New forms of old drugs: improving without changing

Abstract

Objectives In a short approach, we want to present the improvements that have recently been done in the world of new solid forms of known active pharmaceutical ingredients (APIs). The different strategies will be addressed, and successful examples will be given. Key findings This overview presents a possible step to overcome the 10-15 years of hard work involved in launching a new drug in the market: the use of new forms of well-known APIs, and improve their efficiency by enhancing their bioavailability and pharmacokinetics. It discusses some of the latest progresses. Summary We want to present, in a brief overview, what recently has been done to improve the discovery of innovative methods of using well-known APIs, and improve their efficiency. Multicomponent crystal forms have shown to be the most promising achievements to accomplish these aims, by altering API physicochemical properties, such as solubility, thermal stability, shelf life, dissolution rate and compressibility. API-ionic liquids (ILs) and their advantages will be briefly referred. An outline of what has recently been achieved in metal drug coordination and in drug storage and delivery using bio-inspired metal-organic frameworks (BioMOFs) will also be addressed. PreambleIn the last decade, several approaches to attain multicomponent pharmaceutical forms have been used and different kinds have been obtained. The most notorious cases are undoubtedly co-crystals and molecular salts [1] and their design, using crystal engineering principles, strategic and synthetic approaches have been the subject of different reviews.[2-5] Also, their characterization and implications for regulatory control and intellectual property protection have been presented and discussed. Here, we go one step forward and taking into account the recent definition of pharmaceutical co-crystal; from the published outcome of the Indo-US bilateral meeting in 2012 [6] and the FDA guidance draft for co-crystals, [7] which classifies co-crystals as 'dissociable API-excipient molecular complexes' where the co-former is the excipient, we call pharmaceutical companies' attention to the fact that following FDA rules, co-crystals can be treated as drug product intermediate, offering the potential of abbreviated new drug application rather than the full new drug application. This can be looked upon as not only a prompt process involving fewer risks, but also a less cost-effective process. Different steps have also been given to enhance drug properties through API metal coordination, generating metallodrugs and metallopharmaceuticals and more recently bio-inspired metal-organic frameworks (BioMOFs) for drug storage and controlled delivery. Here, we briefly present and discuss some of the recent published work, giving examples where the proposed routes proved to be beneficial.

Characterization and Quality Control of Pharmaceutical Cocrystals

“…25) Some new forms of multi-component crystals have been developed for pharmaceutical applications (e.g., BioMOFs); these materials are beyond the scope of this review. 26) Detailed crystal structures may provide a theoretical basis for the quality control of pharmaceutical cocrystals, which is achieved by the powerful single-crystal XRD technique. However, suitable large, high-quality cocrystals are often difficult to obtain because of their preparation methods.…”

Perbaikan Kelarutan Albendazol Melalui Pembentukan Kristal Multikomponen dengan Asam Malat

“…Salah satu upaya untuk meningkatkan kelarutan obat tanpa mengubah aktivitas farmakologi adalah dengan memodifikasi bentuk padatan obat melalui pembentukan kristal multikomponen, seperti garam dan ko-kristal (Domingos & Duarte, 2015;Elder et al, 2013;Thakuria et al, 2013). Kristal multikomponen terbentuk ketika lebih dari satu molekul zat berbeda mengkristal bersama di dalam satu kisi kristal dengan perbandingan stoikiometrik tertentu melalui ikatan nonkovalen.…”

Solid-State Properties and Solubility Studies of Novel Pharmaceutical Cocrystal of Itraconazole

“…This concept has widely been explored in designing multicomponent solid forms of APIs which possess unfavorable physicochemical properties. Pharmaceutical polymorphs, cocrystals and salts formations are few examples on the utilization of crystal engineering of overcoming the poor solubility of several APIs [7]. Different polymorphic forms of ITZ were reported in previous publications, which showed three polymorphic forms of ITZ (forms I-III) [8,9].…”