尼群地平缓释片剂的研究

研究了尼群地平缓释片剂的处方、制备工艺和溶出速率,用GC-MS法测定了12名健康受试者口服自制缓释片(C)、市售国产片剂(A)和进口某公司片剂(B)后的体内血药浓度,体内数据按零级溶出、一级吸收口服单室模型,经计算求得药动学参数。结果表明,A、C两制剂相对于B制剂的生物利用度为31.8％及64.8％。与普通片剂相比,缓释片血浓度曲线较为平坦且下降缓慢。     

介孔二氧化硅纳米粒增溶型非诺贝特片剂的制备及体内外研究

目的 制备介孔二氧化硅纳米粒(mesoporous silica nanoparticles,HK)增溶型非诺贝特(fenofibrate,FNB)片剂并进行体内外研究。方法 用吸附法以HK为FNB的载体制成固体分散体(FNB-HK)。采用差示扫描量热法、X射线衍射法和傅里叶红外光谱法分析非诺贝特在FNB-HK中的存在状态。通过考察体外溶出度,优化处方并制片。将自制片和市售片分别对家兔单剂量口服给药,采用高效液相色谱法测定家兔血浆药物浓度。结果 FNB-HK表征表明HK能够抑制非诺贝特的结晶。经过处方优化,乳糖做填充剂,8%羧甲基淀粉钠为崩解剂时,片剂能够达到最理想的溶出速率。自制片与市售片相比,体内达峰时间提前,达峰浓度增大,相对生物利用度为149.95%。结论 本研究研制的片剂能显著改善FNB的溶出速率,提高其口服生物利用度。     

循环式溶出速度仪的试制

片剂的溶出速度(或释放度)在一定条件下,能与药物体内吸收的性质相关而可间接作为生物利用度的量度,因此广泛地应用于生物药剂学的生物利用度研究、剂型设计及生产质量控制中。溶出速度测定方法大致有桨叶法、崩解仪法、转篮法等多种,测定用仪器更是繁多,但是近年来较常应用的为转篮法与循环法等,其中转篮法已成为美国药典与美国处方集的     

布洛芬片剂生物利用度的研究

临床反映各种布洛芬片剂疗效并不一致。为了提高布洛芬片剂的相对生物利用度,我们和药厂协作,进行片剂新处方的研制,测定了国产品之一的片剂(A)、新处方片剂(B)和英国布茨公司的片剂(E)的体外溶出度,用 GC 法研究了 A、B 两片剂相对于 E     

尼群地平共研粉末的制备及其体内外评价

目的:制备难溶性药物尼群地平的共研粉末,并对其进行体外溶出度及家兔体内相对生物利用度评价。方法:采用共研磨法制备尼群地平-微晶纤维素-泊洛沙姆共研粉末,测定药物的体外溶出度,并通过物理鉴别方法考察药物的存在状态。采用HPLC法测定6只健康家兔分别口服尼群地平共研粉末(A)、物理混合粉末(B)和市售普通片(C)后不同时间血浆中尼群地平的浓度,计算体内相对生物利用度。结果:共研粉末中尼群地平的溶出度显著提高,药物的粒径也明显减小,主要以微晶状态存在。家兔口服尼群地平共研粉末后,与参比制剂B和C相比,Tm ax变小,Cm ax和AUC明显变大,相对生物利用度分别为341.12%和353.01%。结论:共研磨技术显著的提高了尼群地平的溶出速率和口服相对生物利用度。     

溴新斯的明舌下膜的制备及体内外评价

目的制备溴新斯的明舌下膜并评价其关键质量属性。方法以机械性能、崩解时限、体外溶出行为以及体外稳态渗透速率为评价指标获取膜剂的最佳处方组成,并比较以最佳处方制备的舌下膜剂与溴新斯的明注射剂及片剂在大鼠体内的药动学差异。结果处方中HPMC和 PEG比例分别为59.7%、13.4%时,膜剂的制剂特性最优,其绝对生物利用度为91.76%。结论溴新斯的明舌下膜生物利用度远优于其片剂。     

