清开灵口服制剂安全性风险分析

目的 通过对清开灵口服制剂安全性风险的分析,为临床合理用药提供参考。方法 对国家药品不良反应监测系统（2015年1月1日至2021年12月31日）及国内外文献数据库（建库至2021年12月31日）中清开灵口服制剂相关不良反应情况、监管机构发布的有关清开灵口服制剂风险控制措施等进行分析。结果 国家药品不良反应监测系统共收到涉及清开灵口服制剂的不良反应/事件报告7 185例,累及胃肠系统、皮肤、神经系统等多个系统-器官;文献报道的清开灵口服制剂不良反应/事件累及系统-器官与国家药品不良反应监测系统中的报告数据基本一致。结论 清开灵口服制剂相关不良反应涉及多个系统-器官,临床应关注清开灵口服制剂相关不良反应,促进安全合理用药。     

国内外已上市连续制造口服固体制剂药学审评内容的研究与启示

目的：通过对国内外已上市连续制造口服固体制剂药学审评内容的研究,为开展我国连续制造口服固体制剂的药学审评工作、制定连续制造相关的指导原则或标准、推进ICH《Q13：原料药和制剂的连续制造》指导原则在我国的实施与转化提供科学理论借鉴。方法：在国家药品监督管理局、美国食品药品监督管理局、欧洲药品管理局、日本药品及医疗器械综合机构和英国药品和健康产品管理局的网站,查询以连续制造生产模式获批的口服固体制剂审评报告,从中提取与连续制造生产模式相关的药学审评内容,通过对比分析等研究方法,阐述各国药品监管机构对连续制造口服固体制剂的药学审评关注点,并形成我国药品审评机构未来对此类药品的药学审评启示。结果与结论：连续制造口服固体制剂的药学审评工作应针对原料药和辅料、制剂研发、生产工艺和工艺控制、批次描述、工艺验证、产品放行、稳定性考察、现场检查、上市后变更等方面进行重点审评。此外,在制定连续制造生产模式相关的指导原则和标准时也应将其考虑在内,以监管促发展,不断推进我国口服固体制剂的连续制造研发新局面。     

中国药典1985年版二部新载药品简介

中华人民共和国药典1985年版二部(下简称85版二部)现已出版发行。与中国药典1977年版二部相比,删除药品及其制剂品种147个,淘汰品种多为疗效差、毒、副作用大的药品。85版二部新收载126个药品及制剂。现将新收载药品中较新或疗效较好的四种药品简介如下:1.羟氨苄青霉素别名阿莫西林,系一广谱半合成青霉素,其体外抗菌谱与氨苄青霉素相似。但体内杀菌效果较氨苄青霉素强,本品口服吸收良好且完全,不受食物影响,口服1h左右,血浓度即达高峰,疗效     

儿童口服缓控释制剂研究进展

口服缓控释制剂可减少给药次数、提高患者依从性、减少不良反应发生率,与特定年龄儿童的需求相匹配,是目前药物剂型研发的热点。我们通过调研国内外口服缓控释制剂发展现状及儿童可用的上市口服缓释制剂药品品种情况,对儿童口服缓控释制剂发展现状进行阐述和总结,以期为中国儿童用药研发和应用提供参考意见。     

口服固体制剂仿制药一致性评价体内外相关性研究进展

目前仿制药在我国医药市场占据很大规模,口服固体制剂一致性评价得到的关注最多。其中药品的体内外相关性一直是研究者关注的重点及难点,如何通过控制再评价品种与参比制剂体外某些特性（如溶出、制剂学因素等）的相似,达到两者体内生物等效,对于缩短药品的一致性评价进度,降低研究成本具有重大的意义。就目前口服固体制剂一致性评价体内外相关性的相关研究进展进行综述,以期为开展口服固体制剂一致性评价研究工作提供参考。     

国家食品药品监督管理局发布2009年第4期药品质量公告

为加强药品监管,保障公众用药安全,根据2009年国家药品评价抽验计划,国家食品药品监督管理局近期在全国范围内组织对布洛芬制剂、地高辛片、尼群地平片、盐酸溴己新制剂、格列本脲片、双黄连口服制剂、双黄连注射剂、消渴丸、参麦注射液、血塞通注射液、八珍益母制剂、格列吡嗪制剂、硝苯地平制剂、盐酸雷尼替丁胶囊、柴胡注射液、脉络宁注射液、硫酸沙丁胺醇制剂、奥美拉唑制剂18个国家基本药物品种进行了评价抽验,并于日前公布了抽验结果。     

