Recently tablets that can rapidly disintegrate in the oral cavity have attracted attention as a novel dosage form that can be taken easily and safely even by infants and elderly people. In this research, rapidly disintegrating tablets containing a model drug with relatively low solubility were prepared by the wet compression method. Then, the optimal formulation for tablets having a tensile strength greater than 5 kg/cm2 and disintegration time shorter than 15s was examined, and the mechanisms involved in the disintegration of these tablets were clarified. Using a binary system composed of highly soluble trehalose (Tre) and low solubility lactose (Lac) as excipients, optimal formulations for rapidly disintegrating tablets were investigated by changing Tre/Lac mixing ratios. It became clear that the incorporation of 10-20% Tre made tablets rigid without causing a significant delay in disintegration time, and the tablets had a high water penetration rate because of the large pore size. When Tre content was more than 50%, however, a remarkable delay in disintegration time was observed because of the decrease in both water penetration rate and water uptake ability of the disintegrant.
In the series of 1,4-dihydropyridine-type compounds, manidipine dihydrochloride and benidipine hydrochloride are potent and long-acting calcium antagonists with similar physicochemical properties. Interaction between these drugs and lactose monohydrate, which is widely used as a diluent in the preparations, was observed when the thermal analysis of their physical mixture at a molar ratio of 1:1 was carried out. On the differential thermogram, a new endothermal peak before the melting of manidipine or benidipine was observed, and at this time, weight loss was also observed. This suggests that, during thermal analysis, a portion of the water molecule in lactose monohydrate migrates to drug molecules to form their hydrates. This kind of phenomenon could not be observed in the case of physically mixing these drugs with lactose anhydrate. Moreover, it was found that the degree of conversion to the hydrate form was independent of the degree of crystallinity.
The enhancing effect of switching iontophoresis on transdermal permeation in vitro was estimated as primarily being due to the enhancement of skin hydration. In this study, the effect of switching iontophoresis on transdermal absorption was investigated in vivo using sodium benzoate as a model drug. A couple of glass cells with Pt-electrodes were fixed on the abdominal skin of Wistar rats after hair removal. Four percent sodium benzoate solution was injected into each glass-cell and then the electric current at a constant voltage (5V, DC) was passed through the skin. Iontophoresis was carried out with switching at intervals of 5, 10 and 20 min or without switching. Switching iontophoresis at 10-min intervals showed significantly higher values than without switching. In switching iontophoresis, a rapid increase in the absorption rate was found immediately after switching. The drug absorption rate (%) in switching iontophoresis at 10-min intervals increased almost linearly, and it was clarified that 10-min intervals produced the maximal enhancing effect for transdermal absorption of sodium benzoate in this study. The current measured during iontophoresis increased transiently on switching. A high current value was observed at the time of switching, which was accompanied by the cancellation of skin polarization; thus the enhancing effect of switching iontophoresis on the transdermal absorption of sodium benzoate resulted from not only skin hydration, but also the cancellation of skin polarization.
The present study investigated the inflamed synovial cell-adhesive copoly (dl-lactic/glycolic acid) (PLGA) particulate system to optimize intra-articular drug administration. Using fluorescein 5-isothiocyanate bound to PLGA ([FITC] PLGA), [FITC] PLGA nanospheres were prepared by the modified emulsion solvent diffusion method and the surface of the nanospheres (NS) were coated with a bioadhesive polymer, chitosan (MW: 50,000). The surface coating of the [FITC] PLGA NS with chitosan was confirmed by the zeta-potential profile. The effect of coating the [FITC] PLGA NS with chitosan was evaluated by measuring the binding profile to the cultured synovial cells originated from patients with rheumatoid arthritis. The chitosan-coated nanospheres showed high binding ability to the synovial cells as compared to non-coated nanospheres. It was assumed that the chitosan-coated PLGA NS was delivered more quickly to inflammatory cells after intra-articular administration.
Recent studies have focused on the hair follicle as a potential pathway for both localized and systemic drug delivery. When drug penetration through human scalp skin was investigated using liquid formulations containing lipophilic and hydrophilic drugs in vitro, lipophilic melatonin (MT) and ketoprofen (KP) showed high permeabilities through scalp skin. Absorption enhancers, N-methyl-2-pyrrolidone and isopropylmyristate, only slightly increased the fluxes. Hydrophilic fluorouracil (5FU) and acyclovir (ACV) also penetrated across the skin with relatively large fluxes. However, there was large variability in the fluxes of drugs across scalp skins. There was a correlation between the flux and hair follicle density (r=0.651 for MT and r=0.666 for ACV). Fluorescent probes, nile red and sodium fluorescein, permeated into the junction of the internal and external root sheath of follicles and diffused into the dermis via the outer root sheath at the initial times. The penetration of MT and 5FU through scalp skin was much higher (37 and 48 times, respectively) than that via human abdominal skin. It has been demonstrated that topically-applied liposomes and microspheres are efficient in specifically targeting the delivery of a wide variety of compounds into the hair follicles. Additionally, hair follicles were a significant pathway for electroosmotic solution flow during iontophoresis. This review indicates a basis that drug delivery through human scalp skin will offer an available delivery means for many lipophilic and hydrophilic drugs.