqueous phase of a waterin-oil emulsion influenced the effectiveness of a surface active agent in the formulation.     

Selection of microemulsion composition via study of phase behavior for synthesis of stable monodisperse platinum nanoparticles and optimization of experimental parameters

ABSTRACT

Monodisperse platinum nanoparticles were synthesized by microemulsion technique. Feasibility of formation of microemulsion with chosen proportions of components is a common problem with this method. Here, prior to preparation of microemulsion for synthesis purpose, systematic study was carried to check the suitability of selected microemulsion system by establishing phase diagram for ternary system at constant temperature on triangular coordinates. Temperature dependency of microemulsion was studied by preparing phase diagram of temperature against mass fraction of aqueous phase in ternary mixture. Both these triangular coordinate diagram at constant temperature and temperature dependency plots helped to choose proper concentrations of components in the system. Effects of molar concentration of water-to-surfactant ratio, platinum salt concentration, continuous oil phase concentration, and presence of cosurfactant with surfactant on particle size were investigated for selected system of components. Synthesized platinum nanoparticles were characterized by dynamic light scattering and transmission electron microscope. Light backscattering profiles obtained by Turbiscan were used to judge the stability of microemulsions. Further, partial weightage of affecting parameters on size of synthesized particle were studied by Taguchi orthogonal array method.     

Emulsion-based synthesis of NaA zeolite nanocrystals and its integration towards NaA membranes

NaA zeolite nanoparticles (seed crystals) of size 50–65 nm were synthesized using water-in-oil (w/o) type emulsions at a considerably low temperature of 65 ± 1°C in a short duration of 2 h. The emulsions were stabilized using non-ionic surfactants e.g. sorbitan monooleate (Span 80), sorbitan monolaurate (Span 20), polyoxyethylene(5)nonylphenylether with ethoxy numbers of 5 (Igepal CO-520) and polyoxyethylene sorbitan monooleate (Tween 80) of hydrophilic-lipophilic balance (HLB) values of 4.3, 8.6, 10 and 15 respectively. Among the surfactants, the intermediate HLB values of 8.6 (Span 20) and 10 (Igepal CO-520) were effective in synthesizing highly dispersible NaA nanoparticles of size 50–65 nm. The membrane prepared hydrothermally in multi-steps at 65 ± 1°C, using the Span 20-derived seed crystals deposited on porous support, showed the formation of high quality interlocked NaA coating. Single gas nitrogen (N₂) permeation of the membrane exhibited a permeance value of 1.01 × 10⁻⁸ mol m⁻² s⁻¹ Pa⁻¹ at ambient temperature (30°C).     

Effect of the addition of oxybenzone or octyl-methoxycinnamate on particle size of submicron emulsions

The formulation of sunscreen products requires understanding of the solubilization of these products in different vehicles to obtain aesthetic preparations and to evaluate long-term stability. For this study, two different ultraviolet (UV) filters were selected: oxybenzone (powder) and octyl-methoxycinnamate (liquid). First, the solubility of these UV filters was tested using a three-component simplex-centroid design strategy. The mixtures were prepared with three oily phases used in this field of cosmetics: liquid paraffin, isopropyl myristate, and coconut oil. A phase diagram method was used to carry out a systematic study of submicron oil-in-water emulsions. Phase diagrams were produced by diluting fixed binary mixtures with water. The surfactant consisted of polyoxyethylene-20-sorbitan monostearate/sorbitan monostearate (50/50, w/w). The oily phase contained equal quantities of each oil studied. From this water/surfactant/oil ternary system, we selected two reference emulsions with receptively 75/5/20 and 68/7/25 proportions. Photon correlation spectroscopy (PCS) was used to investigate the influence of these two UV filters at several concentrations on droplet size and distribution of the oil droplets in the material. All emulsions were stored and checked every month for 6 months.     

