Characterization and Stability of Amorphous Tadalafil and Four Crystalline Polymorphs

Wei, Yuanfeng; Ling, Yunni; Su, Meiling; Qin, Lei; Zhang, Jianjun; Gao, Yuan; Qian, Shuai

doi:10.1248/cpb.c18-00450

Cited by 17 publications

(7 citation statements)

References 36 publications

(39 reference statements)

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“…Briefly, 200 mg of tadalafil was dissolved in a solvent mixture comprising of 20 mL of methanol, 25 mL of acetonitrile and 25 mL of dichloromethane, followed by rotary vacuum evaporation at 40–45 °C in a water bath. 35 Amorphous repaglinide was obtained by rotary evaporation of repaglinide acetone solution (∼10 mg mL −1 ) under 55 °C. 36 The solid residue in the flask was collected and vacuum-dried for 24 h at room temperature to remove the residual solvents.…”

Section: Methodsmentioning

confidence: 99%

A novel drug–drug coamorphous system without molecular interactions: improve the physicochemical properties of tadalafil and repaglinide

Xia

Shen

et al. 2020

RSC Adv.

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Section: Methodsmentioning

confidence: 99%

A novel drug–drug coamorphous system without molecular interactions: improve the physicochemical properties of tadalafil and repaglinide

Xia

Shen

et al. 2020

RSC Adv.

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“…As shown in Fig. 9, Tadalafil had a sharp melting point (TM) at 303°C [38,39]. Thermal stability of Tadalafil and its binary mixtures with different excipients are presented in the Table 2.…”

Section: Resultsmentioning

confidence: 96%

Drug-Excipient Compatibility Studies In Binary Mixtures of Tadalafil by Using DSC, TGA and FTIR

Doğantürk

Canbay

2023

Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi

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Objective: During drug preformulation studies, thermal analysis and spectroscopic techniques are used to detect physical or chemical incompatibilities between the active compound and the excipients in the formulation, and to demonstrate the safety and/or efficacy of the final product. It has revolutionized erectile dysfunction with the development of a selective cyclic guanosine monophosphate-specific PDE-5 inhibitors. Tadalafil is one of these inhibitors. Excipients are included in dosage forms to assist in manufacture, absorption or application. Although considered to be pharmacologically inert, the drug active compound may impair effectiveness. Material and Method: DSC, TGA, and FTIR, were used in the work. Ascorbic acid, butylated hydroxyanisole, calcium phosphate dibasic, cellulose, magnesium stearate, mannitol, sodium carboxymethyl cellulose, sucrose, talc, starch, primojel, and citric acid exhibit interaction with Tadalafil. Binary mixtures of drug:excipient have been analyzed. Results: Based on spectroscopic and thermal results; Tadalafil is incompatible with magnesium stearate, mannitol, sucrose, and ascorbic acid. Conclusion: Studies to investigate drug-excipient compatibility are an important step in drug development studies. Thermal and spectroscopic techniques are widely used in such studies.

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“…Form III is more soluble than form I and dihydrate, while the AUC value of form I is larger than AUC value of form III and dihydrate, which may result from the faster transformation of form III to dihydrate in gastrointestinal fluids, causing a reduction of dissolution rate [23]. Another study revealed that tadalafils polymorphic forms II, III, and IV show significantly lower dissolution and dissolution rates than the amorphous form of the API [24]. Polymorphic form II of tibolone is statically more soluble in water, 0.01 mol L −1 HCl and pH 4.5 acetate buffer.…”

Section: Resultsmentioning

confidence: 99%

Structural Polymorphism of Sorafenib Tosylate as a Key Factor in Its Solubility Differentiation

et al. 2021

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The presence of active pharmaceutical ingredients (APIs) in the forms of different polymorphic states can induce differences in their physicochemical properties. In the case of poorly soluble APIs, like the oncological drug sorafenib tosylate, small variations in solubility may result in large bioavailability differences. The control of its therapeutic dose is crucial from the effective pharmacotherapy point of view and the reduction of side effects. Therefore, this study aimed to assess the influence of sorafenib tosylate polymorphic forms on its solubility and, consequently, permeability, based on passive diffusion through membranes simulating the gastrointestinal tract (GIT) conditions. In the first part of the work, two crystalline forms of sorafenib tosylate were identified using the X-ray powder diffraction, FT-IR, and Raman spectroscopy. Subsequently, solubility studies were carried out. Both forms of sorafenib tosylate were insoluble in 0.1 N hydrochloric acid (HCl), in acetate buffer (pH 4.5), and in phosphate buffer (pH 6.8). Solubility (mg/mL) of form I and III of sorafenib tosylate in 0.1 N HCl + 1.0% SDS was 0.314 ± 0.006 and 1.103 ± 0.014, respectively, in acetate buffer pH 4.5 + 1.0% SDS it was 2.404 ± 0.012 and 2.355 ± 0.009, respectively, and in phosphate buffer pH 6.8 + 1.0% SDS it was 0.051 ± 0.005 and 1.805 ± 0.023, respectively. The permeability study was assessed using the parallel artificial membrane permeability assay (PAMPA) model. The apparent permeability coefficient (Papp—cm s−1) of form I and III in pH 1.2 was 3.01 × 10−5 ± 4.14 × 10−7 and 3.15 × 10−5 ± 1.89 × 10−6, respectively, while in pH 6.8 it was 2.72 × 10−5 ± 1.56 × 10−6 and 2.81 × 10−5 ± 9.0 × 10−7, respectively. Changes in sorafenib tosylate concentrations were determined by chromatography using the high-performance liquid chromatography (HPLC)–DAD technique. As a result of the research on the structural polymorphism of sorafenib tosylate, its full spectral characteristics and the possibility of using FT-IR and Raman spectroscopy for the study of polymorphic varieties were determined for the first time, and the HPLC method was developed, which is appropriate for the assessment of sorafenib solubility in various media. The consequences of various physicochemical properties resulting from differences in the solubility of sorafenib tosylate polymorphs are important for pre-formulation and formulation studies conducted with its participation and for the safety of oncological sorafenib therapy.

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Characterization and Stability of Amorphous Tadalafil and Four Crystalline Polymorphs

Cited by 17 publications

References 36 publications

A novel drug–drug coamorphous system without molecular interactions: improve the physicochemical properties of tadalafil and repaglinide

A novel drug–drug coamorphous system without molecular interactions: improve the physicochemical properties of tadalafil and repaglinide

Drug-Excipient Compatibility Studies In Binary Mixtures of Tadalafil by Using DSC, TGA and FTIR

Structural Polymorphism of Sorafenib Tosylate as a Key Factor in Its Solubility Differentiation

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