提高难溶性药物尼群地平溶出率和口服生物利用度的研究

目的通过制剂手段提高难溶性药物尼群地平的体外溶出率和家犬体内的相对生物利用度。方法用共研磨法制备研磨混合物,并用差热分析法、X射线衍射法、显微镜法鉴别药物在共研磨混合物中的存在状态,在此基础上采用直接压片法制备口腔速崩片,测定体外溶出速率,所有试验均以物理混合物为参照进行比较;用HPLC法测定3只健康家犬分别口服尼群地平口腔速崩片(受试制剂)、市售普通片(参比制剂)后不同时间血浆中尼群地平的浓度,计算药物代谢动力学参数及相对生物利用度。结果共研磨混合物中尼群地平的粒径远小于物理混合物,并以微晶状态存在;以共研磨混合物制备的口腔速崩片的溶出速度和程度均大于以物理混合物制备的口腔速崩片;在家犬体内受试制剂和参比制剂的tmax分别为1.5 h和4.25 h,ρmax分别为176.54μg.L-1和111.12μg.L-1,AUC0-t分别为903.78μg.h.L-1和651.99μg.h.L-1,AUC0-∞分别为1 030.46μg.h.L-1和903.68μg.h.L-1,受试制剂的相对生物利用度为138.5%;受试制剂的体内吸收和体外溶出速率均高于参比制剂。结论通过制备共研磨混合物和口腔速崩片的方法,提高了尼群地平的体外溶出度和家犬体内的相对生物利用度。     

布洛芬环糊精包合物的生物利用度研究

用高效液相色谱法研究了布洛芬环糊精包合物在大鼠及健康志愿受试者体内的生物利用度,实验表明包合物在大鼠体内的生物利用度相对于市售片剂为169.8%,表现出生物利用度提高,并且释药迅速,在健康人体内的生物利用度实验中,表现出释药迅速,但AUC与市售片剂相比却并未提高。     

尼群地平片溶出度测定

目的采用不同方法考察市售尼群地平口服片剂和软胶囊的溶出度 ,并提出尼群地平溶出度检查的标准。方法用含不同浓度的十二烷基硫酸钠 (SDS)醋酸盐缓冲液 (pH 4 5 )为溶出介质 ,采用紫外分光光度法检查 ,比较不同厂家尼群地平片和尼群地平软胶囊的体外溶出度。用相似因子法对片剂溶出度数据进行统计分析。结果用 0 3 %SDS醋酸盐缓冲液 (pH 4 5 ) ,除B片和D片之间的 (B片 D片 )相似因子F2 >5 0外 ,其余的F2 ≤ 5 0 ,可以显示出不同厂家生产的尼群地平片的溶出度差异。而用 0 1 %SDS醋酸盐缓冲液可以显示出尼群地平软胶囊与片剂的溶出度差异。结论不同厂家生产的尼群地平片的溶出度存在较大的差异 ,尼群地平片和软胶囊在溶出度方面整体存在较大差异 ,建议《中华人民共和国药典》规定尼群地平片剂的溶出度检查     

格列本脲(优降糖)片剂的生物利用度

对四种格列本脲(Glibenclamide)商品片剂A、B、C、D 及两种对照片E、F,进行体外溶出速度试验,并测定E、F 片剂的体内生物利用度。E、F 的处方及制备方法与商品片剂相同,仅微粒大小不同,E 为未微粉化片剂,F 则为微粉化片剂。以上片剂每片格列本脲含量均为5mg。体外试验,分别对6种片剂进行硬度、含量均匀度、解集速率及溶出速度试验。溶出速度分别在两种不同     

Relative bioavailability of diclofenac after a single administration of a new multiple-unit formulation of enteric-coated pellets

