İlaç Formülasyonu Geliştirilmesinde Deney Tasarımı (DoE) Seçimi ve Kullanımı

Year 2017, Volume: 21 Issue: 2, 216 - 227, 01.04.2017

Önder Demir Buket Aksu Yıldız Özsoy

https://doi.org/10.12991/marupj.277719

Abstract

Son yıllarda ilaç formülasyonu geliştirilmesinde deney tasarımı

(DoE) kullanımı artmış olmasına rağmen hala yeterli seviyede

değildir. Özellikle katı ve yarı-katı dozaj formları gibi birçok

bileşeni olan ve çıktılara etkisi bilinmeyen birçok proses

parametresinin bulunduğu formülasyonlarda kullanılmasının

ne kadar yararlı olduğu bilinmektedir. Ancak formülasyon

geliştirmede deneme-yanılma gibi eski yaklaşımlar yerine DoE

kullanılması ne kadar önemli ise, bu DoE’nin doğru kullanımı

ve seçimi de bir o kadar önemlidir. Doğru seçilmeyen bir DoE

tipi veya uygun olmayacak şekilde yapılan deneme ve ölçümler,

sadece boşa kaynak ve zaman harcanması ile sonuçlanmaz,

çoğu zaman kafa karıştırıcı veya yanıltıcı veriler de üretir. Bu

derlemede DoE, uygun DoE tipinin seçimi, istatiksel eleme

ile faktör sayısının düşürülmesi ve yanıt yüzeyi modellemesi

(RSM) ile ilaç formülasyonlarının optimizasyonu hakkında

özet bilgi verilmesi amaçlanmış olup, bu yöntemlerin ilaç

formülasyonu geliştirmedeki uygulamalarından da kısaca

bahsedilmiştir. Doğru DoE tipinin seçilerek uygulanması

sayesinde; gerçekleştirilen az sayıdaki denemelerden çok fazla

kaliteli bilgi (matematiksel modeller) üretilebilir. Bu sayede

geliştirme süresi ve maliyeti ciddi oranda azaltılabilir. Ayrıca

geliştirilen ürün, değişkenliklere karşı hassas olmayan sağlam

bir prosese sahip olabilir.

Keywords

Deney tasarımı, formülasyon geliştirme, ilaç, yanıt yüzeyi modelleme, optimizasyon

The Use and Selection of Design of Experiments (DoE) in the Development of Drug Product Formulation

Abstract

In recent years, despite of the increasing use of design of

experiments (DoE) in the development of drug product

formulation, it has still not been sufficient. It has been known that

using DoE is very useful particularly formulation of solid and

semi-solid dosage forms including many components and many

process parameters with unknown effect on outputs. Proper use

and selection of the DoE is also important at least as using DoE

in the development of drug product formulation instead of the

old approaches such as trial and error. Non-correctly selected

type of DoE or inappropriately applied experiments and

measurements results not only wasted resources and time, but

also often produces confusing or misleading data. In this review,

summary information about DoE, selection of suitable type of

DoE, reduction of the number of factors by using statistical

screening and optimization of the drug formulations using

response surface modeling (RSM) are intended to give, also

briefly mentioned about the application of these methods in the

development of pharmaceutical formulation. A lot of quality

information (mathematical models) can be produced from the

few trials conducted by means of selecting and implementation

of the correct type of DoE. Thus, the development time and cost

can be reduced significantly. Developed product may also have

a robust process which is not sensitive to variations.

Keywords

Design of experiments, formulation development, drug, response surface modeling, optimization

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