Shogo Hiraoka

Development of Gummi Drugs of Aripiprazole as Hospital Formulations

About half of patients with schizophrenia have poor adherence to taking medication, so many have recurrence, therefore, providing formulations that enable patients to continue their medication without interruption is important. We aimed to develop a gummi drug that contains aripiprazole (which can reduce schizophrenia and manic symptoms in bipolar disorder). We were able to develop gummi drugs (OD-G, PW-G and OS-G) using three commercially available aripiprazole products (Abilify® orally disintegrating tablets, powder formulation, and oral solutions, respectively) as hospital formulations. Furthermore, we developed improved OD-G (iOD-G), which contained high aripiprazole content. Pharmaceutical characteristics of iOD-G were demonstrated to be suitable for hospital formulations, and iOD-G could be stored for ≤1 month. No significant differences in the dissolution and pharmacokinetics of divided portions of iOD-G were observed when compared with commercially available aripiprazole products. This study confirmed that new dosage forms of aripiprazole in gummi drugs can be developed as hospital formulations, which will contribute to improve medication adherence of patients.

Preparation of an Ultrafine Rebamipide Ophthalmic Suspension with High Transparency

A 2% commercially available, milky-white, rebamipide micro-particle suspension is used to treat dry eyes, and it causes short-term blurring of the patients vision. In the current study, to improve the transparency of a rebamipide suspension, we attempted to obtain a clear rebamipide suspension by transforming the rebamipide particles to an ultrafine state. In the initial few efforts, various rebamipide suspensions were prepared using a neutralizing crystallization method with additives, but the suspensions retained their opaque quality. However, as a consequence of several critical improvements in the neutralizing crystallization methods such as selection of additives for crystallization, process parameters during crystallization, the dispersion method, and dialysis, we obtained an ultrafine rebamipide suspension (2%) that was highly transparent (transmittance at 640 nm: 59%). The particle size and transparency demonstrated the fewest level of changes at 25°C after 3 years, compared to initial levels. During that period, no obvious particle sedimentation was observed. The administration of this ultrafine rebamipide suspension (2%) increased the conjunctival mucin, which was comparable to the commercially available micro-particle suspension (2%). The corneal and conjunctival concentration of rebamipide following ocular administration of the ultrafine suspension was slightly higher than that of the micro-particle suspension. The ultrafine rebamipide suspension (eye-drop formulation) with a highly transparent ophthalmic clearness should improve a patients QOL by preventing even a shortened period of blurred vision.