In vitro dissolution considerations associated with nano drug delivery systems

Abstract

Nano drug delivery systems (NDDS) offer promising solution for the translation of future nanomedicines. As bioavailability and therapeutic outcomes can be improved by altering the drug release from these NDDS, it becomes essential to thoroughly understand their drug release kinetics. Moreover, U.S. Food and Drug Administration requires critical evaluation of potential safety, efficacy, and public health impacts of nanomaterials. Spiraling up market share of NDDS has also stimulated the pharmaceutical industry to develop their cost‐effective generic versions after the expiry of patent and associated exclusivity. However, unlike the conventional dosage forms, the in vivo disposition of NDDS is highly intricate and different from their in vitro behavior. Significant challenges exist in the establishment of in vitro–in vivo correlation (IVIVC) due to incomplete understanding of nanoparticles' in vivo biofate and its impact on in vitro experimental protocols. A rational design of dissolution may serve as quality and quantity control tool and help develop a meaningful IVIVC for favorable economic implications. Clinically relevant drug product specifications (critical quality attributes) can be identified by establishing a link between in vitro performance and in vivo exposure. In vitro dissolution may also play a pivotal role to understand the dissolution‐mediated clearance and safety of NDDS. Prevalent in vitro dissolution methods for NDDS and their limitations are discussed in this review, among which USP 4 is gaining more interest recently. Researchers are working diligently to develop biorelevant in vitro release assays to ensure optimal therapeutic performance of generic versions of these NDDS. This article focuses on these studies and presents important considerations for the future development of clinically relevant in vitro release methods. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine

Oral Efficacy of a Diselenide Compound Loaded in Nanostructured Lipid Carriers in a Murine Model of Visceral Leishmaniasis

“…Actually, there is lack of robust and biorelevant in vitro drug release methods, especially for nanoparticle systems. 52 Sink conditions are generally recommended to mimic the removal of released or absorbed drug by the systemic circulation; thus, a mixture of organic solvents (2% v/v PEG 400, 5% w/v d -α-tocopherol polyethylene glycol 1000 succinate and 2.5% v/v DMSO) were used for this purpose. However, permeability limitations of 2h and 2m compounds and their probable enterohepatic circulation complicated their PK profile and their correlation with the in vitro release studies.…”

“…One hour after their administration, 50% of the administered dose was detected in plasma, whereas the percentage of Se released did not reach 20% at short incubation times. Actually, there is lack of robust and biorelevant in vitro drug release methods, especially for nanoparticle systems . Sink conditions are generally recommended to mimic the removal of released or absorbed drug by the systemic circulation; thus, a mixture of organic solvents (2% v/v PEG 400, 5% w/v d -α-tocopherol polyethylene glycol 1000 succinate and 2.5% v/v DMSO) were used for this purpose.…”

Nanopartiküler İlaç Taşıyıcı Sistemlerinin İncelenmesinde Kullanılan İn Vitro Salım Testi Yöntemlerine Genel Bir Bakış

“…İn vitro salım testleri, sadece ilaç kalitesini ve performansını sağlamak için değil, aynı zamanda nanopartiküler ilaç sistemlerinin ürün geliştirme süreçlerinde de yardımcı olmak için önemli bir araçtır. Nanopartiküler sistemler için düzenleyici otoriteler tarafından önerilen resmi in vitro salım yöntemleri mevcut olmaması sebebiyle, mevcut farmakope yöntemlerinin modifikasyonuyla yeni yöntem geliştirilmesi ilk seçenek olarak karşımıza çıkmaktadır [2,21]. Birçok çalışmada, USP aparat 2 (palet), USP aparat 4 (akış hücresi) ve modifiye edilmiş akış hücresi, nanopartiküler sistemlerden in vitro salımı test etmek için kullanılmıştır [38][39][40][41].…”

“…Nanopartiküler sistemlerden ilaç salımı, ilacın güvenliğinin, etkinliğinin ve kalitesinin değerlendirilmesinde kritik bir basamak olup; ilaç formülasyonlarının geliştirilmesinde, geliştirilen formülasyonların in vitro performansının belirlenmesinde, matematiksel modellerin de yardımıyla ilacın in vivo davranışının tahmin edilmesinde karşımıza çıkmaktadır. Bu nedenle, bir nanopartiküler ilaç sisteminin geliştirilmesinde, sistemden ilaç salımının uygun test yöntemi ve koşullarda incelenmesi önemlidir [2,20,21].…”

“…Bu sistemin amacı; BSS'ye göre in vitro salım çalışmalarından hareketle ilacın in vivo davranışını tahmin etmeye yardımcı olmaktır. Bu sayede in vivo çalışmalar azaltılarak, yapılan in vitro salım çalışmalardan in vitro -in vivo korelasyon sağlanarak, biyoeşdeğerlik çalışmalarından muafiyet durumunun belirlenmesi mümkün olmaktadır [20][21][22][23][24].…”