Despite revolutionary progress on the large scale to make therapeutic biodrugs such as peptides and proteins, the effective and convenient non-invasive delivery of these therapeutics remains a major challenge. Oral delivery of peptides and proteins remains an attractive alternative to parenteral delivery, and has resulted in various attempts at delivery development. Buccal insulin and nasal calcitonin were successfully developed and they are already on the market in some countries. Pulmonary insulin is currently in the last stages of clinical development. This review summarizes the non-invasive technologies that are being developed and succeeding in commercialization. In addition, the trends on current technologies under development for biodrugs are commented on.

We investigated various physical properties of granules composed of low-substituted hydroxypropylcellulose (L-HPC) and water-soluble drugs (caffeine anhydrous or ascorbic acid) prepared by wet granulation. The crystalline state of the drugs in the granules was evaluated using powder X-ray diffraction, differential scanning calorimetry, and attenuated total reflectance Fourier transform infrared (FT-IR) spectroscopy. Caffeine anhydrous showed a reduction in crystallinity that was dependent on the amount of purified water added as kneading liquid, while ascorbic acid was observed to be in an amorphous state with any amount of purified water. Deuterated samples of each drug showed decrease in the area of the amorphous OH band of L-HPC in the FT-IR spectra. These results suggested the possibility that both drugs interacted with OH groups of the L-HPC amorphous domain by wet granulation independent of the amount of purified water added. The rate of water vapor sorption by the granules was reduced dependent on the amount of purified water added. The rate of water vapor sorption was suppressed in the presence of drugs. It was considered that the interaction between the drugs and the OH groups of the amorphous domain of L-HPC interfered with water vapor sorption.