Influences of Crystal Anisotropy in Pharmaceutical Process Development

Abstract

Crystalline materials are of crucial importance to the pharmaceutical industry, as a large number of APIs are formulated in crystalline form, occasionally in the presence of crystalline excipients. Owing to their multifaceted character, crystals were found to have strongly anisotropic properties. In fact, anisotropic properties were found to be quite important for a number of processes including milling, granulation and tableting. An understanding of crystal anisotropy and an ability to control and predict crystal anisotropy are mostly subjects of interest for researchers. A number of studies dealing with the aforementioned phenomena are grounded on over-simplistic assumptions, neglecting key attributes of crystalline materials, most importantly the anisotropic nature of a number of their properties. Moreover, concepts such as the influence of interfacial phenomena in the behaviour of crystalline materials during their growth and in vivo, are still poorly understood. The review aims to address concepts from a molecular perspective, focusing on crystal growth and dissolution. It begins with a brief outline of fundamental concepts of intermolecular and interfacial phenomena. The second part discusses their relevance to the field of pharmaceutical crystal growth and dissolution. Particular emphasis is given to works dealing with mechanistic understandings of the influence of solvents and additives on crystal habit. Furthermore, comments and perspectives, highlighting future directions for the implementation of fundamental concepts of interfacial phenomena in the rational understanding of crystal growth and dissolution processes, have been provided.

Impact of Crystal Habit on Solubility of Ticagrelor

“…The rate of crystal growth is mainly related to the rate at which units attach and remove themselves from the growing surfaces. Deposition kinetics of solute molecules on different crystal faces determine the crystal habit [22,50]. Investigations on the single-crystal structure of the TICA-II suggest that elongation is driven by the formation of hydrogen-bond networks in the crystal lattice.…”

“…A beaker containing 150 mL of pH = 1.2 HCl was equilibrated at 37 • C, then approximately 150 mg of samples that had been passed through a 300 mesh sieve beforehand were added to the beaker, which was stirred at 150 rpm on a magnetic stirrer. Slurry was filtered with 0.22 µm nylon filters after 2,4,6,8,10,15,20,25,30,40,50,60,90,120,150,180,210, and 240 min. Each filtered aliquot was assayed by UV analysis at 257 nm.…”

Periodic DFT Calculations—Review of Applications in the Pharmaceutical Sciences

“…Solid form structure affects crystal morphology, which may have an impact on processability of the drug product due to the different mechanical and flow properties [21]. For example, needle shaped crystals are usually undesirable for pharmaceutical applications since they are difficult to handle in the formulation process [22]. Additionally, the crystal morphology greatly influences the bioavailability of the inhaled drugs, i.e., bronchodilators [23].…”

Stability and Rheological Properties of Nourivan(tm)/Antiox(r) Base With Selected Solvents

“…Lack of success or reduction of treatment effects of different dermatological use drugs for may result, inter alia, from poor solubility of the medicinal substance. Many factors influence the solubility of a medicinal substance, such as, e.g lipophilicity, molecular weight, crystallographic form or the solvent type used [11][12][13][14][15][16]. In order to solve this problem, new compositions of ointment vehicles are being developed or existing ones modified.…”