利培酮长效注射剂的药动学特征和临床应用

微球注射剂系采用生物降解聚合物为骨架将药物包裹于微球内的一种可供注射的剂型，它具有长效、安全和用药方便等优点。现综述国内外刚上市的可缓释2周的利培酮微球注射剂（Risperidal Consta^TM，恒德）的药动学特点和临床应用概况。该制剂用药后可以预测的缓释速率释药和较低血药峰谷浓度波动，体现了制剂药动学的优点。用阳性和阴性症状量表（PANSS）平均分值评价结果表明，精神分裂症患者采用本制剂进行短期（12周）和长期（12个月）试验治疗，除具有肯定的疗效外，在耐受性和锥体外系不良反应方面也优于利培酮片剂和目前临床其他常规制剂。由于可减少住院次数和发作所需专业机构护理次数以及缩短了累积住院期间，从药物经济学角度考虑也具有较好的优势。     

长效微球注射剂的研究进展

长效微球注射剂因可延长药物的作用时间、减少用药次数、改善患者的顺应性而成为当前药剂研究的一大热点。本文通过参考专著及近年来微球注射剂的的相关文献,从微球注射剂的特点、材料、制备方法、应用以及技术局限性等方面阐述了微球注射剂作为长效制剂的研究进展。微球注射剂释药长效可控,应用广泛,具有良好的应用前景。     

从药物经济学角度解析长效利培酮微球注射剂的临床应用

注射用利培酮微球注射剂可以改善精神分裂症患者的依从性,降低疾病复发率及再入院率和因病致残率,并减少整体医疗保健成本。现从药物经济学角度解析长效利培酮微球注射剂在欧美国家治疗精神分裂症的优点,并分析该长效新制剂在我国临床应用的利与弊。     

长效利培酮微球注射剂治疗精神分裂症的对照研究

目的观察利培酮长效注射剂对精神分裂症的疗效及安全性。方法 43例精神分裂症患者被随机分为肌注利培酮微球的研究组(21例)及口服利培酮片剂的对照组(22例),观察12周。于入组时及治疗2、4、8、12周末采用阳性和阴性精神症状评定量表(PANSS)评定疗效,采用副反应量表(TESS)于2、4、8、12周末评定不良反应及安全性。结果两组疗效相当,PANSS评分与基线比均自2周末出现显著差异,对照组震颤、口干、闭经及视物模糊副反应相对明显。结论长效利培酮微球注射剂治疗精神分裂症安全有效,病人耐受性高。     

两种长效曲普瑞林注射剂在Beagle犬体内的药动学研究

目的 研究两种长效曲普瑞林注射剂(达必佳3.75 mg及达菲林3.75 mg)在Beagle犬体内的药动学参数.方法 10条健康雄性Beagle犬随机分成2组,肌注达必佳或达菲林,采用经验证的LC-MS/MS法测定Beagle犬血浆中曲普瑞林浓度.使用DAS 3.2.2软件计算药动学参数.结果 达必佳和达菲林主要药动学参数Cmax为(11.95±2.127)与(27.93±8.752) ng/mL、Tmax为(1.2±0.4)与(0.7±0.3)h、T12为(244.7±99.25)与(239.6±87.50)h、AUC(0-t)为(758.8±111.9)与(492.3±125.9) ng·h·mL-1、AUC(0-x)为(778.9±101.3)与(515.6±125.3) ng·h·mL-1.结论 可采用LC-MS/MS法检测达必佳和达菲林的Beagle犬体内药动学参数.两药在Cmax、AUC(0-t)与AUC(0-x)有差异,但两者血药浓度维持在最低定量限(LLOQ)以上的时间均达到28d以上.     

