BİR BETAMETAZON ENJEKSİYONLUK SÜSPANSİYON FORMÜLASYONUNUN GELİŞTİRİLMESİ VE DEĞERLENDİRİLMESİ İÇİN PLACKETT-BURMAN TASARIMININ UYGULANMASI

Öz

Amaç: Bu çalışmada, bir betametazon enjeksiyonluk süspansiyon formülasyonu geliştirmek, formülasyon ve üretim değişkenlerinin formülasyonun kritik kalite özellikleri (CQAs) üzerindeki olası etkilerini araştırmak amacıyla kalite tasarımı yaklaşımı kullanılmıştır. Gereç ve Yöntem: İlk olarak hedef ürün kalite profili (QTPP) dikkate alınarak formülasyonun kritik kalite özelliklerinin partikül büyüklüğü dağılımı, viskozite, sedimentasyon süresi, yoğunluk ve etkin maddeler ile koruyucuların miktar tayini olduğu belirlenmiştir. Formülasyonun kritik kalite özelliklerini etkileyebilecek potansiyel risk faktörleri Ishikawa diagram ile tanımlanmış, seçilen formülasyon ve proses değişkenlerinin etkilerini istatistiksel olarak araştırmak için altı faktörlü, iki seviyeli bir Plackett-Burman deney tasarımı kullanılmıştır. Hazırlanan formülasyonlar test edilmiş, elde edilen veriler ile varyans ve çoklu lineer regresyon analizleri yapılmıştır. Sonuç ve Tartışma: Tek yönlü varyans analizi (ANOVA) ve çoklu lineer regresyon analizleri sonucunda, metil parahidroksibenzoat miktar tayini, propil parahidroksibenzoat miktar tayini ve viskozite için kurulan istatistiksel modeller anlamlı bulunurken, diğer bağımsız değişkenler için kurulan modeller anlamlı bulunmamıştır. Karmelloz kalsiyum konsantrasyonu ve filtre tipinin en kritik formülasyon ve proses değişkenleri olduğu görülmüştür. Sonuç olarak, bu çalışma enjeksiyonluk süspansiyon formülasyonlarının kritik kalite özelliklerini etkileyebilecek formülasyon ve proses değişkenlerinin QbD yaklaşımı ile anlaşılmasının formülasyon geliştirilmesi ve optimizasyonu için fayda sağlayabileceğini göstermiştir.

Anahtar Kelimeler

• Betametazon
• deney tasarımı
• kalite tasarımı
• Plackett-Burman
• süspansiyon

APPLICATION OF PLACKETT-BURMAN DESIGN FOR DEVELOPMENT AND EVALUATION OF A BETAMETHASONE SUSPENSION FOR INJECTION FORMULATION

Öz

Objective: In this study, a quality-by-design (QbD) approach was used to develop a betamethasone suspension for injection formulation and to investigate the possible effects of formulation and process variables on the critical quality attributes (CQAs) of the formulation. Material and Method: It was determined that the CQAs of the formulation were particle size distribution, viscosity, sedimentation time, density and assay of active substances and preservatives, considering the quality target product profile (QTPP). Potential risk factors that may affect the CQAs of the formulation were identified using an Ishikawa diagram, and a six-factor, two-level Plackett-Burman experimental design was used to statistically investigate the effects of selected formulation and process variables. The prepared formulations were tested, and variance and multiple linear regression analyses were performed with the acquired data. Result and Discussion: As a result of the one-way analyses of variance (ANOVA) and multiple linear regression analyses, the established statistical models for the assay of methyl parahydroxybenzoate and propyl parahydroxybenzoate, and viscosity were found to be significant, the established models for other independent variables were not significant. The concentration of carmellose calcium and filter type was found to be the most significant formulation and process variables. In conclusion, this study showed that understanding the formulation and process variables that may affect the CQAs of injectable suspension formulations with a QbD approach could be useful for formulation development and optimization.

Anahtar Kelimeler

• Betamethasone
• design of experiments
• Plackett-Burman
• quality-by-design
• suspension

Kaynakça

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