Dissolution and Solubility Behavior of Fenofibrate in Sodium Lauryl Sulfate Solutions

The solubility of fenofibrate in pH 6.8 McIlvaine buffers containing varying concentrations of sodium lauryl sulfate was determined. The dissolution behavior of fenofibrate was also examined in the same solutions with rotating disk experiments. It was observed that the enhancement in intrinsic dissolution rate was approximately 500-fold and the enhancement in solubility was approximately 2000-fold in a pH 6.8 buffer containing 2% (w/v) sodium lauryl sulfate compared to that in buffer alone. The micellar solubilization equilibrium coefficient (k*) was estimated from the solubility data and found to be 30884 ± 213 L/mol. The diffusivity for the free solute, 7.15 × 10^{? 6} cm²/s, was calculated using Schroeder's additive molal volume estimates and Hayduk-Laurie correlation. The diffusivity of the drug-loaded micelle, estimated from the experimental solubility and dissolution data and the calculated value for free solute diffusivity, was 0.86 × 10^{? 6} cm²/s. Thus, the much lower enhancement in dissolution of fenofibrate compared to its enhancement in solubility in surfactant solutions appears to be consistent with the contribution to the total transport due to enhanced micellar solubilization as well as a large decrease ( ～ 8-fold) in the diffusivity of the drug-loaded micelle.     

Effect of melt sonocrystallization on pharmacotechnical properties of paracetamol,indomethacin and mefenamic acid characterized by dynamic laser scattering and its impact on solubility

The purpose of the research was to employ a novel particle engineering technique-melt sonocrystallization (MSC) for some nonsteroidal anti-inflammatory drugs for development of more soluble forms of the drugs without the use of excipients. The original forms of Paracetamol (OFPCM), Indomethacin (OFIMC) and Mefenamic acid (OFMA) were subjected to MSC to improve physicochemical properties. MSC forms of PCM, IMC and MA were subjected to dynamic laser scattering for particle size analysis to quantize mean particle size, specific surface area, interquartile coefficient of skewness, kurtosis and span. Rheological and solubility analysis, X-ray powder diffraction and scanning electron microscopy were conducted for validating the effect of MSC on powder particles. On melt sonocrystallized form of drug powders exhibited improved micromeritic properties, the mean particle size was reduced while the specific surface area increased effectively. Frequency distribution curves showed reduction in asymmetry and skewness that was confirmed by interquartile coefficient of skewness values. Equilibrium solubility of MSC form of PCM, IMC and MA was higher than the original forms. Similarly the intrinsic dissolution rate was approximately 1.5 times higher in comparison to original form of drugs. X-ray powder diffraction shows decreased relative intensities of peaks of MSC forms due to reduction in the crystallinity that was confirmed by visualization of MSC particles by scanning electron microscopy. Conclusively, MSC is a promising cost-effective technique that may afford powder with improved flow and formulative properties as well as improved solubility and dissolution.     

Powdered self-emulsified lipid formulations of meloxicam as solid dosage forms for oral administration

The objectives of this study were to prepare a powdered self-emulsified (SEDDS) formulation of meloxicam and to compare its oral bioavailability against commercial Mobic^® tablets. The SEDDS formulation was prepared by in situ salt formation of meloxicam in a blend of lipid excipients and aqueous tris (hydroxymethyl) aminomethane solution. The liquid SEDDS was subsequently adsorbed on silica powder and was tested for size, flow, and crystal growth. The flowability index of the powdered SEDDS was borderline acceptable. Absence of crystal growth with storage was confirmed by DSC and PXRD studies. Dissolution of meloxicam from the powdered SEDDS was >90% vs. <12% for powdered meloxicam and <80% for the commercial tablets. Stability of the powdered formulations after storage in gelatin and HPMC capsules was also evaluated to study the effect of water migration from the fill into capsule shells. Capsules softened to a different extent as a function of fill material with HPMC capsules showing greater resistance to water migration. Finally, oral bioavailability of the formulations was evaluated in beagle dogs. Powdered meloxicam SEDDS formulation showed a 1.3-fold increase in AUC vs. commercial Mobic^® tablets. Overall, this study described a novel SEDDS formulation of meloxicam and outlined a systematic approach to adsorbing and testing the flow and stability behavior of powdered SEDDS formulations.     

