sodium-dodecyl-sulfate and stearyl-alcohol

Aspirin has become the gold standard to which newer antiplatelet drugs are compared for reducing risks of cardiovascular diseases, while keeping low cost. Oral aspirin has a repertoire of gastrointestinal side effects even at low doses and requires high frequent dosing because it undergoes extensive presystemic metabolism. Transdermal delivery offers an alternative route that bypasses the gut and may be more convenient and safer for aspirin delivery especially during long-term use. This study comprised formulation of aspirin in different topical bases. Release studies revealed that hydrocarbon gel allowed highest drug release. In vitro permeation studies revealed high drug permeation from hydrocarbon gel. Several chemical penetration enhancers were monitored for augmenting the permeation from this base. Combination of propylene glycol and alcohol showed maximum enhancing effect and, hence, was selected for biological investigation. The biological performance of the selected formulation was assessed by measuring the inhibition of platelet aggregation relevant to different dosage regimens aiming to minimize both drug dose and frequency of application. The results demonstrated the feasibility of successfully influencing platelet function and revealed that the drug therapeutic efficacy in transdermal delivery system is dose independent. Biological performance was re-assessed after storage and the results revealed stability and persistent therapeutic efficacy.

Topics: Administration, Cutaneous; Animals; Aspirin; Carboxymethylcellulose Sodium; Chemistry, Pharmaceutical; Cyclodextrins; Dimethyl Sulfoxide; Drug Delivery Systems; Drug Stability; Drug Storage; Fatty Alcohols; Fibrinolytic Agents; In Vitro Techniques; Male; Mineral Oil; Myristates; Petrolatum; Platelet Aggregation; Polyethylene Glycols; Rats; Rats, Wistar; Skin Absorption; Sodium Dodecyl Sulfate; Urea

The hypothesis to be tested in this study was that toothpastes containing sodium lauryl sulfate (SLS) is unsuitable vehicles for xylitol. The bacteriostatic (and cariostatic) effect of xylitol is assumed to be caused by intracellular accumulation of xylitol-5-P in plaque bacteria. Experiments were designed to investigate whether presence of SLS would affect the uptake of xylitol by interacting with the bacterial membranes and thus inhibit xylitol-5-P formation. It was shown in an in vitro study that even very low concentrations of the strong anionic detergent SLS inhibited uptake of xylitol and xylitol-5-phosphate formation by dental plaque totally. The mild nonionic detergent ethoxylated stearyl alcohol (30x EO) had no such effect. In vivo experiments with toothpastes containing xylitol and either the strong or the mild detergent, showed that xylitol in toothpaste with SLS was not available for the plaque bacteria and gave no adaptation to xylitol, whereas in the presence of 30x EO it was available, and a xylitol adaptation was observed. Glucose metabolism, which was also studied for the plaque samples, was not significantly affected by presence of any of the 2 detergents, indicating that the amounts of xylitol in toothpastes were presumably too low to give clinical significant effects, even when mild detergents are used.

Topics: Acetates; Adult; Bacteria; Cariostatic Agents; Cell Membrane; Dental Plaque; Detergents; Drug Interactions; Fatty Alcohols; Female; Formates; Glucose; Humans; Male; Pharmaceutical Vehicles; Propionates; Sodium Dodecyl Sulfate; Sorbitol; Surface-Active Agents; Toothpastes; Xylitol