Controlled release of glaucocalyxin - a self-nanoemulsifying system from osmotic pump tablets with enhanced bioavailability.

OBJECTIVE: The purpose of this study was to develop a new formulation to enhance the bioavailability simultaneously with controlled release of glaucocalyxin A (GLA). MATERIAL AND METHODS: In this study, controlled release of GLA was achieved by the osmotic release strategy taking advantage of the bioavailability enhancing capacity of self-nanoemulsifying drug delivery systems (SNEDDS). The formulation of GLA-SNEDDS was selected by the solubility and pseudoternary-phase diagrams studies. The prepared GLA-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis and zeta potential. The optimized GLA-SNEDDS were used to prepare GLA-SNEDDS osmotic pump tablet via direct powder compression method. The effect of formulation variables on the release characteristic was investigated. GLA-SNEDDS osmotic pump tablets were administered to beagle dogs and their pharmacokinetics were compared to GLA and GLA-SNEDDS as a control. RESULTS: In vitro drug release studies indicated that the GLA-SNEDDS osmotic pump tablet showed sustained release profiles with 90% released within 12 h. Pharmacokinetic study showed steady blood GLA with prolonged Tmax and mean residence time (MRT), and enhanced bioavailability for GLA-SNEDDS osmotic pump tablet. CONCLUSION: It was concluded that simultaneous controlling on GLA release and enhanced bioavailability had been achieved by a combination of osmotic pump tablet and SNEDDS.

Enhanced oral bioavailability of lurasidone by self-nanoemulsifying drug delivery system in fasted state.

OBJECTIVE: The purpose of this work was to develop a new formulation to enhance the bioavailability and reduce the food effect of lurasidone using self-nanoemulsifying drug delivery systems (SNEDDSs). METHODS: The formulation of lurasidone-SNEDDS was selected by the solubility and pseudo-ternary phase diagram studies. The prepared lurasidone-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis, zeta potential and in vitro drug release. Lurasidone-SNEDDSs were administered to beagle dogs in fed and fasted state and their pharmacokinetics were compared to commercial available tablet as a control. RESULTS: The result showed lurasidone-SNEDDS was successfully prepared using Capmul MCM, Tween 80 and glycerol as oil phase, surfactant and co-surfactant, respectively. In vitro drug release studies indicated that the lurasidone-SNEDDS showed improved drug release profiles and the release behavior was not affected by the medium pH with total drug release of over 90% within 5 min. Pharmacokinetic study showed that the AUC(0-∞) and Cmax for lurasidone-SNEDDS are similar in the fasted and fed state, indicating essentially there is no food effect on the drug absorption. CONCLUSION: It was concluded that enhanced bioavailability and no food effect of lurasidone had been achieved by using SNEDDS.

Gamma Irradiation as a Phytosanitary Treatment of Bactrocera tau (Diptera: Tephritidae) in Pumpkin Fruits.

The fruit fly Bactrocera tau (Walker) is an important quarantine pest that damages fruits and vegetables throughout Asian regions. Host commodities shipped from infested areas should undergo phytosanitary measures to reduce the risk of shipping viable flies. The dose-response tests with 1-d-old eggs and 3-, 5-, 7-, 8-d-old larvae were initiated to determine the most resistant stages in fruits, and the minimum dose for 99.9968% prevention of adult eclosion at 95% confidence level was validated in the confirmatory tests. The results showed that 1) the pupariation rate was not affected by gamma radiation except for eggs and first instars, while the percent of eclosion was reduced significantly in all instars at all radiation dose; 2) the tolerance to radiation increased with increasing age and developmental stage; 3) the estimated dose to 99.9968% preventing adult eclosion from late third instars was 70.9 Gy (95% CL: 65.6-78.2, probit model) and 71.8 Gy (95% CL: 63.0-87.3, logit model); and iv) in total, 107,135 late third instars cage infested in pumpkin fruits were irradiated at the target dose of 70 Gy (62.5-85.0, Gy measured), which resulted in no adult emergence in the two confirmatory tests. Therefore, a minimum dose of 85 and 72 Gy, which could prevent adult emergence at the efficacy of 99.9972 and 99.9938% at the 95% confidence level, respectively, can be recommended as a minimum dose for phytosanitary treatment of B. tau in any host fruits and vegetables under ambient atmospheres.

Controlled release of ziprasidone solid dispersion systems from osmotic pump tablets with enhanced bioavailability in the fasted state.

