Novel high/low solubility classification methods for new molecular entities

Dave, Rutwij A.; Morris, Marilyn E.

doi:10.1016/j.ijpharm.2016.06.060

Cited by 43 publications

(30 citation statements)

References 25 publications

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“…It is noteworthy that the mole-fraction solubility of ribavirin (II) in water at 298.15 K determined in this work is 0.01741, which is a little larger than 0.0103 (142 mgÁmLl À1 ) reported by Benet [19], Goodarzi [20], Dave [21] and Chen [22], 0.0109 (149 mgÁmL À1 ) reported by Vasa [23], and 0.0124 (169.99 mgÁmL À1 ) reported by Prasanthi [24]. The difference may be due to many factors, such as determination method, equilibration time, purity, sampling, analysis method and so on.…”

Section: Solubility Resultscontrasting

confidence: 54%

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Thermodynamic modelling of solubility and preferential solvation for ribavirin (II) in co-solvent mixtures of (methanol, n -propanol, acetonitrile or 1,4-dioxane) + water

Cong

et al. 2017

The Journal of Chemical Thermodynamics

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a b s t r a c tThe equilibrium solubility of ribavirin in solvent mixtures of {methanol (1) + water (2)}, {n-propanol (1) + water (2)}, {acetonitrile (1) + water (2)} and {1,4-dioxane (1) + water (2)} was determined experimentally by using isothermal dissolution equilibrium method within the temperature range from (278.15 to 318.15) K under atmospheric pressure (101.1 kPa). At the same temperature and mass fraction of methanol (n-propanol, acetonitrile or 1,4-dioxane), the mole fraction solubility of ribavirin is greater in (methanol + water) than in the other three solvent mixtures. The preferential solvation parameters were derived from their thermodynamic solution properties by means of the inverse Kirkwood-Buff integrals. The preferential solvation parameters for methanol, n-propanol, acetonitrile or 1,4-dioxane (dx 1,3 ) were negative in the four solvent mixtures with a very wide compositions, which indicated that ribavirin was preferentially solvated by water. Temperature had little effect on the preferential solvation magnitudes. The higher solvation by water could be explained in terms of the higher acidic behaviour of water interacting with the Lewis basic groups of the ribavirin. Besides, the solubility of the drugs was mathematically represented by using the Jouyban-Acree model, van't Hoff-Jouyban-Acree model and Apelblat-Jouyban-Acree model obtaining average relative deviations lower than 1.57% for correlative studies. It is noteworthy that the solubility data presented in this work contribute to expansion of the physicochemical information about the solubility of drugs in binary solvent mixtures and also allows the thermodynamic analysis of the respective dissolution and specific solvation process.

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Section: Solubility Resultscontrasting

confidence: 54%

“…Due to its good properties, ribavirin has been received great attention. Nevertheless, in spite of the usefulness of this drug, the physicochemical properties of ribavirin in aqueous and organic solutions have not been studied systematically in the previous works [19][20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Thermodynamic modelling of solubility and preferential solvation for ribavirin (II) in co-solvent mixtures of (methanol, n -propanol, acetonitrile or 1,4-dioxane) + water

Cong

et al. 2017

The Journal of Chemical Thermodynamics

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“…Recently, Dave and Morris showed that the solubility classification could be evaluated using a 0.3 mg/mL cut-off, 25 , thus not requiring knowledge of the clinical dose, thereby allowing BDDCS classification to be made without knowledge of clinical dose (See Supplementary Figure 1). …”

Section: Introductionmentioning

confidence: 99%

“…Hosey and Benet 24 showed that based on in vitro permeability measurements, PPV for prediction of extensive metabolism were all 90% or greater. And most recently Dave and Morris 25 showed that they were able to correctly predict highly soluble vs. poorly soluble drugs using measured solubility parameters with greater than 85% probability. Thus as seen in Table 1, just knowing if a compound is BDDCS Class 2 prior to drug dosing has the ability to identify DILI potential with 90.2% PPV and 61.6% ACC.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of DILI Predictive Hypotheses in Early Drug Development

Chan

Benet

2017

Chem. Res. Toxicol.

