Copoly (_L-lactic acid/δ-valerolactone) microspheres (PLV-MS) containing p-hydroxybenzoic acid ester (ethyl (PE), n-propyl (PP), n-butyl (PB)) or 3',5'-dibutyryl-2'-deoxy-5-fluorouridine (C4-FUdR) were prepared. The effect of temperature on the drug release rate constant (KH) and the release mechanism from PLV-MS were investigated in vitro. All KH values observed for PLV-MS increased with a rise in temperature. In the relationship between log KH and the reciprocal of absolute temperature, relatively hydrophilic PE and PP gave the liner profiles throughout the temperature range examined; lipophilic PB and C4-FUdR exhibited a break point at a temperature near glass transition temperature (Tg) of copolymer in the profiles. The relationship between the initial content of the drugs in the PLV-MS and KH suggested that PB was contained mainly in the suspended state in PLV-MS and that the release of PB from PLV-MS occurs by the dissolution and diffusion of PB in the copolymer phase, which formed PLV-MS. On the other hand, KH observed in PLV-MS containing PE or PP and the diffusion coefficient of PE or PP in the PLV-MS were independent on the initial content of drugs. Therefore we estimated that PE or PP was contained in the completely dissolved state in PLV-MS. These results suggest that temperature dependency of the release rate from PLV-MS is governed by the states of contained drug in PLV-MS.

In vitro dissolution test conditions to obtain good IVIVCs for slow release enteric-coated pindolol granules were investigated by applying the GE-convolution method that convoluted in vitro dissolution and the GI transition of granules. Four kinds of enteric coated granules were prepared by a combination of two different enteric coatings and two core granules having different dissolution rates. Sustained-release dosage forms consisting of immediate release granules containing 5 mg of deuterium-labeled pindolol and enteric-coated granules containing 10 mg of unlabeled pindolol were administered to healthy volunteers. The plasma concentrations of labeled and unlabeled pindolol were simultaneously determined by the GC-MS selective ion monitoring method, and cumulative absorption profiles of the enteric-coated granules were calculated by the Wagner-Nelson method by using the pharmacokinetic parameters of immediate release granules. The dissolution profiles of the enteric-coated granules in the GI tract were simulated by applying the GE-convolution method to in vitro dissolution profiles in different pH test solutions. As a result, when the pH of the test solution was 5.5, good IVIVC was observed under various food conditions. The GE-convolution method, which can simulate an absorption profile from a dissolution profile obtained under appropriate dissolution test conditions, is considered useful not only for designing enteric-coated granules having optimal dissolution rate, but also for evaluating the efficacy of the drug product

α-Cyclodextrin (α-CD) crystals were heated with polyethylene glycol 4000 (PEG4000) in a sealed glass ampule. Inclusion formation was studied as a function of heating temperature, heating time, and water content of α-CD by X-ray diffraction and thermogravimetry-differential thermal analysis. PEG4000 molecules were included in the α-CD cavity by heating, and the formation of an inclusion compound was accelerated by heating above 90°C. A compressed disk of α-CD crystals was prepared and soaked in molten PEG4000 at 90°C. The results indicate that PEG molecules penetrated into α-CD crystals, and the inclusion compound formation was proceeded as solid state reaction.

Pharmaceutical applications of the ultrasound compacting method proposed by Rodriguez were investigated in this paper. It was found that the compression process of powder by irradiating ultrasound was different from that by direct compression. The decrease of porosity by the ultrasound irradiation was not caused by the elastic and plastic deformation of powder, but by the fusion of powder. The solid dispersions of indomethacin (IM) with various water-soluble polymers prepared by the ultrasound showed a more rapid dissolution behavior of IM than their simple physical mixtures. Compared with the grinding or heat-fusion method to prepare solid dispersion, the merits of the ultrasound method are that the fusion proceeds in a lower temperature and in a shorter period.

Amorphous of cefditoren pivoxil was prepared by grinding or spraydrying. When the amorphous samples were stored at 40°C and 96% relative humidity (RH) or heated by using DSC, crystallization was not observed for the spray-dried sample, but it was for the ground sample. Glass transition accompanying enthalpy relaxation was evaluated for the spray-dried and the ground cefditoren pivoxil by means of a modulated-temperature differential scanning calorimetry (MTDSC). Glass transition temperature (T_g) and relaxation enthalpy (ΔH) of the ground sample were remarkably varied by storage at a temperature below T_g, but for the spray-dried sample no significant change in T_g or ΔH was observed by storage. We could interpret that the ground sample was less stable and that it was stabilized by storage below T_g, but the spray-dried sample was more stable. Since the energy level of the amorphous region between spray-dried and ground samples was different, the difference of the crystallization of the amorphous samples could be observed by storage at 40°C and 96% RH or heating by using DSC.

Prescriptions provide information about drug therapy. We examined outpatient prescriptions in two college hospitals to screen drug candidates that are suitable for orally disintegrating tablets. Since these tablets can be taken without water or with little water, oral medicines that had been prescribed before and/or after meals were omitted at the screening. If several medicines were prescribed to be taken with the orally disintegrating tablets at the same time, patients usually drink water to take them. We then extracted the medicines that had been singly prescribed for one dosage time or one prescription. The obtained prescription survey data were compared with the opinions of 176 pharmacists. Drugs selected from the prescriptions almost completely satisfied the pharmacists except for cathartics, anticancer drugs, and Chinese herbal extract medicines. The final results for the drug candidates were antipyretic analgesics, antiemetics, hypnotics (sedatives), and antispasmodics (against GI diseases).