Preparation of Water-Soluble Compounds Through Salt Formation

Bowker, Michael J.; Stahl, P. Heinrich

doi:10.1016/b978-0-12-374194-3.00037-8

Cited by 18 publications

(8 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sulfonate counterions are likely to show greater intramolecular as well as intermolecular interaction due to their stronger capability to form hydrogen bonding, electrostatic interactions, or steric effects. Thus, sulfonates are likely to show stronger interactions in the crystal lattice, resulting in higher melting points (26). A similar reasoning applies to PRB HCl, which has strong electrostatic interactions as well as hydrogen bonding capability.…”

Section: Effect Of Counterion On Melting Point Of Prazosinmentioning

confidence: 87%

Effect of Counterions on Physicochemical Properties of Prazosin Salts

et al. 2012

View full text Add to dashboard Cite

This study evaluated the effect of counterions on the physicochemical properties of prazosin salts. Salt forms of prazosin, namely, mesylate, besylate, tosylate, camsylate, oxalate, and maleate, were prepared and compared with the marketed anhydrous and polyhydrate forms of prazosin hydrochloride. Physicochemical characterization was performed in the order of crystallinity, hygroscopicity, solubility, and stability to select the optimal salt(s). Permeability study in Caco-2 cell lines and in vivo bioavailability study in rat model were investigated to ascertain their biopharmaceutical advantage. All salt forms were crystalline, nonhygroscopic (except the anhydrous hydrochloride salt), and had solubility in the range of 0.2 to 1.6 mg/ml. All salts were physically and chemically stable at 40°C/75% relative humidity, but degraded in UV-visible light, except the anhydrous hydrochloride salt. Prazosin mesylate was selected as the optimal salt, as it possessed higher solubility, permeability, and bioavailability, compared to the commercial hydrochloride salts. Hydrochloride salt is reported to have poor bioavailability that is partially attributed to its low solubility and extensive common-ion effect in the gastric region. Factors like hydrophilicity of the counterion, hydration state of the salt, and melting point of the salt contribute to the physicochemical properties of the salts. This study has implications in the selection of an optimal salt form for prazosin, which is suitable for further development.

show abstract

Section: Effect Of Counterion On Melting Point Of Prazosinmentioning

confidence: 87%

Effect of Counterions on Physicochemical Properties of Prazosin Salts

et al. 2012

View full text Add to dashboard Cite

show abstract

“…The compressibility of a powder is correlated with the Carr Index. The Carr index was calculated by the formula [25],…”

Section: Carr Index (Ci)mentioning

confidence: 99%

Effect of Maltodextrin Concentration and Inlet Air Temperature on Properties of Spray Dried Powder from Reverse Osmosis Concentrated Sweet Orange Juice

Sidlagatta

Chilukuri

Devana

et al. 2020

Braz. arch. biol. technol.

View full text Add to dashboard Cite

Sweet orange juice is an important part of diet since it is nutritious beverage offering good taste and play significant part in a healthy diet. High hygroscopicity, thermo-plasticity and presence of low molecular weight components in sweet orange juice offer low glass transition temperature (Tg), likely to form soft particle with sticky surface leading to sticky powder during drying. Maltodextrins are amorphous drying aids that tend to inhibit sugar crystallization and form a high Tg product after drying. In this study, the effect of the different spray drying parameters on the quality of powder derived from control and concentrated juice at three inlet air temperatures 120, 130 and 140 °C and at three levels of juice total soluble solids (TSS): maltodextrin levels at 1:0.5; 1:1 and 1:1.5 were studied. The impact of inlet air temperature and maltodextrin concentration has significantly affected various properties of sweet orange powder. For control juice, process yields increased with increase in inlet air temperature and maltodextrin concentration. However, for reverse osmosis (RO) concentrate, process yield increased with increase in maltodextrin concentration and decreased with increase in inlet air temperature. For control juice, process yields obtained were in the range of 12.59-41.16% and in case of concentrated juice, the process yield obtained was in the range of 21.35-56.95% at different combinations of inlet air temperature and maltodextrin concentrations. Spray-dried powder was considered as "possible" and "fair" in terms of flowability and cohesiveness. Vitamin C retention was high at lower inlet air temperature with lower concentration of maltodextrin. HIGHLIGHTS Powder properties obtained from spray drying of concentrated and control sweet orange juices were compared. Spray dried powder from concentrated juice offered better powder properties in comparison to the powder from control juice  Better retention of vitamin C in powder obtained from concentrated juice observed. In terms of flowability and cohesiveness, spray dried sweet orange powder was classified as "possible and fair". 2 Vishnuvardhan; et al.

