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

Abstract

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.

Understanding the effect of solvent polarity on the habit modification of monoclinic paracetamol in terms of molecular recognition at the solvent crystal/interface

“…For the production of these drug materials, crystallization from solution is a vital unit operation which is highly responsible for achieving the chemicals with high purity and to produce the desired final crystal form . Solubility, crystallinity and crystal properties of an active pharmaceutical ingredient (API) play a crucial role in the worth series of pharmaceutical development, manufacturing and formulation . Because these properties are all solvent dependent, solvent is the fundamental and foremost important factor for promoting or inhibiting certain crystal motif and to produce correlated effects to the success of required drug material compatibility for the end‐user.…”

“…Because these properties are all solvent dependent, solvent is the fundamental and foremost important factor for promoting or inhibiting certain crystal motif and to produce correlated effects to the success of required drug material compatibility for the end‐user. The use of different solvents during crystallization profoundly affects the crystal habit of the purified drug, leading to the variation in raw material charac teristics such as flowability, compaction, chemical stability, dissolution and packing . The amount of drug dissolved with time depends on the size and number of crystal faces exposed to the dissolution medium.…”

Crystal Morphologies and Polymorphs in Tolbutamide Microcrystalline Powder

“…Apart from the works wherein TB has been studied for crystallographic purposes,24–29 the most chosen solvents in which it has been solubilized are alcohols—as for polymorph III. In a detailed study on TB solubility, acetonitrile is not even taken into account while different alcohols are studied; interestingly, TB is reported as nonsoluble in water 47. This is in agreement with the use of water as nonsolvent for the crystallization of polymorph III and confirms that TB solubility behavior decreases as the solvent polarity increases—water is more polar than acetonitrile, which is in turn more polar than alcohols.…”

Technical crystallization for application in pharmaceutical material engineering: Review article

“…In general, a knowledge of how crystal grow from the crystal nuclei and the effects of the various factors which may influence crystal growth is not studied from pharmaceutical viewpoint in as much as chemical or physical viewpoints. So crystal growth for any pharmaceutical ingredients may be in general affected by two factors [31], [32], and [33]:…”