Strickley Robert G, Iwata Quynh, Wu Sylvia, Dahl Terrence C
Formulation and Process Development, Gilead Sciences, Inc. 333 Lakeside Drive, Foster City, California 94404, USA.
J Pharm Sci. 2008 May;97(5):1731-74. doi: 10.1002/jps.21101.
Pediatric oral formulations can be quite scientifically challenging to develop and the prerequisites for both a measurable dosage form to administer based upon bodyweight, and also taste-masking are two of the challenges unique for pediatric oral formulations. The physicochemical and organoleptic properties of the active drug substance such as solubility, chemical stability, and taste along with the intended dose can determine which formulations are feasible to develop. Oral pediatric formulations are available in 17 different varieties and can be either a ready-to-use formulation such as a solution, syrup, suspension, tablet, scored tablet, chewable tablet, orally disintegrating tablet, or thin strip, or can also be a formulation that requires manipulation such as a powder for constitution to a suspension, tablet for constitution to a suspension, powder for constitution to a solution, drops for reconstitution to a suspension, concentrated solution for dilution, effervescent tablet, bulk oral granules, bulk oral powder, or solid in a capsule to mix with food or drink. Recently there has been an increase in pediatric formulation development inspired by increased regulatory incentives. The intent of this review is to educate the reader on the various types of formulations administered orally to pediatrics, the rationale in deciding which type of formulation to develop, the excipients used, development challenges, the in-use handling of oral pediatric formulations, and the regulatory incentives.
儿科口服制剂的研发在科学上颇具挑战性，基于体重给药的可测量剂型以及掩味是儿科口服制剂独有的两大挑战。活性药物成分的物理化学和感官特性，如溶解度、化学稳定性和味道，以及预期剂量，可决定哪些制剂在研发上是可行的。儿科口服制剂有17种不同类型，既可以是即用型制剂，如溶液剂、糖浆剂、混悬剂、片剂、刻痕片、咀嚼片、口腔崩解片或细条剂，也可以是需要调配的制剂，如用于配制成混悬剂的粉末、用于配制成混悬剂的片剂、用于配制成溶液的粉末、用于复溶成混悬剂的滴剂、用于稀释的浓溶液、泡腾片、口服散剂、口服散粒剂或与食物或饮料混合的胶囊剂。最近，受监管激励措施增加的影响，儿科制剂的研发有所增加。本综述的目的是让读者了解儿科口服的各类制剂、决定研发哪种制剂的依据、所用辅料、研发挑战、儿科口服制剂的使用处理以及监管激励措施。
