Sublimation/evaporation behaviors of borneol in-situ forming matrix

Abstract

Practically, biodegradability is required for the carrier of the drug delivery systems such as the matrix of in situ forming matrix (ISM). Borneol is a white crystal-colored monoterpene alcohol that is insoluble in water. It possesses the properties of low toxicity and biocompatibility. These borneol properties exhibited the potential characteristics as matrix former in the ISM comprising 5% doxycycline hyclate as an antimicrobial agent, 40% borneol as matrix former, and 5% triacetin as co-solvent dissolved in N-methyl pyrrolidone (NMP) as termed of BTN for periodontitis treatment. The self-degradability is desirable for this localized drug delivery system after injection to the targeted periodontal pocket. The purpose of this study is to investigate the evaporation or sublimation rate at 37 °C of borneol-based ISM with phosphate buffer solution (PBS)-induced phase inversion as the in vitro degradation of borneol-matrix over time and compare with intact ISM. Additionally, the degradation patterns of each component in the BTN formulation were examined, including intact borneol, NMP, triacetin, and PBS. Triacetin exhibited slight evaporation over time due to low vapor pressure whereas intact borneol sublimated at a rate of 0.27 mg.hr−1.cm−2. NMP absorbed moisture from its surroundings during the first 12 hr and evaporated at a rate of 0.80 mg.hr−1.cm−2 after 12 hr. The evaporation rate of intact ISM was faster than that of triacetin and borneol but slower than that of NMP. Intact ISM required 10 days for 80% complete evaporation. While the weight of ISM contacted PBS (BTNw) was reduced during the first 12 hr owing to the evaporation of water from PBS. Furthermore, the evaporation pattern of BTN and BTNw after 1 day was similar. The borneol-based matrix of ISM showed self-degradation via evaporation for up to 14 days; thus, borneol was suited as a matrix-forming agent due to its water-insoluble, non-toxic, biocompatible, and sublimation characteristic. These evaporation behavior data of borneol-based ISM and its component are valuable for developing the self-degradable ISM formulation.