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Drug-induced liver injury (DILI) is a leading cause of drug failure in clinical trials and a major reason for drug withdrawals. DILI has been shown to be dependent on both daily dose and extent of hepatic metabolism. Yet, early in drug development daily dose is unknown. Here, we perform a comprehensive analysis of the published hypotheses that attempt to predict DILI, including a new analysis of the Biopharmaceutics Drug Disposition Classification System (BDDCS) in evaluating the severity of DILI warning in drug labels approved by the FDA and the withdrawal status due to ADRs. Our analysis confirms that higher doses ≥ 50mg/day lead to increased DILI potential but this property alone is not sufficient to predict DILI potential. We evaluate prior attempts to categorize DILI such as Rule of 2, BSEP inhibition, and measures of key mechanisms of toxicity compared to BDDCS classification. Our results show that BDDCS Class 2 drugs exhibit the highest DILI severity, and that all of the published methodologies evaluated here, except when daily dose is known, do not yield markedly better prediction than BDDCS. The assertion that extensive metabolized compounds are at higher risk of developing DILI is confirmed, but can be enhanced by differentiating BDDCS Class 2 from Class 1 drugs. We do not propose that BDDCS classification, which does not require knowledge of the clinical dose, is sufficiently predictive/accurate of DILI potential for new molecular entities, but suggest that comparison of proposed DILI prediction methodologies with BDDCS classification is a useful tool to evaluate the potential reliability of newly proposed algorithms. Conclusion The most successful approaches to predict DILI potential all include a measure of dose, yet there is a quantifiable uncertainty associated with the predicted dose early in drug development. Here we compare the possibility of predicting DILI potential using BDDCS classification versus previously published methods, and suggest that comparison of predictive metrics versus the outcome by just avoiding BDDCS Class 2 drugs may serve as a useful baseline in evaluating these metrics.

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“…Sulfasalazine has a poor aqueous solubility, which is predicted to be 0.0024 mg/mL [25]. Preliminary tests in the current study showed that the drug solubility increased to 1 mg/mL, confirming that SSZ molecules interact with BSA.…”

Section: Preliminary Drug Release and Solubility Datamentioning

confidence: 50%

Desolvation Conditions for Production of Sulfasalazine Based Albumin Nanoparticles: Physical Properties

Olaitan¹,

Chaw²

2019

Pharm Front

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Background: Albumin-based nanoparticles have been used as drug carriers to improve therapeutic effect. This study aimed to produce sulfasalazine (SSZ)-loaded bovine serum albumin (BSA) nanoparticles by desolvation technique and characterize their physical properties. Drug loading effect was also investigated.Methods: SSZ albumin nanoparticles were batch produced by desolvation technique and lyophilized. Physical characteristics of nanoparticles including size distribution, zeta potential and entrapment efficiency were studied.Results: Nanoparticles were spherical and typically 200-400 nm with low polydispersity (PDI). The zeta potentials of nanoparticles ranged from −21 to −41 mV, which were attributed to BSA and SSZ. The highest actual drug loading was close to 0.5%w/w. The addition of 2% sucrose during lyophilization was essential to avoid cake collapse and the particle sizes increased slightly where their PDI values were low. Although the presence of sucrose led to a slight reduction in zeta potential, it had limited effect on zeta potential of the nanoparticles. The interactions between SSZ and formulation excipients were also confirmed with FTIR and DSC analyses.Conclusion: Desolvation technique produced stable sulfasalazine-loaded nanoparticles that can be administered parenterally.

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Novel high/low solubility classification methods for new molecular entities

Cited by 43 publications

References 25 publications

Thermodynamic modelling of solubility and preferential solvation for ribavirin (II) in co-solvent mixtures of (methanol, n -propanol, acetonitrile or 1,4-dioxane) + water

Thermodynamic modelling of solubility and preferential solvation for ribavirin (II) in co-solvent mixtures of (methanol, n -propanol, acetonitrile or 1,4-dioxane) + water

Evaluation of DILI Predictive Hypotheses in Early Drug Development

Desolvation Conditions for Production of Sulfasalazine Based Albumin Nanoparticles: Physical Properties

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