Improvement of the stability of doxycycline hydrochloride pellet-containing tablets through a novel granulation technique and proper excipients

Abstract Objective Granulated pellet-containing tablets (GPCT) prepared by a novel granulation technique showed better uniformity and compressibility over traditional pellet-containing tablets (PCT). The superiority of GPCT was mainly due to the excipient layer, which was laid over the coated pellets and modified the surface of pellets with increased roughness. Microcrystalline cellulose (MCC) was the main layering component which greatly influenced the stability of GPCT in storage, so was the additional excipients. The purpose of this study was to investigate the influence of excipient layer on the stability of GPCT. Methods GP were prepared by layering the combination of various excipients with MCC over the coated pellets, and further compressed into GPCT. The drug release profiles from the coated pellets, GP, and GPCT were compared, and the drug degradation rate in GP and GPCT were evaluated under high temperature, strong light, and high humidity conditions for up to 10 days. Results The drug content in GP and GPCT was above 97% after storage under high temperature and strong light, but dropped to 93%–96% under high humidity. The drug degradation rate in GP followed the order of excipient hygroscopicity as PVPP > CMC-Na > Lactose, while GPCT with PVPP showed the least drug degradation, suggesting the stability of GPCT was mainly determined by the excipient compressibility. Conclusions All formulations under high temperature and strong light were stable, indicating the influence of temperature and light could be ignored. Under high humidity conditions, the drug degradation in GP was in accordance with the excipient hygroscopicity, while it was dominated by excipient compressibility in GPCT. Therefore, the binary mixture of MCC and PVPP with the best compressibility may be ideal layering excipients to prepare acceptable GPCT for humidity sensitive drugs.