新的溶解方法用于长效注射剂的药物释放测试
Nilesh Malavia1, Quanying Bao1, Diane J Burgess1
1University of Connecticut, Department of Pharmaceutical Sciences, Storrs, CT 06269 USA.
International journal of pharmaceutics
|August 25, 2024
概括
新型适配器改善了长效注射剂的药物释放测试,使持续药物输送系统可靠的体外-体内相关性 (IVIVC) 成为可能. 这些适配器提高了亲肠道产品的可复制性和区分能力.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 分析化学 分析化学
背景情况:
- 长效的门内药物需要可靠的体外释放测试来进行开发和通用药物的批准.
- 目前用于测试长效注射剂释放药物的方法具有很高的可变性,可重复性差,并且缺乏体内相关性.
- 由于释放时间短,现有的方法往往不适合开发体外-体内相关性 (IVIVC).
研究的目的:
- 开发和验证USP型II和IV溶解装置的新型适配器,以改进长效亲肠道产品的药物释放测试.
- 评估这些适配器在可复制性,可变性,区分能力和释放持续时间方面的性能.
- 评估基于适应器的方法是否适合在体外与体内相关性 (IVIVC) 的发展.
主要方法:
- 开发了三种新型适配器设计:两个开放式 (圆形,圆形) 用于USP-type-IV设备,一个封闭式 (圆形) 用于USP-type-II设备.
- 使用Depo Provera 150® (长效注射悬浮剂) 和其Q1/Q2等效的验证.
- 使用USP-type-II适配器评估在位形成植入物的RISPERIDONE.
主要成果:
- 这三种新型适配器设计都成功地保留了悬浮物和植入物,实现了3-6周和最多一个月的释放时间.
- 方法表现出良好的可重现性 (RSD≤5%),最小的可变性和强大的区分能力.
- 对于Depo SubQ Provera 104®及其同类产品,使用USP型IV装置与形适配器,成功建立了A级IVIVC.
结论:
- 开发的新型适配器显著提高了长期起作用的亲肠道药物产品的体外释放测试,包括悬浮剂和植入物.
- 基于适配器的溶解方法适合IVIVC开发,解决当前测试协议的局限性.
- 这些适配器为可靠的体外释放测试提供了一个有前途的解决方案,用于各种长期起作用的亲肠道药物产品.
相关概念视频
01:23Factors Affecting Dissolution: Particle Size and Effective Surface Area
766
Dissolution kinetics, an essential aspect of oral drug delivery, is significantly influenced by the drug's particle size. According to the Noyes-Whitney dissolution model, the dissolution rate correlates directly with the drug's surface area. The larger the surface area, the higher the drug's solubility in water, leading to a faster drug dissolution rate. Reducing particle size increases the effective surface area, enhancing the dissolution process. Micronization and nanosizing are...
766
01:28Factors Influencing Drug Absorption: Pharmaceutical Parameters
123
Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...
123
01:15Theories of Dissolution: Diffusion Layer Model
715
Dissolution, the process by which drug particles dissolve in a solvent, is explained by the diffusion layer model, a theoretical framework that simulates the absorption of oral drugs and allows us to analyze experimental data.
This process starts with a thin layer, saturated with the drug, forming at the interface between the solid and liquid. The solute then diffuses from this layer into the main solution. The Noyes-Whitney equation suggests that the rate of dissolution relies on the diffusion...
This process starts with a thin layer, saturated with the drug, forming at the interface between the solid and liquid. The solute then diffuses from this layer into the main solution. The Noyes-Whitney equation suggests that the rate of dissolution relies on the diffusion...
715
01:27Factors Influencing Drug Absorption: Drug Dissolution
434
The pharmacokinetic journey of drugs from solid oral dosage forms into systemic circulation is multifaceted. It begins with disintegration, a prerequisite ensuring a solid dosage form's subdivision into minute particles. Dissolution occurs next as these granulated entities solubilize in gastrointestinal fluids. This solubilization is crucial for the succeeding stage, permeation, which describes the traversal of the drug across the intestinal membrane and its subsequent entry into the blood...
434
01:09Theories of Dissolution: The Danckwerts' Model and Interfacial Barrier Model
278
Various dissolution theories provide insight into the factors that influence the dissolution rate. Danckwerts' Model suggests that turbulence, rather than a stagnant layer, characterizes the dissolution medium at the solid-liquid interface. In this model, the agitated solvent contains macroscopic packets that move to the interface via eddy currents, facilitating the absorption and delivery of the drug to the bulk solution. The regular replenishment of solvent packets maintains the...
278
01:21Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism
291
Polymorphism refers to the existence of a drug substance in multiple crystalline forms, known as polymorphs. Recently, this term has been expanded to include solvates (forms containing a solvent), amorphous forms (non-crystalline forms), and desolvated solvates (forms from which the solvent has been removed).
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
291