蛋白多肽类药物长效化技术研究进展

近年来,蛋白多肽类药物因在治疗疾病方面具有显著的优点,普遍受到研究者的青睐;另一方面,蛋白多肽类药物半衰期一般较短,影响患者用药顺应性。结合蛋白多肽类药物药动学特点,总结蛋白多肽类药物长效化方法的研究进展,主要包括氨基酸替代、定点修饰突变、通过基因手段与其他蛋白融合、糖基化、环化、与聚合物缀合、钉合肽,以及新剂型开发等方法,希望能对药物研发工作者有所帮助。     

脑靶向给药技术研究进展

目的了解目前国内外脑靶向给药技术。方法通过文献查阅对药物通过血脑屏障方式进行综述。结果与结论尽管脑靶向给药技术还不尽完善,但目前的研究已展现其实用性和重要意义。     

棕榈酸帕利哌酮长效注射剂仿制药药学研究探究

长效注射剂已逐渐用于抗精神分裂症治疗,棕榈酸帕利哌酮长效注射剂有效控制药物释放,有良好的安全性、临床治疗效果和明显的临床优势,可以一定程度上提高患者依从性。本文通过检索相关国外审评报告和文献资料,概述国内外上市申报的棕榈酸帕利哌酮长效注射剂情况,对此类药物的药学研究进行探讨,提出关注处方工艺和质量控制等研究的考虑,为其研究开发提供一定的参考。     

Microfabrication technologies for oral drug delivery

Micro-/nanoscale technologies such as lithographic techniques and microfluidics offer promising avenues to revolutionalize the fields of tissue engineering, drug discovery, diagnostics and personalized medicine. Microfabrication techniques are being explored for drug delivery applications due to their ability to combine several features such as precise shape and size into a single drug delivery vehicle. They also offer to create unique asymmetrical features incorporated into single or multiple reservoir systems maximizing contact area with the intestinal lining. Combined with intelligent materials, such microfabricated platforms can be designed to be bioadhesive and stimuli-responsive. Apart from drug delivery devices, microfabrication technologies offer exciting opportunities to create biomimetic gastrointestinal tract models incorporating physiological cell types, flow patterns and brush-border like structures. Here we review the recent developments in this field with a focus on the applications of microfabrication in the development of oral drug delivery devices and biomimetic gastrointestinal tract models that can be used to evaluate the drug delivery efficacy.     

Polymeric nanoparticle drug delivery technologies for oral delivery applications

Introduction: Many therapeutics are limited to parenteral administration. Oral administration is a desirable alternative because of the convenience and increased compliance by patients, especially for chronic diseases that require frequent administration. Polymeric nanoparticles (NPs) are one technology being developed to enable clinically feasible oral delivery.

Areas covered: This review discusses the challenges associated with oral delivery. Strategies used to overcome gastrointestinal (GI) barriers using polymeric NPs will be considered, including mucoadhesive biomaterials and targeting of NPs to transcytosis pathways associated with M cells and enterocytes. Applications of oral delivery technologies will also be discussed, such as oral chemotherapies, oral insulin, treatment of inflammatory bowel disease, and mucosal vaccinations.

Expert opinion: There have been many approaches used to overcome the transport barriers presented by the GI tract, but most have been limited by low bioavailability. Recent strategies targeting NPs to transcytosis pathways present in the intestines have demonstrated that it is feasible to efficiently transport both therapeutics and NPs across the intestines and into systemic circulation after oral administration. Further understanding of the physiology and pathophysiology of the intestines could lead to additional improvements in oral polymeric NP technologies and enable the translation of these technologies to clinical practice.     

Patented pulsatile drug delivery technologies for chronotherapy

Introduction: Oral-controlled and modified-release drug delivery systems with zero-order sustained-release kinetics have been developed and proven suitable for meeting increasingly sophisticated therapeutic needs. Nevertheless, the impact of basic chronobiology concepts on the practice of medicine is still ongoing and to address chronotherapy needs, various types of pulsatile drug delivery systems have been innovated. The purpose of this review is to highlight these innovations in the field of chronotherapy.

Areas covered: The present review discusses in depth on recent patents and developments related to pulsatile drug delivery systems with eroding, soluble or rupturable barrier coatings, and systems with capsular structures. Besides focusing on all recent innovations, the review addresses the novelty and feasibility of all upcoming technologies being exploited considering pulsatile drug delivery systems.

Expert opinion: There has been a growing interest in pulsatile delivery, which generally refers to the liberation of drugs following a programmable and well-defined lag phase from the time of administration. From 1981 until the present date, patent publications related to pulsatile drug delivery have shown more promising systems with numerous developments in arena of drug delivery. Future development of chronotherapeutic medications requires proper assessment and integration with other emerging disciplines such as hydrogel and transdermal delivery systems. The selection of the appropriate chronopharmaceutical technology should take into considerations with the ease of manufacturing and the cost-effectiveness.     

