プレガバリン中空型坐剤の院内製剤化に向けた製剤学的特性およびウサギを用いた生物学的同等性の評価

抄録

Patients with cancer often report a lower quality of life due to neuropathic pain, which is difficult to manage because resistance to opioids often develops. Pregabalin (PGB) is recommended as an adjuvant analgesic for neuropathic cancer-related pain; however, PGB administration is currently limited to the oral route. We examined the pharmaceutical properties of a PGB hollow-type suppository for hospital use and assessed bioequivalence through examination of the pharmacokinetic parameters in rabbits.

The suppositories were prepared using melting (m-) and hollow (h-) methods with bases of polyethylene glycol (P), Witepsol H-15 (H), or Witepsol S-55 (S), yielding the following combinations: m-P, m-H, m-S, h-P, h-H, and h-S. Pharmaceutical properties, namely hardness, dispersibility, long-term stability, and drug release, were measured for each combination and were compared for orally administered (po) drugs and hollow-type suppositories.

Sufficient hardness was demonstrated for all h-suppositories compared with m-suppositories. The release rate of PGB was higher from h-suppositories than from m-suppositories, particularly the h-S group, and bioavailability was similar in the h-S and po groups. The h-S group exhibited significant pathological changes compared with the h-H group. To reduce injury from the repeated administration of suppositories, an S:H blending ratio of 1:1 significantly reduced the pathological changes.

Hollow-type suppositories may be useful as they are pharmaceutically stable and, when used with an S-base, able to deliver the same effects as orally administered drugs. The suppository was shown to be effective and is a promising clinical treatment owing to the enhanced convenience when used in hospitals.