Modified‐release oral pellets for duodenum delivery of doxycycline hyclate

Abstract

To minimize the gastric and esophageal injury effect, a system to deliver doxycycline hyclate (DOXY) to the duodenum area is needed. DOXY‐containing modified‐release oral pellets (DMOP) coated with hydroxypropyl methylcellulose phthalate HP‐55 (HPMCP HP‐55) and hydroxypropyl methylcellulose E15 (HPMC E15) appear to be a reasonable choice. This coating layer dissolves at pH 5.5, which is the pH of the duodenum, but not at a gastric pH (1.2). The formulation and preparation of DMOP were optimized, and a scale‐up test was performed. The results showed that the production reproducibility was acceptable, and the quality of DMOP well met the standards of Chinese Pharmacopeia (Ch.P, 2015 edition). Notably, the accumulated DOXY release was lower than 50% at pH 1.2 (20 min) and higher than 85% at pH 5.5, which met the USP40‐NF35 standard for DOXY modified‐release formulations. Moreover, the storage stability of DMOP with different packages was investigated by stress testing, accelerated and long‐term testings. The stability of DMOP was maintained up to 12 months, in terms of DOXY content and in vitro release behavior. The results seem to suggest that DMOP could be a promising duodenum delivery system.

Long-term gastrointestinal adverse effects of doxycycline

“…These include taking the pill with copious amounts of water (at least 100 mL), keeping sitting or standing upright after swallowing it, and timing it further from bedtime to avoid lying down for at least 30-60 minutes after dose administration [21][22][23]. One novel strategy that was developed by Huang et al was the design of a new formulation for the delivery of doxycycline, where the drug is incorporated in modified-release pellets that skip the stomach and dissolve in the duodenum [24]. In this formulation, doxycycline is coated with a layer that dissolves at the duodenal pH of 5.5 (about 85%) rather than the gastric pH of 1.2.…”