The dynamics of drug release from suppositories. Part 2: Phenylpyrazolone derivatives in animal experimentation (author's transl)

The authors studied the in vivo absorption of aminophenazone and aminoantipyrine from suppositories produced by means of, respectively, hydrophilic vehicles (PEG 1000, PEG 1500, PEG 2800, PEG 4000, PEG 5000) and lipophil vehicles (Witepsol H 15 and cocoa butter). It was found that the above-mentioned drugs were absorbed more rapidly from the suppositories with a hydrophilic vehicle than from those with a lipophil vehicle. The absorption time decreased with the increase in molecular mass of the polyethylene glycols used. The absorption times of the two drugs from suppositories with cocoa butter and Witepsol H 15 were relatively short. A correlation has been established between in vitro release and in vivo absorption.     

生物粘附性达那唑缓释栓剂的处方筛选与体外释放度考察

目的 :生物粘附性达那唑栓剂的处方筛选 ,并考察其体外释放规律。方法 :以羟丙甲基纤维素 (HPMC)为缓释材料 ,将等量聚乙二醇6000(PEG6000)和聚乙二醇600(PEG600)以熔融法制备含不同HPMC量的缓释栓剂 ,考察释放度与HPMC用量之间的关系。结果 :随着HPMC用量增加 ,栓剂释药减慢 ,当HPMC与PEG的比例为1∶6 5时 ,栓剂中药物在体外12h内缓慢释放 ,符合一级释放规律。结论 :生物粘附性骨架材料HPMC能延缓达那唑从栓剂中释放 ,当HPMC与PEG的比例为1∶6 5时栓剂能达到设计要求。     

Improvement of solubility and dissolution properties of clotrimazole by solid dispersions and inclusion complexes

Solid dispersions of a slightly water-soluble drug, clotrimazole, were prepared in different weight ratios using polyethyleneglycol 4000 and different molecular weight polyvinyl pyrrolidones as carriers. Moreover, binary and ternary β-cyclodextrin complexes were prepared in different molar ratios. Both solid dispersions and β-cyclodextrin complexes were prepared by solvent evaporation technique. A phase solubility method was used to evaluate the effect of the tested carriers on the aqueous solubility of clotrimazole. The dissolution of all the preparations was tested using the USP paddle method. The selected solid dispersions and inclusion complexes were characterized by differential scanning calorimetry and X-ray powder diffractometry studies, and results clarified the role of the tested carriers in decreasing the crystallinity of clotrimazole and complexing abilities. Based on physical characters and in vitro drug release pattern, polyvinylpyrrolidone solid dispersions (1:1 weight ratio) and ternary cyclodextrin complexes (clotrimazole-β-cyclodextrin complexes with either polymer, 1:1 molar ratio) were selected as ideal batches for suppositories. Suppocire AM/50 mg carbopol 940, was chosen as a suppository base and the suppositories were prepared by molding technique. The prepared suppositories were characterized for weight variation, softening time and drug content. All these properties were found to be ideal. The in vitro drug release pattern was determined in citrate buffer (pH 4.5) containing 1% sodium lauryl sulfate. The in vitro release of clotrimazole from its solid dispersions and inclusion complexes incorporated suppositories was markedly improved when compared to the intact drug incorporated suppositories. Polyvinyl pyrrolidone solid dispersions incorporated suppositories were found to possess excellent antifungal activity.     

Characterization of ternary solid dispersions of itraconazole, PEG 6000, and HPMC 2910 E5

In order to reduce the crystallinity of PEG 6000, blends were prepared by spray drying and extrusion with the following polymers; PVP K25, PVPVA 64, and HPMC 2910 E5. The maximal reduction of crystallinity in PEG 6000 was obtained by co-spray drying with HPMC 2910 E5. In the next step the model drug Itraconazole was added to the blend and the resulting ternary solid dispersions were characterized. The results of this study show that the addition of PEG 6000 to the Itraconazole/HPMC 2910 E5 system leads to phase separation that in most cases gives rise to recrystallization of either PEG 6000 or Itraconazole. For all ternary dispersions containing 20% of Itraconazole the drug was highly amorphous and the dissolution was improved compared to the binary 20/80 w/w Itraconazole/HPMC 2910 E5 solid dispersion. For all ternary dispersions containing 40% of Itraconazole, the drug was partially crystalline and the dissolution was lower than the dissolution of the binary 40/60 w/w Itraconazole/HPMC 2910 E5 dispersion. These results show that provided Itraconazole is highly amorphous the addition of PEG 6000 to HPMC 2910 E5 leads to an increase in drug release.     