口服控释制剂质量标准的建立

质量标准不仅反映了药品是否满足安全、有效的基本要求,对于口服控释制剂,质量标准同时是对控释技术的评价与反映。本文依据现行药典内容和要求,介绍口服控释制剂与药物释放度相关的检查项建立原则与影响因素。     

我院口服钙制剂的应用分析

目的通过了解我院口服钙制剂的应用情况,分析其应用的合理性及必要性并预测发展趋势。方法通过调查我院2003年~2005年的口服钙制剂的应用情况,并统计分析该类药品的品种、用药金额、DDDs。结果含碳酸钙尔奇D和凯思立D不论是用药金额还是DDDs均排在前列。结论我院口服钙制剂主要以碳酸钙为主要药物,同时应合理补钙。     

酮康唑口服制剂的肝毒性

日前,国家药品不良反应监测中心发布了第40期《药品不良反应信息通报》,提醒医务工作者、药品生产经营企业以及公众警惕酮康唑口服制剂的严重肝毒性问题。酮康唑口服制剂是咪唑类抗真菌药,在我国上市的有片剂和胶囊剂,规格为200毫克,商品名     

我院住院药房口服固体制剂标记情况浅析

目的：为我院住院药房口服固体制剂的标记提供参考。方法：对我院住院药房实行中心摆药的共348种口服固体制剂标记情况按不同形式进行分类统计,并分析各类标记形式的作用。结果：未标记的口服固体制剂为218种;而有标记的口服固体制剂为130种,占中心摆药药品总数的37.36%。药品标记形式大致可以分为6类：Ⅰ类：标记了药品商品名;Ⅱ类：标记了药品通用名;Ⅲ类：标记了药品商品名或药品通用名,并标注生产企业名;Ⅳ类：标记了药品生产企业名;Ⅴ类：标记了主药含量;Ⅵ类：标记了不明意图的记号。采用药品名或生产企业名＋主药含量进行标记易于识别和核对,一些制剂采用异形片形式或者丸剂形式等,即使没有标记也很容易识别和核对。结论：药品生产企业应在口服固体制剂上标记通用名＋主药含量,以便识别和核对,利于保证患者用药安全。     

In vitro and in vivo techniques used in drug development for evaluation of dose delivery of inhaled corticosteroids

Oral inhaled corticosteroids are important in the treatment of asthma since their delivery is targeted directly to the lung, which is the site of action. Triamcinolone acetonide (TAA) is an effective and safe corticosteroid that is marketed as a metered-dose inhaler (MDI) with an integrated spacer (Azmacort) for the treatment of asthma. Due to the phasing out of chlorofluorocarbon (CFC) propellants, Azmacort has been reformulated with a non-CFC propellant. Due to the complexities of oral inhaled formulations and the topical nature of drug delivery to the lung for efficacy, the reformulation of oral inhaled MDIs requires careful consideration and support throughout their development, using a combination of in vitro and in vivo studies to ensure clinical comparability for both efficacy and safety. This paper describes a chronological series of studies designed to support the reformulation of Azmacort. These included in vitro studies to estimate respirable fraction, in vivo pulmonary deposition studies, in vivo pharmacokinetic-pharmacodynamic studies to estimate the systemic effects of each formulation, and final clinical studies in adult and pediatric patients to confirm the clinical comparability of the new formulation of Azmacort. The results of these studies, performed at various stages during the development of new formulations, were critical in guiding the reformulation efforts for Azmacort.     

Quantifying the Value of Orally Delivered Biologic Therapies: A Cost-Effectiveness Analysis of Oral Semaglutide

Oral semaglutide, which has undergone multiple phase 3 clinical trials, represents the first oral biologic medication for type 2 diabetes in the form of a daily capsule. It provides similar efficacy compared with its weekly injection counterpart, but it demands a dose on the order of 100 times as high and requires more frequent administration. We perform a cost effectiveness analysis using a first and second order Monte Carlo simulation to estimate quality-adjusted life expectancies associated with an oral daily capsule, oral weekly capsule, daily injection, and weekly injection of semaglutide. We conclude that the additional costs incurred to produce extra semaglutide for the oral formulation are cost effective, given the greater quality of life experienced when taking a capsule over a weekly injection. We also demonstrate that the potency of semaglutide allows the formulation to be cost effective, and less potent drugs will require increased oral bioavailability to make a cost effective oral formulation.     

