A study on the effect of the polymeric additive HPMC on morphology and polymorphism of ortho-aminobenzoic acid crystals

Simone, Elena; Cenzato, Maria V.; Nagy, Zoltán K.

doi:10.1016/j.jcrysgro.2016.04.034

Cited by 24 publications

(29 citation statements)

References 44 publications

(32 reference statements)

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“…[38][39][40][41] It was suggested in an early study that the polymer (PVP) formed a netlike structure on crystal surfaces, from which the drug (sulfathiazole) grew into finger-like protrusions leading to rough surfaces. 42 A similar roughening effect was observed with felodipine crystals in the presence of HPMCAS under atomic force microscopy, in which the roughening effect was suggested to be the result of HPMCAS pinning the growth steps of felodipine crystals.…”

Section: Combined Effect Of Polymer and Testing Mediamentioning

confidence: 99%

Compositional effect of complex biorelevant media on the crystallization kinetics of an active pharmaceutical ingredient

Ormes

Lowinger

et al. 2017

CrystEngComm

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Bile salts are endogenous surfactants present in the human gastrointestinal tract in the form of mixed micelles that also contain phospholipids. Due to the inevitable encounter of oral drug formulations with bile salts, it is important to understand the impact of bile salts on the crystallization tendency of poorly soluble compounds that form supersaturated solutions in vivo in order to maximize oral drug absorption. Although there has been an increasing number of studies focusing on the role of individual bile salts on drug crystallization, the effects of mixed micelles and biorelevant media composition on crystallization kinetics have only been studied to a limited extent. In this study, we evaluated the ability of binary and ternary bile salt combinations to maintain supersaturated aqueous solutions of telaprevir. Crystallization kinetics were also compared in more complex media that also contained the phospholipid, lecithin. These included fasted state simulated intestinal fluid (FaSSIF) (a widely used medium for formulation testing which contains a single bile salt, sodium taurocholate), and media that contained several endogenous bile salts. Finally, the combined effects of a polymer, hydroxypropylmethyl cellulose acetate succinate, and the testing media on crystallization kinetics were evaluated to provide insights into supersaturation formulation design. Solution bile salt composition was found to significantly influence crystallization kinetics. However, the presence of the polymer increased induction times sufficiently that differences between media were minimized. This study suggests that when evaluating the crystallization kinetics of systems with a propensity to undergo supersaturation in vivo, attention should be paid to selecting biorelevant media.

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Section: Combined Effect Of Polymer and Testing Mediamentioning

confidence: 99%

Compositional effect of complex biorelevant media on the crystallization kinetics of an active pharmaceutical ingredient

Ormes

Lowinger

et al. 2017

CrystEngComm

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“…21 Insoluble additives often influence nucleation and crystal growth by acting as templates or scaffolds on which heterogeneous nucleation can occur. The presence of soluble additives can also have an impact on the crystallization process and the end product crystals, either in terms of their habit, 14,22 size [23][24][25] or solid form (e.g. by controlling the polymorphic form).…”

Section: Introductionmentioning

confidence: 99%

Tuning Morphology in Active Pharmaceutical Ingredients: Controlling the Crystal Habit of Lovastatin through Solvent Choice and Non-Size-Matched Polymer Additives

Hatcher

Payne

et al. 2020

Crystal Growth & Design

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Additive crystallization routes to control the crystal habit of the active pharmaceutical ingredient (API) lovastatin are presented, at small scale up to 25 mL. Lovastatin is an archetypical example of an API that forms needle-like crystals via solution-based recrystallization, causing issues for downstream pharmaceutical processing stages. In this work, the size and shape of lovastatin needles are shown to be subtly influenced by the crystallization solvent, concentration and crystallization procedure, with moderately hygroscopic ethyl acetate solvent producing needles with improved aspect ratios in comparison to the acetone/water mixtures primarily used for industrial recrystallization. Further, the inclusion of soluble, non-size-matched polymer additives, at very low concentrations (0.5% wt/wt), into the solution has a pronounced impact on the crystal habit. While the inclusion of the hydrophilic polymer poly(ethyleneglycol) promotes the formation of even longer, thinner needles than those formed by non-additive routes, the use of hydrophobic poly(propyleneglycol) improves the habit from needles towards plate-like crystals. The product materials are analyzed by a combination of microscopy, thermal analysis and diffraction-based techniques, with the latter enabling rationalization of the habit control via identification of the prominent crystal faces and growth directions with respect to the underlying crystal structure.

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“…Impurities that have a molecular structure similar to the crystallizing compound (Agnew, Cruickshank, McGlone, & Wilson, ; Thomas, Wales, Zhao, & Wilson, ; Tian, Baldursdottir, & Rantanen, ) have the tendency to block the movement of surface steps, kinks, or terraces, and may be incorporated into the growing crystals (Simone, Steele, & Nagy, ), especially under unfavorable processing conditions (Meenan, Anderson, & Klug, ). In some cases, impurities are deliberately added to crystals to engineer crystallization with a desired morphology or polymorphic form (Alonzo et al, ; Ilevbare, Liu, Edgar, & Taylor, ; Klapwijk, Simone, Nagy, & Wilson, ; Lopez‐Mejías, Kampf, & Matzger, ; Oucherif, Raina, Taylor, & Litster, ; Simone, Cenzato, & Nagy, ; Trasi & Taylor, ; Vetter, Mazzotti, & Brozio, ; Yu, Dang, Black, & Wei, ).…”

Section: Introductionmentioning

confidence: 99%

Influence of Cationic Surfactants on the Crystallization of Cis‐ and Trans‐Isomers

Qiao

et al. 2018

J Surfact & Detergents

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The crystals of cis‐ and trans‐isomers present in principle similar chemical groups on their respective crystal faces. Here, the crystallization of cis‐ and trans‐isomers (maleic acid and fumaric acid) in an aqueous solution containing cationic surfactants with different hydrophobic chains (the long hydrophobic chains of dodecyltrimethylammonium bromide < cetyltrimethylammonium bromide < trimethylstearylammonium bromide) was investigated. Results showed that the surfactants presented different effects on the crystallization of cis‐ and trans‐isomers. For trans‐isomers (fumaric acid), the surfactants with longer hydrophobic chains or higher solution concentrations will favor a wider metastable zone width (MZW) and a greater morphology change. By contrast, both the MZW and morphology development of cis‐isomers (maleic acid) were not affected by these surfactants. The chemical groups on crystal faces, surface grooves, and molecular polarity were compared to reveal the different influences of surfactants on the crystallization of cis‐ and trans‐isomers.

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A study on the effect of the polymeric additive HPMC on morphology and polymorphism of ortho-aminobenzoic acid crystals

Cited by 24 publications

References 44 publications

Compositional effect of complex biorelevant media on the crystallization kinetics of an active pharmaceutical ingredient

Compositional effect of complex biorelevant media on the crystallization kinetics of an active pharmaceutical ingredient

Tuning Morphology in Active Pharmaceutical Ingredients: Controlling the Crystal Habit of Lovastatin through Solvent Choice and Non-Size-Matched Polymer Additives

Influence of Cationic Surfactants on the Crystallization of Cis‐ and Trans‐Isomers

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