Physicochemical properties of tadalafil solid dispersions – Impact of polymer on the apparent solubility and dissolution rate of tadalafil

Wlodarski, K.; Sawicki, Wiesław; Haber, K.; Knapik, J.; Wojnarowska, Ż.; Paluch, Marian; Lepek, P.; Hawełek, ᴌ.; Tajber, Lidia

doi:10.1016/j.ejpb.2015.04.031

Cited by 75 publications

(50 citation statements)

References 25 publications

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“…Ninety-two of the 101 studies reported solubility and dissolution studies (71–74,77–79,81–92,95,97–107,109–111,113–119,121,123,124,126–133,135–139,141–154,156,157,160,161,166,168–176). The USP in vitro dissolution type II apparatus was the most commonly used instrument (67%), followed by the USP type I apparatus (6%), while the remaining 27% used various other apparatuses, including modified versions of the USP type I only (148) or paired with confocal Raman microscopy (98), USP types I and II apparatus (72), USP type IV (152), closed loop of USP types II and IV (152), a perspex flow cell (73,142), a rotary mixer (131), a Chinese pharmacopoeia type III apparatus (118), an in-house miniaturized USP type II apparatus (175), Sirius T3 apparatus (146), μFLUX dissolution-permeation apparatus (141), Raman UV-Vis flow cell system (99), a centrifuge (88), high throughput screening using a 96-well plate (82,115,157), Wood’s apparatus (99,137), an orbital shaking incubator (156), and another shake-flask method (171) (Fig. 6).…”

Section: Current Status Of Research On Amorphous Formulationsmentioning

confidence: 99%

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

2017

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The alarming numbers of poorly soluble discovery compounds have centered the efforts towards finding strategies to improve the solubility. One of the attractive approaches to enhance solubility is via amorphization despite the stability issue associated with it. Although the number of amorphous-based research reports has increased tremendously after year 2000, little is known on the current research practice in designing amorphous formulation and how it has changed after the concept of solid dispersion was first introduced decades ago. In this review we try to answer the following questions: What model compounds and excipients have been used in amorphous-based research? How were these two components selected and prepared? What methods have been used to assess the performance of amorphous formulation? What methodology have evolved and/or been standardized since amorphous-based formulation was first introduced and to what extent have we embraced on new methods? Is the extent of research mirrored in the number of marketed amorphous drug products? We have summarized the history and evolution of amorphous formulation and discuss the current status of amorphous formulation-related research practice. We also explore the potential uses of old experimental methods and how they can be used in tandem with computational tools in designing amorphous formulation more efficiently than the traditional trial-and-error approach.

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Section: Current Status Of Research On Amorphous Formulationsmentioning

confidence: 99%

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

2017

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“…The drug and polymer were selected based on our previous study in which aqueous solubility and the dissolution rate of Td were significantly improved by its incorporation in the PVP-VA matrix [23]. An interesting aspect of the current work is that the glass transition temperature (Tg) of the polymer (107.…”

Section: Introductionmentioning

confidence: 99%

Physical stability of solid dispersions with respect to thermodynamic solubility of tadalafil in PVP-VA

Wlodarski

Sawicki

Kozyra

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

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The aim of this paper was to evaluate physical stability of solid dispersions in respect to the drug, tadalafil (Td), in vinylpyrrolidone and vinyl acetate block copolymer (PVP-VA). Nine solid dispersions of Td in PVP-VA (Td/PVP-VA) varied in terms of quantitative composition (1:9-9:1, w/w) were successfully produced by spray-drying. Their amorphous nature, supersaturated character and molecular level of mixing (a solid solution structure) were subsequently confirmed using DSC, PXRD, SEM and calculation of Hansen total solubility parameters. Due to thermal degradation of both components before the melting point of Td

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“…As previously reported, TD-I showed typical stretching vibrations of the secondary amine group (N-H) at 3326.8 cm −1 and lactam at 1677.3 and 1647.6 cm −1 . [24][25][26] Comparing with TD-I, TD-II showed bathochromic shifts (3326.8 3317.7 cm −1 ) for secondary amine group. The typical C=O stretching of TD-III demonstrated a significant hypsochromic shift (1647.6 1657.9 cm −1 ) and the peak at 1490 cm −1 split into two peaks as 1501.0 and 1485.6 cm −1 .…”

Section: Resultsmentioning

confidence: 90%

Characterization and Stability of Amorphous Tadalafil and Four Crystalline Polymorphs

Wei

Ling

et al. 2018

Chem. Pharm. Bull.

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Tadalafil (TD), a phosphodiesterase-5 (PDE-5) inhibitor with poor oral bioavailability. The aim of the study was to prepare and characterize three crystalline polymorphs of TD (II, III, and IV) and the tadalafil amorphous form (TD-AM). TD polymorphs and TD-AM were prepared and characterized by polarized light microscope (PLM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), X-ray powder diffractometry (XRPD), and Fourier-transform (FT)IR, followed by the dissolution testing, physical stabilities and polymorphic transformation studies. TD-I and TD-II were found to be enantiotropically related, while TD-III was monotiotropically related to TD-I with heat release. Among all studied polymorphs, TD-AM demonstrated an extremely high intrinsic dissolution rate with most prolonged higher saturated concentration during dissolution, while TD-II, TD-III, and TD-IV converted to TD-I easily by supersaturation-mediated phase transformation. Upon heating under 60°C for 3 h and storing at long-term stability condition for 3 months, no phase transformation was detected for TD-I, TD-III, and TD-AM, while TD-II and TD-IV easily transformed to TD-I and TD-III, respectively. The higher intrinsic dissolution rate, prolonged supersaturated state during dissolution and favorable physical stability of TD-AM made it to be a very promising candidate for further product development.

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Physicochemical properties of tadalafil solid dispersions – Impact of polymer on the apparent solubility and dissolution rate of tadalafil

Cited by 75 publications

References 25 publications

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

Physical stability of solid dispersions with respect to thermodynamic solubility of tadalafil in PVP-VA

Characterization and Stability of Amorphous Tadalafil and Four Crystalline Polymorphs

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