Solubility parameters as predictors of miscibility in solid dispersions

Greenhalgh, David J.; Williams, Adrian C.; Timmins, Peter; York, Peter

doi:10.1021/js9900856

Cited by 578 publications

(351 citation statements)

References 33 publications

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“…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] . These values agree with what predicted by the Hildebrand's solubility parameters: the carriers used to prepare co-precipitates and nifedipine display Δδ values well below the critical limit [21,22] (Table 2). These values indicate likely miscibility and make it possible to predict the formation of a homogeneous dispersion of the drug into the carriers; while for the sucrester it could be expected that the drug could be present partly in undissolved/re-precipitated form, being borderline the δ value reported for the sucrester P1670 [23] .…”

Section: Figure 1 (Abcd): Sem Imagessupporting

confidence: 85%

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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Section: Figure 1 (Abcd): Sem Imagessupporting

confidence: 85%

Release Problems for Nifedipine in the Presence of Soluplus

Fini¹,

Cavallari²,

Ternullo³

et al. 2016

JPP

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“…48,49 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Quantification analysis for the composite systems was performed by DVS and NIR due to their enhanced sensitivity at detecting low amorphous content levels, compared to DSC and pXRD.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the Capacity of Low Glass Transition Temperature Excipients to Minimize Amorphization of Sulfadimidine on Comilling

Curtin

Amharar

et al. 2012

Mol. Pharmaceutics

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The co-processing of active pharmaceutical ingredient (API) with an excipient which has a high glass transition temperature (Tg) is a recognised strategy to stabilise the amorphous form of a drug. This work investigates whether co-processing a model API, sulfadimidine (SDM) with a series of low Tg excipients prevents or reduces amorphisation of the crystalline drug. It was hypothesised that these excipients could exert a Tg lowering effect, resulting in composite Tg values lower than that of the API alone and promote crystallisation of the drug. Milled SDM and co-milled SDM with glutaric acid (GA), adipic acid (AA), succinic acid (SA) and malic acid (MA) were characterised with respect to their thermal, X-Ray diffraction, spectroscopic and vapour sorption properties.SDM was predominantly amorphous when milled alone, with an amorphous content of 82 %.No amorphous content was detected by dynamic vapour sorption (DVS) on co-milling SDM with 50 % w/w GA, and amorphous content of the API was reduced by almost 30 %, relative to the API milled alone, on co-milling with 50 % w/w AA. In contrast, amorphisation of SDM was promoted on co-milling with 50 % w/w SA and MA, as indicated by near infrared (NIR) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 2 spectroscopy. Results indicated that the API was completely amorphised in the SDM:MA comilled composite.The saturated solubility of GA and AA in the amorphous API was estimated by thermal methods.It was observed that the Tg of the co-melt quenched composites reached a minimum and levelled out at this solubility concentration. Maximum crystallinity of API on co-milling was reached at excipient concentrations comparable to the saturated concentration solubility of excipient in the API. Moreover, the closer the Hildebrand solubility parameter of the excipient to the API, the greater was the inhibition of API amorphisation on co-milling.The results reported here indicate that an excipient with a low Tg coupled with high solubility in the API can prevent or reduce the generation of an amorphous phase on co-milling.

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“…The synthesis of cocrystals success rate was improved by using the components which have similar miscibility [67] . It was demonstrated that the two components should be miscible if total HSPs difference was <7MP a 0.5 , otherwise immiscible [68] . Another method estimates the miscibility of two components if the difference is ≤5 MP 0.5 between two substances which are supposed to be cocrystal formation [69,70] .…”

Section: Hansen Solubility Parametermentioning

confidence: 99%