Showing papers by "Changquan Calvin Sun published in 2013"
TL;DR: The focus of this review is on the crystal engineering and pharmaceutical literature in the last 5 years, however, classical literature is also examined when relevant.
Abstract: Introduction: Cocrystallization is an effective crystal engineering approach for modifying the crystal structure and properties of drugs. The number of examples of solving drug formulation and manufacture problems by cocrystallization is rapidly growing. An updated review that systematically examines the cocrystal research in the context of drug delivery is timely and valuable. Areas covered: Topics covered in this review include nature of cocrystal, impact of cocrystallization on key pharmaceutical properties (both enhancement and deterioration), cocrystal preparation method and future directions in this field. The focus of this review is on the crystal engineering and pharmaceutical literature in the last 5 years. However, classical literature is also examined when relevant. Expert opinion: The most effective cocrystal research relies on both in-depth understanding of structure–property relationship and efficient preparation of desired cocrystals. The future cocrystal research will see growth in the are...
187 citations
TL;DR: In this paper, a molecule-centered approach is presented toward crystal habit modification of celecoxib and its effect on oral bioavailability, and two crystal habits of CEL, acicular crystal habit (CEL-A) and a plate-shaped crystal habit(CEL)-P, were obtained by recrystallization from toluene at 25 and 60 °C, respectively.
Abstract: Poor biopharmaceutical performance of Biopharmaceutical Classification System (BCS) class II drug molecules is a major hurdle in the design and development of pharmaceutical formulations. Anisotropic surface chemistry of different facets in crystalline material affects physicochemical properties, such as wettability, of drugs. In the present investigation, a molecule-centered approach is presented toward crystal habit modification of celecoxib (CEL) and its effect on oral bioavailability. Two crystal habits of CEL, acicular crystal habit (CEL-A) and a plate-shaped crystal habit (CEL-P), were obtained by recrystallization from toluene at 25 and 60 °C, respectively. Compared to CEL-A, CEL-P exhibited significantly faster dissolution kinetics in aqueous media and significantly higher Cmax and shorter Tmax in an oral bioavailability study. The significant enhancement in dissolution and biopharmaceutical performance of CEL-P was attributed to its more abundant hydrophilic surfaces compared to CEL-A. This concl...
69 citations
TL;DR: The cocrystallization between a carboxylic acid and its conjugate base forms materials exhibiting improved physical and chemical stability over corresponding regular salts as mentioned in this paper, which is a common technique in the field of chemical engineering.
Abstract: The cocrystallization between a carboxylic acid and its conjugate base forms materials exhibiting improved physical and chemical stability over corresponding regular salts.
56 citations
TL;DR: In this article, the applicability of coating with silica nanoparticles using a dry comilling process to effectively enhance flowability of formulated pharmaceutical powders was investigated using a shear cell, including the total number of comilling cycles, silica loading level, type of screen (mesh size), impeller speed, and impeller type, on the efficiency of the nanocoating process.
48 citations
TL;DR: Strategies for robust synthesis of both structures of 5-fluorocytosine and hemicytosinium by controlling the strength of an acid used for protonation and its concentration are reported.
Abstract: Cytosine, a nucleobase, can exhibit two protonated states, cytosinium and hemicytosinium. The controlled synthesis of structures containing these ions is highly desired but not yet achieved. Herein, we report strategies for robust synthesis of both structures by controlling the strength of an acid used for protonation and its concentration. The duplex structure is always obtained by using an acid with a pKa > 4.2, which is incapable of disrupting the relatively stable duplex structure. When stronger acids (pKa < 4.19) are used, the duplex structure is obtained by controlling acid concentration to protonate a half of cytosine in solution, and the cytosinium structure is obtained with excess acid. These strategies are successfully applied to synthesize both forms of 5-fluorocytosine, an antifungal drug. The hemicytosinium structure exhibits superior physicochemical properties than the parent drug and the cytosinium salt. These strategies may be useful to prepare materials important to various branches of sc...
35 citations
TL;DR: The pharmaceutically acceptable saccharin salt of FC exhibits superior phase stability and, hence, has the potential to address the instability problem of FC associated with hydration.
Abstract: 5-Fluorocytosine (FC), an antifungal drug and a cytosine derivative, has a complex solid-state landscape that challenges its development into a drug product. A total of eight new FC salts, both cytosinium and hemicytosinium, with four strong acids were prepared by controlling acid concentration in the crystallization medium. The pharmaceutically acceptable saccharin salt of FC exhibits superior phase stability and, hence, has the potential to address the instability problem of FC associated with hydration.
26 citations
TL;DR: In this article, the authors aimed at improving properties of powders used in Fufang Danshen tablet, a popular TCM for treating angina pectoris, by particle surface engineering.
24 citations
TL;DR: In this article, the preference of 12 possible synthons in oxygen protonated amide structures was identified, and the two previously missing synthons, R22(8) and R12(6), in primary amides were realized for the first time.
Abstract: Although the amide functional group is weakly ionizable, there have been serendipitous discoveries of amide salts. To facilitate their systematic design, we sought to identify the preference of 12 possible synthons in oxygen protonated amide structures. An analysis of a total of 81 protonated amide crystal structures retrieved from the Cambridge Structural Database and 12 new protonated amide structures prepared by us, revealed that ∼86% of these structures involving charge assisted short strong hydrogen bonds, including ∼54% of the hydrogen bridged dimers formed between protonated and neutral amide. The probability of forming hydrogen bridged dimers increases in the order of primary amide < secondary amide < tertiary amide. The two previously missing synthons, R22(8) and R12(6), in primary amides are realized for the first time in this work. However, the two predicted ring (R) hydrogen bonding synthons, R22(8) and R12(6), for cis secondary amides remain to be discovered.
20 citations
TL;DR: Equation 1 has been routinely used to describe the compactibility of a powder (dependence of tablet tensile strength on tablet porosity) and is useful in guiding the scale-up of a tableting process wherein the manufacturing tableting speed is significantly higher.
6 citations