School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.
Drug Dev Ind Pharm. 2013 Aug;39(8):1167-74. doi: 10.3109/03639045.2012.681053. Epub 2012 Apr 27.
Mini-tablets are compact dosage forms, typically 2-3 mm in diameter, which have potential advantages for paediatric drug delivery. Extended release (ER) oral dosage forms are intended to release drugs continuously at rates that are sufficiently controlled to provide periods of prolonged therapeutic action following each administration, and polymers such as hypromelllose (HPMC) are commonly used to produce ER hydrophilic matrices.
To develop ER mini-tablets of different sizes for paediatric delivery and to study the effects of HPMC concentration, tablet diameter and drug solubility on release rate.
The solubility of Hydrocortisone and theophylline was determined. Mini-tablets (2 and 3 mm) and tablets (4 and 7 mm) comprising theophylline or hydrocortisone and HPMC (METHOCEL™ K15M) at different concentrations (30, 40, 50 and 60%w/w) were formulated. The effect of tablet size, HPMC concentration and drug solubility on release rate and tensile strength was studied.
Increasing the HPMC content and tablet diameter resulted in a significant decrease in drug release rate from ER mini-tablets. In addition, tablets and mini-tablets containing theophylline produced faster drug dissolution than those containing hydrocortisone, illustrating the influence of drug solubility on release from ER matrices. The results indicate that different drug release profiles and doses can be obtained by varying the polymer content and mini-tablet diameter, thus allowing dose flexibility to suit paediatric requirements.
This work has demonstrated the feasibility of producing ER mini-tablets to sustain drug release rate, thus allowing dose flexibility for paediatric patients. Drug release rate may be tailored by altering the mini-tablet size or the level of HPMC, without compromising tablet strength.
微型片剂是一种直径通常为 2-3 毫米的紧凑型剂型，在儿科药物输送方面具有潜在优势。延长释放（ER）口服剂型旨在以足够控制的速度连续释放药物，以在每次给药后提供延长的治疗作用期，并且通常使用聚合物如羟丙甲纤维素（HPMC）来生产 ER 亲水基质。
开发用于儿科给药的不同大小的 ER 微型片剂，并研究 HPMC 浓度、片剂直径和药物溶解度对释放速率的影响。
确定了 Hydrocortisone 和茶碱的溶解度。微型片剂（2 和 3 毫米）和片剂（4 和 7 毫米）由茶碱或 Hydrocortisone 和 HPMC（METHOCEL™ K15M）组成，浓度分别为 30、40、50 和 60%w/w。研究了片剂大小、HPMC 浓度和药物溶解度对释放速率和拉伸强度的影响。
增加 HPMC 含量和片剂直径会导致 ER 微型片剂中药物释放速率显著降低。此外，含有茶碱的片剂和微型片剂比含有 Hydrocortisone 的片剂和微型片剂更快地溶解药物，这说明了药物溶解度对 ER 基质中释放的影响。结果表明，通过改变聚合物含量和微型片剂直径可以获得不同的药物释放曲线和剂量，从而使剂量具有灵活性，以适应儿科患者的需求。
这项工作表明，可以生产 ER 微型片剂以维持药物释放速率，从而使儿科患者的剂量具有灵活性。可以通过改变微型片剂的大小或 HPMC 的水平来调整药物释放速率，而不会影响片剂的强度。
