Pharmacokinetics profiles of Ara-A (vidarabine) after a single dermal application to rats at a dosage of 10 mg Ara-A/kg as a cream formulation containing [³H] Ara-A were compared with those of Ara-A ointment. Using whole-body autoradiography (WARG), for both formulations it was observed that most radioactivity remained on the skin surface at the application site and its periphery at 4 hr after application. Further, both formulations showed similar changes in the concentration of radioactivity in the epidermis at the application site, and no significant difference was observed in maximum concentration of radioactivity (C_max) and area under the concentration of radioactivity-time curve to 48 hr (AUC_0-48hr). In addition, radioactivity was not observed in systemic circulation up to 48 hr after application of either formulation. From these results, it was considered there is no difference in the pharmacokinetics of Ara-A after a dermal application as a cream or ointment formulation.

The objective of this study was to confirm the feasibility of polymer coating of liposomes with various hydrophilic polymers bearing hydrophobic anchors (HPMC-R, PVP-R, PVA-R) for designing injectable drug carriers for passive targeting of drugs. The small unilamellar liposomes (egg phosphatidylcholine: cholesterol= 5:5, 7:3 or DMPC: DCP: cholesterol= 7:1:3 in a molar ratio) were applied to the polymer coating. The polymer coating of liposomes was carried out by mixing the liposomal suspensions with the polymer solutions (sol-mixing method) or by hydrating the lipid film with the polymer solutions followed by sonication (pre-mixing method). The formation of a thick polymer layer with HPMC-R and PVA-R on the surface of the liposomes was confirmed by comparing the particle size and zeta potential of the liposomes before and after polymer coating. The coating layer formed with PVP-R was not as thick as that of HPMC-R or PVA-R. The HPMC-R coated liposomes showed a significantly improved circulation compared to that of non-coated ones as had been observed for the PVA-R coated liposomes (previously reported), while no significant improvement was observed for the PVP-R coated ones. It was concluded that a thick and flexible coating layer on the surface of liposomes with HPMC-R or PVA-R could prolong the circulation time of the liposomes and that PVP-R could not form such a steric coating layer owing to its molecular structure.

Proglumetacin maleate (PGM), one of the indomethacin (IND) derivatives, has been developed as an anti-inflammatory and antipyretic analgesic drug because of its low gastrointestinal disorder action. From the results of powder X-ray diffractometry and differential scanning calorimetry, it was confirmed that PGM had two crystal forms showing polymorphism. A distinct difference in surface active properties between two forms was observed; the surface of form I crystals were hydrophilic, whereas those of form II was less hydrophilic. These difference in wettability of the crystal forms remarkably affected the dissolution profiles of capsules containing crystals of each form. However, no correlation was found between dissolution profiles and bioavailability in human.

We investigated the preparation of rapidly disintegrating tablets by using the surface modifying method in this study develop easily swallowed tablets for elderly and pediatric patients. Ibuprofen were modified by a high-speed agitating granulator with surface modifying material, which was light anhydrous silicic acid, talc, or titanium oxide. As result, light anhydrous silicic acid effective as a surface modifying material. Ibuprofen modified with a light anhydrous silicic acid indicated good flowability for direct compression. The surface modified ibuprofen was mixed with a disintegrator and excipients; then the tablets were prepared by direct compression. These tablets were disintegrated within 30 sec by a disintegration test in JP X III. As result of this study, it was found that rapidly disintegrating tablets could be prepared by direct compression by the use of the surface-modifying method.

Delivery of drugs via the skin has many attractions, including avoidance of gastro-intestinal disturbance and first-path metabolism, long-term maintenance of therapeutic plasma concentration and increased patient acceptability. This paper discusses the factors influencing the percutaneous absorption of drugs: lipophilicity, molecular size, melting point, cutaneous metabolism and skin binding of drugs. Additionally, quantitative structure-permeability relationships (QSPR) for skin penetration were discussed based on the octanol-water partition coefficient, molecular weight and electronic charge of drugs. Nonirritant enhancement methods, such as use of nonirritant penetration enhancers and formation of a complex or an ion pair, for drug penetration through skin were also described. As a result, the suitability of a drug for transdermal drug delivery was proposed.