Efficacy and economic evaluation of pilocarpine in treating radiation-induced xerostomia

Xerostomia, resulting from therapeutic irradiation of the head and neck, can be debilitating and destructively impact the patient's quality of life. The first priority of treatment of radiation-induced xerostomia should be to preserve oral and dental health. Therapeutic doses of fluoride and meticulous dental hygiene are the treatments of choice for this purpose. Measures taken to prevent superinfection with cariogenic bacteria and fungi are also important. In addition to minimising damage to the dentition, it is important to provide palliative therapy to help the patient live a more normal life. Salivary substitutes help some patients but muscarinic, cholinergic sialogogues provide a more physiological replacement in those patients who have measurable residual salivary function. An oral formulation of pilocarpine hydrochloride is approved to treat radiation-induced xerostomia. In such cases, it has been shown to effectively stimulate salivary flow and relieve subjective symptoms associated with oral dryness. Administration of this drug is associated with predictable, but generally tolerable, adverse effects. Similar drugs, approved for other indications, have been shown to produce comparable results. These drugs are generally less expensive than the oral formulation of pilocarpine. As treatment of irradiation-induced xerostomia with muscarinic, cholinergic sialogogues is palliative, not curative, administration of these drugs should be individualised and guided by the patient's willingness to balance symptomatic efficacy with adverse effects and the expense of treatment.     

Coaxial electrospray formulations for improving oral absorption of a poorly water-soluble drug

Development of oral dosage forms containing poorly water-soluble drugs is a major challenge in the pharmaceutical industry. This paper describes the use of coaxial electrospray deposition as a promising formulation technology for oral delivery of poorly water-soluble drugs. The technology produced core-shell particles composed of griseofulvin and poly(methacrylic acid-co-methyl methacrylate) (Eudragit L-100), with a diameter of around 1 μm. The drug phase was in an amorphous state when the griseofulvin core was coated with the Eudragit L-100 shell. The in vitro dissolution and in vivo oral absorption studies revealed that the core-shell formulation significantly improved dissolution and absorption behaviors, presumably because of a reduction in particle size, improvement in dispersity, and amorphization. Results demonstrated that coaxial electrospray deposition possesses great potential as novel formulation technology for enhancing oral absorption of poorly water-soluble drugs.     

纳米载体提高难溶性药物口服生物利用度的研究进展

纳米载体是药剂学备受关注的研究领域,作为一类新型给药系统,它能显著提高难溶性药物的溶解度、生物利用度和稳定性,且具有明显的缓释作用,因此得到了广泛的应用。目前常用于提高难溶性药物口服生物利用度的纳米载体有纳米脂质体、固体脂质纳米粒、纳米胶束、和纳米结晶等,它们的粒径、表面性质及其释药环境等是影响纳米载体药物口服吸收的主要因素。本文对纳米载体提高难溶性药物口服生物利用度的研究进展作一综述。     

Chemotherapeutic efficacy of nanoparticle encapsulated antitubercular drugs

Our objective was to evaluate the chemotherapeutic potential of oral poly lactide-co-glycolide (PLG, a synthetic polymer) nanoparticle encapsulated ethambutol in combination with PLG-nanoparticle encapsulated-(rifampicin + isoniazid + pyrazinamide) in a murine tuberculosis (TB) model. Our formulation was prepared by the multiple emulsion technique and administered orally to mice for the biodistribution, pharmacokinetic, and chemotherapeutic studies. A single oral administration of the formulation to mice could maintain sustained drug levels in the plasma for 5 days and in the organs (lungs, liver, spleen) for 7-9 days. There was a striking improvement in the pharmacokinetic parameters such as half-life and mean residence time as compared with free drugs. The relative/absolute bioavailability of the 4 antituberculosis drugs was enhanced several fold. Repeated administration of the formulation did not produce any hepatotoxicity as assessed on a biochemical basis. In M. tuberculosis H₃₇Rv infected mice, just 3 oral doses of the 4-drug formulation administered at every 10th day resulted in undetectable bacilli in the organs replacing 28 conventional doses of free drugs. We concluded that polymeric nanoparticle based oral 4-drug combination bears significant potential to shorten the duration of TB chemotherapy, besides reducing the dosing frequency.     

