As personalized medicine continues to evolve, the formulations required must be able to adequately meet the needs of a relatively small and diverse patient population from the earliest phases of new drug development, while at the same time being low cost. Personalized formulations for use by children and the elderly often rely on clinical site compounding. From the time a new drug product is designed, formulations should be universally designed to be crushed, suspended, and administered by tube. Orally disintegrating tablets have characteristics similar to those of universal design, but they interact with thickened water, which is used by the elderly who have difficulty swallowing to take their medication, and children should be cautious because they do not like orally flavored formulations. In contrast, clinical trials have shown that mini tablets can be taken even by infants, and therefore, the mini tablets are considered promising as a pediatric formulation in the future.

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The number of research papers about the 3D printing of medicine has increased rapidly in the last five years after the approval of tablets manufactured with 3D printers in the United States, and research is being conducted from various aspects around the world. In this review, we explain the basics of 3D printers in relation to the research on manufacturing of pharmaceuticals. Since many model researches on pharmaceuticals that take advantage of the characteristics of 3D printers have been published, we have picked up recent articles and explained about them. On-demand manufacturing, hospital preparation, pediatric formulations, composite tablets & controlled drug release, and research on fusion of technologies from different fields were mentioned and introduced as topics.

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One of the challenges in predicting human intestinal absorption of drugs is that existing experimental systems have shown poor predictability especially for drugs whose intestinal absorption is dynamically regulated by metabolic enzymes and transporters. We have shown that human crypt-derived intestinal stem cells can undergo continuous expansion and form monolayers of differentiated absorptive epithelial cells on culture dishes or culture inserts by simply changing culture medium. This experimental system is characterized by the expression of multiple uptake and efflux transporters and metabolic enzymes at levels comparable to those of human intact intestinal tissue. Moreover, our cells can reproduce a pattern of gene expression/function of intestinal epithelial cells at the site of crypt collection. This property enables to utilize for quantitative prediction of human intestinal absorption and risk assessment of drug-induced intestinal toxicity.

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Some of the factors that cause interindividual and intraindividual differences in drug absorption from orally administered formulations are derived from the differences in pharmaceutical properties of the drugs and their formulations by the fluctuations of gastrointestinal physiology and their differences among patient populations. Especially gastrointestinal pH and gastric emptying rate significantly impact variability of drug absorption, and the difference in bile secretion in fed or fasted state further complicates it. Formulation evaluation technologies that precisely reflect fluctuations in gastrointestinal physiology such as individual patient’s age, illness, co-administered drugs, and fed or fasted, can support formulation development with small fluctuations in drug absorption. Furthermore, it is expected to become an evaluation technology that supports the era in which formulations are designed and manufactured individually for each patient.

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Oral drugs, which are superior in terms of convenience and safety, are the most preferred dosage form from the perspective of a patient’s quality of life. In both clinical practice and drug development, an important aspect of handling oral drugs is the understanding of gastrointestinal（GI） absorption. Drug absorption from the GI tract includes disintegration of the drug product, dissolution of the drug substance, and membrane permeation through the epithelial cells of the GI tract. All of these processes are easily affected by the conditions of administration and the physiological environment in the GI tract and are influenced by various factors that can change the physiological environment in the GI tract, such as disease/pathology, food/beverage, concomitant medications, age, and gender. This complex and highly sensitive physiological environment of the GI tract is thought to be the cause of the large inter-individual variability observed in the pharmacokinetics of oral drugs, but it is not fully understood. Our research group has recently found that the osmotic environment in the GI tract alters luminal fluid volume, leading to changes in drug absorption by altering drug concentration. In this article, we review the physiological environment and functions in the GI tract that should be understood as the basis for predicting drug absorption in individual patients, focusing on the fluid absorption/secretion behavior caused by osmotic pressure in the GI tract and its effect on drug absorption dynamics.

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Azimycin^Ⓡ ophthalmic solution 1％ is the only macrolide antibiotic ophthalmic solution containing azithromycin hydrate as the active pharmaceutical ingredient in Japan. Azithromycin is a drug characterized by good tissue penetration and stability at acidic pH. In addition, the formulation technology of Azimycin^Ⓡ ophthalmic solution 1％ used the ophthalmic Drug Delivery System technology “DuraSite^Ⓡ” that contains polycarbophil and other ingredients. The effect of polycarbophil increases viscosity and mucous membrane adhesion. The effect improves drug retention on the ocular surface and intraocular penetration of the drug as well. The drug characteristics and formulation technology enable the treatment of ocular infections with fewer number of dosing per day than the number of dosing of other antibacterial ophthalmic solutions. It expects to improve patient adherence.

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