Amorphization of Drugs for Transdermal Delivery-a Recent Update

Abstract

Amorphous solid dispersion is a popular formulation approach for orally administered poorly water-soluble drugs, especially for BCS class II. But oral delivery could not be an automatic choice for some drugs with high first-pass metabolism susceptibility. In such cases, transdermal delivery is considered an alternative if the drug is potent and the dose is less than 10 mg. Amorphization of drugs causes supersaturation and enhances the thermodynamic activity of the drugs. Hence, drug transport through the skin could be improved. The stabilization of amorphous system is a persistent challenge that restricts its application. A polymeric system, where amorphous drug is dispersed in a polymeric carrier, helps its stability. However, high excipient load often becomes problematic for the polymeric amorphous system. Coamorphous formulation is another approach, where one drug is mixed with another drug or low molecular weight compound, which stabilizes each other, restricts crystallization, and maintains a single-phase homogenous amorphous system. Prevention of recrystallization along with enhanced skin permeation has been observed by the transdermal coamorphous system. But scalable manufacturing methods, extensive stability study and in-depth in vivo evaluation are lacking. This review has critically studied the mechanistic aspects of amorphization and transdermal permeation by analyzing recent researches in this field to propose a future direction.

Hydrotropic Antisolvent Crystallization for the Reduction in the Particle Size of Methylcobalamin

“…There were no intense peaks in particles obtained after HAC treatment compared to raw particles, indicating an amorphous form. For the transdermal drug delivery system, amorphization enhances the thermodynamic activity, which improves the active transport through the skin 43 and hence is favorable.…”

Senyawa Peningkat Penetrasi pada Sistem Penghantaran Obat Topikal Berdasarkan Lipofilisitas Senyawa Obat

“…Namun, kondisi kulit yang memiliki banyak lapisan sebagai penghalang dari zat luar menjadi keterbatasan utama dari rute ini yang menyebabkan sulitnya penetrasi obat melalui kulit (10). Selain itu, tidak semua obat memenuhi kriteria fisikokimia yaitu memiliki berat molekul rendah, cukup lipofil (log P = 1-3), dan titik leleh rendah (< 200°F atau < 93,33°C) untuk dapat berpenetrasi secara pasif dalam jumlah terapeutik sehingga jika obat tersebut dihantar melalui kulit akan menurunkan efikasinya (11)(12)(13). Efikasi obat topikal bergantung pada tingkat penetrasi sediaan obat tersebut ke kulit, di mana obat topikal harus dapat menembus stratum corneum untuk dapat melewati lapisan epidermis dan dermis yang lebih dalam untuk dapat memberikan efek (11,14).…”

Microneedle‐assisted transdermal delivery of nanoparticles: Recent insights and prospects

“…“The molecular weight of a compound must be 500 Da to allow skin absorption” (Bos & Meinardi, 2000). This statement has been considered as an immovable dogma in pharmaceutical skin research (Brown et al, 2006; Chatterjee et al, 2022). However, more and more researchers question this idea since recent experimental evidence shows important exceptions (Billich et al, 2005; Lenn et al, 2018).…”