Solubility of Two Polymorphs of Erlotinib Hydrochloride in Isopropanol and Acetone from (273.15 to 303.15) K

Abstract

In this work the solubility of two polymorphic forms A and B of erlotinib hydrochloride in isopropanol (IPA) and acetone were determined by means of high-performance liquid chromatography (HPLC) in the temperature range from (273.15 to 303.15) K. The experimental data were correlated with the modified Apelblat equation. In particular, the effect of the surfactant Tween 80 on the solubility of both polymorphs was studied as well. The results show that the solubility of both polymorphs generally increases with the temperature, and polymorph A has a higher solubility than polymorph B which indicates that polymorph A is the metastable form. The modified Apelblat equation shows a good agreement with the experimental data with a percent error less than 3 %. Furthermore, the solubility of both polymorphs increases in a linear fashion with increasing the content of Tween 80 in organic solvents, wherein Tween 80 presents a same solubilization capacity to both polymorphs and a higher solubilization capacity in acetone than in IPA.

Solubility Measurement and Correlation of Two Erlotinib Hydrochloride Polymorphs in Alcohols and Ketones from 273.15 to 323.15 K

“…Form B of erlotinib hydrochloride and form II of clopidogrel hydrogen sulfate (mass fraction purity ≥0.995) were purchased from Lixin Pharmaceutical Co., Ltd. (Suzhou, China). Form A of erlotinib hydrochloride and form I of clopidogrel hydrogen sulfate were prepared in-house following the procedures as described in refs and , respectively. All organic solvents were analytical reagent grade and supplied by Sinopharm Reagent Co., Ltd. (Shanghai, China).…”

“…The solubility was measured by dissolution method as described in our previous work . Organic solvents were first precisely weighted and filled into jacketed 200 mL glass crystallizers which were controlled at the desired temperatures by Julabo F12-ME refrigerated/heating circulators (Seelbach, Germany) with a precision of 0.01 K. Then an excess amount of form A or form B was added into the solvents followed by vigorous stirring.…”

“…Erlotinib hydrochloride ( N -(3-ethynylphenyl)-6,7-bis­(2-methoxyethoxy)-quinazolin-4-amine hydrochloride, formula: C 22 H 24 ClN 3 O 4 , relative molecular weight: 429.90 g·mol –1 , CAS registry number: 183319-69-9, Figure ), a 4-aminophenylquinazoline oral anticancer drug which can inhibit the activity of epidermal growth factor receptor, has been reported to have seven polymorphs including forms A, B, E, L, M, N, and P. Among these polymorphs, form B is the medicinal form, and form A is being developed as the alternative . From literature review, Lu et al have studied the effect of the nonionic surfactant Tween 80 on the solubility of forms A and B of erlotinib hydrochloride in isopropanol and acetone from 273.15 to 303.15 K. Nevertheless, the corresponding work on the solubility of the polymorphs of erlotinib hydrochloride in series of organic solvents over an abroad temperature range has not yet been conducted. In this work, the solubilities of forms A and B of erlotinib hydrochloride in methanol, ethanol, isopropanol (IPA), acetone, methyl ethyl ketone (MEK), and methyl isobutyl ketone (MIBK) from 273.15 to 323.15 K were measured, and the modified Apelblat equation and the Buchowski–Ksiazczak λ h equation were employed to correlate the experimental solubility data.…”

Solubility Measurement of Crystal Form II and Form V Ticagrelor in Several Pure Organic Solvents

“…By the method of solution crystallization, the final product was usually the mixture of Form II and Form V crystals rather than the pure target form. The solubility of different crystal forms was usually different and could be used in the determination of crystal stability. − Generally, the crystallization process of the unstable form should be accurately developed. − …”

Deep eutectic solvent for an expeditious sono-synthesis of novel series of bis -quinazolin-4-one derivatives as potential anti-cancer agents

“…Some quinazolines which are well known as drugs, such as mecloqualone (Casfen), mebroqualone and methaqualone (Quaalude) possessed anxiolytic, calmative and hypnotic properties and are used for treating insomnia [5,6]. Presently, the quinazoline moiety is recognized to have a broad scope of beneficial biological activities, for instance, anti-cancer, anti-inflammatory, antitumour, protein kinase inhibitor, anti-microbial cholinesterase inhibitor, antifolate, antiviral and are the essential moiety of HIV reverse transcriptase inhibitors [7][8][9][10][11]. Proportional with the importance of this heterocyclic motif, considerable synthetic protocols have been reported to develop access to quinazolines with diversified substituents [12][13][14][15].…”