Kuru göz hastalığı tedavisine yönelik insert formülasyonunun geliştirilmesi
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Dosyalar
Tarih
2023
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Trakya Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Siklosporin A (siklosporin), Tolypocladium inflatum ve Beauveria nevus isimli mantarların u?rettig?i siklik bir peptiddir. siklosporin A, T-hu?cre aktivitesini ve inflamatuar sitokin u?retimini inhibe ederek; immu?nsu?presyon sag?layan, bir kalsino?rin inhibito?ru?du?r. BCS Sınıf II kategorisinde yer alıp suda c?o?zu?nmeyen ve du?s?u?k biyoyararlanım go?steren bir moleku?ldu?r. Oftalmik preparatları genellikle go?z damlası dozaj formu olarak yaygın kullanılmaktadır. Siklosporin oftalmik insert dozaj s?ekli oku?ler yu?zeyde daha uzun su?re kalabilen, su?rekli etki sag?layan bo?ylece sıklıkla uygulama zorunlulug?unu ortadan kaldırarak terapo?tik etkinlig?i daha yu?ksek olan okuler, mikro boyutta etkin ic?erikli, QbD’ye dayalı insert formu?lasyonları gelis?tirilip in-vitro c?alıs?maları yapılmıs?tır. Çalıs?mamızda QbD’nin ilk adımları olan Kritik Kalite O?zelliklerinin de (CQA), Hedef U?ru?n Kalite Profili (TPQP), bunlara bag?lı olarak Kritik Proses Parametreleri (CPP) belirlenmis? ve Bas?langıc? Risk Analiz Deg?erlendirmeleri yapılmıs?tır. U?retilen her seri u?ru?n ic?in belirlenen (CQA) ve Kritik Proses Parametrelerinin (CPP) daima belirli spesifikasyonları sag?lamasına ve bu amac?la olus?turulan limit sınırları ic?erisinde kalarak c?alıs?ılmıs?tır. Siklosporin oftalmik insert formulasyonu etkin madde siklosporin, yardımcıların; sodyum aljinatı emu?lgato?r ve kıvam artırıcı olarak, gliserinin plastifiyan ve nemlendirici o?zellig?i tas?ıması, jelatinin plastifiyan o?zellig?i ve tas?ıyıcı olarak enjeksiyonluk suyun birles?tirilmesi ile uzun salım sag?lanmıs? ve yumus?ak, go?z yu?zeyine kolay yapıs?abilen bir form elde edilmis?tir. Hazırlanan siklosporin oftalmik insert formulasyonunda karakterizasyon c?alıs?maları ic?in yog?unluk, pH, kırılma indisi, nem miktarı, viskozite, zeta potansiyeli, salım su?resi ve miktar tayini analizlerinin sonuc?larına go?re belirlenen kritik u?ru?n kalite o?zelliklerini sag?lamıs?tır. Bas?langıc? risk analiz deg?erlendirmesine go?re o?ngo?ru?len bazı yu?ksek risk parametrelerinin, kritik proses o?zelliklerine bag?lı olarak gelis?tirilen formu?lasyonlar ve analizleri sonucunda; du?s?u?k risk tes?kil ettig?i go?ru?lmu?s?tu?r. Bo?ylelikle yapılan sonuc? risk analiz deg?erlendirmesine go?re u?retim yo?ntem ve parametrelerinin u?ru?nu?n kalitesini yas?amı boyunca sag?layacag?ı ve gu?venli alan ic?erisinde kalacag?ı yapılan test ve analizlere dayanarak go?sterilmis?tir. Siklosporin Oftalmik insert ic?in 25 ± 2°C ve %60 ± 5ve 40 ± 2°C ve %75 ± 5’de 3 ay stabilite takibi yapılmıs?tır. Stabilite periyodunda sıcaklıg?ın salım su?resine etkisi oldug?u tespit edilmis?tir.