OBJECTIVE: The purpose of this work was to develop a controlled release of ziprasidone with no food effect by the osmotic release strategy. METHODS: The solution of ziprasidone and poloxamer188 (P188) with different weight ratios was spray-dried to form solid dispersion of ziprasidone (SD-ZIP). The SD-ZIP was characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (X-RD) and solubility testing. The SD-ZIP osmotic pump tablets were prepared by wet granulation method. The effect of formulation variables on the release characteristic was investigated. The SD-ZIP osmotic pump tablets were administered to fasted and fed beagle dogs and their pharmacokinetics were compared to commercial formulation Zeldox® as a control. RESULTS: The results of DSC and X-RD indicated that ziprasidone resides in P188 with no crystalline changes. Solubility studies demonstrated that the solubility of SD-ZIP was substantially improved compared to ziprasidone and physical mixtures of ziprasidone and P188. The optimized formulation and drug release profiles of SD-ZIP osmotic pump tablets in different medium were obtained which showed typical osmotically controlled release and could fitted to zero-order kinetics with good linear correlation. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolong actions and no food effect was achieved simultaneously in SD-ZIP osmotic pump tablet compared with Zeldox®. CONCLUSION: The SD-ZIP osmotic pump tablet could be able to enhance the bioavailability in the fasted state and showed sustained release with prolonged actions.

Clinical efficacy and safety of adjunctive treatment of chronic ischemic heart failure with Qishen Yiqi dropping pills: a systematic review and meta-analysis.

Objectives: Our study was to evaluate the effect of Qishen Yiqi Dropping Pills(QSYQ) on the prognosis of chronic ischemic heart failure(CIHF) and its safety. Methods: Databases including CNKI, Wanfang, VIP, CBM, PubMed, Web of Science, The Cochrane Library and EMbase were searched from their inception to April 2023 to screen relevant randomized controlled trials (RCTs). Primary indicators included readmission rates, rates of major adverse cardiovascular events (MACE), and all-cause mortality rates. The quality of the literature was assessed according to the Cochrane Reviewers' Handbook 5.0 and the Modified Jadad Scale (with a score of 4-7 rated as high quality). Meta-analysis was performed using the meta-package created by R software version 4.2.3, continuous data were compared using SMDs, and dichotomous and ordered data were compared using ORs; and the I2 test was used to assess the heterogeneity. Results: Fifty-nine studies out of 1,745 publications were finally included, totalling 6,248 patients. Most studies were poorly designed and had some publication bias, with only 26 high-quality papers (Jadad score ≥4). Meta-analysis showed that the combined application of QSYQ was able to reduce the readmission rate [OR = 0.42, 95% CI (0.33, 0.53), P < 0.001], all-cause mortality rate [OR = 0.43, 95% CI (0.27, 0.68), P < 0.001], and the incidence of MACE [OR = 0.42, 95% CI (0.31, 0.56), P < 0.001]. Also, the treatment method can improve clinical effectiveness [OR = 2.25, 95% CI (1.97, 2.58), P < 0.001], increase 6-min walking distance (6MWD) [SMD = 1.87, 95% CI (1.33, 2.41), P < 0.0001] and left ventricular ejection fraction (LVEF) [SMD = 1.08, 95% CI (0.83, 1.33), P < 0.0001], and decrease the Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores [SMD = -2.03, 95% CI (-3.0, -1.07), P < 0.0001], BNP levels [SMD = -2.07, 95% CI (-2.81, -1.33), P < 0.0001] and NT-ProBNP levels [SMD = -2.77, 95% CI (-4.90, -0.63), P < 0.05]. A total of 21 studies (n = 2,742) evaluated their adverse effects, of which 13 studies reported no adverse effects and 8 studies reported minor adverse effects. Conclusion: Our results suggest that the combined application of QSYQ can further improve patients' cardiac function and exercise tolerance, improve their quality of life, and ultimately improve patients' prognosis with a favorable safety profile. Nonetheless, limited by the quality and high heterogeneity of the literature, we must be conservative and cautious about the present results. Systematic Review Registration: PROSPERO (CRD42023449251).

Combination of GLP-1 and sodium butyrate promote differentiation of pancreatic progenitor cells into insulin-producing cells.

We identified that nestin-EGFP-positive cells isolated by fluorescent-activated cell sorting (FACS) were downstream progenitor cells from colony-initiating pancreatic precursor cells. Under differentiation condition, these nestin-EGFP-positive cells could generate islet and neural cells. To investigate the conditions that allowed nestin-EGFP-positive progenitor cells (NPPCs) to efficaciously differentiate into insulin-producing cells in vitro, protocols were designed with glucagon-like peptide-1 (GLP-1) and the histone deacetylase inhibitor, sodium butyrate. We demonstrated that the combination of GLP-1 and sodium butyrate resulted in the increasing of levels of transcripts encoding pancreatic developmental factors and insulin. As a consequence, the amount of insulin-producing cells and insulin secretion were enhanced. These results indicated that NPPCs which were cultured in the presence of GLP-1 and sodium butyrate could specially differentiate into insulin-producing cells.