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

Wlodarski, K.; Sawicki, Wiesław; Kozyra, Agnieszka; Tajber, Lidia

doi:10.1016/j.ejpb.2015.07.026

Cited by 55 publications

(43 citation statements)

References 21 publications

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“…According to the thermodynamics of mixing, the rst condition for the interactions to take place between a drug in polymer is obtaining negative change in free energy of mixing. [1][2][3][4] The change in free energy of mixing is related to the enthalpy and entropic contributions according to the following equation (eqn (1)).…”

Section: Introductionmentioning

confidence: 99%

Studies of intermolecular interactions in solid dispersions using advanced surface chemical analysis

et al. 2015

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The aim of this study is to utilise an advanced surface chemical analysis based on X-ray photoelectron spectroscopy (XPS) to determine and characterise drug/polymer interactions in solid dispersions manufactured via hot melt extrusion (HME). Cetirizine HCl (CTZ) and verapamil HCl (VRP) were used as model cationic drugs while Eudragit® grade L100 and L100-55 polymers were used as anionic carriers. A molecular dynamics (MD) based simulation approach predicted drug/polymer interactions while scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS) mapping showed homogenous distribution of the drug particles onto the polymer matrices. Hot stage microscopy (HSM) characterised the solid state of the drugs in extruded formulations. XPS analysis revealed the strength and nature of interaction between the -NH 3 groups of the APIs with the -COOH groups of the polymers.The results obtained from XPS were supported by XRD and NMR studies. The estimation of non-protonated/ protonated N atom (N/N 0 ) ratios using XPS revealed the strength of the intermolecular interaction in drug/ polymer extrudates which can be used as an efficient tool to study the drug/polymer interaction.

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Section: Introductionmentioning

confidence: 99%

Studies of intermolecular interactions in solid dispersions using advanced surface chemical analysis

et al. 2015

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“…However, suffering from poor aqueous solubility, tadalafil is a BCS class II drug. Numerous approaches for enhancing its dissolution rate were reported including the use of solid dispersions 29 , complexation with cyclodextrins 30 , inclusion in microporous silicas 31 , formulation of nanosuspensions 32 , use of self-nanoemulsifying drug delivery systems (SNEDDS) 33 , and nanostructured lipid carriers (NLCs) 34 . However, to the best of our knowledge, liquisolid technique has never been utilized to promote the dissolution of tadalafil in the reported literatures.…”

Section: Introductionmentioning

confidence: 99%

Dissolution enhancement of tadalafil by liquisolid technique

Xing

Yang

et al. 2016

Pharmaceutical Development and Technology

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This study aimed to enhance the dissolution of tadalafil, a poorly water-soluble drug by applying liquisolid technique. The effects of two critical formulation variables, namely drug concentration (17.5% and 35%, w/w) and excipients ratio (10, 15 and 20) on dissolution rates were investigated. Pre-compression tests, including particle size distribution, flowability determination, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and scanning electron microscopy (SEM), were carried out to investigate the mechanism of dissolution enhancement. Tadalafil liquisolid tablets were prepared and their quality control tests, dissolution study, contact angle measurement, Raman mapping, and storage stability test were performed. The results suggested that all the liquisolid tablets exhibited significantly higher dissolution rates than the conventional tablets and pure tadalafil. FT-IR spectrum reflected no drug-excipient interactions. DSC and XRD studies indicated reduction in crystallinity of tadalafil, which was further confirmed by SEM and Raman mapping outcomes. The contact angle measurement demonstrated obvious increase in wetting property. Taken together, the reduction of particle size and crystallinity, and the improvement of wettability were the main mechanisms for the enhanced dissolution rate. No significant changes were observed in drug crystallinity and dissolution behavior after storage based on XRD, SEM and dissolution results.

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“…To retain the solubility advantage of the amorphous state, amorphous solid dispersions (ASDs) have been proposed as an effective strategy to "kinetically stabilize" amorphous drugs [4]. ASDs refer to drug -carrier systems, where the drug is dispersed at a molecular level in the carrier, usually an amorphous polymer [5,6]. ASDs can be produced by several processes such as freeze-drying [7,8], hot-melt extrusion [9,10], rotary solvent evaporation [11]; ball milling [12]; cryo-milling [13]; supercooling [14] and spray drying [6,15,16].…”

Section: Introductionmentioning

confidence: 99%

Determination of drug-polymer solubility from supersaturated spray-dried amorphous solid dispersions: A case study with Efavirenz and Soluplus®

Costa

Sauceau

Confetto

et al. 2019

European Journal of Pharmaceutics and Biopharmaceutics

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Amorphous solid dispersions (ASDs) are found to be a well-established strategy for overcoming limited aqueous solubility and poor oral bioavailability of active pharmaceutical ingredients (APIs). One of the main parameters affecting ASDs physical stability is the API solubility in the carrier, because this value determines the maximal API load without a risk of phase separation and recrystallization. Phase-diagrams can be experimentally obtained by following the recrystallization of the API from a supersaturated homogeneous API-polymer solid solution, commonly produced by processes as solvent casting or comilling, which are very time-consuming (hours). The work deals with the construction of a temperature-composition EFV-Soluplus® phase diagram, from a thermal study of recrystallization of a supersaturated solid solution (85 wt% in EFV) generated by spray drying. This supersaturated solution is kept at a given annealing temperature to reach the equilibrium state and the amount that still remains dispersed in the polymer carrier at this equilibrium temperature is determined by means of the new glass transition temperature of the binary mixture. From our knowledge, this is the first study employing a fast process (spray drying) to prepare a supersaturated solid solution of an API in a polymer aiming to determine a temperature-composition phase diagram. The EFV solubility in Soluplus ranges from 20 wt% at 25°C to 30 wt % at 40°C. It can be a very useful preformulation tool for researchers studying amorphous solid dispersions of Efavirenz in Soluplus, to assist for predicting the stability of EFV-Soluplus ASDs at different EFV loadings and under different thermal conditions.

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

Cited by 55 publications

References 21 publications

Studies of intermolecular interactions in solid dispersions using advanced surface chemical analysis

Studies of intermolecular interactions in solid dispersions using advanced surface chemical analysis

Dissolution enhancement of tadalafil by liquisolid technique

Determination of drug-polymer solubility from supersaturated spray-dried amorphous solid dispersions: A case study with Efavirenz and Soluplus®

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