Preparation and Characterization of Caffeine Loaded Liposome and Ethosome Formulations for Transungual Application

Abstract

Amaç: Bu tasarım çalışması "International Conference on Harmonization" rehberleri kapsamındaki tasarımda kalite yaklaşımı çerçevesinde uygulanmıştır. Yapay sinir ağları (ANN) kullanılarak ketiapin fumaratın değiştirilmiş salımlı tablet formülasyonunun kalitesi değerlendirilmiş ve referans ürüne benzer olan yeni bir formülasyon tespit edilmiştir. Gereç ve Yöntemler: On iki farklı formül üretilmiş ve test edilmiştir. Referans ürünün analiz sonuçları ve deneysel sonuçlarımız çıktı olarak Intelligensys Ltd. şirketine ait programlarında ANN'nin eğitimi için kullanılmıştır. Bulgular: INForm V.4 ANN programı tarafından önerilen yeni bir formülasyon (F13) ile gastrointestinal sistemdeki üç farklı pH da çözünme testleri yapılmıştır. Bu formülasyonun uygunluğu da f2 benzerlik testi sonuçları karşılaştırılarak doğrulanmıştır. Sonuç: Bu programların kullanılması, çoklu değerlendirme yöntemleri ve daha düşük maliyetle Ar-Ge süreçlerini desteklemekte ve alternatif formülasyonlar daha hızlı tespit edilebilmektedir. Anahtar kelimeler: Ketiapin fumarat, tasarımda kalite, yapay sinir ağları, bulanık mantık, uzatılmış salım tabletler, yaş granülasyon Objectives: This design study was implemented within the scope of the quality by design approach, which included the "International Conference on Harmonization" guidelines. We evaluated the quality of a modified-release tablet formulation of quetiapine fumarate, which was designed using artificial neural networks (ANN), and determined a new formulation that was similar to the reference product. Materials and Methods: Twelve different formulations were produced and tested. The reference product's results and our experimental results were used as outputs for the training of the ANN programs of Intelligensys Ltd. Results: Dissolution tests were performed with the new formulation (F13) suggested by the INForm V.4 ANN program in three different pHs of the gastrointestinal system. The compliance of this formulation was confirmed by comparing the results with an f2 similarity test. Conclusion: Use of these programs supports research and development processes with multiple evaluation methods and alternative formulations may be determined faster and at lower cost.

Interaction of Caffeine with Model Lipid Membranes

“…If added to a water solution, even at a concentration very close to the solubility limit, caffeine molecules do not partition into a bilayer environment. This is in line with earlier reports on the low encapsulation of caffeine in liposomes. ,− Overall, these findings provide a novel point of view to improve the delivery of caffeine via membrane permeation and for its use in drug formulations and dietary supplements.…”

“…It is worth remarking that caffeine stacking was observed both computationally and experimentally for the concentration used in the present work and that such a phenomenon could contribute to the change in viscosity observed in QCM-D experiments. A higher affinity of caffeine for the water solution can also explain the low encapsulation efficiency reported for liposomes in earlier studies. ,− …”

“… 18 , 19 In pharmaceutical sciences, caffeine is commonly used as a psychoactive drug, and it has been also proposed for the treatment of cellulitis. 20 − 23 In this case, to enhance its delivery via skin permeation, caffeine was encapsulated in liposomes having lecithin as the main component plus a variable class of excipients. Several works have reported that caffeine has a low affinity to liposomes composed only of lecithin (mainly phosphatidylcholine-based lipids), the encapsulation efficiency being very low 20 , 22 − 24 and caffeine being spontaneously released from these lipid carriers.…”

“…These results might also support the low encapsulation efficiency characteristic of pure lecithin liposomes and their spontaneous tendency of releasing caffeine molecules. 20 , 22 , 23 All of the studies of encapsulation efficiency were performed dissolving together caffeine and phospholipids in organic solvents before the preparation of liposomes. Even if the encapsulation efficiency resulted to be limited, between 3 and 9% of the total caffeine content resulted enclosed in the bilayer part of the liposomes.…”

“…Interaction of purine molecules with cell membranes is of large interest for making predictions for the pharmacokinetic properties of new synthetic purine drugs, as mercaptopurines, and for the large use of caffeine as coadjuvant of drug molecules, especially of analgesics. , In pharmaceutical sciences, caffeine is commonly used as a psychoactive drug, and it has been also proposed for the treatment of cellulitis. − In this case, to enhance its delivery via skin permeation, caffeine was encapsulated in liposomes having lecithin as the main component plus a variable class of excipients. Several works have reported that caffeine has a low affinity to liposomes composed only of lecithin (mainly phosphatidylcholine-based lipids), the encapsulation efficiency being very low ,− and caffeine being spontaneously released from these lipid carriers. The use of excipients increased the encapsulation efficiency and delayed the spontaneous caffeine release.…”