sodium-dodecyl-sulfate and tocophersolan

Andrographolide (ADG) is a diterpenoid isolated from

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Biological Transport; Caco-2 Cells; Diterpenes; Humans; Interleukin-1; Male; Mice; Nanoparticles; Nanotechnology; Nitric Oxide; Particle Size; Rats, Sprague-Dawley; Sodium Dodecyl Sulfate; Solubility; Superoxide Dismutase; Suspensions; Time Factors; Tumor Necrosis Factor-alpha; Vitamin E

The aim of this study was to assess the effect of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on the physicochemical characterization and oral bioavailability of a novel l-sulpiride-loaded quaternary microcapsule (QMC). The effect of carriers on drug solubility was investigated. Among the carriers tested, polyvinyl pyrrolidone (PVP), sodium lauryl sulphate (SLS) and TPGS were selected as polymer, surfactant and absorption enhancer, respectively, due to their high drug solubility. Using the solvent evaporation method, numerous QMCs with different ratios of l-sulpiride, PVP, SLS and TPGS were prepared, and their physicochemical properties, solubility and release were evaluated. In addition, the influence of TPGS concentration on the oral bioavailability of various drug doses was evaluated. All QMCs converted the crystalline drug to the amorphous form and remarkably improved the solubility, release and oral bioavailability of the drug. Furthermore, the TPGS concentration in the QMCs hardly affected the crystallinity, particle size and release, but considerably increased the solubility and oral bioavailability of the drug. In particular, as the dose of administered drug was increased, TPGS provided a greater improvement in oral drug bioavailability. Thus, TPGS played an important role in improving the oral bioavailability of l-sulpiride. Moreover, the QMC with a drug/PVP/SLS/TPGS weight ratio of 5:12:1 :20 with approximately 3.3-fold improved oral bioavailability would be recommended as a commercial pharmaceutical product for oral administration of l-sulpiride.

Topics: Administration, Oral; Animals; Biological Availability; Capsules; Drug Carriers; Drug Delivery Systems; Male; Polymers; Povidone; Rats; Rats, Sprague-Dawley; Sodium Dodecyl Sulfate; Solubility; Sulpiride; Surface-Active Agents; Tissue Distribution; Vitamin E

Curcumin, a natural polyphenol compound, has been widely reported for diverse pharmacological effects and already been investigated for eye diseases. However, the water-insolubility of curcumin and the inherent penetration barriers in cornea make it difficult for curcumin to enter eye. This work aimed to develop ion-sensitive curcumin-loaded Pluronic P123 (P123)/D-a-tocopheryl polyethylene glycolsuccinate (TPGS) mixed micelle in situ gels (CUR-MM-ISGs) to prolong ocular retention time and improve cornea permeability. Central composite design-response surface methodology was applied for the optimization of curcumin-loaded P123/TPGS mixed micelles (CUR-MMs). Characterization tests showed that CUR-MMs were in spherical shape with small size and low critical micelle concentration. After dispersing the micelles in gellan gum solution (0.2%, w/w) at the ratio of 3:1 and 1:1 (v/v), respectively, CUR-MM-ISGs were formed and presented transparent appearance. Sustained release profile was obtained in vitro for both CUR-MM-ISGs (3:1 or 1:1, v/v). The irritation test proved that CUR-MM-ISGs as ophthalmic formulations were gentle and biocompatible towards ocular tissues. In addition, the ex vivo corneal penetration study indicated that the cumulative drug permeation amount of CUR-MM-ISGs (3:1, v/v) was respectively 1.16-fold and 1.32-fold higher than CUR-MM-ISGs (1:1, v/v) and curcumin solution. It can be concluded from these results that the developed ion-sensitive mixed micelle in situ gel system is a potential ophthalmic delivery carrier for curcumin as a poorly soluble drug.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Transport; Cornea; Curcumin; Drug Carriers; Drug Liberation; Factor Analysis, Statistical; Hydrophobic and Hydrophilic Interactions; Inflammation; Irritants; Kinetics; Male; Micelles; Particle Size; Permeability; Poloxalene; Polyethylene Glycols; Polysaccharides, Bacterial; Rabbits; Sodium Dodecyl Sulfate; Solubility; Vitamin E; Water

