自制双氯芬酸钠缓释片及其与原研药扶他林缓释片的体外释放一致性研究

目的 :采用乙基纤维素和羟丙甲纤维素为缓释材料制备双氯芬酸钠缓释片,并与原研药扶他林缓释片(Voltaren Retard,100 mg/片)比较体外释放的一致性.方法 :先将双氯芬酸钠原料药与乳糖混匀,于流化床中以固含量10%乙基纤维素的95%乙醇溶液制粒.干燥后的颗粒再与羟丙甲纤维素混匀,加入硬脂酸镁后压制成双氯芬酸钠缓释骨架片,最后以标准型欧巴代对片剂进行包衣,包衣增重3%(w/w).分别采用不同pH介质的中国药典篮法和使用生物相关介质的美国药典往复筒法对自制双氯芬酸钠缓释片与扶他林缓释片的体外释放度进行检测和比较.结果与结论 :使用乙基纤维素和羟丙甲纤维素制备的双氯芬酸钠缓释片的体外释放趋势与扶他林缓释片相近.     

盐酸二甲双胍1000mg缓释片的制备及其体外释药机制考察

目的:制备1000mg规格的盐酸二甲双胍缓释片,考察其体外释药行为并与吡格列酮二甲双胍缓释片(Actoplus MetXR)中的二甲双胍缓释部分比较。方法:用亲水骨架结合缓释膜包衣技术制备盐酸二甲双胍缓释片,以羟丙甲纤维素(HPMC)K100M为片芯缓释材料,以丙烯酸树脂(尤特奇)NE30D为缓释包衣膜,以ActoplusMetXR中的二甲双胍缓释部分(规格:1000mg)为对照药,以两者体外释放曲线比较的相似因子(f2)为考察指标,采用星点设计-效应面法优化处方,同时考察最佳处方的体外释药机制。结果:最佳处方为片芯HPMCK100M/盐酸二甲双胍为0.15(m/m)、缓释膜HPMCE6/尤特奇NE30D为0.18(m/m)、包衣增质量控制在4%～6%;缓释片体外释放行为符合Higuchi方程(r=0.9954),以扩散机制为主,类似骨架系统释药。结论:盐酸二甲双胍1000mg缓释片可以达到与对照药相似的体外释药行为。     

阿昔洛韦缓释片的T艺研究

目的研究制备阿昔洛韦缓释片最佳工艺.方法以羟丙甲纤维素和卡波普为亲水凝胶型骨架材料,聚乙烯吡咯烷酮溶液为黏合剂,采用湿法制粒压片,制备阿昔洛韦缓释片.进行体外释放度试验,并与普通片剂进行比较.结果与结论研制的缓释片缓释效果良好,比普通片有更好的释药性能,药物释放规律符合Higuchi方程.     

盐酸二甲双胍胃漂浮缓释片的制备及体外释放

采用羟丙甲纤维素作为骨架材料制备了盐酸二甲双胍胃漂浮缓释片；研究了压片方式、规格及体外释放测定方法对其体外释放的影响。结果表明，该胃漂浮缓释片具有良好的漂浮和缓释特性。     

吡格列酮/二甲双胍缓释片的处方筛选及工艺研究

目的确定吡格列酮/二甲双胍缓释片处方及制备工艺。方法分别以释放度及溶出度为指标对二甲双胍缓释骨架层及吡格列酮速释层进行处方和工艺研究,并对吡格列酮/二甲双胍缓释片的释放度进行考察。结果吡格列酮/二甲双胍缓释片缓释层体外释放行为与模型药物Glucophage XR(格华止)相似,速释层吡格列酮与模型药物Actos(艾可拓)体外溶出行为不相似,但30 min累计溶出药物总量相似。结论所制备的吡格列酮/二甲双胍缓释片处方组成合理,工艺可行。     

阿昔洛韦缓释片的工艺研究

目的　研究制备阿昔洛韦缓释片最佳工艺。方法　以羟丙甲纤维素和卡波普为亲水凝胶型骨架材料,聚乙烯吡咯烷酮溶液为黏合剂,采用湿法制粒压片,制备阿昔洛韦缓释片。进行体外释放度试验,并与普通片剂进行比较。结果与结论　研制的缓释片缓释效果良好,比普通片有更好的释药性能,药物释放规律符合Higuchi方程     

茶碱缓释片药物释放影响因素研究

目的:制备茶碱缓释片剂,考察高分子缓释材料及片剂硬度对其释放度的影响。方法:调节乙基纤维素与羟丙甲纤维素的配比,制备不同的缓释片剂;再用优选配比的同一批颗粒分别压制成不同硬度的缓释片剂,测定其释放度。结果:缓释材料的配比不同,缓释片的释放度也不同,但片剂硬度不影响缓释片的释放度。结论:优选配比所制备的片剂,体外释药性能良好,适合于工业化生产。     

