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
Kaynakça
- 1. Chen, M.Y., Tang, Y.J., Wang, Y.C., Wang, C.Z., Yuan, C.S., Chen, Y., Tan, Z.R., Huang, W.H., Zhou, H.H. (2016). Quantitative determination of betamethasone sodium phosphate and betamethasone dipropionate in human plasma by UPLC-MS/MS and a bioequivalence study. Analytical Methods, 8(17), 3550-3563. [CrossRef]
- 2. Salem, I.I., Najib, N.M. (2012). Pharmacokinetics of betamethasone after single-dose intramuscular administration of betamethasone phosphate and betamethasone acetate to healthy subjects. Clinical Therapeutics, 34(1), 214-220. [CrossRef]
- 3. Simon, A., de Almeida Borges, V.R., Cabral, L.M., de Sousa, V.P. (2013). Development and validation of a discriminative dissolution test for betamethasone sodium phosphate and betamethasone dipropionate intramuscular injectable suspension. AAPS PharmSciTech, 14, 425-434. [CrossRef]
- 4. Cromarty, R., Sigal, A., Liebenberg, L.J., Mckinnon, L.R., Abdool Karim, S.S., Passmore, J.A.S., Archary, D. (2021). Betamethasone induces potent immunosuppression and reduces HIV infection in a PBMC in vitro model. Journal of Investigative Medicine, 69(1), 28-40. [CrossRef]
- 5. U.S. Food and Drug Administration. (2022). Orange book: Approved drug products with therapeutic equivalence evaluations. From https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm. Access date: 01.05.2022
- 6. Byrne, J., Wyraz, A., Velasco-Torrijos, T., Reinhardt, R. (2017). Formulation factors affecting the isomerization rate of betamethasone-17-valerate in a developmental hydrophilic cream–a HPLC and microscopy based stability study. Pharmaceutical Development and Technology, 22(4), 537-544. [CrossRef]
- 7. U.S. Food and Drug Administration. (2022). Celestone® Soluspan® Label From https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/014602Orig1s065lbl.pdf. Access date: 01.05.2022.
- 8. Türkiye İlaç ve Tıbbi Cihaz Kurumu Web site. (2022). From https://titck.gov.tr/. Erişim tarihi: 20.05.2022
- 9. Yu, L.X., Amidon, G., Khan, M.A., Hoag, S.W., Polli, J., Raju, G.K., Woodcock, J. (2014). Understanding pharmaceutical quality by design. The AAPS Journal, 16, 771-783. [CrossRef]
- 10. Yerlikaya, F., Ozgen, A., Vural, I., Guven, O., Karaagaoglu, E., Khan, M.A., Capan, Y. (2013). Development and evaluation of paclitaxel nanoparticles using a quality-by-design approach. Journal of Pharmaceutical Sciences, 102(10), 3748-3761. [CrossRef]
- 11. Haaland, P.D. (2020). Experimental design in biotechnology. CRC press, p.85.
- 12. Vining, G., Kowalski, S. (2006). An overview of composite designs run as split-plots. Frontiers in Statistical Quality Control 8, 342-351. [CrossRef]
- 13. Beg, S., Rahman, Z. (2021). Central composite designs and their applications in pharmaceutical product development. Design of Experiments for Pharmaceutical Product Development: Volume I: Basics and Fundamental Principles, 63-76. [CrossRef]
- 14. Rantanen, J., Khinast, J. (2015). The future of pharmaceutical manufacturing sciences. Journal of Pharmaceutical Sciences, 104(11), 3612-3638. [CrossRef]
- 15. European Medicines Agency Web site. (2000). ICH topic Q 6 A specifications: Test procedures and acceptance criteria for new drug substances and new drug products: Chemical substances, From https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q-6-test-procedures-acceptance-criteria-new-drug-substances-new-drug-products-chemical_en.pdf. Access date: 14.02.2023
- 16. Bodhe, R., Deshmukh, R.K., Shinde, R., Patil, K. (2021). Formulation development and evaluation of injectable depot suspension. International Journal of Medicine and Healthcare Reports, 1(1), 1-12 [CrossRef]
- 17. Burgess, D.J., Crommelin, D.J., Hussain, A.S., Chen, M.L., (2004). Assuring quality and performance of sustained and controlled release parenterals: EUFEPS workshop report. AAPS PharmSci, 6(1), E11. [CrossRef]
- 18. Mascia, A., Cirafici, A.M., Bongiovanni, A., Colotti, G., Lacerra, G., Di Carlo, M., Digilio, F.A., Liguori, G.L., Lanati, A., Kisslinger, A. (2020). A failure mode and effect analysis (FMEA)-based approach for risk assessment of scientific processes in non-regulated research laboratories. Accreditation and Quality Assurance, 25, 311-321. [CrossRef]
- 19. Alexopoulos, E.C. (2010). Introduction to multivariate regression analysis. Hippokratia, 14(Suppl 1), 23-28.