The purpose of this study was to investigate the impact of surfactants on the rate of crystal growth of amorphous celecoxib, both in the presence and absence of a polymer. Celecoxib is a poorly water-soluble non-steroidal anti-inflammatory drug. Such compounds may be formulated as amorphous solid dispersions to improve bioavailability, and solid dispersions can contain both a surfactant and a polymer. While the impact of polymers on crystal growth rates has been studied, the effect of surfactants is largely unexplored. Herein, the effect of sodium lauryl sulfate (SLS), sucrose palmitate and d-α tocopherol polyethylenglycol 1000 succinate (TPGS) at a 10% (w/w) concentration on the crystal growth rate of celecoxib was investigated. Linear crystal growth rates as a function of temperature (70-120 °C) were measured using optical microscopy. The mixtures were characterized using differential scanning calorimetry (DSC), infrared spectroscopy, and X-ray diffraction. The results indicate that the surfactants increase the crystal growth rate of amorphous celecoxib. However, addition of polyvinyl pyrrolidone (PVP) helped to mitigate the increase in growth rates, although the ternary systems were highly complex. Thus it is clear that the impact of a surfactant on the physical stability of an amorphous solid dispersion should be considered during formulation.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Calorimetry, Differential Scanning; Celecoxib; Chemistry, Pharmaceutical; Crystallization; Drug Compounding; Drug Stability; Polyethylene Glycols; Polymers; Povidone; Pyrazoles; Sodium Dodecyl Sulfate; Solubility; Sucrose; Sulfonamides; Surface-Active Agents; Temperature; Vitamin E; X-Ray Diffraction

Curcumin, a naturally occuring polyphenolic phytoconstituent, is isolated from the rhizomes of Curcuma longa Linn. (Zingiberaceae). It is water insoluble under acidic or neutral conditions but dissolves in alkaline environment. In neutral or alkaline conditions, curcumin is highly unstable undergoing rapid hydrolytic degradation to feruloyl methane and ferulic acid. Thus, the use of curcumin is limited by its poor aqueous solubility in acidic or neutral conditions and instability in alkaline pH. In the present study, curcumin nanocrystals were prepared using high-pressure homogenization, to improve its solubility. Five different stabilizers [polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), sodium dodecyl sulfate (SDS), carboxymethylcellulose sodium salt] possessing different stabilization mechanism were investigated. The nanoparticles were characterized with regard to size, surface charge, shape and morphology, thermal property, and crystallinity. A short-term stability study was performed storing the differently stabilized nanoparticles at 4°C and room temperature. PVA, PVP, TPGS, and SDS successfully produced curcumin nanoparticle with the particle size in the range of 500-700 nm. PVA, PVP, and TPGS showed similar performance in preserving the curcumin nanosuspension stability. However, PVP is the most efficient polymer to stabilize curcumin nanoparticle. This study illustrates that the developed curcumin nanoparticle held great potential as a possible approach to improve the curcumin solubility then enhancing bioavailability.

Topics: Carboxymethylcellulose Sodium; Chemistry, Pharmaceutical; Coumaric Acids; Curcumin; Drug Stability; Excipients; Hydrogen-Ion Concentration; Hydrolysis; Methane; Nanoparticles; Nanotechnology; Particle Size; Polyethylene Glycols; Polyvinyl Alcohol; Povidone; Pressure; Sodium Dodecyl Sulfate; Solubility; Surface Properties; Technology, Pharmaceutical; Temperature; Vitamin E

Wet media milling by top down method has proved to be an effective method to prepare nanosuspension of poorly soluble drugs/APIs. Few or no attempts have been made so far to understand the feasibility of nanosuspension formulation in terms of the mechanism of stabilization as a function of drug properties. The objective of this study was to understand the effect of drug substance and stabilizer properties to form a successful nanosuspension product. From this study, logP and enthalpy were concluded to have a direct correlation on the feasibility of formation of a stable nanosuspension. The most likely candidate for media milling was a drug substance with a high enthalpy and hydrophobicity which can be stabilized either electrostatically or sterically. The least likely candidate will be one that is hydrophilic and having a very low enthalpy value. Also the choice of an ideal stabilizer/surfactant was found to be influenced by the degree of hydrophobicity of the drug itself. Finally the morphology of the starting drug was found to significantly affect the milling time required to produce submicron particles.