盐酸二甲双胍缓释制剂研究进展

盐酸二甲双胍(MH)是双胍类降血糖药,其缓释制剂可有效降低盐酸二甲双胍在临床大剂量反复用药时产生的毒副作用。盐酸二甲双胍在水中的溶解度>2.4mol/L,通常采用骨架缓释技术,普通缓释制剂主要在结肠释药,利用率低,国外已有规格为500mg/片的二甲双胍缓释片(格华止XR)在国内上市,盐酸二甲双胍缓释制剂的研究也随着全球制剂技术的发展不断深入。现对盐酸二甲双胍缓释制剂的研究进展作一综述。     

阿昔洛韦缓释片的工艺研究

目的 研究制备阿昔洛韦缓释片最佳工艺。方法 以羟丙甲纤维素和卡波普为亲水凝胶型骨架材料，聚乙烯吡咯烷酮溶液为黏合剂，采用湿法制粒压片，制备阿昔洛韦缓释片。进行体外释放度试验，并与普通片剂进行比较。结果与结论 研制的缓释片缓释效果良好，比普通片有更好的释药性能，药物释放规律符合Higuchi方程。     

pH敏感型羟丙甲基纤维素衍生物的控释研究

目的制备羟丙甲基纤维素接枝共聚物缓释片并研究此缓释片的体外释放行为。方法选用茶碱为模型药物,以不同DM含量的羟丙甲基纤维素接枝共聚物水分散体进行包衣,考察包衣片在蒸馏水和模拟胃液中的缓释效果。结果 DM含量为2.5%和5%时,包衣片在水中和模拟胃液中的释放符合Higuchi缓释释放模式,DM含量达到7%时片剂释放明显加快。结论羟丙甲基纤维素接枝共聚物是pH敏感型缓释包衣材料。     

Beta-glucuronidase-mediated drug release

The selective activation of a relatively non-toxic prodrug by an enzyme present only in the tumour should enhance the drug concentration at the tumour site and result in a better anti-tumour effect and a reduction in systemic toxicity as compared to conventional chemotherapy. beta-Glucuronidase is such an enzyme. It is normally expressed in the lysosomes of cells. In larger tumours, however, high levels of the enzyme are present in necrotic areas. Several glucuronide prodrugs have been synthesised that can be activated by beta-glucuronidase. They are relatively non-toxic due to their hydrophilic nature, which prevents them from entering cells and thus from contact with lysosomal beta-glucuronidase. The main problem of glucuronide prodrugs for clinical use is their fast renal clearance. Special attention should be paid to the development of new less hydrophilic prodrugs with slower clearance, as this would result in a prolonged exposure to beta-glucuronidase at the site of the tumour and a reduction of the amount of prodrug needed. A number of interesting anthracyclin-based glucuronide prodrugs have been synthesised and have shown favourable therapeutic effects compared to treatment with the parent drug. The tumoural levels of beta-glucuronidase can even be enhanced by two-step approaches, in which exogenous enzyme is targeted to the tumour by an antibody (ADEPT) or by the gene encoding the enzyme in transduced tumour cells (GDEPT). The ADEPT and GDEPT approaches in combination with glucuronide prodrugs have shown enhanced efficacy in experimental tumour models. Further improvement of ADEPT and GDEPT is warranted to optimise the tumour uptake and retention of antibody-enzyme fusion proteins and the efficiency and safety of current gene delivery methods. In conclusion, it is clear that glucuronide prodrugs hold promise for future use in the treatment of cancer in patients as monotherapy. Enhancement of the therapeutic effects of glucuronide prodrugs, also in patients with small tumour lesions, may possibly be achieved by techniques that target beta-glucuronidase specifically to the site of the tumour.     

Modeling transdermal drug release

The stratum corneum forms the outermost layer of the skin and is essentially a multilamellar lipid milieu punctuated by protein-filled corneocytes that augment membrane integrity and significantly increase membrane tortuosity. The lipophilic character of the stratum corneum, coupled with its intrinsic tortuosity, ensure that it almost always provides the principal barrier to the entry of drug molecules into the organism; the only exceptions being highly lipophilic species which might encounter problems at the stratum corneum-viable epidermis interface where they must partition into a predominantly aqueous environment. Drugs can be administered either as suspensions or as solutions and the formulation can range in complexity from a gel or an ointment to a multilayer transdermal patch. In this review we describe the theoretical principles used to describe transdermal release and we show that relatively simple membrane transport models based on the appropriate solution to Fick's second law of diffusion can be used to explain drug release kinetics into this complex biological membrane.     

Chronopharmacology and controlled drug release

Circadian rhythms in the body are well established and are an important factor to consider when administering drugs. Many diseases display symptoms and onset characteristics that are not randomly distributed within 24 h (e.g., coronary infarction, angina pectoris, asthmatic attacks and peptic ulcer perforations); therefore, it is not surprising that the effects and/or pharmacokinetics of drugs can display significant daily variations. Recent data, primarily concerned with the chronopharmacokinetics of antiasthmatics, histamine H2-blockers and cardiovascular active drugs (e.g., propanolol, organic nitrate and nifedipine) are described as representative examples in this review. The data demonstrate that biological rhythms should have been taken into account when evaluating drug delivery systems, galenic formulations and pharmacokinetics as a basis for drug treatment.     

