We designed various novel drug delivery systems based on biopharmaceutical aspects. One is to develop lymphatic delivery systems, especially for anticancer drugs. Another is to develop the intestinal delivery of poorly absorbed drugs by using absorption enhancers and chemical modification. When large substances (or carriers) are taken up into lymph vessels, lymph-selective mechanisms occur passively because of the structural difference between blood and lymph capillaries. Therefore, by using this characteristic of lymph capillary, we can develop the lymphatic delivery system through the use of appropriate carriers. These carriers may involve water-soluble macromolecules, hydrophobic microspheres, and lipoidal vesicles, which are biocompatible or biologically inert and to which active compounds can effectively be attached. The successful lymphatic targeting of anticancer drugs enhances their therapeutic efficacy and reduces their systemic toxic effects. On the other hand, to enhance the intestinal absorption of poorly absorbable drugs, including antibiotics and peptide and protein drugs, various strategies such as the use of absorption enhancers, the chemical modification of drugs to produce prodrugs and analogues, and the use of dosage forms have been examined. Of these strategies, the use of absorption enhancers is a highly popular strategy to enhance the intestinal absorption of poorly absorbed drugs. We examined the absorption-enhancing effects of unsaturated fatty acids, such as oleic acid, and found that membrane SH proteins as well as lipid portion of the membrane played an important role in their absorption enhancing effects. Furthermore, absorption enhancers with high effectiveness and less toxicity should be developed in clinical applications. An alternative strategy to improve the intestinal absorption of a poorly absorbed drug is to modify the chemical structure of drugs. We synthesized various acyl-derivatives of peptide and protein drugs by chemical modification with fatty acids. We found that the intestinal absorption of these acyl-derivatives was higher than that of native drugs, indicating that a chemical modification is also a promising strategy to improve the intestinal absorption of drugs, especially peptide and protein drugs.

The fast Fourier transform (hereinafter FFT) technique with a personal computer was used to conduct concurrent precise analysis of the vibration of the probe, which was inserted into the powder layer of the high-speed mixer, to monitor the granulation process, relative to the mass median diameter of the granules. In the previous study,¹⁾ it was demonstrated that the wet granulation process can be concurrently monitored and controlled by the elemental strength of the wave at impeller blade frequency (ESWF) converted by FFT, in case of the optimum high-speed mixer formulation. In this study, the influence of the drug substance to the ESWF, in terms of solubility was evaluated with acetaminophen, ethenzamide, and ascorbic acid. It was demonstrated that the wet granulation process could be also monitored by ESWF, and it could be used to determine the end point of the granulation process in terms of the mass median diameter of the granules, regardless of the differences of the solubility of drug substances.

To develop an ointment formulation suitable during the recovery stages of bedsores, including the proliferation period of granulation and the formative period of epidermis, the physicochemical properties of macrogol ointment (MO) containing various hydrophilic polymers, which have gel-forming ability, were tested. The resultant ointments were evaluated in drug-releasing property, hardness, and amount of water absorbed. Carbopol- (CP) added MO showed the highest water absorbing property, and the drug release from the base was also sustained (T₅₀=65min). However, its hardness was too high to be clinically applied. When the mixture of CP and (hydroxypropyl cellulose) HPC was added to MO instead of CP, the hardness of the resultant ointment became a suitable value, and the sustained drug release property was also improved more (T₅₀=90min) compared with the CP-added MO. The improved drug-releasing property was attributed to the improved water-absorbing rate of the ointment by the presence of HPC.

To reduce the gritty feeling of orally administered calcium polystyrene sulfonate powder (PS-Ca), we have developed a jelly dosage form containing PS-Ca. The jelly form (PS-Ca jelly), containing gelatin, carrageenan, and pectin, was confirmed to show a less gritty feeling when it was evaluated by the human volunteer's sensory test. Moreover, these additives seemed to regulate its adhesiveness and cohesiveness. In vitro potassium exchange profiles of PS-Ca jelly obtained by the press-through method and the paddle bead method showed no difference between PS-Ca jelly and PS-Ca powder (Kalimate^®), which was selected as a reference dosage form. A bioequivalence test of these forms was also performed with measuring serum potassium concentration changes, using nephrectomized rats. No statistically significant difference was found. The physical appearance of PS-Ca jelly stored at 60°C for 28 days remained unchanged, and the loss of water was within 2%. We have concluded that the newly formulated PS-Ca jelly will be able to contribute to the improvement of a patient's QOL.