# Study of Different Crystal Habits of Apreptiant: Dissolution and Material Attributes
## 1 Introduction  
Polymorphism is the ability of a molecule to pack in different crystal lattices whereas crystal habit is the external appearance of a compound [1, 2]. Crystal habit modification and polymorphism have an important role in the formulation and development of poorly water-soluble drugs as it improves dissolution and other material properties which in turn improve pharmaceutical and biopharmaceutical performance [1, 3, 4]. Crystal habit affects material attributes such as flow property, packing, compressibility, dissolution [5, 6]. Material properties of active pharmaceutical ingredient (API) take an important place in the high-dose formulations where API occupies a large volume. Issues of improper flow, blend uniformity, non-uniform filling of capsules on capsule filling machine, results in variation in content uniformity and dissolution. In this scenario, improvement of material attributes ofAPI itself such as bulk density, flowability is of utmost importance [7]. The size and shape of API crystal habits are directly linked to flow, cohesiveness, bulk density, tensile strength, and compatibility of API powder [8]. Crystals with high aspect ratios such as needle, bar, tabular are notorious for bad powder flow properties [9]. Bad powder flow creates a non-uniform filling of the die on the compression machine and capsule filling. Formulation choices such as direct compression and capsule filling are preferred over others due to the simple and time-saving process but still require a good flow of blend [5; 10]. The purpose of the granulation step during tablet manufacturing is to improve the flow of material. Direct compression avoids the granulation step and the use of organic solvents, helping to design the environment-friendly manufacturing process at a larger scale. To eliminate granulation step flow properties of API need to be improved. Suitable crystal habit for the API can be evaluated among the possible crystal habits for improved flow and other material attributes. Approaches such as solvent recrystallization, co-crystallization are used to develop a suitable crystal habit to improve the processing of powder blend at a large scale. The nature of the solvent and its saturation level impact the growth rate of crystal facets [11]. Solvent nature alters the wettability of crystal surface which impacts dissolution [12]. Internalization of functional groups which are less attracted toward a solvent occurs during crystallization [13]. Ammonia solution used for recrystallization of sulpha-diazine significantly reduced dissolution rate [14]. Dissolution of plate shape crystals of ibuprofen recrystallized using acetone and ethanol was higher than that of rod-shaped crystals recrystallized from propylene glycol and 2-propanol [15]. The symmetry of the crystals impacts dissolution, where symmetric crystals due to equal exposure of all surfaces found to give faster dissolution [16]. APT is an off-white crystalline solid which is practically insoluble in water with oral bioavailability of 60-65% [17]. APT is a selective high-affinity antagonist of neurokinin 1 (NK1) receptors and is indicated for the prevention of acute and delayed nausea related to enterogenic cancer chemotherapy and prevention of postoperative nausea and vomiting [17; 18]. APT exists in the crystalline form I and form II [19]. [PERSON] et al. [18] prepared single crystals of both polymorphic forms I and II and studied their spectral and thermochemical differences, crystal packing modes, and molecular interactions using Hirshfeld surface analysis. Oral nanocrystalline powder capsule formulation is available in the market but no research has been done on crystal habits of APT and their impact on pharmaceutical properties such as flow, bulk density, cohesiveness, tensile strength, compactibility, and dissolution. In current research work, we found that APT after recrystallization gives tabular and long tabular crystal habits.