Cyclodextrin-based controlled drug release system

Because of their bioadaptability and multi-functional characteristics, cyclodextrins (CDs) are capable of alleviating the undesirable properties of drug molecules in various routes of administration through the formation of inclusion complexes. This article outlines the current application of natural and chemically modified CDs in the design of advanced dosage forms. In an oral drug delivery system (DDS), the hydrophilic and ionizable CDs can serve as potent drug carriers in the immediate release- and delayed release-formulations, respectively, while the release rate of water-soluble drugs can be retarded by hydrophobic CDs. Since CDs are able to extend the function of pharmaceutical additives, the combination of molecular encapsulation with other carrier materials will become effective and a valuable tool in the improvement of drug formulation. Moreover, the most desirable attribute for the drug carrier is its ability to deliver a drug to a targeted site; conjugates of a drug with CDs can be a versatile means of constructing a new class of colon-targeting prodrugs. On the basis of this knowledge, the advantages and limitations of CDs in DDS are addressed.     

Chronopharmacology and controlled drug release

Circadian rhythms in the body are well established and are an important factor to consider when administering drugs. Many diseases display symptoms and onset characteristics that are not randomly distributed within 24 h (e.g., coronary infarction, angina pectoris, asthmatic attacks and peptic ulcer perforations); therefore, it is not surprising that the effects and/or pharmacokinetics of drugs can display significant daily variations. Recent data, primarily concerned with the chronopharmacokinetics of antiasthmatics, histamine H2-blockers and cardiovascular active drugs (e.g., propanolol, organic nitrate and nifedipine) are described as representative examples in this review. The data demonstrate that biological rhythms should have been taken into account when evaluating drug delivery systems, galenic formulations and pharmacokinetics as a basis for drug treatment.     

Polymer particle erosion controlling drug release. I. Factors influencing drug release and characterization of the release mechanism

The present study deals with controlled drug delivery from hydrocolloid tablets by polymer particle erosion. The influence of excipients and formulation factors on the dissolution behaviour of the methyl hydroxyethyl cellulose (MHEC)-tablets is investigated. Linear drug release with low susceptibility to hydrodynamic stress is obtained. The use of drugs with higher solubility leads to a slight acceleration of the release due to the contribution of diffusion to the release process. Higher drug loading and consequently lower polymer content expedites dissolution as well as changes in the tablets' geometry resulting in enlarged release surfaces. Furthermore, alterations of the composition of the dissolution medium affect drug release. However, neither viscosity grade nor the particle size of the polymer or compaction pressure has a marked impact on the dissolution. Investigations to clarify the mechanism of polymer particle erosion include erosion studies and the comparison of different batches of MHEC, of products from different manufacturers and of fibrous trial products. There is evidence that the insoluble fibres within the water soluble MHEC are responsible for the occurrence of polymer particle erosion by disturbing swelling and formation of a thick coherent gel layer and thus, causing erosion of the hydrocolloid tablet with synchronous drug release.     

利巴韦林缓释片的制备及其释放度测定

目的:制备利巴韦林缓释片,对其释放机制进行考察.方法:建立高效液相色谱(HPLC)体外释放度测定法,以羟丙基甲基纤维素(HPMC)为主要辅料,制备亲水凝胶型骨架片,采用单因素试验筛选辅料种类,通过均匀设计优化出缓释片的处方.结果:所制备的缓释片在8 h内呈良好的零级释药特征.结论:以均匀设计优选的利巴韦林缓释片处方合理,体外释放性能良好.     

阿西美辛缓释片的制备及体外释放度测定

目的:制备阿西美辛缓释片并对其体外释放度进行研究.方法:采用4因素3水平正交试验设计法筛选、优化最佳处方,以进口缓释胶囊(优妥)为对照,采用转蓝法测定体外释放度,319 nm波长处UV法定量.结果:两剂型体外释药相似,释药方程分别为对照品F1=0.2032 0.197t1/2(r=0.9706),样品F2=0.1535 0.2971t1/2(r=0.9701).结论:以正交法优选的阿西美辛缓释片处方合理.     

胰岛素-壳聚糖缓释微球释药机制的研究

目的：研制具有良好缓释效果的胰岛素微球，并研究胰岛素-壳聚糖微球的释药机制。方法：用乳化交联技术制备了胰岛素微球，并对胰岛素-壳聚糖缓释微球缓释机制进行了初步探讨。结果：该微球具有良好缓释效果。结论：胰岛素-壳聚糖微球的释药机制为药物的突释效应、亚胺键的水解、壳聚糖的吸水膨胀以及药物通过胶状黏稠层向外扩散等几个相互衔接的步骤。