Nano-encapsulation of azole antifungals: potential applications to improve oral drug delivery

The present study was designed to improve the oral bioavailability of two clinically important antifungal drugs-clotrimazole and econazole. Each drug was encapsulated in nanoparticles of a synthetic polymer (polylactide-co-glycolide, PLG) or a natural polymer (alginate stabilized with chitosan). The nanoparticles were prepared by the emulsion-solvent-evaporation technique in case of PLG and by the cation-induced controlled gelification in case of alginate. Drug encapsulation efficiency was better (>90%) for the alginate formulation compared with the PLG formulation (nearly 50%). The formulations were orally administered to mice and the drugs were analyzed in plasma by a validated HPLC technique. The biodistribution/pharmacokinetic data suggested that there was a controlled drug release for 5-6 days with each of the formulations, compared with unencapsulated drugs, which were cleared within 3-4 h of oral/intravenous administration. There was a striking improvement in the relative and absolute bioavailability of each drug. Further, the drugs were detected in the tissues (lungs, liver and spleen) till 6-8 days in case of nanoparticles whereas free drugs were cleared by 12 h. Overall, the alginate formulation appeared to be better than the PLG formulation. The results emphasize the power of nanotechnology to make the concept of enhancement in oral bioavailability of azole antifungal drugs come to reality.     

Intelligent hydrogels for the oral delivery of chemotherapeutics

A novel approach toward improvements of oral chemotherapeutic formulations has evolved, which combines solubilisation (molecular dispersion) of the hydrophobic anticancer drugs in micelles attached to large macromolecules or microparticles. The large size of the macromolecules or microgels prevents the gel components from being transported into the systemic circulation. The discussed gels comprise copolymers of poly(acrylic acid) (PAA) and Pluronic surfactants, linked via C-C bonds. The Pluronic-PAA copolymers are non-irritating when administered orally. The micelles formed in the Pluronic-PAA solutions and in crosslinked microgels can be loaded with chemotherapeutic drugs and then released in contact with the intestine. The microgels are collapsed at the acidic pH of the stomach and expand, thus releasing the loaded drugs at the pH of the lower gastrointestinal tract. Yet the microgels are mucoadhesive and enable longer retention time and prolonged release in the colon. Ease of preparation and formulation of the drugs with the Pluronic-PAA polymers and gels may enable the wider use of oral chemotherapy, resulting in a better patient compliance and improved quality of life of the patients.     

口服药物吸收中的生物药剂学性质

目的综述药物的生物药剂学性质对药物口服吸收的影响。方法依据本课题组在该领域的工作,查阅国内外30篇相关文献,并结合最新进展进行归纳总结。结果药物的溶解性、稳定性、膜通透性和首过作用等生物药剂学性质是影响药物口服后经胃肠道吸收的主要因素。结论药物的生物药剂学性质显著影响口服药物的吸收,在药物结构设计、制剂处方设计、临床合理用药及口服给药系统开发中应重视评价药物的生物药剂学性质。     

Chemotherapeutic Efficacy of Nanoparticle Encapsulated Antitubercular Drugs

Our objective was to evaluate the chemotherapeutic potential of oral poly lactide-co-glycolide (PLG, a synthetic polymer) nanoparticle encapsulated ethambutol in combination with PLG-nanoparticle encapsulated-(rifampicin + isoniazid + pyrazinamide) in a murine tuberculosis (TB) model. Our formulation was prepared by the multiple emulsion technique and administered orally to mice for the biodistribution, pharmacokinetic, and chemotherapeutic studies. A single oral administration of the formulation to mice could maintain sustained drug levels in the plasma for 5 days and in the organs (lungs, liver, spleen) for 7–9 days. There was a striking improvement in the pharmacokinetic parameters such as half-life and mean residence time as compared with free drugs. The relative/absolute bioavailability of the 4 antituberculosis drugs was enhanced several fold. Repeated administration of the formulation did not produce any hepatotoxicity as assessed on a biochemical basis. In M. tuberculosis H₃₇Rv infected mice, just 3 oral doses of the 4-drug formulation administered at every 10th day resulted in undetectable bacilli in the organs replacing 28 conventional doses of free drugs. We concluded that polymeric nanoparticle based oral 4-drug combination bears significant potential to shorten the duration of TB chemotherapy, besides reducing the dosing frequency.