Influence of water soluble additives and HPMCP on drug release from sureleaseê-coated pellets containing tamsulosin hydrochloride

The objective of this study was to investigate the influence of various water-soluble additives and HPMCP as an enteric polymer into Surelease for the developement of oral controlled release system containg tamsulosin hydrochloride. The drug loaded pellets were coated with only Surelease or Surelease containing HPMC, PEG 4000, mannitol and HPMCP (20% w/w). In case of HPMC and PEG 4000 as additives into Surelease film, the rapid drug release was observed in pH 1.2 while the higher drug release was achieved by adding HPMCP into Surelease as well as by increasing the amount of HPMCP (10, 20, and 30% w/w) in pH 7.2. The incorporation of HPMCP into Surelease showed pH-denpendent drug release due to its pH-dependent nature. Therefore, the incorporation of HPMCP into Surelease based on aqueous coating formulation is an effective way to develop oral controlled release delivery systems containing tamsulosin hydrochloride.     

In situ gelling, bioadhesive nasal inserts for extended drug delivery: in vitro characterization of a new nasal dosage form.

The purpose of this study was the preparation and characterization of sponge-like, in situ gelling inserts based on bioadhesive polymers. Hydrophilic polymers (carrageenan, Carbopol, chitosan, hydroxypropyl methylcellulose (HPMC) K15M and E5, sodium alginate, sodium carboxy methylcellulose (NaCMC), polyvinyl pyrrolidone (PVP) 90, xanthan gum) were dissolved with/without the model drug oxymetazoline HCl in demineralized water and lyophilized into small inserts. The drug release, water uptake, mechanical properties, X-ray diffraction and bioadhesion potential of the nasal inserts were investigated. A sponge-like structure of nasal inserts was formed with amorphous, but not with crystalline polymers during the freeze-drying process. The insert hardness increased with the glass transition temperature of the polymer (PVP25相似文献   

茶碱脉冲栓剂的制备及体外释药性考察

目的:制备茶碱脉冲栓剂并评价其体外释药性质。方法:以处方基质中泊洛沙姆、羧甲基纤维素钠(CMC-Na)、聚乙二醇6000(PEG6000)、PEG400的不同用量为因素,以释药时滞及累积释药率为指标采用单因素法筛选栓剂处方组成,并考察填充不同内容物(茶碱原料、茶碱-PVP物理混合物和茶碱-PVP固体分散体)的栓剂的累积释药率。结果:较优基质处方组成为70%泊洛沙姆、6%CMC-Na、12%PEG6000、12%PEG400,其体外释药时滞为4h,90min累积释药率为85%以上;3种填充不同内容物的栓剂累积释药率分别为58.8%、65.8%、91%。结论:所制茶碱脉冲栓剂具有较好的脉冲释药作用。     

Mucoadhesive patches of Salbutamol sulphate for unidirectional buccal drug delivery: development and evaluation

Mucoadhesive buccal patches of Salbutamol Sulphate were prepared using five different polymers (polyvinylpyrrolidone [PVP]), polyvinyl alcohol [PVA], water soluble chitosan [CH(WS)], acid soluble chitosan [CH(AS)], hydroxypropyl methyl cellulose [HPMC])in various proportions and combinations (CH(WS)/PVP/HPMC, CH(WS)/PVA/HPMC, CH(AS)/PVP/HPMC, and CH(AS)/PVA/HPMC). A 3(2) full factorial design was used to design the experiments. A total of 72 patches were prepared. Thickness of the patches ranged between 0.3±0.003 and 0.6±0.009 mm. Mass of the patches were in the range of 68.12±4.6 to 95.02±7.2 mg. Patches showed increased mass whenever PEG -400 was used as plasticizer. The surface pH of patches were acidic to neutral (pH 4-pH 7). Patches showed satisfactory drug loading efficiency (85%to 97%). Eight formulations(C9, C18, C27, C36, D9, D18, D27, and D36)-which showed high folding endurance- were selected for further characterization. Patches with PEG -400 showed higher swelling index when compared to PG. The residence time of the patches ranged between 115 min and 120 min. Formulation C18 showed the maximum in vitro drug release of 101.4 % over a period of 120 min. Formulations D36 and C36 were best fitted to Higuchi model. The remaining formulations were best fitted to the Korsmeyer-Peppas model. Drug permeation was fast and showed the similar profile as that of the in vitro drug release. Patches were stable, during and at the end of the accelerated stability study.     

