Vaginal Film Drug Delivery of the Pyrimidinedione IQP-0528 for the Prevention of HIV Infection
Vaginal Film Drug Delivery of the Pyrimidinedione IQP-0528 for the Prevention of HIV Infection
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DOI：
10.1007/s11095-012-0715-7
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发表时间：
2012-07-01
影响因子：
3.7
通讯作者：
Buckheit, Robert W., Jr.
中科院分区：
文献类型：
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作者：
Ham, Anthony S.;Rohan, Lisa Cencia;Buckheit, Robert W., Jr.
聚合物速溶膜剂是一种用于阴道给药的高效、无毒、双作用HIV非核苷逆转录酶抑制剂（NNRTI）嘧啶二酮（IQP-0528）的外用杀微生物剂固体剂型。基于由目标产品特征（TPP）定义的定量物理化学评价来评价膜制剂。给予0.1%（w/w）IQP-0528的膜在10分钟内崩解，超过50%的药物释放，并且在30分钟后接近100%的总药物释放。基于测定和生物活性，具有亚纳摩尔的抗HIV-1感染功效。在12个月的稳定性方案中，IQP-0528薄膜在人用药品注册技术要求国际协调会（ICH）推荐的标准（25 A ℃/65%相对湿度（R.H.））下未表现出显著降解。并加速（40 A ℃/75% R.H.）基于上述评价，阴道膜制剂已被鉴定为用于局部杀微生物剂候选物IQP-0528的阴道递送的潜在固体剂型。
Polymeric quick-dissolving films were developed as a solid dosage topical microbicide formulation for the vaginal delivery of the highly potent and non-toxic, dual-acting HIV nonnucleoside reverse transcriptase inhibitor (NNRTI) pyrimidinedione, IQP-0528.Formulated from approved excipients, a polyvinyl alcohol (PVA) based film was manufactured via solvent casting methods. The film formulations were evaluated based upon quantitative physicochemical evaluations defined by a Target Product Profile (TPP)Films dosed with 0.1% (w/w) of IQP-0528 disintegrated within 10 min with over 50% of drug released and near 100% total drug released after 30 min. The IQP-0528 films were found to be non-toxic in in vitro CEM-SS and PBMC cell-based assays and biologically active with sub-nanomolar efficacy against HIV-1 infection. In a 12 month stability protocol, the IQP-0528 films demonstrated no significant degradation at International Conference on Harmonization (ICH) recommended standard (25A degrees C/65% relative humidity (R.H.)) and accelerated (40A degrees C/75% R.H.) environmental conditions.Based on the above evaluations, a vaginal film formulation has been identified as a potential solid dosage form for the vaginal delivery of the topical microbicide candidate IQP-0528.