苦参碱固体脂质纳米粒的制备及其体外透皮研究

目的制备苦参碱固体脂质纳米粒(matrine solid lipid nanoparticles,MA-SLN),并考察其药剂学性质与体外透皮给药行为。方法采用微乳-低温固化法制备MA-SLN,以粒径、ζ电位和包封率为评价指标,通过正交试验筛选最佳处方和工艺;扫描电子显微镜(SEM)和透射电子显微镜(TEM)观察MA-SLN的形态;差示扫描量热法(DSC)和X射线衍射扫描(XRD)分析苦参碱在MA-SLN中的包埋状态;体外透皮实验考察药物的透皮及释放行为。结果最佳处方工艺制得的MA-SLN包封率可达(56.12±0.82)%,激光粒度仪(DLS)检测MA-SLN的平均粒径为(196.31±6.26)nm,电位为(-37.18±2.36)mV。SEM和TEM显示MA-SLN呈规整的均匀球状或类球状结构;DSC和XRD检测可确定苦参碱可完全包裹在SLN内,苦参碱与SLN骨架材料相容性良好;体外透皮实验显示,9 h时累积透过量(ΔM)达到500μg/cm~2,且可持续释放至24 h,表明MA-SLN能够显著提高苦参碱的透皮吸收效率并具有较好的缓释行为。结论采用微乳-低温固化法制备MA-SLN,其工艺简单、周期短、可控性高,易于产业化推广;且制成的MA-SLN性能优良、透皮吸收率高与缓释行为显著,可为透皮给药制剂提供一种较好的给药模型,为苦参碱进一步开发应用奠定基础。     

载药量对后交联祖师麻凝胶贴膏剂流变学及体外经皮渗透特性的影响

目的通过载药量对后交联凝胶贴膏流变学及体外经皮渗透特性的影响,考察后交联凝胶贴膏基质的载药量。方法采用流变学技术测定不同载药量时胶料的各项流变学参数,并以祖师麻乙醇提取物为模型药物,以祖师麻甲素的累积透过率及皮肤滞留率为指标,对成品贴膏进行体外经皮渗透试验,确定基质载药量。结果当载药量在4.0%～12.4%时,含药胶料的结构强度、黏弹性、耐温耐剪切性及抗变形能力、稳定性均符合要求,其中以载药量为6.8%时最佳;祖师麻甲素的累积透过率随载药量逐渐增大,皮肤滞留率分别变化不明显。结论通过比较流变学及体外经皮渗透试验结果,确定基质处方的最佳载药量为6.8%。     

透皮促进剂对肤康祛斑凝胶体外透皮吸收的影响

目的考察透皮促渗剂对肤康祛斑凝胶的主药熊果苷体外经皮渗透的影响。方法对优化后的肤康祛斑凝胶处方,以大鼠离体皮肤作为渗透屏障,用高效液相色谱法测定凝胶中熊果苷经皮透入接收液含量。考察氮酮、氮酮-薄荷油、氮酮-冰片作为促渗剂对熊果苷透皮吸收的影响。结果肤康祛斑凝胶中熊果苷的体外累积渗透率符合Weibull分布,以氮酮-薄荷油作为促渗剂的处方中,熊果苷累积渗透率最高,渗透促进剂的促透效果为:氮酮-薄荷油>氮酮-冰片>氮酮。结论以氮酮-薄荷油作为促渗剂,对熊果苷有较好的促渗作用。     

微透析法研究罗通定经皮给药在大鼠体内不同部位的浓度分布

目的研究罗通定经皮给药后,药物在大鼠脑、皮下、血管3个部位微透析液和尾静脉血浆的浓度变化。方法采用微透析技术取样,HPLC测定不同时间点大鼠脑、皮下、血管的微透析液的药物浓度以及尾静脉血浆的药物浓度,DAS2．0药动学软件计算药动学参数。结果罗通定20cm^2经皮给药后,在大鼠体内消除缓慢,脑、皮下、血管和血浆AUC0→10h分别为（387．19±162．81）、（245．97±74．60）、（211．41±65．19）和（1677．05±598．83）min·mg·L^-1。体内药物含量血浆中最高,脑微透析次之,血管微透析最低,经皮给药后的AUC脑／AUC血浆、AUC皮下／AUC血浆、AUC血管／AUC血浆分别为（23．45±6．51）％、（15．66±5．03）％和（13．87±5．84）％。结论微透析法能很好地应用于罗通定经皮给药后大鼠不同部位的浓度研究,反映脑、皮下和血管之间的关系。     

微乳在经皮给药系统中的应用

微乳经皮给药是目前国内外药学工作者研究的重点,也是目前药物制剂研发热点之一。本文主要从微乳的组成、促渗机制、微乳在经皮给药中的应用3个方面进行了综述。微乳经皮给药具有很好的应用前景。     

Inpatient Prescribing and Monitoring of Fentanyl Transdermal Systems: Adherence to Safety Regulations

Background:

National safety guidelines were developed to minimize the occurrence of serious adverse drug events (ADEs) associated with the use of the fentanyl transdermal system (FTS), however, reports of use in opioid-naïve patients for treatment of acute pain and associated ADEs continue to occur.

