DESIGN AND PHARMACOKINETIC EVALUATION OF IBRUTINIB BY SELF-NANO-EMULSIFYING DRUG DELIVERY SYSTEM
INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES AND RESEARCH
Authors: Prasad, Dasari; Mohanta, G. P.; Sudhakar, M.
Abstract
The objective of present research work is design and in-vivo evaluation of ibrutinib self-nanoemulsifying drug delivery system (SNEDDS) for the enhancement of oral bioavailability. Box-Behnken design was used for the study and the results analysed using response surface methodology. Ibrutinib SNEDDS were prepared with various oils, surfactants and co-surfactants and tested particle size, PDI, zeta potential, refractive index, drug release and TEM studies. The optimized ibrutinib SNEDDS has the composition of capryol 90, cremophore EL and transcutol HP. Based on the particle size and entrapment efficiency and in-vitro dissolution studies; F2 is identified as optimized formulation with 85% drug released, whereas less than 1% was released from pure drug at end time of 30 min. In-vivo bioavailability data reported in male wistar rats indicate higher concentration of drug in plasma implying enhanced systemic absorption of ibrutinib from SNEDDS formulation. The C-max and AUC(0-inf) values of optimized SNEDDS was considerably higher (p<0.05) than pure drug formulation. The oral bioavailability of optimized SNEDDS increased around 12 folds when compared with pure drug. Ibrutinib SNEDDS was successfully prepared, and results indicate that oral bioavailability of ibrutinib optimized SNEDDS was significantly improved when compared with pure drug. Therefore, the results suggest that the optimized formulation has a great potential for clinical application in the effective management of lymphocytic leukaemia.
Responses to intra-luteal administration of cloprostenol in dairy cows
ANIMAL REPRODUCTION SCIENCE
Authors: Andrlikova, M.; Andrlova, P.; Barbato, O.; Tabery, J.; Bina, V; Vostry, L.; Cech, S.
Abstract
The aim of the study was to determine the luteolytic dose of cloprostenol administered directly into the corpus luteum (CL; infra-luteal treatment, ILT) in dairy cattle. Cows of two control groups were treated with 500 mu g of cloprostenol (Estrumate (R)) intramuscularly (IM-500) or via ILT with 0.2 mL of physiological solution (ILT-0). Cows of four experimental groups were treated by ILT with cloprostenol in doses 5, 25, 50 and 100 mu g (ILT-5, -25, -50 and -100 groups). Progesterone concentrations (P4) and size of CL were evaluated to assess luteolysis at 0, 0.5, 1, 2, 4, 8, 24 and 48 h or at 0, 24 and 48 h after ILT, respectively. Cows in the ILT-0 and -5 groups were unaffected by ILT. The P4 concentrations were less in cows of the IM-500, as well as ILT-25, -50 and -100 groups at 48 h subsequent to ILT. The size of the CL was less in cows of IM-500, as well as ILT-25, -50 and -100 groups at 48 h after ILT. There were P4 concentrations of about 1 ng/mL 48 h after ILT in cows of the IM-500, as well as ILT-50 and -100 groups. In conclusion, the cloprostenol dose of 50 mu g administered intra-luteally is a luteolytic dose in cows.