Lan Zhang,Shirui Mao

Shenyang Pharmaceutical University,Shenyang 110016,China

Applications of quality by design(QbD)and its tools in drug delivery

Lan Zhang,Shirui Mao*

Shenyang Pharmaceutical University,Shenyang 110016,China

A R T I C L E I N F O

Article history:

Available online 25 November 2015

Quality by Design(QbD)

Critical quality attributes(CQAs)

Design of experiment(DoE)

Process analytical technology(PAT)

Quality byTest(QbT)was the only way to guarantee the quality of drug products before FDA launches current Good Manufacturing Practice(cGMP)[1],which is an approach without clear understanding of the processes.In order to solve this problem, FDA generalized Quality by Design(QbD)in the feld of pharmacy[2].In pharmaceutical industry,QbD brings cost-effciency and simplicity of manufacturing process into reality.Several tools are utilized to make QbD system easily applied to pharmaceutical feld,namely design of experiment(DoE),risk assessment and process analytical technology(PAT).QbD is based on the thorough understanding of how materials and process parameters affect the profle of fnal products.The following parameters are defned to describe those characteristics: Quality target product profle(QTPP);critical quality attributes(CQAs);critical material attributes(CMAs)and critical process parameters(CPPs)[3].

The applications of DoE and PAT in pharmaceutical feld are discussed in detail in this review.DoE combines parameters such as CPPs,CMAs and CQAs into QbD system,which is a reasonable method to determine the relationship between the input and output of a process.In addition,full factorial design, Plackett–Burman(PB)screening design,fractional factorial statistical design,central composite–face centered–response surface design and Box–Behnken design can be used to establish a design space(DS)for a given process to guarantee the quality of fnal products.In addition to DoE,PAT is also an important tool of QbD;by obtaining technological and material parameters online,it plays a role in real-time monitoring of pharmaceutical process without interruption.In order to achieve successful PAT implementation,there are three-stepprocess(namely design,analyze and control)and four PAT tools in the design and optimization of drug formulations and manufacturing process;the four PAT tools are as follows:(1) multivariate tools for design,data acquisition and analysis;(2) process analyzers;(3)process control tools;and(4)continuous improvement and knowledge management tools.In conclusion,with the assistance of DoE and PAT together with other QbD tools,thorough understanding of pharmaceutical process can be achieved and stable quality of products can be assured.

Fig.1–Comparison between QbT and QbD.

R E F E R E N C E S

[1]Food&Drug Administration.Pharmaceutical current good manufacturing practices(cGMPs)for the 21st century–a riskbased approach.2002.

[2]International Conference on Harmonization(ICH).Guidance for industry:Q8(R2)pharmaceutical development,ICH harmonised tripartite guideline,step 4.2009.

[3]Yu LX,Amidon G,Khan MA,et al.Understanding pharmaceutical quality by design.AAPS J 2014;16:771–783.

*E-mail address:zhanglanaixuexi@163.com.

Peer review under responsibility of Shenyang Pharmaceutical University.

http://dx.doi.org/10.1016/j.ajps.2015.11.084

1818-0876/?2016 Production and hosting by Elsevier B.V.on behalf of Shenyang Pharmaceutical University.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).