• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Effects of Formulation Factors and Pharmaceutical Quality on Oral Drug Absorption.
【24h】

Effects of Formulation Factors and Pharmaceutical Quality on Oral Drug Absorption.

机译：配方因素和药物质量对口服药物吸收的影响。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The overall objective of this dissertation was to study the effects of formulation factors and pharmaceutical quality on oral drug absorption. Aim 1 investigated the impact of large amounts of 14 commonly used excipients on oral absorption of Biopharmaceutics Classification System (BCS) class 3 drugs. FDA and EMA allow biowaivers for BCS class 3 drugs but indicate that test product should be qualitatively the same and quantitatively very similar in composition to the reference product. Capsules containing combination of three excipients in quantities larger than those present in immediate-release (IR) solid oral dosage forms were investigated. Results indicated that 12 out of 14 common excipients were found to not impact BCS class 3 drug absorption in humans, such that these excipients need not be qualitatively the same nor quantitatively very similar to reference, but rather simply be not more than the quantities studied here. Aim 2 addressed the question concerning therapeutic equivalence of brand and generic lamotrigine tablets. A potential contributor to such concerns is pharmaceutical quality. Biopharmaceutics risk of brand and generic lamotrigine 100 mg tablets from several manufacturers was assessed. Results indicated that lamotrigine's favorable biopharmaceutics from a drug substance perspective and favorable quality characteristics from a tablet formulation perspective suggest multisource lamotrigine tablets to exhibit a low biopharmaceutic risk. Aim 3 investigated impact of in vitro dissolution volume on dissolution of IR tablets of three anti-epileptic drugs (AEDs), levetiracetam, lamotrigine, and oxcarbazepine. FDA recently issued two draft guidances that recommend 500 mL dissolution media for BCS class 1 and 3 drugs. Results indicate that reducing dissolution volume from 900 mL to 500 mL was of no apparent significance when at least 3-fold sink conditions prevailed at 500 mL. However, reducing dissolution volume from 900 mL to 500 mL slowed dissolution in the absence of 3-fold sink conditions, per f2. Aim 4 describes the case report of an epileptic patient who observed levetiracetam extended-release (ER) tablet remnants in stool from one generic source but not others. Analysis of tablet remnant indicates that no drug remained in the tablet, even though tablets are mostly composed of drug.
机译：本文的总体目标是研究配方因素和药物质量对口服药物吸收的影响。目标1研究了14种常用赋形剂对生物药物分类系统（BCS）3类药物口服吸收的影响。 FDA和EMA允许BCS 3类药物获得生物豁免，但指出测试产品的成分应与参考产品在质量上相同且在数量上非常相似。研究了包含三种赋形剂组合的胶囊，其数量大于速释（IR）固体口服剂型中的赋形剂。结果表明，发现14种常见赋形剂中有12种不影响BCS 3类药物在人体中的吸收，因此这些赋形剂在质量上不必与参考文献相同，也不必在数量上非常相似，而仅是不超过此处研究的数量。 。目标2解决了有关品牌和通用拉莫三嗪片的治疗等效性的问题。引起此类担忧的潜在因素是药品质量。评估了多家制造商生产的品牌和通用拉莫三嗪100 mg片剂的生物制药风险。结果表明，拉莫三嗪从原料药的角度看是有利的生物制药，从片剂的角度看是有利的质量特性，这表明多源拉莫三嗪片具有较低的生物制药风险。目的3研究了体外溶出量对三种抗癫痫药（AED），左乙拉西坦，拉莫三嗪和奥卡西平的IR片溶出的影响。 FDA最近发布了两份指南草案，建议BCS 1类和3类药物使用500 mL溶出介质。结果表明，当溶出条件从900 mL降至500 mL时，至少有3倍的水槽条件存在于500 mL时，没有明显意义。但是，在没有3倍水槽条件下，每f2将溶解量从900 mL减少到500 mL会减慢溶解速度。目的4描述了一名癫痫患者的病例报告，该患者从一种通用来源中但未从其他通用来源中观察到粪便中的左乙拉西坦缓释片残留。对片剂残留物的分析表明，即使片剂主要由药物组成，片剂中也没有残留药物。

著录项

  • 作者

    Vaithianathan, Soundarya.;

  • 作者单位

    University of Maryland, Baltimore.;

  • 授予单位 University of Maryland, Baltimore.;
  • 学科 Pharmaceutical sciences.
  • 学位 Ph.D.
  • 年度 2016
  • 页码 154 p.
  • 总页数 154
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 地球物理学;
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号