Application of HPLC to assess the compatibility of bisoprolol fumarate with selected excipients in mixtures by isothermal stress testing.

In the present study, the compatibility between bisoprolol fumarate and selected excipients (ascorbic acid, citric acid anhydrous, butylated hydroxyanisole, polyvinylpyrrolidone, glycerol, mannitol and sorbitol) in mixtures (1:10 ratio of drug and excipient) was investigated by subjecting the samples to isothermal stress conditions (90 °C for 48 h). A new HPLC method was developed, validated and employed for determining the drug content of the stressed compatibility samples. Results of HPLC revealed that major degradation of bisoprolol fumarate was observed with butylated hydroxyanisole (89.4%), citric acid anhydrous (89%), mannitol (77%) and glycerol (61.9%).

Forced degradation studies, and effect of surfactants and titanium dioxide on the photostability of paliperidone by HPLC.

Forced degradation study of paliperidone under hydrolytic, oxidative, thermal and photolytic stress conditions was conducted using HPLC. The drug was found to be labile under hydrolytic, oxidative and photolytic stress conditions; whereas, it was stable under dry heat stress conditions. Effect of anionic, cationic and non-ionic surfactants applied to the concentration exceeding critical micellar concentration on the photostability of paliperidone was also studied by exposing the samples to sunlight for 72h. Major degradation of the drug was found in presence of cationic and non-ionic surfactants. Effect of titanium dioxide on the photo-degradation of paliperidone in solution state was also studied and it was found that 53% of the drug was degraded after 72h of exposure to sunlight. A common degradation peak was observed in oxidative and TiO2 photocatalysed samples. This peak may be due to the generation of N-oxide of paliperidone. The same degradation peak was also observed in all other photostability samples. Chromatographic separation of drug and its degradation products was achieved on an Alltima C8 (250mm×4.6mm, 5µm) analytical column, using a mobile phase consisting of acetonitrile-ammonium acetate buffer with 0.2% triethylamine (pH 3.5; 20mM) (60:40, v/v) at a flow rate of 1mL/min. Quantification was performed with UV detection at 280nm. The method was validated as per ICH guidelines.

Plaque regrowth effects of a triclosan/pyrophosphate dentifrice in a 4-day non-brushing model.

Triclosan is a lipophilic antimicrobial agent which, when present in an aqueous dentifrice vehicle, is complexed by or in close contact with polymers and surface-active molecules, emulsifying agents, flavoring oils and other hydrophobic ingredients. Because of this, dentifrice products containing triclosan may not have triclosan in a bioavailable state and, hence, the products themselves can not be assumed to possess antimicrobial activity. In order to determine the antimicrobial effects on dental plaque of a triclosan/pyrophosphate dentifrice relative to a negative control (without triclosan or pyrophosphate), a crossover 4-day non-brushing study was conducted. Thirty-four subjects were enrolled in this randomized two-period, double-blind crossover investigation with thirty-three subjects completing all aspects. Following a baseline plaque examination and complete plaque removal at the start of the first 4-day treatment period, subjects initiated a twice-daily supervised dosing regimen, during which they rinsed with their first assigned dentifrice in slurry form while refraining from tooth-brushing and all other oral hygiene procedures. Evaluations to quantify test product effects on plaque were conducted on Day 5. After a week-long interim washout period, subjects repeated the twice daily rinsing regimen over Days 1-4 of Treatment Period 2 with their second assigned product, again with examinations on Day 5. Analysis of data demonstrated subjects had significantly (p = 0.0296) less plaque when rinsing with the triclosan/pyrophosphate dentifrice slurry as compared to the negative control dentifrice slurry; the relative treatment difference as determined by the primary examiner was 12.7%. A trainee examiner observed a 16.0% reduction on a subset of subjects (p = 0.0139). This efficacy result compares favorably with results from other studies of triclosan-containing products. The examinations for oral safety demonstrated no meaningful clinical differences between the triclosan/pyrophosphate dentifrice and control dentifrice.

Sulcus temperature distributions in the absence and presence of oral hygiene.

In this study we investigated the possibility of using sulcus temperature measurements as an early indicator for the beginning of gingival inflammation. Sulcus temperature distributions over the arches appeared to obey a quadratic polynomial. With a test group of 10 volunteers, all dental students, small changes in temperature were measured after subjects refrained from all oral hygiene: A slight but significant tendency for the frontal temperature to increase after 14 days of no oral hygiene was, however, present. The quality of a quadratic polynomial fit of the temperature distributions over the arches decreased significantly, already after 3 d of non-oral hygiene. This indicates that the coefficient of quadratic correlation for the temperature distributions over the arches is a measure for the oral hygiene of patients and for changes in the physiology of gingival tissues. Furthermore, as its decrease was concurrent with an increase in plaque and gingival indices, it might serve as an early indicator for the beginning of gingival inflammation. However, further development work is needed in order to make this approach useful as a clinical tool.

Protective effect of topically applied conjugated hexadienes against ultraviolet radiation-induced chronic skin damage in the hairless mouse.

Albino hairless mice (SkH:HR-1) exposed chronically to suberythemal doses of ultraviolet B (UVB) radiation display visible skin wrinkling and tumors. Topical treatment of mice with solutions of conjugated dienes (2,4-hexadien-1-ol and derivatives of it) prior to each UVB radiation exposure reduces significantly the severity of these visible alterations. Chronic suberythemal doses of ultraviolet A radiation induce skin sagging, a distinctly different visible skin alteration. The severity of skin sagging is not reduced by topical application of the conjugated dienes tested here.