Topics: 1-Octanol; Dioctyl Sulfosuccinic Acid; Drug Compounding; Drug Stability; Hypromellose Derivatives; Methylcellulose; Molecular Weight; Nanoparticles; Naproxen; Pharmaceutical Preparations; Poloxamer; Polyethylene Glycols; Sodium Dodecyl Sulfate; Solubility; Surface-Active Agents; Suspensions; Transition Temperature; Vitamin E; Water

The influence of optical parameters, additional techniques (e.g. PIDS technology) and the importance of light microscopy were investigated by comparing laser diffraction data obtained via the conventional method and an optimized analysis method. Also the influence of a possible dissolution of nanocrystals during a measurement on the size result obtained was assessed in this study. The results reveal that dissolution occurs if unsaturated medium or microparticle saturated medium is used for the measurements. The dissolution is erratic and the results are not reproducible. Dissolution can be overcome by saturating the measuring medium prior to the measurement. If nanocrystals are analysed the dispersion medium should be saturated with the nanocrystals, because the solubility is higher than for coarse micro-sized drug material. The importance of using the optimized analysis method was proven by analysing 40 different nanosuspensions via the conventional versus the optimized sizing method. There was no large difference in the results obtained for the 40 nanosuspensions using the conventional method. This would have led to the conclusion, that all the 40 formulations investigated are physically stable. However, the analysis via the optimized method revealed that from 40 formulations investigated only four were physically stable. In conclusion an optimized analysis saves time and money and avoids misleading developments, because discrimination between "stable" and "unstable" can be done reliably at a very early stage of the development.

Topics: Chemistry Techniques, Analytical; Cyclosporine; Drug Stability; Excipients; Light; Microscopy; Nanoparticles; Particle Size; Poloxamer; Polyethylene Glycols; Polysorbates; Refractometry; Rutin; Scattering, Radiation; Scattering, Small Angle; Sodium Dodecyl Sulfate; Solubility; Temperature; Vitamin E

This study attempted to characterise the in-vitro release profiles of fenofibrate (FFB) from a self-microemulsifying drug-delivery system (SMEDDS) for optimising formulation factors and dissolution conditions for in-vivo absorption.. The study was conducted by profiling the release of FFB formulated with either a complete solution or a micronised dispersion system (MDS) in a SMEDDS composed of medium-chain triglyceride (MCT) oil and surfactant mixtures S(mix) of TPGS and Tweens at different ratios (K(m) =TPGS/Tweens), with and without adding water. Optimised FFB SMEDDS formulations were then selected for in-vivo bioavailability study.. The release rates of FFB from TPGS/Tween 20 systems were faster than those from TPGS/Tween 80 systems at the same K(m) value. In both systems, the release rates of FFB increased with a decrease in the K(m) value. Furthermore, both the release rates and the amounts of FFB from MDS in the water medium decreased with an increasing percentage of S(mix) added to both water contents. However, the release rates and amounts of FFB from MDSs increased with an increasing percentage of S(mix) in a 0.025 M sodium lauryl sulfate (SLS) solution. It was further illustrated that the release of FFB from SMEDDSs was complete within 30 min in both the 0.025 M SLS solution and water medium, but the release of FFB from Tricor® or MDSs was limited in water medium. An optimised FFB SMEDDS with either Tween 20(E5(20)) or Tween 80(E5(80)) and one MDS were selected for a pharmacokinetic study to compare with Tricor(®). The results demonstrated that the area under the receiver operating curve and C(max) values were in the order of Tricor(®) > E5(80)≅E5(20) > MDS and Tricor(®)≅E5(80) > E5(20) > MDS, respectively. Conclusions  The absorption of drug carried by SMEDDS might not be enhanced as a result of the smaller volume of water taken with oral administration of SMEDDSs and the agitation rate of the gastrointestinal tract not being strong enough to efficiently promote the self-microemulsification process to facilitate the in-vivo dissolution rate.

Topics: Biological Availability; Drug Delivery Systems; Emulsifying Agents; Excipients; Fenofibrate; Hypolipidemic Agents; Polyethylene Glycols; Polysorbates; Propylene Glycol; Sodium Dodecyl Sulfate; Solubility; Triglycerides; Viscosity; Vitamin E