The relative bioavailability of diclofenac (CAS 15307-86-5) was investigated after a single administration of a multiple-unit formulation containing 75 mg diclofenac sodium in enteric-coated pellets (A) in comparison to an enteric-coated tablet with 50 mg diclofenac sodium (B), a capsule containing 140 mg diclofenac resinate (C) and a dispersible tablet containing 46.5 mg diclofenac acid (D). The study was carried out in a four-way crossover design in 16 healthy male volunteers. Serum concentrations of diclofenac were determined with a validated and specific HPLC-method. After dose normalisation, a mean relative bioavailability of 99% (B), 142% (C) and 116% (D) was determined for the pellet formulation. According to the corresponding 90%-confidence interval, bioequivalence for the extent of bioavailability of the test formulation can be concluded compared to the enteric-coated tablet. In comparison to the formulations C and D, the test formulation showed an increased extent of bioavailability. Further differences in pharmacokinetics were observed for the rate-dependent parameters. For the test formulation, the highest mean maximum serum concentration (1595 ng/ml) was measured with a corresponding tmax of 0.8 h. For the reference formulations, mean peak serum concentrations of 1285 ng/ml after 2.0 h (B), 370 ng/ml after 1.8 h (C) and 735 ng/ml after 1.9 h (D) were observed. Despite the enteric-coating of the pellets, a short lagtime of 0.4 h was determined for the test formulation. For the other rapid-release formulation (D), the lagtime was of a similar magnitude (0.3 h), while drug release and absorption from the enteric-coated tablet and the diclofenac resinate capsule were delayed (1.8 and 0.7 h, respectively). Due to the rapid and high bioavailability of diclofenac, the multiple-unit formulation fulfills the prerequisites for the oral treatment of acute painful conditions when prompt analgesic and anti-inflammatory efficacy is desired.     

Analysis of formulation and food effect on the absorption of metoclopramide

OBJECTIVES: Assessment of the relative and absolute bioavailability of immediate release and sustained release formulations of metoclopramide. Assessment of the effect of a high-fat meal on the pharmacokinetics of sustained release metoclopramide. MATERIAL AND METHODS: In a balanced 4-way crossover study in 16 healthy male volunteers, a sustained release (SR) formulation of metoclopramide was compared with a solution for injection (A) and an immediate release tablet (B). The SR formulation was administered after a fasting period (C) as well as after a high-fat meal (D). A single dose of 30 mg metoclopramide was investigated in each treatment. Metoclopramide concentrations were determined by HPLC. RESULTS: The absolute bioavailability of the sustained release formulation (fasting state) was 58% and thus about 17% lower than the bioavailability of the immediate release formulation. Comparing the treatments C (sustained release, fasting state) and D (sustained release, high-fat meal) no significant influence of food on the absorption of sustained release metoclopramide could be detected.     

贝诺酯片剂的研制及生物利用度研究

通过减小药物粒径,提高贝诺酯片剂的生物利用度。在市售片以A(500mg)基础上研制了新处方片剂B(400mg)。建立贝诺酯片剂体外溶出度试验方法,即以表面活性剂溶液作溶出介质,以浆法进行溶出度测定。用HPLC法测定贝诺酯在体内的水解产物水杨酸和扑热息痛的血药浓度。结果表明药物研磨粉碎前后体外溶出速度常数分别为0.0152min-1及0.0337min^-1(P<0.001)。A及B体外平均溶出时间分别为42.25min及15.77min(P<0.001)。体内研究表明A及B水杨酸的C_max,T_p,AUC之间均无显著性差异(P>0.1)(A,B的服用量分别为4.5g及3.6g),B的相对生物利用度为125.59%。     

布洛芬片剂生物利用度的研究

本文试制出新处方布洛芬片剂,选择山东新华制药厂三种片剂:市售处方A、新处方片剂B和C,以及英国Boots公司的片剂D,进行体外溶出速率和人体生物利用度试验,并测定了生产A,B(和C),D片剂的布洛芬原料A′,B′,D′的粒度,比较了A′,D′的晶型。实验表明,国内外原料晶型相同,A′,B′,D′平均粒径分别为130.0,36.6,56.6μm。A与D生物不等效,B和C与D生物等效。提高国产片剂生物利用度的因素主要与原料粒度、处方组成和制备工艺有关。     

