Use of the Flory–Huggins theory to predict the solubility of nifedipine and sulfamethoxazole in the triblock, graft copolymer Soluplus

Altamimi, Mohammad A.; Neau, Steven H.

doi:10.3109/03639045.2015.1075033

Cited by 31 publications

(18 citation statements)

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“…The reduction of the chemical potential is an indicator of the drug-polymer miscibility. The data can be used to calculate the Flory-Huggins interaction parameter and construct the drug-polymer miscibility phase diagram 6,[12][13][14][15][16] . Although this method has proven to be more reliable than the solubility parameter calculation, there are two significant drawbacks of this approach.…”

Section: Introductionmentioning

confidence: 99%

Novel Thermal Imaging Method for Rapid Screening of Drug–Polymer Miscibility for Solid Dispersion Based Formulation Development

et al. 2018

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This study aimed to develop a rapid, simple and inexpensive screening method for selecting the best polymeric candidates possessing high active pharmaceutical ingredient (API) miscibility during the early stages of formulation development of solid dispersion based pharmaceutical products. A new thermal imaging based method, thermal analysis by structural characterization (TASC), was used as a thermoptometeric tool in conjunction with data analysis software to detect the melting point depression and post-melting dissolution of felodipine particles screened over thin spin-coated films of ten polymers commonly used in the pharmaceutical field. On the polymeric substrates the drug showed different degrees of melting point reduction, reflecting their different levels of polymer-drug miscibility. Using TASC to detect melting point depression is significantly (20-40 times) faster than the conventional DSC method without loss of the sensitivity of detection. The quantity of the material required for the screening is less than 1/1000 th of the material used in conventional DSC tests which significantly reduce the material wastage. Isothermal TASC tests and IR imaging confirmed the occurrence of thermal dissolution of the drug in the polymer for more miscible pairs. The real-time stability tests validate the accuracy of the polymer-drug miscibility screening results. These results demonstrate TASC as a promising screening tool for rapidly selecting the polymeric excipients for pharmaceutical formulations development.

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Section: Introductionmentioning

confidence: 99%

Novel Thermal Imaging Method for Rapid Screening of Drug–Polymer Miscibility for Solid Dispersion Based Formulation Development

et al. 2018

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“…We should also note that χ dp is temperature dependent, and is usually given the empirical form χ dp (T ) = α T + β (5) where α, β are constants. Flory-Huggins theory has frequently been used to analyse the stability of binary solid dispersion systems in storage; see, for example, [11,37,36,4,9,1,8,24,39,40]. In many of these studies, the Flory-Huggins interaction parameter is first estimated using the melting point depression method [25], or using the Hildebrand and Scott method [19], which involves the estimation of solubility parameters.…”

Section: Introductionmentioning

confidence: 99%

Modelling phase separation in amorphous solid dispersions

2019

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Much work has been devoted to analysing thermodynamic models for solid dispersions with a view to identifying regions in the phase diagram where amorphous phase separation or drug recrystallization can occur. However, detailed partial differential equation non-equilibrium models that track the evolution of solid dispersions in time and space are lacking. Hence theoretical predictions for the timescale over which phase separation occurs in a solid dispersion are not available. In this paper, we address some of these deficiencies by (i) constructing a general multicomponent diffusion model for a dissolving solid dispersion; (ii) specializing the model to a binary drug/polymer system in storage; (iii) deriving an effective concentration dependent drug diffusion coefficient for the binary system, thereby obtaining a theoretical prediction for the timescale over which phase separation occurs; and (iv) presenting a detailed numerical investigation of the HPMCAS/Felodipine system assuming a Flory-Huggins activity coefficient. The numerical simulations exhibit numerous interesting phenomena, such as the formation of polymer droplets and strings, Ostwald ripening/coarsening, phase inversion, and dropletto-string transitions.

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“…Nifedipine solubility in solid soluplus was reported ranging between 7.3 and 3.55 % w/w, according to the temperature parameter considered, applying the Flory-Huggins theory to predict the solubility [15] . The miscibility limit of nifedipine/soluplus co-precipitates was reported to be 30% w/w drug loading, using different preparation methods (freeze drying, melting and solvent evaporation) [12] .…”

Section: Figure 1 (Abcd): Sem Imagesmentioning

confidence: 99%

“…In the case of the association nifedipine/soluplus literature has been mainly concerned with the study of interaction between the drug and the polymer, the miscibility limits, the effects of the preparing techniques and aging on dissolution behavior [12][13][14][15] . The original aim of our research was to compare a range of hydrophilic carriers, including soluplus, such as Gelucires, PEGs and Lutrols, in the nifedipine release improvement from co-precipitates.…”

Section: Introductionmentioning

confidence: 99%

“…Few examples can be found for nifedipine tested with soluplus, a new attractive carrier [12][13][14][15] to prepare co-precipitate of drug by hot-melt extrusion [16] . It represents a hydrophilic non-ionic multipurpose carrier for its ability to act as polymer matrix former suitable for co-precipitates; and is considered as a member of the fourth generation of co-precipitate carriers [17] .…”

Section: Introductionmentioning

confidence: 99%

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Release Problems for Nifedipine in the Presence of Soluplus

Fini¹,

Cavallari²,

Ternullo³

et al. 2016

JPP

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Nifedipine/soluplus co-precipitates were prepared at 1:9 and 1:1 weight ratios, using the solvent method, with the aim to obtain an improvement of the drug release. The release, though accelerated with respect to physical mixtures and pure drug, resulted slow with respect to similar systems containing soluplus and are characterized by the appearance in suspension of micro-particulates that, at the optical microscope, revealed a large variety of shapes typical of flower-like aggregates, not previously reported. For comparison systems were also prepared with PVP K30 and sucrester P1670 and two mixtures, without any evidence of this last phenomenon. The systems were studied by thermal (differential scanning calorimetry -DSC, thermomicroscopy -HSM) and spectroscopic (SEM, FT-IR, micro-Raman) analysis. Slow release of nifedipine and formation of colloidal micro-particulates were hypothesized due to the gelling tendency of soluplus associated to drug/polymer multi-site-interactions: when one of these parameters is absent in the system the two phenomena could not be observed together, such as in the case of PVP K30 or sucrester P1670, when used as carriers for nifedipine release.

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Use of the Flory–Huggins theory to predict the solubility of nifedipine and sulfamethoxazole in the triblock, graft copolymer Soluplus

Abstract: The Flory-Huggins Theory indicates that Soluplus® interacts effectively with each drug, making solid solution formation feasible. The predicted solubility of the drugs in Soluplus® compared favorably across the methods and supports the use of the onset of melting.

Cited by 31 publications

References 50 publications

Novel Thermal Imaging Method for Rapid Screening of Drug–Polymer Miscibility for Solid Dispersion Based Formulation Development

Novel Thermal Imaging Method for Rapid Screening of Drug–Polymer Miscibility for Solid Dispersion Based Formulation Development

Modelling phase separation in amorphous solid dispersions

Release Problems for Nifedipine in the Presence of Soluplus

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