methylcellulose and vinyl-acetate

The objective of the present investigation was to design and evaluate a nerodilol-based transdermal therapeutic system (TTS) for finding its ability in providing the desired steady-state plasma concentration of nicorandil in human volunteers. The influence of EVA2825 membrane, adhesive-coated EVA2825 membrane and adhesive-coated EVA2825-rat skin composite on the in vitro permeation of nicorandil from a nerodilol-based HPMC gel drug reservoir was studied against a control (excised rat skin alone). The flux of nicorandil from the nerodilol-based HMPC drug reservoir across excised rat skin (control) was 384.0+/-4.6 microg/cm2 h and this decreased to 222.7+/-7.1 microg/cm2 h when studied across EVA2825 membrane indicating that EVA2825 membrane was effective as rate controlling membrane. The flux of the drug decreased to 183.8+/-5.7 microg/cm2 h on application of a water-based acrylic adhesive (TACKWHITE A 4MED) coat to EVA2825 membrane. However, the flux of nicorandil across adhesive-coated EVA2825-membrane-rat-skin composite was 164.8+/-1.8 microg/cm2 h, which was 1.74-times of the required flux that prompted for preparation of TTS. The nerodilol-based drug reservoir system was sandwiched between a composite of adhesive-coated EVA2825 membrane-release liner and a backing membrane. The resultant sandwich was heat-sealed to produce circle-shaped TTS (20 cm2) that were subjected to bioavailability study in human volunteers against immediate release nicorandil tablet. The nerodilol-based TTS provided a steady-state plasma concentration of 25.5 ng/ml for 24 h in human volunteers. It was concluded that the nerodilol-based TTS of nicorandil provided the desired plasma concentration of the drug for the predetermined period of time with minimal fluctuations.

Topics: Administration, Cutaneous; Adult; Animals; Anti-Arrhythmia Agents; Biological Availability; Cross-Over Studies; Drug Carriers; Gels; Humans; Hypromellose Derivatives; In Vitro Techniques; Male; Methylcellulose; Nicorandil; Polymers; Rats; Sesquiterpenes; Skin Absorption; Vasodilator Agents; Vinyl Compounds

The properties of adhesive mortars can change due to heating, compromising the durability of the coating systems. The aim of this article was to evaluate the influence of cement and polymer contents on the tensile bond strength of adhesive mortars after thermal storage. Ceramic tiling system specimens were prepared with seventeen formulations of adhesive mortars. These specimens were stored under dry (reference) at temperature of 23 ± 2 °C and 60 ± 5% of relative humidity and thermal (temperature of 70 ± 2 °C) conditions. The results showed that the cement content was the major factor concerning tensile bond strength. The vinyl acetate-ethylene (VAE) polymer improved the tensile bond strength of mortars under thermal storage. However, the hydroxypropyl methyl cellulose (HPMC) content contributed to the tensile bond strength only when higher cement contents were used. Besides, microstructure analysis showed that ettringite was degraded during thermal storage.

Topics: Adhesives; Methylcellulose; Polyethylenes; Polymers; Resin Cements; Surface Properties; Tensile Strength

The aim of this research was to study the interplay of solid and solution state phase transformations during the dissolution of ritonavir (RTV) amorphous solid dispersions (ASDs).. RTV ASDs with polyvinylpyrrolidone (PVP), polyvinylpyrrolidone vinyl acetate (PVPVA) and hydroxypropyl methylcellulose acetate succinate (HPMCAS) were prepared at 10-50% drug loading by solvent evaporation. The miscibility of RTV ASDs was studied before and after exposure to 97% relative humidity (RH). Non-sink dissolution studies were performed on fresh and moisture-exposed ASDs. RTV and polymer release were monitored using ultraviolet-visible spectroscopy. Techniques including fluorescence spectroscopy, confocal imaging, scanning electron microscopy (SEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC) and nanoparticle tracking analysis (NTA) were utilized to monitor solid and the solution state phase transformations.. All RTV-PVP and RTV-PVPVA ASDs underwent moisture-induced amorphous-amorphous phase separation (AAPS) on high RH storage whereas RTV-HPMCAS ASDs remained miscible. Non-sink dissolution of PVP- and PVPVA-based ASDs at low drug loadings led to rapid RTV and polymer release resulting in concentrations in excess of amorphous solubility, liquid-liquid phase separation (LLPS) and amorphous nanodroplet formation. High drug loading PVP- and PVPVA-based ASDs did not exhibit LLPS upon dissolution as a consequence of extensive AAPS in the hydrated ASD matrix. All RTV-HPMCAS ASDs led to LLPS upon dissolution.. RTV ASD dissolution is governed by a competition between the dissolution rate and the rate of phase separation in the hydrated ASD matrix. LLPS was observed for ASDs where the drug release was polymer controlled and only ASDs that remained miscible during the initial phase of dissolution led to LLPS. Techniques such as fluorescence spectroscopy, confocal imaging and SEM were useful in understanding the phase behavior of ASDs upon hydration and dissolution and were helpful in elucidating the mechanism of generation of amorphous nanodroplets.

Topics: Crystallization; Cytochrome P-450 CYP3A Inhibitors; Delayed-Action Preparations; Drug Liberation; Excipients; HIV Protease Inhibitors; Humidity; Methylcellulose; Phase Transition; Povidone; Ritonavir; Solubility; Vinyl Compounds

Polymers for aqueous film coating, such as hydroxypropyl methylcellulose (HPMC), often require the inclusion of a plasticizer to reduce brittleness and increase flexibility and ductility. A vinyl pyrrolidone/vinyl acetate copolymer (S630) was investigated for its influence on HPMC film coating parameters, comparing the results with a commonly used plasticizer, polyethylene glycol and another copolymer, polyvinyl alcohol. The viscous properties of the solutions and the glass transition temperatures of the equivalent polymer films were evaluated. Its effect on the film properties, such as appearance, surface roughness, moisture permeation and mechanical properties, as well as its ability to promote better adhesion of the film coat to the core surface, was compared. S630 was able to reduce the viscosity of the polymer solution and glass transition temperature of HPMC, as well as, enhance the mechanical properties of the cast film. The moisture permeation was slightly reduced but not to the same extent as polyethylene glycol. A 10% concentration of S630 increased the adhesive strength and toughness of the HPMC film coat. In conclusion, S630 was effective as a film-former, substrate adhesive and plasticizer. It has the potential to be used to replace the more volatile plasticizers which have problems of loss or migration.

Topics: Adhesives; Humidity; Hypromellose Derivatives; Methylcellulose; Permeability; Pyrrolidinones; Vinyl Compounds