Revolutionizing technologies of nanomicelles for combinatorial anticancer drug delivery

Archives of Pharmacal Research - Insufficient efficacy of current single drug therapy of cancers have led to the advancement of combination drug-loaded formulations. Specifically, polymeric...     

Rapidly disintegrating oramucosal drug delivery technologies

In addition to successfully delivering drugs to a specific site within the body, a goal of any drug delivery system is to improve patient compliance. Thus, rapidly disintegrating oramucosal drug delivery systems are the focus of extensive research due to their ability to rapidly and efficiently deliver drugs. These drug delivery systems are able to release the drug as soon as they come into contact with saliva, thus obliviating the need for water during administration which is an attribute that makes them highly attractive for patient groups such as infants, pediatrics and geriatrics. The significant physiological and anatomical structural features of the oral cavity, the rationale behind the formulation and use of rapidly disintegrating technologies for oramucosal drug delivery, and the technologies that are currently available on the market or that are still under various stages of development is also discussed in this review article. The various technologies are described in terms of their methods of formulation and known mechanisms of drug release. The challenges posed by accurate in vitro disintegration and dissolution testing of rapidly disintegrating drug delivery systems employing conventional and the most recent novel methodologies are also discussed, including the use of ex-vivo permeation studies and in vivo models.     

Inhalation drug delivery devices and emerging technologies

Driven by the pharmaceutical industry to realise the full potential of the lungs for local and systemic treatment of diseases, pulmonary drug delivery by inhalation aerosols has been undergoing rapid development in the past decade. This has led to novel invention of aerosol delivery devices including the propellant-driven metered-dose inhalers, dry powder inhalers and atomisers. Closely coupled to these inhaler devices are the formulations and new technologies that are required to produce particles of defined characteristics for improved delivery. This review highlights some of the recent advances in this expanding field.     

Cutting-edge technologies in colon-targeted drug delivery systems

Oral colon-targeted drug delivery systems have gained enormous attention among researchers in the last two decades. The significance of this site-specific drug delivery system can be measured by its usefulness for delivering a variety of therapeutic agents, both for the treatment of local diseases or for systemic therapies. With the arrival of newer innovations, a large number of breakthrough technologies have emerged for targeting a drug molecule to the colon. Researchers have attempted various approaches in the development of these formulation technologies, such as pH-dependent, time-dependent and microflora-activated systems. Recently, a number of approaches have been proposed that utilize a novel concept of di-dependent drug delivery systems, that is, the systems in which the drug release is controlled by two factors: pH and time, and pH and microflora of the colon. This Editorial article is not intended to offer a comprehensive review on drug delivery, but shall familiarize the readers with the formulation technologies that have been developed for attaining colon-specific drug delivery.     

Cutting-edge technologies in colon-targeted drug delivery systems

Oral colon-targeted drug delivery systems have gained enormous attention among researchers in the last two decades. The significance of this site-specific drug delivery system can be measured by its usefulness for delivering a variety of therapeutic agents, both for the treatment of local diseases or for systemic therapies. With the arrival of newer innovations, a large number of breakthrough technologies have emerged for targeting a drug molecule to the colon. Researchers have attempted various approaches in the development of these formulation technologies, such as pH-dependent, time-dependent and microflora-activated systems. Recently, a number of approaches have been proposed that utilize a novel concept of di-dependent drug delivery systems, that is, the systems in which the drug release is controlled by two factors: pH and time, and pH and microflora of the colon. This Editorial article is not intended to offer a comprehensive review on drug delivery, but shall familiarize the readers with the formulation technologies that have been developed for attaining colon-specific drug delivery.     

Brain drug delivery technologies: novel approaches for transporting therapeutics

The blood-brain barrier (BBB) denies many therapeutic agents access to brain tumours and other diseases of the central nervous system (CNS). Despite remarkable advances in our understanding of the mechanisms involved in the development of the brain diseases and the actions of neuroactive agents, drug delivery to the brain remains a challenge. For more than 20 years, extensive efforts have been made to enhance delivery of therapeutic molecules across vascular barriers of the CNS. The current challenge is to develop drug-delivery strategies that will allow the passage of drug molecules through the BBB in a safe and effective manner, and this review will provide an insight into some of the strategies developed to enhance drug delivery across the BBB.