Modification of Crystal Habit and Its Role in Dosage Form Performance

Tiwary, Ashok K.

doi:10.1081/ddc-100107327

Cited by 93 publications

(61 citation statements)

References 56 publications

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“…12) DiŠerences in crystal habit may strongly in‰uence the particle orientation and modify the ‰owability, packing, compaction, compressibility, and dissolution characteristics of a drug powder. 13) Powder X-Ray DiŠraction PXRD is an authentic and fool-proof method for determining the crystallinity and identiˆcation of a polymorphic form of a substance. The X-ray diŠraction pattern of a solid form is characteristic and gives direct information about the molecular arrangement within the crystal.…”

Section: Solubility Determination Of Drug In Solventsmentioning

confidence: 99%

Role of Additives like Polymers and Surfactants in the Crystallization of Mebendazole

2008

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Crystallization in the presence of additives like surfactants and polymers is a relatively less explored area but is important for polymorphic screening of a compound during its developmental stage. Surfactants and polymers act by various mechanisms to in‰uence either the growth or the nucleation phase, resulting in modiˆcation of either the polymorphic form or the crystal habit. The present study was aimed at understanding the crystallization behavior of the model drug mebendazole (MBZ) in the presence of an inert polymer polyvinyl pyrrolidone (PVP) and an anionic surfactant sodium lauryl sulphate (SLS). Crystals were generated by the antisolvent approach using the surfactant and polymer solutions in water as the antisolvents. Change in habit from needles to plates took place as a result of modiˆca-tion of the crystallization process in the presence of additive molecules. This was conˆrmed by quantiˆcation of these additives using speciˆc analytical methods, which revealed their presence in small amounts in theˆnal product (0.02, 0.15, and 0.24％ w/w SLS in crystals generated using 0.5, 1.0, and 2.0％ SLS, respectively, and 0.94, and 1.24％ w/w PVP K30 and PVP K90, respectively). Their presence in the crystals led to modiˆcation in the dissolution of the drug. SLS improved the extent of dissolution while PVP had a negative impact and led to reduction in the amount of MBZ released even below that of the pure drug. The study highlights the in‰uence of polymeric and surfactant additives on the crystallization process leading to modiˆed performance.

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Section: Solubility Determination Of Drug In Solventsmentioning

confidence: 99%

Role of Additives like Polymers and Surfactants in the Crystallization of Mebendazole

2008

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“…Though a single internal structure with different external morphologies often exists for the particular API, vice versa however is rarely evident. Nevertheless, the change in external and internal structures of the API within dosage form itself should affect not only the chemical and physical stabilities but also the performance of the dosage forms which includes dissolution, flowability, tableting, and syringeability (2)(3)(4). Since there is no single reliable method that existed to be able to legally secure all possible drug forms, it becomes therefore necessary for both innovator and generic drug companies to make every effort to find new and efficient (in terms of time and/or resources) screening methods.…”

Section: Introductionmentioning

confidence: 99%

Studies on Aspirin Crystals Generated by a Modified Vapor Diffusion Method

et al. 2015

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Abstract. The objectives of the current investigation were (1) to study the influence of selected two different non-solvents (diethylether and dichloromethane) on the drug crystal formation of a model drug, aspirin (ASP-I) by the modified vapor diffusion method and (2) to characterize and compare the generated crystals (ASP-II and ASP-III) using different analytical techniques with that of unprocessed ASP-I. When compared to the classical vapor diffusion method which consumes about 15 days to generate drug crystals, the modified method needs only 12 h to get the same. Fourier transform-infrared spectroscopy (FT-IR) reveals that the internal structures of ASP-II and ASP-III crystals were identical when compared with ASP-I. Although the drug crystals showed a close similarity in X-ray diffraction patterns, the difference in the relative intensities of some of the diffraction peaks (especially at 2θ values of around 7.7 and 15.5) could be attributed to the crystal habit or crystal size modification. Similarly, the differential scanning calorimetry (DSC) study speculates that only the crystal habit modifications might occur but without involving any change in internal structure of the generated drug polymorphic form I. This is further substantiated from the scanning electron microscopy (SEM) pictures that indicated the formation of platy shape for the ASP-II crystals and needle shape for the ASP-III crystals. In addition, the observed slow dissolution of ASP crystals should indicate polymorph form I formation. Thus, the modified vapor diffusion method could routinely be used to screen and legally secure all possible forms of other drug entities too.

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“…Therefore, habit modification seems to provide an alternative means of modifying the dissolution behavior of drugs (8,10,11). Use of different solvents alters crystal habit, which may alter dissolution rate.…”

Section: Introductionmentioning

confidence: 99%

Effect of Solvent on Crystal Habit and Dissolution Behavior of Tolbutamide by Initial Solvent Screening

Keraliya¹,

Soni²,

Thakkar³

et al. 2010

Dissolution Technol.

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By an initial solvent screening of 18 solvents, 14 pure good solvents were selected for the crystallization of tolbutamide. Solid generation by the solvent-change method was carried out using the pure good solvents. Crystals were generated in only 10 of the 14 solvents. Different crystal forms of tolbutamide were obtained. Crystals were subjected to evaluation tests such as differential scanning calorimetry, optical microscopy, and in vitro dissolution. All crystals were determined as isomorphic by differential scanning calorimetry. Dissolution rate was influenced by crystal form. Thus, the choice of suitable crystal habit and proper selection of solvent is important in manufacturing the drug tolbutamide.

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Modification of Crystal Habit and Its Role in Dosage Form Performance

Cited by 93 publications

References 56 publications

Role of Additives like Polymers and Surfactants in the Crystallization of Mebendazole

Role of Additives like Polymers and Surfactants in the Crystallization of Mebendazole

Studies on Aspirin Crystals Generated by a Modified Vapor Diffusion Method

Effect of Solvent on Crystal Habit and Dissolution Behavior of Tolbutamide by Initial Solvent Screening

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