Cyclosporine A (cyclosporine). It is a cyclic peptide produced by the fungi Tolypocladium inflatum and Beauveria nevus. cyclosporine A by inhibiting T-cell activity and inflammatory cytokine production; It is a calcineurin inhibitor that provides immunosuppression. Ophthalmic preparations are commonly used as eye drops dosage form. In-vitro studies have been carried out by developing ocular, micro-sized active ingredient, QbDbased insert formulations with cyclosporine ophthalmic insert dosage form, which can stay on the ocular surface for a longer time, provide a continuous effect, thus eliminating the necessity of frequent application and higher therapeutic effectiveness. In our study, Critical Quality Characteristics (CQA), Target Product Quality Profile (TPQP), which are the first steps of ObD, Critical Process Parameters (CPP) were determined and Initial Risk Analysis Evaluations were made. It has been tried to ensure that the (CQA) and Critical Process Parameters (CPP) determined for each serial product produced always meet certain specifications and stay within the limits established for this purpose. Cyclosporine ophthalmic insert formulation active substance cyclosporine, auxiliaries; By combining sodium alginate as emulsifier and thickener, glycerin's plasticizer and moisturizing properties, gelatin's plasticizer properties and injection water as carrier, a long release was achieved and a soft, easily adhered form to the eye surface was obtained. For the characterization studies of the prepared cyclosporine ophthalmic insert formulation, it provided the critical product quality properties determined according to the results of density, pH, refractive index, moisture content, viscosity, zeta potential, release time and quantification analysis. As a result of the formulations and analyzes developed depending on the critical process properties of some high risk parameters predicted according to the initial risk analysis evaluation; found to be low risk. Thus, the result has been shown based on the tests and analyzes made, according to the risk analysis evaluation, that the production methods and parameters will ensure the quality of the product throughout its life and remain in the safe area. For the Cyclosporine Ophthalmic insert, 3 months stability was monitored at 25+ 2°C and 60% ± 5% and 40 ± 2°C and 75 ± 5%. It has been determined that the temperature has an effect on the release time during the stability period.
Cyclosporine A (cyclosporine). It is a cyclic peptide produced by the fungi Tolypocladium inflatum and Beauveria nevus. cyclosporine A by inhibiting T-cell activity and inflammatory cytokine production; It is a calcineurin inhibitor that provides immunosuppression. Ophthalmic preparations are commonly used as eye drops dosage form. In-vitro studies have been carried out by developing ocular, micro-sized active ingredient, QbDbased insert formulations with cyclosporine ophthalmic insert dosage form, which can stay on the ocular surface for a longer time, provide a continuous effect, thus eliminating the necessity of frequent application and higher therapeutic effectiveness. In our study, Critical Quality Characteristics (CQA), Target Product Quality Profile (TPQP), which are the first steps of ObD, Critical Process Parameters (CPP) were determined and Initial Risk Analysis Evaluations were made. It has been tried to ensure that the (CQA) and Critical Process Parameters (CPP) determined for each serial product produced always meet certain specifications and stay within the limits established for this purpose. Cyclosporine ophthalmic insert formulation active substance cyclosporine, auxiliaries; By combining sodium alginate as emulsifier and thickener, glycerin's plasticizer and moisturizing properties, gelatin's plasticizer properties and injection water as carrier, a long release was achieved and a soft, easily adhered form to the eye surface was obtained. For the characterization studies of the prepared cyclosporine ophthalmic insert formulation, it provided the critical product quality properties determined according to the results of density, pH, refractive index, moisture content, viscosity, zeta potential, release time and quantification analysis. As a result of the formulations and analyzes developed depending on the critical process properties of some high risk parameters predicted according to the initial risk analysis evaluation; found to be low risk. Thus, the result has been shown based on the tests and analyzes made, according to the risk analysis evaluation, that the production methods and parameters will ensure the quality of the product throughout its life and remain in the safe area. For the Cyclosporine Ophthalmic insert, 3 months stability was monitored at 25+ 2°C and 60% ± 5% and 40 ± 2°C and 75 ± 5%. It has been determined that the temperature has an effect on the release time during the stability period.
Açıklama
Anahtar Kelimeler
Siklosporin,, İnsert, İn-Vitro, QbD, Cyclosporine