Effect of the Addition of Oxybenzone or Octyl-Methoxycinnamate on Particle Size of Submicron Emulsions

The formulation of sunscreen products requires understanding of the solubilization of these products in different vehicles to obtain aesthetic preparations and to evaluate long-term stability. For this study, two different ultraviolet (UV) filters were selected: oxybenzone (powder) and octyl-methoxycinnamate (liquid). First, the solubility of these UV filters was tested using a three-component simplex-centroid design strategy. The mixtures were prepared with three oily phases used in this field of cosmetics: liquid paraffin, isopropyl myristate, and coconut oil. A phase diagram method was used to carry out a systematic study of submicron oil-in-water emulsions. Phase diagrams were produced by diluting fixed binary mixtures with water. The surfactant consisted of polyoxyethylene-20-sorbitan monostearate/sorbitan monostearate (50/50, w/w). The oily phase contained equal quantities of each oil studied. From this water/surfactant/oil ternary system, we selected two reference emulsions with receptively 75/5/20 and 68/7/25 proportions. Photon correlation spectroscopy (PCS) was used to investigate the influence of these two UV filters at several concentrations on droplet size and distribution of the oil droplets in the material. All emulsions were stored and checked every month for 6 months.     

Synthesis of nanocrystalline photocatalytic TiO2 thin films and particles using sol–gel method modified with nonionic surfactants

A simple sol–gel route has been developed for the preparation of nanocrystalline photocatalytic TiO₂ thin films and particles at 500 °C. The synthesis involved a novel chemistry method employing nonionic surfactant molecules as a pore directing agent along with acetic acid-based sol–gel route without direct addition of water molecules. This study investigated the effect of surfactant type and concentration on the homogeneity, morphology, light absorption, dye adsorption and degradation, and hydrophilicity of TiO₂ films as well as on the structural properties of the corresponding TiO₂ particles. The method resulted in the synthesis of mesoporous TiO₂ material with enhanced structural and catalytic properties including high surface area, large pore volume, pore size controllability, small crystallite size, enhanced crystallinity, and active anatase crystal phase. The prepared TiO₂ thin films were super-hydrophilic and possessed thermally stable spherical bicontinuous mesopore structure with highly interconnected network. Highly porous TiO₂ films prepared with polyethylene glycol sorbitan monooleate surfactant exhibited four times higher photocatalytic activity for the decoloration of methylene blue dye than the nonporous control TiO₂ films prepared without the surfactant. This sol–gel method modified with surfactant templates is useful in the preparation of nanostructured anatase TiO₂ thin films with high photocatalytic activity and desired pore structure.     

In situ investigation of surfactants’ effect onto electrochemical synthesis and properties of polyfurans

Polyfuran (PFu) films were electrochemically deposited onto gold electro-quartz crystal microbalance (EQCM) electrodes using acetonitrile (ACN)/LiClO₄ solvent-electrolyte in presence of dodecylbenzenesulfonic acid (anionic, DBSA) and polyethylene glycol sorbitan monolaurate (non-ionic, Tween 20) surfactants. The effect of surfactants on structural and conductivity properties of the polymer films was investigated using Fourier transform-infrared spectroscopy (FT-IR) and four-probe conductivity measurements. The doping effects of surfactants onto the properties of PFu were correlated with mass gain using in situ EQCM. The conductivity of PFu polymer was measured for PFu with no surfactant and for PFu in presence of two surfactants (Tween 20 and DBSA). Our data indicate that although a fast polymerization, a sharp shift in the frequency and mass changes of the polymer films as well as the highest recorded conductivity of 0.048 S cm^?1 were all obtained for the PFu/Tween 20-2 sample, significantly more PFu films formed with PFu/DBSA than with PFu/Tween 20 samples. We concluded that more PFu films can be obtained when an oxidant and an anionic surfactant (DBSA) are used than when an oxidant is used alone, or when an oxidant is used with a non-ionic surfactant (Tween 20). A part of an anionic surfactant can be incorporated into a PFu structure like an oxidant anion and can act as co-dopant.     