- 20. European Medicines Agency Web site. (2022). ICH topic Q 2 (R1) Validation of analytical procedures: Text and methodology, from https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q-2-r1-validation-analytical-procedures-text-methodology-step-5_en.pdf. Access date: 14.02.2023
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
- 1. Chen, M.Y., Tang, Y.J., Wang, Y.C., Wang, C.Z., Yuan, C.S., Chen, Y., Tan, Z.R., Huang, W.H., Zhou, H.H. (2016). Quantitative determination of betamethasone sodium phosphate and betamethasone dipropionate in human plasma by UPLC-MS/MS and a bioequivalence study. Analytical Methods, 8(17), 3550-3563. [CrossRef]
- 2. Salem, I.I., Najib, N.M. (2012). Pharmacokinetics of betamethasone after single-dose intramuscular administration of betamethasone phosphate and betamethasone acetate to healthy subjects. Clinical Therapeutics, 34(1), 214-220. [CrossRef]
- 3. Simon, A., de Almeida Borges, V.R., Cabral, L.M., de Sousa, V.P. (2013). Development and validation of a discriminative dissolution test for betamethasone sodium phosphate and betamethasone dipropionate intramuscular injectable suspension. AAPS PharmSciTech, 14, 425-434. [CrossRef]
- 4. Cromarty, R., Sigal, A., Liebenberg, L.J., Mckinnon, L.R., Abdool Karim, S.S., Passmore, J.A.S., Archary, D. (2021). Betamethasone induces potent immunosuppression and reduces HIV infection in a PBMC in vitro model. Journal of Investigative Medicine, 69(1), 28-40. [CrossRef]
- 5. U.S. Food and Drug Administration. (2022). Orange book: Approved drug products with therapeutic equivalence evaluations. From https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm. Access date: 01.05.2022
- 6. Byrne, J., Wyraz, A., Velasco-Torrijos, T., Reinhardt, R. (2017). Formulation factors affecting the isomerization rate of betamethasone-17-valerate in a developmental hydrophilic cream–a HPLC and microscopy based stability study. Pharmaceutical Development and Technology, 22(4), 537-544. [CrossRef]
- 7. U.S. Food and Drug Administration. (2022). Celestone® Soluspan® Label From https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/014602Orig1s065lbl.pdf. Access date: 01.05.2022.
- 8. Türkiye İlaç ve Tıbbi Cihaz Kurumu Web site. (2022). From https://titck.gov.tr/. Erişim tarihi: 20.05.2022
- 9. Yu, L.X., Amidon, G., Khan, M.A., Hoag, S.W., Polli, J., Raju, G.K., Woodcock, J. (2014). Understanding pharmaceutical quality by design. The AAPS Journal, 16, 771-783. [CrossRef]
- 10. Yerlikaya, F., Ozgen, A., Vural, I., Guven, O., Karaagaoglu, E., Khan, M.A., Capan, Y. (2013). Development and evaluation of paclitaxel nanoparticles using a quality-by-design approach. Journal of Pharmaceutical Sciences, 102(10), 3748-3761. [CrossRef]
- 11. Haaland, P.D. (2020). Experimental design in biotechnology. CRC press, p.85.
- 12. Vining, G., Kowalski, S. (2006). An overview of composite designs run as split-plots. Frontiers in Statistical Quality Control 8, 342-351. [CrossRef]
- 13. Beg, S., Rahman, Z. (2021). Central composite designs and their applications in pharmaceutical product development. Design of Experiments for Pharmaceutical Product Development: Volume I: Basics and Fundamental Principles, 63-76. [CrossRef]
- 14. Rantanen, J., Khinast, J. (2015). The future of pharmaceutical manufacturing sciences. Journal of Pharmaceutical Sciences, 104(11), 3612-3638. [CrossRef]
- 15. European Medicines Agency Web site. (2000). ICH topic Q 6 A specifications: Test procedures and acceptance criteria for new drug substances and new drug products: Chemical substances, From https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q-6-test-procedures-acceptance-criteria-new-drug-substances-new-drug-products-chemical_en.pdf. Access date: 14.02.2023
- 16. Bodhe, R., Deshmukh, R.K., Shinde, R., Patil, K. (2021). Formulation development and evaluation of injectable depot suspension. International Journal of Medicine and Healthcare Reports, 1(1), 1-12 [CrossRef]
- 17. Burgess, D.J., Crommelin, D.J., Hussain, A.S., Chen, M.L., (2004). Assuring quality and performance of sustained and controlled release parenterals: EUFEPS workshop report. AAPS PharmSci, 6(1), E11. [CrossRef]
- 18. Mascia, A., Cirafici, A.M., Bongiovanni, A., Colotti, G., Lacerra, G., Di Carlo, M., Digilio, F.A., Liguori, G.L., Lanati, A., Kisslinger, A. (2020). A failure mode and effect analysis (FMEA)-based approach for risk assessment of scientific processes in non-regulated research laboratories. Accreditation and Quality Assurance, 25, 311-321. [CrossRef]
- 19. Alexopoulos, E.C. (2010). Introduction to multivariate regression analysis. Hippokratia, 14(Suppl 1), 23-28.
- 20. European Medicines Agency Web site. (2022). ICH topic Q 2 (R1) Validation of analytical procedures: Text and methodology, from https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q-2-r1-validation-analytical-procedures-text-methodology-step-5_en.pdf. Access date: 14.02.2023
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Eczacılık ve İlaç Bilimleri |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Erken Görünüm Tarihi | 17 Mayıs 2023 |
| Yayımlanma Tarihi | 20 Mayıs 2023 |
| Gönderilme Tarihi | 19 Ocak 2023 |
| Kabul Tarihi | 23 Şubat 2023 |
| Yayımlandığı Sayı | Yıl 2023 Cilt: 47 Sayı: 2 |
Kaynak Göster
Kapsam ve Amaç
Ankara Üniversitesi Eczacılık Fakültesi Dergisi, açık erişim, hakemli bir dergi olup Türkçe veya İngilizce olarak farmasötik bilimler alanındaki önemli gelişmeleri içeren orijinal araştırmalar, derlemeler ve kısa bildiriler için uluslararası bir yayım ortamıdır. Bilimsel toplantılarda sunulan bildiriler supleman özel sayısı olarak dergide yayımlanabilir. Ayrıca, tüm farmasötik alandaki gelecek ve önceki ulusal ve uluslararası bilimsel toplantılar ile sosyal aktiviteleri içerir.