METFORMİN UZATILMIŞ SALIMLI TABLETLERİN (MERT) GELİŞTİRİLMESI VE OPTİMİZASYONUNDA BOX-BEHNKEN TASARIM YAKLAŞIMI (BBDA)

Öz

Amaç: Bu çalışma, tasarımla kalite (QbD) yaklaşımı kullanılarak MERT formülasyonunun geliştirilmesini ve Box-Behnken Tasarım (BBD) yöntemiyle optimize edilmesini ele almaktadır. Tabletlerin sertliği ve kümülatif etkin madde salım yüzdesi (% CDR) (2. ve 10. saatlerde) hedef ürün kalite profiline (QTPP) dayalı olarak belirlenmiştir. Kritik kalite özellikleri (CQA) tanımlanmış ve bağımsız değişkenler olarak seçilmiştir. Bu doğrultuda, MERT formülasyonunun geliştirilmesinde HPMC K 100M, Eudragit RL 100 ve yardımcı madde olarak MCC yüksek ve düşük seviyelerde bağımsız değişkenler olarak değerlendirilmiştir. Gereç ve Yöntem: Design-Expert® programı tahminlerine göre toplam 19 farklı formülasyon hazırlanmıştır. Her biri 850 mg ağırlığında olan tabletler doğrudan basım yöntemiyle üretilmiştir. Her bir formülasyon için yanıtlar belirlenmiş ve en uygun konsantrasyonun belirlenmesi amacıyla analiz edilmiştir. Sonuç ve Tartışma: HPMC K 100M, Eudragit RL 100 ve MCC'nin, 2. ve 10. saatlerdeki % CDR üzerinde antagonist etkiler gösterdiği tespit edilmiştir. Tanısal grafiklerden elde edilen veriler, normal artıklar grafiği ve tahmin edilene karşı gerçek değerler doğrultusunda tüm veri noktalarının doğruya yakın bir dağılım sergilediğini göstermektedir. Optimizasyon çalışmaları sonucunda belirlenen istenen değerlere göre en yüksek uygunluğu sağlayan HPMC K 100M, Eudragit RL 100 ve MCC konsantrasyonları sırasıyla 76,75 mg, 203 mg ve 58 mg olarak belirlenmiştir. Optimum formülasyon ile hazırlanan tabletler, 10 saatten daha uzun süre boyunca etkin madde salımı gerçekleştirebilmiştir.

Anahtar Kelimeler

• Box Behnken Tasarımı
• QbD
• metformin
• uzatılmış salımlı tabletler

BOX-BEHNKEN DESIGN APPROACH (BBDA) IN DEVELOPMENT AND OPTIMIZATION OF METFORMIN EXTENDED RELEASE TABLETS (MERT)

Öz

Objective: The present research outlines the use of quality by design (QbD) method to formulate MERT using Box-Behnken Design approach (BBDA). Based on quality target product profile (QTPP) to achieve tablets hardness and % cumulative Drug Release (% CDR) (at 2 hour and 10 hour), Critical quality attribute (CQA)were identified and selected as independent variable. In this present work, HPMC K 100M, Eudragit RL 100, and excipients MCC are selected as independent variables at their high and low levels in development of MERT. Material and Method: As per Design-Expert® prediction, total 19 formulations are prepared where each tablets of weight of 850 mg prepared by direct compression method. For each formulation, responses are determined and analyzed to find most optimized concentration. Result and Discussion: HPMC K 100 M, Eudragit RL 100 and MCC have antagonistic effects on the % CDR after 2 hour and 10 hours. From diagnostic plot it has been observed normal distribution of all data points near to straight line for normal plot of residuals, and predicted vs. actual. The desirability cube and the contour graph showing maximum desirability for optimized values of 76.75 mg, 203 mg and 58 mg for HPMC K 100M, Eudragit RL 100 and MCC respectively which are selected as independent factors in formulation of MERT. Prepared optimized tablets of MERT releases drug for more than 10 hr.

Anahtar Kelimeler

• Box Behnken Design
• extended release tablets
• QbD
• metformin

Etik Beyan

Nil

Kaynakça

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