复合表面活性剂对油包水型高内相乳状液流变性和稳定性的影响

为了研究复合表面活性剂对油包水型高内相乳状液流变性和稳定性的影响,选用由PIBSA-TEA和油酸二乙醇酰胺、椰子油酸二乙醇酰胺、失水山梨醇单油酸酯等小分子表面活性剂组成的复合表面活性剂制备HCEs,并检测所制得HCEs的流变性和储存稳定性。结果表明:表面活性剂对HCEs的剪切应力和储能模量有较大的影响。采用复合表面活性剂制备的HCEs具有较高的剪切应力和储能模量。但是,复合表面活性剂制备的HCEs储存稳定性明显下降。在油相黏度比较高时,复合表面活性剂制备的HCEs储存稳定性有一定的提高。     

Microencapsulation of Sulfadiazine with Cellulose Acetate Pethalate

Microencapsulation of a relatively insoluble drug sulfadiazine was carried out by allowing drops of' a suspension of the drug in an aqueous cellulose acetate phthalate solution to fall into an acetic acid hardening solution. Spherical microcapsules could readily be obtained when a surfactant polyoxyethylene 20 sorbitan monooleate was added to the suspensior. Increased drug concentration in the suspension yielded larger microcapsules with shorter disintegration times. The incorporation of viscosity agents into the suspension yielded microcapsules with altered disintegration times     

Formulation optimization and pharmacokinetics evaluation of oral self-microemulsifying drug delivery system for poorly water soluble drug cinacalcet and no food effect

The present research indicated that a new self-microemulsifying drug delivery systems (SMEDDS) were used to reduce the food effect of poorly water-soluble drug cinacalcet and enhance the bioavailability in beagle dogs by oral gavage. Ethyl oleate, OP-10, and PEG-200 was selected as the oil phase, surfactant and co-surfactant of cinacalcet-SMEDDS by the solubility and phase diagram studies. Central Composite Design-Response Surface Methodology was used to determine the ratio of surfactant and co-surfactant, the amount of oil for optimizing the SMEDDS formation. The prepared formulations were further characterized by the droplet size, self-microemulsifying time, zeta potential, polydispersity index (PDI), and robustness to dilution. The in vitro release profile of cinacalcet-SMEDDS was determined in four different release medium and in fasted state and fed state of simulated gastrointestinal fluid. Cinaclcet-SMEDDS were implemented under fed and fasted state in dogs and product REGPARA^® was used as a comparison to the prepared formulation in the pharmacokinetics. The result showed the components of SMEDDS, the amount of oil, the ratio of surfactant, and co-surfactant was optimized using solubility, pseudo-ternary phase diagram studies, and response surface methodology. In vitro drug release studies indicated that the cinacalcet-SMEDDS eliminated the effect of pH variability in release medium and variational gastroenteric environments with improved drug release performance. Pharmacokinetic studies revealed that the profiles of cinacalcet-SMEDDS were similar both in the fasted and fed state compared with commercial product, indicating the formulation significantly promoted the absorption, enhanced bioavailability and had no food effect essentially. It is concluded that poorly water-soluble drug cinacalcet was improved in the solubility and bioavailability by using a successful oral dosage form the SMEDDS, and eliminated food effect as well.     

Development of an Emulsion-Solvent Evaporation Technique for Microencapsulation of Drus-Resin complexes

Abstract

Chlorpheniramine maleate was complexed with a carboxylic acid cation-exchange resin and the complexes were microencapsulated with polymethyl methacrylate using an emulsion-solvent evaporation technique. Microcapsules of larger mean diameters resulted from polymer solutions of increased viscosities. Addition of 3% finely divided solids to the encapsulation vehicle resulted in smaller microcapsules, whereas a 6% concentration had the opposite effect, an increased capsule mean diameter. Emulsion stabilizers, such as magnesium stearate, up to a 1% concentration reduced microcapsule size by as much as 50%. The process efficiency ranged from 73% to 99%, depending on the formulation and manufacturing conditions used. The rate of drug release from the microcapsules was directly related to the amount of polymer deposited and inversely proportional to the capsule size.