show abstract

“…Although disproportionation is observed in solid state systems, the presence of water is known to be necessary for the disproportionation process, with higher water contents driving the process, indicating that it is a solution mediated reaction. ,, The pH of maximum solubility (pH max ) and the microenvironmental pH are two pivotal parameters required to understand the likelihood of disproportionation occurring. , Herein, only the disproportionation of salts of weak bases will be discussed; examples relating to the stability of weakly acidic salt can be found in the literature. − pH max , viewed as the threshold value of disproportionation, is determined by the dissociation constant (p K a ) of the base, the intrinsic solubility of the free base, and the salt solubility. , Solids of both salt and free base are considered to coexist at pH max with the formation of an equilibrium between unionized and ionized drug substance in solution. Microenvironment, a theoretical concept, is postulated as an idealistic medium for proton transfer in a microscopic water layer on the surface of solid particles.…”

Section: Introductionmentioning

confidence: 99%

Impact of Metallic Stearates on Disproportionation of Hydrochloride Salts of Weak Bases in Solid-State Formulations

Nie

Xu²,

Ren

et al. 2016

Mol. Pharmaceutics

View full text Add to dashboard Cite

Excipient-induced salt disproportionation (conversion from salt form to free form) in the solid state during storage or manufacturing is a severe formulation issue that can negatively influence product performance. However, the role of excipient properties on salt disproportionation and mechanisms of proton transfer between salt and excipients are still unclear. Moreover, knowledge about the formation of disproportionation products and the consequent impact of these reactions products on the disproportionation process is still inadequate. In the present study, three commonly used lubricants (sodium stearate, calcium stearate, and magnesium stearate) were mixed with a hydrochloride salt as binary mixtures to examine their different capabilities for inducing salt disproportionation at a stressed storage condition (40 °C/65% RH). The overall objective of this research is to explore factors influencing the kinetics and extent of disproportionation including surface area, alkalinity, hygroscopicity, formation of new species, etc. In addition, we also aim to clarify the reaction mechanism and proton transfer between the model salt and stearates to provide insight into the in situ formed reaction products. We found that the properties of stearates significantly affect the disproportionation process in the initial stage of storage, while properties of the reaction products negatively affect the hygroscopicity of the powder mixture promoting disproportionation during longer-term storage. In addition, lubrication difference among three stearates was evaluated by performing compaction studies. The findings of this study provide an improved understanding of the proton transfer mechanism between the ionized form of an active pharmaceutical ingredient and excipients in solid dosage forms. It also provides pragmatic information for formulation scientists to select appropriate lubricants and other excipients, and to design robust formulations.

show abstract

Preparation of Water-Soluble Compounds Through Salt Formation

Cited by 18 publications

References 27 publications

Effect of Counterions on Physicochemical Properties of Prazosin Salts

Effect of Counterions on Physicochemical Properties of Prazosin Salts

Effect of Maltodextrin Concentration and Inlet Air Temperature on Properties of Spray Dried Powder from Reverse Osmosis Concentrated Sweet Orange Juice

Impact of Metallic Stearates on Disproportionation of Hydrochloride Salts of Weak Bases in Solid-State Formulations

Contact Info

Product

Resources

About