阿奇霉素缓释阴道栓的处方优化

目的:优化阿奇霉素缓释阴道栓的处方。方法:采用硬脂酸聚烃氧酯(S-40)为基质,以羟丙基甲基纤维素(HPMC)为缓释材料、甘油为保湿剂等制备阿奇霉素缓释阴道栓。以累积释药百分率和栓剂硬度为考察指标、8%HPMC和甘油在处方中的用量为考察因素,采用正交设计法进行处方优化,并进行验证试验及体外释药模型拟合。结果:优化后处方组成为阿奇霉素6g,8%HPMC23.52g,甘油29.40g,无水乙醇3g,尼泊金乙酯0.59g,S-40294g。由优化后处方制备的3批栓剂平均含量99.5%,硬度符合要求,体外释放重复性和均一性良好,180min时累积释药百分率均大于98%,体外释药动力学符合Higuchi方程。结论:优化后的阿奇霉素缓释阴道栓处方可行,制备工艺稳定,重复性好,符合缓释制剂要求。     

盐酸二甲双胍胃漂浮片的制备及体外释放研究

目的探讨盐酸二甲双胍胃漂浮片的制备及体外释放。方法采用干法直接压片法,以羟丙甲纤维素为主要骨架材料,以十八醇和碳酸氢钠作助漂剂制备盐酸二甲双胍胃漂浮缓释片。对影响释药的因素如骨架材料、碳酸氢钠含量、释放介质等进行考察,并在此基础上采用正交试验设计筛选出最优处方。结果片剂具有良好的漂浮特性,药物释放时间可达6 h以上。最优处方:每片含盐酸二甲双胍60 mg,HPMC 108 mg,十八醇10 mg,NaHCO35.2 mg,乙基纤维素14 mg,聚乙二醇(PEG6000)0.1mg。结论药物通过扩散和凝胶骨架溶蚀共同作用释放,释药曲线较好地符合单指数加Higuchi平方根律方程。     

盐酸曲马多多层控释骨架片的体外释药规律

以羟丙基甲基纤维素为主要骨架材料 ,将高水溶性药物盐酸曲马多制成多层控释骨架片 ,研究了影响多层骨架片体外释药速率的因素。结果表明 ,通过改变盐酸曲马多多层骨架片各层组成 ,可以灵活地改变其释药速率。多层骨架片系统可以避免初始的突释现象 ,而且其体外释药规律可以接近零级。因此 ,多层骨架片系统是制备高水溶性药物控释制剂的有效方法     

盐酸丁螺环酮缓释片的制备及其体外释放研究

目的:制备盐酸丁螺环酮缓释片,并考察其释药行为及其影响因素。方法:采用羟丙基甲基纤维素(HPMC)为亲水凝胶骨架材料,乙基纤维素(EC)为阻滞剂,湿法制粒制备盐酸丁螺环酮缓释片。考察不同释放递质,HPMC、EC的不同含量及不同黏度对该缓释片体外释放的影响。结果:制备出的缓释片24h的释药量超过90%,释药速率符合Higuchi方程。HPMC、EC含量的增加均会减慢缓释片的释放;随着HPMC黏度的增大,片剂的释药速率减慢,而EC的黏度及释放递质对释药速率均无明显影响。结论:以HPMC和EC为骨架材料,能制备出持续释药24h的盐酸丁螺环酮缓释片。     

以HPMC为骨架的盐酸丁螺环酮缓释片的制备

以HPMC单用或与卡波姆934p合用，制备盐酸丁螺环酮缓释片并进行体外释放度的测定。结果表明本品可持续释药24h，且加入卡波姆比单用HPMC为骨架具有更好的缓释效果。     

盐酸二甲双胍缓释骨架片的研制

目的:制备盐酸二甲双胍缓释骨架片.方法:采用亲水性高分子材料HPMC为骨架,制备盐酸二甲双胍缓释片,并用正交试验法优选制剂工艺.结果:以药物与20%HPMC K4M及乳糖适量混合,用10%PVP乙醇液为黏合剂,湿法制粒压片为最佳工艺.结论:本品制备工艺简便,药物体外释放接近Higuchi模型(Q=28.892 7t1/2 1.170 4,r=0.995),T50=2.87 h,Td=4.65 h,能维持药物12 h内缓慢释放.     