Dissolution rate enhancement of the anti-inflammatory drug diflunisal by coprecipitation with a biocompatible polymer using carbon dioxide as a supercritical fluid antisolvent

Dissolution rate enhancement of the anti-inflammatory drug diflunisal was achieved using for the first time a supercritical fluid technology. The supercritical fluid antisolvent (SAS) method was applied to precipitate diflunisal alone and to coprecipitate the drug together with the biocompatible polymer polyvinylpyrrolidone (PVP K-30 and K-10). The untreated and SAS processed diflunisal, and the coprecipitates were characterized in terms of size, morphology, crystallinity, compositions, drug-polymer interactions, and drug release. SAS processed diflunisal exhibited a polymorphic form different from that of the untreated drug. Diflunisal crystallinity disappeared in the coprecipitates. Three different drug: polymer mass ratios were studied: 75:25, 50:50, and 25:75. Microparticle size decreased and aggregation disappeared as the relative amount of polymer increased. The 25:75 coprecipitate consisted of loose spherical particles exhibiting mean particle size of 410 nm while the 75:25 coprecipitate consisted of bigger aggregated particles. The SAS method was shown to be a suitable technology to form solid dispersions of a poorly soluble drug.     

Acrylic Resins as Rate-Controlling Membranes in Novel Formulation of a Nine-Day 17β-Estradiol Transdermal Delivery System: In Vitro and Release Modifier Effect Evaluation

The feasibility of transdermal controlled delivery system of 17 β-estradiol was investigated by conducting in vitro release studies. Several new 17 β-estradiol unilaminate adhesive devices capable of releasing 17 β-estradiol in a controlled fashion over a 24-h, 36-h, 96-h, 104-h, 168-h, and 216-h period have been developed using acrylic resins (Eudragits E100, RSPO, and RLPO) as adhesive and rate-controlling polymers. The in vitro release profiles of 17 β-estradiol from various TDS unilaminate devices were characterized in a new developed dissolution tester vessel (total volume 200 ml), using a new paddle. The release of drug from different formulations was measured by a sensitive high-performance liquid chromatographic (HPLC) method. The release of drug from all prepared adhesive devices seems to obey zero-order kinetics (r > 0.98). The effect of two different plasticizers (acetyltributyl citrate [ATBC] and triethyl citrate [TEC]) on the release patterns of 17 β-estradiol from TDS formulations was studied, and they were almost identical. The effect of two different release modifiers, propylene glycol (PG) and myristic acid (MA), on the release pattern of 17 β-estradiol from prepared unilaminate devices was evaluated. It was shown that the use of these release modifiers significantly increased the release of 17 β-estradiol from a TDS unilaminate patch. Furthermore, these data clearly demonstrated that the acrylic resins are suitable polymers for the preparation of 17 β-estradiol TDS adhesive devices.     

A LIBRARY FOR DOING POLYHEDRAL OPERATIONS

Abstract

The design and implementation of a library of C-code procedures to perform operations on rational polyhedra is described. The library supports intersection, union, difference, simplification in context, convex hull, affine image, affine preimage, and computation of dual forms. Since not all of these functions are closed over polyhedra, the library is extended to operate on finite unions of polyhedra. The major design decisions made during the implementation of the library are discussed. The data structure used for representing finite unions of polyhedra is developed and validity rules for the representation of polyhedra are derived. And finally, the algorithms used to implement the various functions in the library are presented.     

Grey and black-box modelling based on neural networks and artificial immune systems applied to solid dissolution by rotating disc method

The dissolution rates of urea, sodium bicarbonate, and sodium carbonate in water and aqueous solutions were determined using the rotating disc technique. The experiments showed that the dissolution rate increases with increasing disc surface area, temperature, and rotating speed, while it decreases with the solute concentration increase in the dissolution medium. The comparison between experimental values for the dissolution rate and those calculated from Levich equation evidenced a satisfactory agreement in the case of the urea dissolution and poor compliance for the sodium bicarbonate and sodium carbonate dissolution. This poor results and the lack of a good model for making predictions in different situations determined the generation of empirical and semiempirical models (black and grey box approaches) which include neural networks developed with Clonal Selection algorithm (belonging to the Artificial Immune System class) and combination between neural network and phenomenological model. Satisfactory results were obtained with neural networks (black box models) and hybrid models (grey box models).     

Measurement of the amount and rate of methane dissolution in pure water and aqueous solution of SDS + multi-wall carbon nanotubes + β-cyclodextrin

In this paper, the impact of the mixture of sodium dodecyl sulfate (SDS) + multi-wall carbon nanotubes (MWCNTs) + β-cyclodextrin on the quantity and initial rate of methane dissolved in water is investigated. The experiments were performed at a temperature range of 278.15–303.15 K and an initial pressure of 0.5 MPa. The experimental results show that simultaneous utilization of β-cyclodextrin (0.01 mass fraction), MWCNTs (0.0005 mass fraction), and SDS (0.001 mass fraction) at 278.15 K increases the amount and the rate of methane dissolution in water by 29.90% and 173.78%, respectively, compared to pure water. An increase in the temperature decreases the quantity and the initial rate of methane dissolution in all solutions containing additives. However, no consistent relationship is observed between the temperature and the enhancement percentage of solubility of methane in solutions containing additives.