罗红霉素片剂生物利用度的比较研究

为比较不同剂型罗红霉素的生物利用度,用微生物管碟检定法(藤黄微球菌CMCC(B)28001)测定了10名男性健康受试者口服罗红霉素分散片(制剂A)和罗红霉素片(制剂B)后不同时间血浆中活性药物的浓度,绘制了血药浓度—时间曲线。结果表明,受试者交叉口服含罗红霉素150mg的制剂A和制剂B后,血浆T_max分别为1.7±0.9和3.7±1.6h,C_max分别为4.97±1.17和2.04±1.26μg·ml^-1,AUC_0→∞分别为62.2±11.9和35.0±16.9μg·h·ml^-1。以制剂A为参比,制剂B中罗红霉素的相对生物利用度仅为59.8%±32.6%,两种制剂的药物吸收程度有显著差异(P<0.01)。初步分析提示,罗红霉素在胃中的迅速溶出是保证其片剂生物利用度的关键之一。     

尼莫地平片剂生物利用度和健康人药代动力学研究

用高效液相色谱法测定了6名健康志愿者口服二种尼莫地平片剂的相对生物利用度和药代动力学参数。结果表明:尼莫地平在人体内的浓度—时间数据可用一室开放模型拟合,主要动力学参数与国外文献报道一致。新片剂和普通片的人体相对生物利用度分别为82.39%和16.01%。     

Oral absorption profile of nitrendipine in healthy subjects: a kinetic and dynamic study.

1. In nine healthy male subjects the kinetics of nitrendipine were assessed after i.v. administration and its absorption profile was studied when given by a tablet formulation and by an osmotic pumping device (Osmet) with a zero-order in vitro release of 2.62 +/- 0.19 mg h-1 for 13 h. 2. Plasma concentrations of nitrendipine and its pyridine metabolite, heart rate and blood pressure were determined at regular intervals after drug administration. 3. After i.v. nitrendipine, the plasma concentration declined triexponentially with a mean terminal elimination half-life of 11.7 +/- 5.4 h. The mean systemic plasma clearance was 1.47 +/- 0.22 l min-1. 4. Administration of the Osmet resulted in a relatively smooth plasma concentration-time profile in comparison with the tablet. The mean plateau concentration was 2.63 +/- 1.31 ng ml-1 and the duration of this plateau was 10.7 +/- 3.2 h. The intake of food gave rise to a transient increase of the plasma concentration of both nitrendipine and its pyridine metabolite. 5. The mean bioavailability of nitrendipine from the Osmet (8.2 +/- 1.6%) was lower than from the tablet (11.1 +/- 4.5%), which is probably due to release of nitrendipine in lower parts of the G.I. tract where absorption is not or less possible. 6. Intravenous administration caused a transient decrease in DBP of 26 +/- 4%, accompanied by a maximal reflex tachycardia of 46 +/- 17%. No clear haemodynamic effects were observed after oral administration. The Osmet produced less side-effects (headache) than the tablet.     

Single dose absorption profiles and bioavailability of two different salbutamol tablets

In a single dose cross-over experiment in twelve healthy adults a comparison of the absorption profiles and the relative bioavailability was made between a new salbutamol containing tablet (preparation A = Salbutax) and a commercially available and accepted formulation as reference (preparation B), both containing 4 mg salbutamol. Salbutamol plasma concentrations were measured frequently during a period of 16 h post dosing. Maximum salbutamol plasma concentrations after intake of product A and product B on an empty stomach were reached after 2.3 +/- 0.9 (= mean +/- S.D.) and 2.4 +/- 1.1 h, respectively, and accounted for 14.3 +/- 2.5 and 12.8 +/- 2.6 micrograms X l-1, respectively. The differences were not found to be significant (p greater than 0.05). The areas under the plasma concentration-time curves (AUC0----16), as obtained after administration of tablet A and tablet B, accounted for 73.5 +/- 14.0 and 65.0 +/- 11.8 micrograms X l-1 X h, respectively, the difference being marginally significant (p = 0.05). This results in a relative bioavailability of 114.3 +/- 15.7% for the product A 4-mg tablets. It is concluded that both products can be considered as having comparable bioavailability.