盐酸地尔硫延迟起释型缓释片的研制

目的制备盐酸地尔硫(diltiazam hydrochloride,DIL)延迟起释型缓释片,解析释药机制,并考察外衣层组成对药物释放的影响。方法用干压包衣技术制备盐酸地尔硫的延缓片,用释药时滞(T_lag)及释药速率常数(k)将各因素(外衣层中的HPMC用量和粘度,PVP K30用量、EC粘度及压片压力)对药物的释放效果进行评价。结果 HPMC用量或粘度增大,T_lag延长,k减慢;PVP K30用量增大,T_lag减短,k加快;在一定范围内EC粘度及压片压力波动对释药行为无影响。结论延缓片中药物主要是通过溶蚀机制释放,外衣层的溶蚀速率是决定释药时滞的关键因素。     

盐酸丁螺环酮口腔粘附片的制备及释药机理初步研究

口腔粘附制剂是指将药物与适宜的生物粘附剂等辅料经加工制成的制剂 ,使用时将制剂粘附于口腔粘膜上 ,恒定释放药物。口腔粘附制剂不仅能够局部治疗口腔疾病 ,而且药物可以透过口腔粘膜吸收 ,进入血液循环 ,起到全身治疗作用。药物经口腔粘膜吸收时 ,避免了胃肠道及肝脏的首过作用 ,因此对于易受胃肠道酸和酶降解的蛋白质、肽类及其他大分子药物 ,以及受肝脏首过代谢作用严重的药物 ,通过口腔粘膜给药可以提高生物利用度[1] 。本文选择的药物盐酸丁螺环酮 (ｂｕｓｐｉｒｏｎｅｈｙｄｒｏｃｈｌｏｒｉｄｅ)是一个新型的非苯二氮类抗焦虑症…     

盐酸溴己新缓释片的制备及体外释放度研究

目的制备盐酸溴已新（Bromhexine hydrochloride．BH）缓释片。方法以聚乙烯毗咯烷酮（PVP）为载体。将盐酸溴己新制成固体分散体．再以羟丙甲基纤维素（HPMC）为骨架材料,采用湿法制粒压片制备盐酸溴己新缓释片,并进行体外释放度试验。结果所制备的缓释片12h内呈现良好的缓释特性,符合Higuchi方程。结论盐酸澳己新缓释片体外释药缓慢、平稳,符合设计要求。     

盐酸昂丹司琼渗透泵片的制备与体外释放

目的制备盐酸昂丹司琼渗透泵型控释片剂(OND-OPT)并考察体外释药特性。方法以锅包衣法制备OND-OPT。通过释放度试验筛选处方并考察OND-OPT的释放特性；通过均匀设计试验建立持续释药时间与衣膜厚度、衣膜中PEG含量和释药孔孔径的关系；考察OND-OPT的释药机制。结果释药孔朝向对不含HPMC的制剂释药有明显影响，而对含HPMC的制剂释药无影响。持续释药时间与衣膜厚度和衣膜中PEG含量有关，与释药孔孔径无显著关系。OND-OPT主要以渗透泵机制释放药物。结论通过调节衣膜厚度和衣膜中PEG含量，OND-OPT可以实现理想的药物控制释放。     

盐酸帕罗西汀肠溶缓释片的制备及体外释放研究

目的制备盐酸帕罗西汀肠溶缓释片,并对其体外释放度进行考察。方法采用HPMC K100LV和HPMC K4M作为骨架材料,以水乳糖为填充剂制备盐酸帕罗西汀缓释片芯,再使用Eudragit L30D-55包肠溶衣,制成盐酸帕罗西汀肠溶缓释片,并采用f_2相似因子法评价自制制剂和参比制剂在释放介质中的体外释放行为。结果体外释放度实验显示,自制制剂和参比制剂的f_2相似因子值大于50。结论制备的盐酸帕罗西汀肠溶缓释片的释药行为与参比制剂的体外释放行为相似。     

The influence of concentration on the release of drugs from gels and matrices containing Methocel

The release of propranolol hydrochloride from hydroxypropylmethylcellulose and methylcellulose matrices has been examined at constant cellulose ether contents. As the drug content decreased, the release rate of propranolol became disproportionately higher. HPMC K4M, HPMC F4M and HPMC E4M all performed similarly. However, with methylcellulose matrices, a burst release at low drug levels was apparently due to a failure of the matrix to maintain integrity. Explanations were sought on the basis of diffusional studies. Apparent diffusion coefficients were in the order of 3.1–3.8 × 10⁻⁶ cm² s⁻¹ for propranolol hydrochloride. Each of the four grades performed similarly. Using similar diffusional studies, but HPMC K15M as the polymer, an apparent diffusion coefficient of 3.6 × 10⁻⁶ cm² s⁻¹ was derived, indicating that the coefficient was independent of molecular weight. The coefficient was dependent on HPMC content decreasing from approx. 5.5 × 10⁻⁶ to 3 × 10⁻⁶ cm² s⁻¹ as the HPMC content was increased from 5 to 15% w/w. The diffusion coefficients of tetracycline hydrochloride were lower and conversion to the free base is postulated as the explanation of previously described anomolous release for this drug from matrix tablets. The tortuosity of the gels was independent of the included drug.