Objective:

To evaluate the prescribing patterns of the FTS for adherence to recent US regulatory recommendations and identify the impact of health information technology (HIT) on adherence rates.

Methods:

A retrospective pre- and postintervention analysis was performed in hospitalized adult patients receiving FTS. Electronic medication order instructions and text questions were incorporated into FTS electronic medication orders. The primary outcome measure was adherence of FTS medication orders to regulatory guidelines defined as (a) a new order in an opioid-tolerant patient for use in moderate to severe chronic pain or (b) continuation of the documented home dose in use for at least 7 days. Safety measures included respiratory rate and documented ADEs.

Results:

Adherence rates were significantly increased in the postintervention cohort as compared to the preintervention cohort (48.7% vs 85.0%; P < .0001). Incidence of ADEs was significantly lower post intervention (34.7% vs 23.3%; P = .043), including a lower incidence of respiratory depression (16.7% vs 8.3%; P = .043). Documentation was increased in the postintervention cohort (76% vs 100%). However, supporting documentation confirmed responses in only 59.2% of records reviewed.

Conclusions:

Incorporation of HIT via electronic order text questions increased overall adherence rates to regulatory recommendations, increased documentation, and decreased the rate of associated ADEs.     

盐酸奥昔布宁醇脂质体凝胶的制备及质量评 价简

目的 制备盐酸奥昔布宁醇脂质体凝胶剂,并评价体外经皮渗透性、pH、外观形态等方面的质量.方法 以羟丙基纤维素（HPC）为基质制备OXB醇脂质体凝胶;采用Franz透皮扩散实验仪考察醇脂质体凝胶和普通凝胶的经皮渗透性;高效液相色谱法测定其中主药含量,并评价其质量.结果 醇脂质体凝胶（4％ OXB）的累积渗透率是普通凝胶（10％ OXB）的3.9倍.盐酸奥昔布宁线性范围为10 ～1 000 μg/mL,平均回收率为99.58％.结论 制备的醇脂质体凝胶经皮渗透性高,质量稳定可控.     

细胞促渗肽在透皮给药中的应用

细胞促渗肽（CPP）最早于细胞研究中发现,此后被引入透皮制剂领域,相关透皮机制尚未阐明。CPP在透皮制剂领域中应用广泛,对小分子药物、多肽、蛋白质、核酸和胶粒载体均有皮肤促渗作用。本文综述CPP在透皮领域中的应用。     

Transdermal patches loaded with L-cysteine HCL as a strategy for protection from mobile phone emitting electromagnetic radiation hazards

Mobile phone usage has been increased in the last few years emitting electromagnetic radiation (EMR), which disturbs normal cellular processes via oxidative stress. L-cysteine, a glutathione precursor, prevents oxidative damage. Transdermal patches (TDPs) loaded with L-cysteine hydrochloride (L-CyS-HCL) were fabricated by dispersion of L-CyS-HCL 5% w/w and different concentrations of sorbitol as a plasticizer in room-temperature vulcanizable synthetic silicone matrices (RTV-Si). The effect of sorbitol on patch physicochemical parameters was assessed; in-vitro L-CyS-HCL release profiles and ex-vivo permeation were studied. Pharmacokinetic parameters of endogenous synthetized in-vivo glutathione, after receiving IV bolus dose of L-CyS-HCl and L-CyS-HCl-RTV-Si-TDPs were studied in rat model. The influence of L-CyS-HCL-RTV-Si-TDPs against damaging effects of mobile phone EMR on rats' blood and brain tissues was studied. The results revealed that patch plasticity, intensity reflections, surface porosity, L-CyS-HCL release rate and skin permeation increased with increasing sorbitol concentration. Pharmacokinetic profile for IV dose and L-CyS-HCl-RTV-Si-TDPs revealed that the L-CyS-HCl-RTV-Si-TDPs provided a sustained glutathione plasma concentration–time profile over entire patch application. High significant differences in biological parameters (blood and brain samples) were observed for radiated rats using the patch in study compared with positive control rats. Promising long-term strategy for protection against mobile phone hazards was obtained.